Wuxi People's Hospital

BACKGROUND: We aimed to report the clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu Province. METHODS: We retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed cases of COVID-19 with World Health Organization interim guidance in 3 grade IIIA hospitals of Jiangsu from 22 January to 14 February 2020. Real-time RT-PCR was used to detect the new coronavirus in respiratory samples. RESULTS: Of the 80 patients infected with COVID-19, 41 were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. Nine patients were unconfirmed until a third nucleic acid test; 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 (78.75%) and 51 (63.75%) cases, respectively. Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (68.75%) showed abnormal density shadow and 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Currently, 21 cases have been discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days. CONCLUSIONS: Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptibility. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that in Wuhan. Notably, infected patients may be falsely excluded based on 2 consecutively negative respiratory pathogenic nucleic acid test results.

Iron oxide nanoparticles (IONPs) have been increasingly used in biomedical applications, but the comprehensive understanding of their interactions with biological systems is relatively limited. In this study, we systematically investigated the in vitro cell uptake, cytotoxicity, in vivo distribution, clearance and toxicity of commercially available and well-characterized IONPs with different sizes and coatings. Polyethylenimine (PEI)-coated IONPs exhibited significantly higher uptake than PEGylated ones in both macrophages and cancer cells, and caused severe cytotoxicity through multiple mechanisms such as ROS production and apoptosis. 10 nm PEGylated IONPs showed higher cellular uptake than 30 nm ones, and were slightly cytotoxic only at high concentrations. Interestingly, PEGylated IONPs but not PEI-coated IONPs were able to induce autophagy, which may play a protective role against the cytotoxicity of IONPs. Biodistribution studies demonstrated that all the IONPs tended to distribute in the liver and spleen, and the biodegradation and clearance of PEGylated IONPs in these tissues were relatively slow (>2 weeks). Among them, 10 nm PEGylated IONPs achieved the highest tumor uptake. No obvious toxicity was found for PEGylated IONPs in BALB/c mice, whereas PEI-coated IONPs exhibited dose-dependent lethal toxicity. Therefore, it is crucial to consider the size and coating properties of IONPs in their applications.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

The discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the outbreak of coronavirus disease 2019 (COVID-19) are causing public health emergencies. A handful pieces of literature have summarized its clinical and radiologic features, whereas therapies for COVID-19 are rather limited. To evaluate the efficacy of convalescent plasma therapy in COVID-19 patients, we did this timely descriptive study. Six laboratory-confirmed COVID-19 patients were enrolled and received the transfusion of ABO-compatible convalescent plasma. The efficacy of this intervention was determined by the alleviation of symptoms, changes in radiologic abnormalities and laboratory tests. No obvious adverse effect observed during the treatment. Transfusion of convalescent plasma led to a resolution of ground-glass opacities and consolidation in patients #1, #2, #3, #4, and #6. In patients #1 and #5 who presented with SARS-CoV-2 in throat swab, convalescent plasma therapy elicited an elimination of the virus. Serologic analysis indicated an immediate increase in anti-SARS-CoV-2 antibody titers in patients #2 and #3, but not in patient #1. This study indicates that convalescent plasma therapy is effective and specific for COVID-19. This intervention has a special significance for eliminating SARS-CoV-2 and is believed to be a promising state-of-the-art therapy during COVID-19 pandemic crisis.

The gut microbiota can significantly affect the function of the intestinal barrier. Some intestinal probiotics (such as Lactobacillus, Bifidobacteria, a few Escherichia coli strains, and a new generation of probiotics including Bacteroides thetaiotaomicron and Akkermansia muciniphila) can maintain intestinal epithelial homeostasis and promote health. This review first summarizes probiotics' regulation of the intestinal epithelium via their surface compounds. Surface layer proteins, flagella, pili and capsular polysaccharides constitute microbial-associated molecular patterns and specifically bind to pattern recognition receptors, which can regulate signaling pathways to produce cytokines or inhibit apoptosis, thereby attenuating inflammation and enhancing the function of the gut epithelium. The review also explains the effects of metabolites (such as secreted proteins, organic acids, indole, extracellular vesicles and bacteriocins) of probiotics on host receptors and the mechanisms by which these metabolites regulate gut epithelial barrier function. Previous reviews summarized the role of the surface macromolecules or metabolites of gut microbes (including both probiotics and pathogens) in human health. However, these reviews were mostly focused on the interactions between these substances and the intestinal mucosal immune system. In the current review, we only focused on probiotics and discussed the molecular interaction between these bacteria and the gut epithelial barrier.

