Classification of nasal polyps and inverted papillomas using CT-based radiomics.

OBJECTIVES: Nasal polyp (NP) and inverted papilloma (IP) are two common types of nasal masses. And their differentiation is essential for determining optimal surgical strategies and predicting outcomes. Thus, we aimed to develop several radiomic models to differentiate them based on computed tomography (CT)-extracted radiomic features. METHODS: A total of 296 patients with nasal polyps or papillomas were enrolled in our study. Radiomics features were extracted from non-contrast CT images. For feature selection, three methods including Boruta, random forest, and correlation coefficient were used. We choose three models, namely SVM, naive Bayes, and XGBoost, to perform binary classification on the selected features. And the data was validated with tenfold cross-validation. Then, the performance was assessed by receiver operator characteristic (ROC) curve and related parameters. RESULTS: In this study, the performance ability of the models was in the following order: XGBoost > SVM > Naive Bayes. And the XGBoost model showed excellent AUC performance at 0.922, 0.9078, 0.9184, and 0.9141 under four conditions (no feature selection, Boruta, random forest, and correlation coefficient). CONCLUSIONS: We demonstrated that CT-based radiomics plays a crucial role in distinguishing IP from NP. It can provide added diagnostic value by distinguishing benign nasal lesions and reducing the need for invasive diagnostic procedures and may play a vital role in guiding personalized treatment strategies and developing optimal therapies. CRITICAL RELEVANCE STATEMENT: Based on the extraction of radiomic features of tumor regions from non-contrast CT, optimized by radiomics to achieve non-invasive classification of IP and NP which provide support for respective therapy of IP and NP. KEY POINTS: • CT images are commonly used to diagnose IP and NP. • Radiomics excels in feature extraction and analysis. • CT-based radiomics can be applied to distinguish IP from NP. • Use multiple feature selection methods and classifier models. • Derived from real clinical cases with abundant data.

Baicalin Protects Against Acute Pancreatitis Involving JNK Signaling Pathway via Regulating miR-15a.

Acute pancreatitis (AP) is a kind of reversible inflammatory process of the exocrine pancreas. During the process, systemic inflammatory syndromes are involved, which relates closely to inflammatory mediators. Baicalin is a type of flavone compound extracted from Scutellaria baicalensis Georgi and exhibits anti-inflammation effect in several cancers. In this study, baicalin displayed a suppressing role on IL-1[Formula: see text], TNF[Formula: see text] and IL-6 in both cell and mice models. Necrosis was decreased in the baicalin treatment group and got a markedly lower pathological score. In this study, miR-15a is the core intermediate in baicalin regulation, which increased through baicalin treatment and protected pancreas cells and tissues, inhibiting the JNK signaling pathway by targeting MAP2K4. The long non-coding RNA MALAT1 is also a direct target of miR-15a and forms a competitive endogenous RNA (ceRNA) network with MAP2K4, which can be regulated by baicalin. In addition, upstream genes, including CDC42 and MAP3K1, were also regulated by baicalin, of which CDC42 was confirmed to form the second ceRNA network with MALAT1 and miR-15a. In conclusion, baicalin exhibits therapeutic activity towards AP by pumping up miR-15a level and inhibiting CDC42/MAP3K1, which affects AP as a brake by targeting MAP2K4 and inhibiting the JNK signaling pathway.

Quercetin inhibits caerulein-induced acute pancreatitis through regulating miR-216b by targeting MAP2K6 and NEAT1.