Cancer immunotherapies that engage immune cells to fight against tumors are proving to be powerful weapons in combating cancer and are becoming increasingly utilized in the clinics. However, for the majority of patients with solid tumors, little or no progress has been seen, presumably due to lack of adequate approaches that can reprogram the local immunosuppressive tumor milieu and thus reinvigorate antitumor immunity. Tumor-associated macrophages (TAMs), which abundantly infiltrate most solid tumors, could contribute to tumor progression by stimulating proliferation, angiogenesis, metastasis, and by providing a barrier against antitumor immunity. Initial TAMs-targeting strategies have shown efficacy across therapeutic modalities and tumor types in both preclinical and clinical studies. TAMs-targeted therapeutic approaches can be roughly divided into those that deplete TAMs and those that modulate TAMs activities. We here reviewed the mechanisms by which macrophages become immunosuppressive and compromise antitumor immunity. TAMs-focused therapeutic strategies are also summarized.

BACKGROUND: At present, the severity of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a focal point. METHODS: To assess the factors associated with severity and prognosis of patients infected with SARS-CoV-2, we retrospectively investigated the clinical, imaging and laboratory characteristics of confirmed 280 cases of novel coronavirus disease (COVID-19) from 20 January to 20 February 2020. RESULTS: The median age of patients in the mild group was 37.55 years, whilst that in the severe group was 63.04 years. The proportion of patients aged over 65 years in the severe group was significantly higher than that of the mild group (59.04% vs. 10.15%, P < 0.05). 85.54% of severe patients had diabetes or cardiovascular diseases, which was significantly higher than that of the mild group (51.81% vs. 7.11%, P = 0.025; 33.73% vs. 3.05%, P = 0.042). Patients in the mild group experienced earlier initiation of antiviral treatment (1.19 ± 0.45 vs. 2.65 ± 1.06 days in the severe group, P < 0.001). Our study showed that comorbidity, time from illness onset to antiviral treatment and age >=65 were three major risk factors for COVID-19 progression, whilst comorbidity and time from illness onset to antiviral treatment were two major risk factors for COVID-19 recovery. CONCLUSIONS: The elderly and patients with underlying diseases are more likely to experience a severe progression of COVID-19. It is recommended that timely antiviral treatment should be initiated to slow the disease progression and improve the prognosis.

Mesenchymal stem cell (MSC) transplantation is now considered as an effective treatment strategy for traumatic spinal cord injury (SCI). However, several key issues remain unresolved, including low survival rates, cell dedifferentiation, and tumor formation. Recent studies have demonstrated that the therapeutic effect of transplanted stem cells is primarily paracrine mediated. Exosomes are an important paracrine factor that can be used as a direct therapeutic agent. However, there are few reports on the application of exosomes derived from bone MSCs (BMSCs-Exos) in treating SCI. In this study, we demonstrated that BMSCs-Exos possessed robust proangiogenic properties, attenuated neuronal cells apoptosis, suppressed glial scar formation, attenuated lesion size, suppressed inflammation, promoted axonal regeneration, and eventually improved functional behavioral recovery effects after traumatic SCI. Briefly, lesion size was decreased by nearly 60%, neuronal apoptosis was attenuated by nearly 70%, glial scar formation was reduced by nearly 75%, average blood vessel density was increased by nearly 60%, and axonal regeneration was increased by almost 80% at day 28 after SCI in the BMSC-Exos group compared to the control group. Using a series of in vitro functional assays, we also confirmed that treatment with BSMCs-Exos significantly enhanced human umbilical vein endothelial cell proliferation, migration, and angiogenic tubule formation, attenuated neuronal cells apoptosis, and suppressed nitric oxide release in microglia. Moreover, our study demonstrated that administration of BMSCs-Exos suppressed inflammation efficiently after traumatic SCI and suppressed activation of A1 neurotoxic reactive astrocytes. In conclusion, our study suggested that the application of BMSCs-Exos may be a promising strategy for traumatic SCI.

On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus COVID-19 a pandemic. There are patients in psychiatric hospitals in China who have been infected with COVID-19, however, the knowledge and attitudes of psychiatric hospital staff towards infectious diseases and their willingness to work during the COVID-19 outbreak has not yet been investigated. This study was performed to assess the knowledge and attitudes of medical staff in two Chinese mental health centers during the COVID-19 outbreak. We included 141 psychiatrists and 170 psychiatric nurses in the study. We found that during the COVID-19 epidemic, 89.51% of the medical staff of the psychiatric hospitals studied had extensive knowledge of COVID-19, and 64.63% of them received the relevant training in hospitals. Furthermore, about 77.17% of participants expressed a willingness to care for psychiatric patients suffering from COVID-19 virus infection. Independent predictors of willingness to care for patients included advanced training and experience of caring for patients with COVID-19. In conclusion, this study suggests that increased attention should be paid to the knowledge and attitudes of medical staff at psychiatric hospitals during the COVID-19 outbreak.