Acute pancreatitis (AP) is a common acute abdominal disease with high mortality and mortality rates. Increasing evidences clarified that Traditional Chinese Medicine (TCM) adjuvant therapy for AP can be used and it gives a positive effect. Quercetin (3,3',4',5,7-pentahydroxyflavone, QE) is a type of flavone compound with positive effect on cancer and inflammation prevention. The current study aims to identify the effect of QE on AP and potential molecular effect. In this case, caerulein (CAE) induced AP cell and mice model were used. QE alleviated inflammatory mediators TNF-α, IL-6, and IL-10 in experiments. In addition, miR-216b was increased based on QE treatment. In further study, MAP2K6 of p38/MAPK signaling pathway was identified as a direct target of miR-216b, and QE inhibited p38/MAPK signaling pathway through up-regulating miR-216b. Our study also first confirmed that long non-coding RNA NEAT1 is a direct target of miR-216b and can be suppressed by QE. Because of the target, NEAT1, miR-216b, and MAP2K6 formed a competitive endogenous RNA (ceRNA) network. Besides direct target mediated by QE, it also decreased TNF-α which down-regulated TRAF2 and MAP3K5 located on upstream of p38/MAPK signaling and formed a feedback loop. In conclusion, QE has a protective effect on AP through inhibiting p38/MAPK signaling pathway by up-regulating miR-216b and suppressing TNF-α.

Higher maternal embryonic leucine zipper kinase mRNA expression level is a poor prognostic factor in non-small-cell lung carcinoma patients.

Aim: To elucidate potential prognostic significance of MELK mRNA expression in non-small-cell lung carcinoma patients. Methods: A loop algorithm based on R software was used to select genes with the best prognostic value. Mantel-Haenszel method and functional enrichment analysis were used to perform this analysis. Results:MELK mRNA expression level in tumor tissue is significantly higher than that in normal/benign tissue (p < 0.001), and gradually increases from stage I to IV (lung adenocarcinoma: p = 0.011; lung squamous cell carcinoma: p = 0.002), and is negatively correlated with prognosis in lung adenocarcinoma patients (HR: 2.025 in univariate analysis; HR: 2.162 in multivariate analysis). However, it does not show a significant correlation in lung squamous cell carcinoma patients. Conclusion:MELK is a poor biomarker for non-small-cell lung carcinoma patients and can potentially be used as a therapeutic target.

[Validation of a septic myocardial inhibition model by intraperitoneal injection of endotoxin in rats].

OBJECTIVE: To establish septic myocardial inhibition rat model by echocardiography. METHODS: Twenty adult male Sprague-Dawley (SD) rats were divided into control group and model group according to the random number table method, with 10 rats in each group. The rat model of septic myocardial inhibition was reproduced by intraperitoneal injection of 10 mg/kg lipopolysaccharide, while the control group was given the same volume of saline. The left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic diameter (LVDs), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), right ventricular end-diastolic diameter (RVDd), right ventricular end-systolic diameter (RVDs), heart rate (HR), positive pulmonary artery flow rate and aortic flow rate were measured at 8 hours after model establishment by echocardiography. Then the rats were sacrificed to harvest serum and myocardial tissue. The levels of serum tumor necrosis factor-α (TNF-α), nuclear factor-ΚB (NF-ΚB), interleukin-1 (IL-1), cardiac troponin I (cTnI) and B-type brain natriuretic peptide (BNP) were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of TNF-α, IL-1 and NF-ΚB in myocardium were detected by real-time polymerase chain reaction (real-time PCR). The pathological changes of myocardium were observed by hematoxylin-eosin (HE) staining under light microscope. RESULTS: Compared with control group, myocardial inhibition was obviously observed in model group, manifesting as enlargement of overall shape of heart, and prominent increase of HR (bpm: 449.0±21.1 vs. 356.7±23.3, P < 0.01); left ventricular and right ventricular functions were affected, LVDd, LVDs, LVEDV, LVESV were enlarged [LVDd (mm): 10.03±0.95 vs. 7.04±0.71, LVDs (mm): 5.95±0.71 vs. 3.07±0.05, LVEDV (mL): 2.11±0.53 vs. 0.81±0.21, LVESV (mL): 0.51±0.16 vs. 0.07±0.01, all P < 0.05], LVEF was significantly decreased (0.760±0.046 vs. 0.901±0.025, P < 0.01), RVDd was significantly increased (mm: 4.48±0.58 vs. 3.22±0.20, P < 0.05), and positive pulmonary artery velocity was significantly decreased (cm/s: 64.2±9.3 vs. 89.0±0.8, P < 0.05). Compared with control group, the levels of serum NF-ΚB, TNF-α, IL-1, BNP and cTnI in model group were significantly increased [NF-ΚB (ng/L): 103.84±6.55 vs. 57.29±41.34, TNF-α (ng/L): 1 198.32±164.07 vs. 835.45±24.01, IL-1 (ng/L): 1 089.90±221.96 vs. 746.19±165.83, BNP (ng/L): 1 097.36±293.84 vs. 454.71±197.79, cTnI (ng/L): 6 938.59±1 400.21 vs. 3 731.90±1 349.31, all P < 0.01], the mRNA expressions of TNF-α, NF-ΚB and IL-1 in myocardial tissue were significantly increased (2-ΔΔCT: 1.50±0.42 vs. 0.71±0.40, 1.10±0.17 vs. 0.63±0.06, 1.77±0.67 vs. 0.10±0.03, all P < 0.05). It was shown by HE staining that the structure of myocardial tissue in control group was distinct, the arrangement of myocardial fibers was neat, and transverse was clear; the structure of myocardial tissue in model group was loose, blurred, and the cells were swollen, with obvious pathological changes. CONCLUSIONS: Cardiac function was assessed by echocardiography, expression of inflammatory factors, myocardial markers and pathological changes. It was verified that intraperitoneal injection of 10 mg/kg endotoxin could successfully prepare a rat model of septic myocardial inhibition.