Abstract Purpose: Long non-coding RNAs (lncRNAs) play key roles in human cancers. Here, FEZF1-AS1, a highly overexpressed lncRNA in colorectal cancer, was identified by lncRNA microarrays. We aimed to explore the roles and possible molecular mechanisms of FEZF1-AS1 in colorectal cancer. Experimental Design: LncRNA expression in colorectal cancer tissues was measured by lncRNA microarray and qRT-PCR. The functional roles of FEZF1-AS1 in colorectal cancer were demonstrated by a series of in vitro and in vivo experiments. RNA pull-down, RNA immunoprecipitation and luciferase analyses were used to demonstrate the potential mechanisms of FEZF1-AS1. Results: We identified a series of differentially expressed lncRNAs in colorectal cancer using lncRNA microarrays, and revealed that FEZF1-AS1 is one of the most overexpressed. Further validation in two expanded colorectal cancer cohorts confirmed the upregulation of FEZF1-AS1 in colorectal cancer, and revealed that increased FEZF1-AS1 expression is associated with poor survival. Functional assays revealed that FEZF1-AS1 promotes colorectal cancer cell proliferation and metastasis. Mechanistically, FEZF1-AS1 could bind and increase the stability of the pyruvate kinase 2 (PKM2) protein, resulting in increased cytoplasmic and nuclear PKM2 levels. Increased cytoplasmic PKM2 promoted pyruvate kinase activity and lactate production (aerobic glycolysis), whereas FEZF1-AS1–induced nuclear PKM2 upregulation further activated STAT3 signaling. In addition, PKM2 was upregulated in colorectal cancer tissues and correlated with FEZF1-AS1 expression and patient survival. Conclusions: Together, these data provide mechanistic insights into the regulation of FEZF1-AS1 on both STAT3 signaling and glycolysis by binding PKM2 and increasing its stability. Clin Cancer Res; 24(19); 4808–19. ©2018 AACR.

Abstract Purpose: Tumor-associated macrophages (TAMs) are frequently associated with poor prognosis in human cancers. However, the effects of TAMs in colorectal cancer are contradictory. We therefore investigated the functions, mechanisms, and clinical significance of TAMs in colorectal cancer. Experimental Design: We measured the macrophage infiltration (CD68), P-gp, and Bcl2 expression in colorectal cancer tissues using IHC staining. Coculture of TAMs and colorectal cancer cells both in vitro and in vivo models was used to evaluate the effects of TAMs on colorectal cancer chemoresistance. Cytokine antibody arrays, ELISA, neutralizing antibody, and luciferase reporter assay were performed to uncover the underlying mechanism. Results: TAM infiltration was associated with chemoresistance in patients with colorectal cancer. Colorectal cancer–conditioned macrophages increased colorectal cancer chemoresistance and reduced drug-induced apoptosis by secreting IL6, which could be blocked by a neutralizing anti-IL6 antibody. Macrophage-derived IL6 activated the IL6R/STAT3 pathway in colorectal cancer cells, and activated STAT3 transcriptionally inhibited the tumor suppressor miR-204-5p. Rescue experiment confirmed that miR-204-5p is a functional target mediating the TAM-induced colorectal cancer chemoresistance. miR-155-5p, a key miRNA regulating C/EBPβ, was frequently downregulated in TAMs, resulting in increased C/EBPβ expression. C/EBPβ transcriptionally activated IL6 in TAMs, and TAM-secreted IL6 then induced chemoresistance by activating the IL6R/STAT3/miR-204-5p pathway in colorectal cancer cells. Conclusions: Our data indicate that the maladjusted miR-155-5p/C/EBPβ/IL6 signaling in TAMs could induce chemoresistance in colorectal cancer cells by regulating the IL6R/STAT3/miR-204-5p axis, revealing a new cross-talk between immune cells and tumor cells in colorectal cancer microenvironment. Clin Cancer Res; 23(23); 7375–87. ©2017 AACR.

Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsy. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lung estimated by chest CT scan, were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analysed by RNA sequencing of lung specimens and BALF. Results: Neutrophilia occurred in 6 of 8 severe patients at 7 to 19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0·8, 0·3-1·2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular traps (NETs) associated genes in COVID-19 patients, which related with innate immunity and interacted with T/NK /B cells, as supported by protein-protein interaction network analysis. Conclusion: Excessive neutrophils and associated NETs could explain pathogenesis of lung injury in COVID-19 pneumonia.