A negative Smad2/miR-9/ANO1 regulatory loop is responsible for LPS-induced sepsis.

The roles of miR-9 in tumor progression are well-defined, however, its roles and the mechanisms in sepsis are still unclear. This work aims to explore miR-9 roles and related mechanism in LPS-induced sepsis. We found that miR-9 level was significantly upregulated in septic patients and RAW264.7 cells with LPS treatment, knockdown of miR-9 attenuated the induced effects of LPS on IL-6 and TNF-α secretion. In vivo experiments showed that miR-9 expression was increased in septic mice and knockdown of miR-9 partially reversed the upregulation of IL-6 and TNF-α levels in septic mice and prolonged the survival of septic mice. Mechanistic studies revealed that miR-9 could target ANO1, which inactivates the TGF-ß/Smad2 signaling. Conversely, Smad2 could bind to the promoter of miR-9 and promote miR-9 expression. Notably, ANO1 overexpression or Smad2 knockdown attenuated miR-9 knockdown-mediated inhibition on LPS-induced sepsis. Therefore, these results suggest that the negative Smad2/miR-9/ANO1 regulatory loop is responsible for LPS-induced sepsis.

OCT4B-190 protects against ischemic stroke by modulating GSK-3ß/HDAC6.

OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B and OCT4B1. The 190-amino-acid protein isoform (OCT4B-190) is one of the major products of OCT4B mRNA, the biological function of which is still not well defined. Recent evidence suggests that OCT4B-190 may function in the cellular stress response. The glycogen synthase kinase-3ß (GSK-3ß) and histone deacetylase 6 (HDAC6) are also key stress modulators that play critical roles in the ischemic cascades of stroke. Hence, we here further investigated the effects of OCT4B-190 in the experimental stroke, and explored the underlying roles of GSK-3ß and HDAC6. We found that OCT4B-190 overexpression enhanced neuronal viability at 24 h after oxygen-glucose deprivation (OGD) treatment. Moreover, in male C57BL/6 mice subjected to transit middle cerebral artery occlusion (MCAO), OCT4B-190 overexpression reduced infarct volume and improved neurological function after stroke. Notably, we found spatio-temporal alterations of GSK-3ß and HDAC6 in the ischemic cortex and striatum, which were affected by adenovirus-mediated OCT4B-190 overexpression. OCT4B-190 demonstrated similar impacts on neuronal cultures in vitro, downregulating OGD-induced GSK-3ß activity and HDAC6 expression. In addition, we found that GSK-3ß and HDAC6 were co-expressed in the cytoplasm of neurons, and OCT4B-190 had an effect on interactions between GSK-3ß and HDAC6 in neuronal cultures subjected to OGD treatment. These findings suggest that OCT4B-190 exerts neuroprotection in the experimental stroke potentially by regulating actions of GSK-3ß and HDAC6 simultaneously, which may be an attractive therapeutic strategy for ischemic stroke.