Background Early stage hepatocellular carcinoma (HCC) is the ideal candidate for resection in patients with preserved liver function; however, cancer will recur in half of these patients and no reliable prognostic tool has been established. Purpose To investigate the effectiveness of radiomic features in predicting tumor recurrence after resection of early stage HCC. Materials and Methods In total, 295 patients (median age, 58 years; interquartile range, 50–65 years; 221 men) who underwent contrast material–enhanced CT and curative resection for early stage HCC that met the Milan criteria between February 2009 and December 2016 were retrospectively recruited from three independent institutions. Follow-up consisted of serum α-fetoprotein level, liver function tests, and dynamic imaging examinations every 3 months during the first 2 years and then every 6 months thereafter. In the development cohort of 177 patients from institution 1, recurrence-related radiomic features were computationally extracted from the tumor and its periphery and a radiomics signature was built with least absolute shrinkage and selection operator regression. Two models, one integrating preoperative and one integrating pre- and postoperative variables, were created by using multivariable Cox regression analysis. An independent external cohort of 118 patients from institutions 2 and 3 was used to validate the proposed models. Results The preoperative model integrated radiomics signature with serum α-fetoprotein level and tumor number; the postoperative model incorporated microvascular invasion and satellite nodules into the above-mentioned predictors. In both study cohorts, two radiomics-based models provided better predictive performance (concordance index ≥0.77, P < .05 for all), lower prediction error (integrated Brier score ≤0.14), and larger net benefits, as determined by means of decision curve analysis, than rival models without radiomics and widely adopted staging systems. The radiomics-based models gave three risk strata with high, intermediate, or low risk of recurrence and distinct profiles of recurrent tumor number. Conclusion The proposed radiomics models with pre- and postresection features helped predict tumor recurrence for early stage hepatocellular carcinoma. © RSNA, 2020 Online supplemental material is available for this article.

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Plenty of immune cells infiltrate into the tumor microenvironment (TME) during tumor progression, in which myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with immunosuppressive activity. Tumor cells and stromal cells facilitate the activation and expansion of MDSCs in TME via intercellular communication, and expanded MDSCs suppress anti-tumor immune responses through direct and indirect mechanisms. Currently, exosomes, which are a kind of extracellular vesicles (EVs) that can convey functional components, are demonstrated to participate in the local and distal intercellular communication between cells. Numerous studies have supposed that tumor-derived exosomes (TEXs), whose assembly and release can be modulated by TME, are capable of modulating the cell biology of MDSCs, including facilitating their activation, promoting the expansion, and enhancing the immunosuppressive function. Therefore, in this review, we mainly focus on the role of TEXs in the cell-cell communication between tumor cells and MDSCs, and discuss their clinical applications.

The early diagnosis of infectious diseases is critical because it can greatly increase recovery rates and prevent the spread of diseases such as COVID-19; however, in many areas with insufficient medical facilities, the timely detection of diseases is challenging. Conventional medical testing methods require specialized laboratory equipment and well-trained operators, limiting the applicability of these tests. Microfluidic point-of-care (POC) equipment can rapidly detect diseases at low cost. This technology could be used to detect diseases in underdeveloped areas to reduce the effects of disease and improve quality of life in these areas. This review details microfluidic POC equipment and its applications. First, the concept of microfluidic POC devices is discussed. We then describe applications of microfluidic POC devices for infectious diseases, cardiovascular diseases, tumors (cancer), and chronic diseases, and discuss the future incorporation of microfluidic POC devices into applications such as wearable devices and telemedicine. Finally, the review concludes by analyzing the present state of the microfluidic field, and suggestions are made. This review is intended to call attention to the status of disease treatment in underdeveloped areas and to encourage the researchers of microfluidics to develop standards for these devices.

To date, a variety of delivery systems based on organic or inorganic materials have been investigated. Among them, hydrogels have become one of the most promising field in drug delivery system due to their unique properties. Temperature-sensitive hydrogels, which gelation at physiological temperature, gift the delivery system with excellent spatial and temporal control, and have a widely application in drug delivery, tissue engineering, imaging, and wound dressing. This review provides a brief overview on the concept and classification of temperature-sensitive hydrogels, and covers the application of temperature-sensitive gel systems in delivery of biotherapeutic molecules.

As a spore-forming probiotic bacterium, Bacillus coagulans has become a focus of research due to its high tolerance of extreme environments and probiotic characteristics. Several beneficial effects of B. coagulans have been reported. Firstly, B. coagulans can promote intestinal digestion. For example, B. coagulans strains can produce various enzymes that facilitate excretion and digestion. Secondly, B. coagulans can regulate host symbiotic microbiota and inhibit the growth of pathogenic bacteria. Lastly, due to its ability to normalize both the quantitative parameters of the immune system and immune cells’ functional activity, B. coagulans can significantly benefit the host immune system. Due to the evidence supporting various probiotic effects of B. coagulans, many B. coagulans strains have been studied in the management and alleviation of several human diseases. Therefore, the administration of B. coagulans may be an attractive preventive and/or therapeutic approach for human diseases.

BACKGROUND: More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. RESULTS: Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo, while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. CONCLUSIONS: Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention.

Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME). In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers. Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy. Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism. Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.