Effect of interleukin-31 on septic shock through regulating inflammasomes and interleukin-1ß.

Sepsis with severe systemic inflammation remains a great challenge for the intensive care unit in clinics. Although biomarkers have been identified to diagnose, monitor and predict these syndromes, novel therapeutic approaches are required for the amelioration of symptoms of sepsis and septic shock. The present study demonstrated that interleukin (IL)-31 was able reduce the mortality rate of lipopolysaccharide (LPS)-induced sepsis with the reduction of inflammatory cytokines in the sera. IL-31 also inhibited IL-1ß production in the peritoneal lavage fluid in LPS-induced or cecal ligation and puncture-induced sepsis. The in vitro mechanism responsible for IL-31 regulation on peritoneal IL-1ß activation following LPS challenge was explored. It was demonstrated that IL-1ß secretion was suppressed by IL-31 treatment from LPS-challenged peritoneal macrophages following adenosine triphosphate stimulation, which is an activator of NLR family, pyrin domain-containing 3 (NLRP3). Furthermore, IL-31 inhibited the expression of NLRP3 at the transcriptional level. In human THP-1 cells, anti-IL-31/anti-IL-31 receptor (R) neutralizing antibody enhanced NLRP3 expression as well as IL-1ß activation, suggesting a role of the IL-31-IL-31R-NLRP3-IL-1ß signaling axis in the physiological status of sepsis. On the other hand, IL-31 displayed a negative effect on the NLRP1 inflammasome, but not on NLRP3 on the LPS-primed human peripheral blood monocytes, resulting in reduction of the inflammatory cytokine, tumor necrosis factor (TNF)-α, in the supernatant. Taken together, the present data implied that T helper 2-type cytokine, IL-31, may be a promising therapeutic option for treatment of sepsis and septic shock in clinics.

Dexmedetomidine improves the outcomes in paediatric cardiac surgery: a meta-analysis of randomized controlled trials.

OBJECTIVES: Dexmedetomidine has been shown to decrease cardiac complications in adults undergoing cardiac surgery. Results from clinical trials of dexmedetomidine on outcomes following paediatric cardiac surgery are controversial. METHODS: We searched EMBASE, PubMed and Cochrane CENTRAL databases for randomized controlled trials comparing the effect of dexmedetomidine versus placebo or other anaesthetic drugs in paediatric patients undergoing cardiac surgery. The primary outcome was the duration of mechanical ventilation. The secondary outcomes were intensive care unit stay, hospital length of stay (LOS), incidence of junctional ectopic tachycardia and postoperative deaths. RESULTS: Nine trials with a total of 837 patients were selected. Compared with controls, dexmedetomidine significantly reduced the postoperative duration of mechanical ventilation [in hours; n = 837; weighted mean difference -2.20, 95% confidence interval (CI) -3.51 to -0.90; P = 0.001; I2 = 97%], intensive care unit LOS (in days; n = 737; weighted mean difference -0.47, 95% CI -0.90 to -0.03; P = 0.03; I2 = 97%) and hospital LOS (in days; n = 291; weighted mean difference -1.80, 95% CI -3.36 to -0.25; P = 0.02; I2 = 96%). Dexmedetomidine also significantly reduced the incidence of postoperative junctional ectopic tachycardia (21/292 vs 50/263; risk ratio 0.40, 95% CI 0.25-0.64; P = 0.0001; I2 = 0.0%), but there was no difference between groups in postoperative deaths (4/182 vs 6/153; odds ratio 0.54, 95% CI 0.15-1.93; P = 0.34; I2 = 0.0%). CONCLUSIONS: Perioperative administration of dexmedetomidine to paediatric patients undergoing cardiac surgery may shorten the duration of mechanical ventilation, LOS in the intensive care unit and in the hospital and reduce the incidence of junctional ectopic tachycardia. More high-quality randomized controlled trials are encouraged to verify the beneficial effect of dexmedetomidine before its clinical application in paediatric patients undergoing surgery for congenital heart disease.

MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN.

Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC.

Doxorubicin nanobubble for combining ultrasonography and targeted chemotherapy of rabbit with VX2 liver tumor.

A new class of multifunctional nanobubble using poly(lactic-co-glycolic acid) (PLGA) has been developed as ultrasound imaging contrast agents, doxorubicin carriers, and enhancers of ultrasound-mediated drug delivery. The doxorubicin nanobubble (DOX-NB) wrapping carbon tetrafluoride gas was prepared with double emulsion method. We evaluated the enhanced ultrasonic function of the DOX-NB in vivo; its antitumor function was confirmed. The diameter of the prepared bubble was 500 nm, and the potential was -23 mV. The drug loading and encapsulation efficiency of the bubble were 78.6 and 7.4 %, respectively. Therefore, the DOX-NB greatly enhanced ultrasound imaging in vivo. Ultrasound combined with DOX-NB had significant antitumor effect. Compared with other groups, the tumor growth rate and the proliferation index were the lowest while the survival rate and apoptosis index were the highest.

Computed tomography for the diagnosis of solitary thin-walled cavity lung cancer.

BACKGROUND AND AIM: Lung cancer is the most commonly diagnosed neoplasm and the leading cause of cancer-related death worldwide. Despite the high incidence of lung cancer, the diagnosis of solitary thin-walled cavity lung cancer is rare. The aim of this review is to explore the potentials of computed tomography (CT) as diagnostic tool for solitary thin-walled cavity lung cancer. METHOD: The literature search was made in electronic databases including PudMed, Ovid SP, Embase, Web of Sciences, EBSCO and Wiley online by using relevant key terms. Because of the rarity of the subject, no precise exclusion or inclusion criteria were used for article selection and the outcome dissemination was decided to be more descriptive rather than quantitative. RESULTS: The detection of cavitation in lungs is frequently done utilizing chest radiographs CT scans. However, the diagnostic challenge remains the accurate detection of solitary thin-walled cavity lung cancer among the prevalence of cavitary lung lesions in multiple thoracic disorders including benign disorders, infectious disease and malignant tumors. Moreover, an accurate diagnosis of solitary thin-walled cavity lung cancer is further complicated by its subjective classification within the literature. In order to facilitate early diagnosis of this disease and circumvent the need for more invasive tests that may not be warranted, the overarching goal is to establish definitive radiological features of lung cavities that are indicative of malignancy. Herein, we describe the benefits of using CT to identify and diagnose solitary thin-walled cavity lung cancer, as well as explore the underlying mechanisms that contribute to thin-walled cavity formation in oncology patients. CONCLUSION: CT is the best modality for the noninvasive differentiation between malignant and nonmalignant cavities as it provides reliable information regarding the morphology and density of lesions. Besides, CT densitometry can efficiently detect the calcifications in lesions.

SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGFß-mediated epithelial to mesenchymal transition in human lung cancer cell line A549.

A post-transcriptional pathway by which TGF-ß modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism. Steady-state transcript and protein expression levels of Dab2 and ILEI were examined in A549 cells treated with TGF-ß for up to 48 h. Induction of translational de-repression in this model was quantified by polysomal fractionation followed by qRT-PCR. The underlying mechanism of isoform-specific activation of Akt2 was elucidated through a combination of co-immunoprecipitation studies. TGF-ß induced EMT in A549 cells concomitant with translational upregulation of Dab2 and ILEI proteins through isoform-specific activation of Akt2 followed by phosphorylation of PCBP1 at serine-43. Our experiments further elucidated that the adaptor protein SchA is phosphorylated at tyrosine residues following TGF-ß treatment, which initiated a signaling cascade resulting in the sequential recruitment of p85 subunit of PI3K and focal adhesion kinase (FAK). The SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1. Inhibition of the p85 subunit through phosphorylated 1257 peptide completely attenuated EMT in these cells. We have defined the underlying mechanism responsible for isoform-specific recruitment and activation of Akt2, not Akt1, during TGF-ß-mediated EMT in A549 cells. Inhibition of the formation of this complex thus represents an important and novel therapeutic target in metastatic lung carcinoma.

[Effects of human umbilical cord mesenchymal stem cells on the proliferation of hematopoietic malignancies].

OBJECTIVE: To study the effects of human umbilical cord mesenchymal stem cells (UC-MSCs) on proliferation of eight tumor cell lines from leukemia, lymphoma and multiple myeloma in vitro. METHODS: Tumor cells were labeled with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE). UC-MSCs were co-cultured with tumor cells at different ratios as experimental groups, meanwhile, tumor cells were cultured without UC-MSCs as control groups. After three days, mean fluorescence intensity and cell division generations of the tumor cells were measured by flow cytometry. RESULTS: UC-MSCs inhibited the proliferation of HL60, THP1, K562 and RPMI8226 cell lines, but promoted the proliferation of Raji and NCIH929 cell lines. UC-MSCs promoted the proliferation of Jurkat cells only at 1:1 ratio; as for U937 cells, UC-MSCs inhibited the proliferation at 2:1 ratio (UC-MSCs: U937), promoted proliferation at 1:4 and 1:16, whereas had no obvious effect at 1:1. CONCLUSION: UC-MSCs have different effects on the proliferation of different hematopoietic tumor cell lines. They have no promoting effects on four leukemic cell lines, but have bidirectional (promotion/inhibition) effects on lymphoma and multiple myeloma cell lines. The U937 cell line may serve as a good model for the mechanism study of this contradictory phenomenon.

Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis.

PURPOSE: Metastatic renal cell carcinoma (mRCC), as one of the most immunogenic tumors has been the focus of adoptive cellular immunotherapy (ACI), but the effects of ACI on objective response and survival in patients with mRCC are still controversial. Therefore, a systematic review and meta-analysis was performed to address this issue. METHODS: A search was conducted in the PubMed database for randomized clinical trials (RCTs) with ACI in mRCC. All included articles in this study were assessed according to the selection criteria and were divided into two groups: ACI versus no ACI. Outcomes were toxicity, objective response, 1-, 3- and 5-year survival. Risk ratio (RR) and 95% confidence intervals (CI) were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by value of I(2) or P. RESULTS: 4 studies (469 patients) were included. Most of ACI-related adverse reactions were grade 1 or 2 and reversible. ACI provided significant benefit in terms of objective response (RR = 1.65; 95% CI, 1.15 to 2.38; P = 0.007, I(2) = 49%), 1-year survival (RR = 1.30; 95% CI, 1.12 to 1.52; P = 0.0008, I(2) = 0%), 3-year survival (RR = 2.76; 95% CI, 1.85 to 4.14; P<0.00001, I(2) = 46%) and 5-year survival (RR = 2.42; 95% CI, 1.21 to 4.83; P = 0.01, I(2) = 28%). CONCLUSIONS: ACI may be a safe and effective treatment for improving objective response, 1-, 3- and 5-year survival in patients with mRCC. Besides, five obstacles for ACI, including high degree of personalization, unsuitable WHO/RECIST response criteria, inadequate identification of tumor-associated antigens (TAAs), lack of effective combination treatments and less attention paid to the quality of ACI products, should be overcome during the successful development of more potent ACI for cancer in the future.