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Heavy metals (HMs) contamination of water bodies severely threatens human and ecosystem health. There is growing interest in the use of duckweeds for HMs biomonitoring and phytoremediation due to their fast growth, low cultivation costs, and excellent HM uptake efficiency. In this review, we summarize the current state of knowledge on duckweeds and their suitability for HM biomonitoring and phytoremediation. Duckweeds have been used for phytotoxicity assays since the 1930s. Some toxicity tests based on duckweeds have been listed in international guidelines. Duckweeds have also been recognized for their ability to facilitate HM phytoremediation in aquatic environments. Large-scale screening of duckweed germplasm optimized for HM biomonitoring and phytoremediation is still essential. We further discuss the morphological, physiological, and molecular effects of HMs on duckweeds. However, the existing data are clearly insufficient, especially in regard to dissection of the transcriptome, metabolome, proteome responses and molecular mechanisms of duckweeds under HM stresses. We also evaluate the influence of environmental factors, exogenous substances, duckweed community composition, and HM interactions on their HM sensitivity and HM accumulation, which need to be considered in practical application scenarios. Finally, we identify challenges and propose approaches for improving the effectiveness of duckweeds for bioremediation from the aspects of selection of duckweed strain, cultivation optimization, engineered duckweeds. We foresee great promise for duckweeds as phytoremediation agents, providing environmentally safe and economically efficient means for HM removal. However, the primary limiting issue is that so few researchers have recognized the outstanding advantages of duckweeds. We hope that this review can pique the interest and attention of more researchers.
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Metais Pesados , Poluentes do Solo , Humanos , Biodegradação Ambiental , Monitoramento Biológico , Ecossistema , Poluentes do Solo/análise , Metais Pesados/toxicidade , Metais Pesados/análise , SoloRESUMO
The Qinghai-Tibetan Plateau harbors rich and diverse wetlands that provide multiple ecological functions simultaneously. Although the relationships between biodiversity and wetland functioning have been well studied in recent decades, the links between the multiple features of plant and microbial communities and soil multifunctionality (SMF) remain unknown in the high-altitude wetlands that are extremely sensitive to human disturbance. Here, using the single function, averaging, weighted, and multiple-threshold methods, we calculated the SMF of Qinghai-Tibetan wetlands based on 15 variables associated with soil nutrient status, nutrient cycle, and greenhouse gas emission. We then related SMF to multidimensional (species, phylogenetic, and functional) diversity of plants and soil microorganisms and microbial network modules. The results showed that plant diversity explained more variance in SMF than soil microbial diversity, and plant species richness and phylogenetic distance were positive predictors of SMF. Bacterial network modules were more positively related to SMF than fungal network modules, and the alpha diversity of bacterial network modules contributed more to SMF than the diversity of the whole bacterial community. Pediococcus, Hirsutella, and Rhodotorula were biomarkers for SMF and had significant relationships with nitrogen mineralization and greenhouse gas emissions. Together, these results highlight the importance of plant diversity and bacterial network modules in determining the SMF, which are crucial to predicting the response of ecosystem functioning to biodiversity loss under intensifying anthropogenic activities.
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Biodiversidade , Microbiologia do Solo , Solo , Áreas Alagadas , Tibet , Solo/química , Plantas , Filogenia , Ecossistema , Bactérias/classificaçãoRESUMO
A novel Gram-stain-negative strain, WQ 117T, isolated from the faeces of Rhinopithecus bieti collected at Yunnan Snub-nosed Monkey National Park, Yunnan province, PR China, was subjected to a polyphasic taxonomic study. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate represented a member of the genus Faecalibacter, sharing 97.64â% sequence similarity with the type strain Faecalibacter macacae YIM 102668T. The G+C content of the genomic DNA of WQ117T was 30.5 mol%. The predominant isoprenoid quinone was MK-6. The major cellular fatty acids was iso-C15â:â0. The whole genome average nucleotide identity (gANI) values and the digital DNA-DNA hybridization values between WQ 117T and YIM 102668T were 79.66â% and 22.20â%, respectively. Growth occurred at 0-50 °C (optimally at 28-35 °C), pH 7.0-9.0 (optimally at pH 8.0) and with 0-2â% (w/v) NaCl (optimally without NaCl). On the basis of the taxonomic evidence, a novel species, Faecalibacter rhinopitheci sp. nov., is proposed. The type strain is WQ 117T (=KCTC 82394T=CCTCC AA 2020027T).
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Bacteroidetes/classificação , Filogenia , Presbytini , Animais , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes/microbiologia , Hibridização de Ácido Nucleico , Presbytini/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
Morphogenesis of the soil hypotrich ciliate, Holostichides chardezi Foissner, 1987, collected from southeastern China, was investigated using the protargol staining method. The main morphogenetic events follow a similar process with that of its congeners. Phylogenetic analyses based on the SSU rDNA sequence data indicate that Holostichides is nonmonophyletic; H. chardezi, the type species of Holostichides, clusters with H. heterotypicus, while H. terrae is distinctly separate from these species. H. terrae can be distinguished from H. chardezi (type species of Holostichides) and H. heterotypicus by undulating membranes relatively long and distinctly curved (vs. relatively short and straight), pharynx with (vs. without) rod-shaped structure, and two (vs. more than two) frontoterminal cirri. Therefore, a new genus, Anteholostichides nov. gen., has been proposed for H. terrae. Further, the diagnosis of the genus Holostichides is improved.
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Hypotrichida/crescimento & desenvolvimento , Hypotrichida/isolamento & purificação , Filogenia , Solo/parasitologia , China , DNA de Protozoário/genética , DNA Ribossômico/genética , Hypotrichida/classificação , Hypotrichida/genética , MorfogêneseRESUMO
OBJECTIVE: This study aims to explore the effects of microRNA-27a (miR-27a) on the proliferation and invasiveness of colon cancer cells through the Secreted Frizzled-related protein 1 (SFRP1) and the Wnt/ß-catenin signaling pathway. METHODS: Colon cancer tissues and adjacent normal tissues from 125 colon cancer patients, together with the HCEpic, HCT-116, HT-29, SW480 and SW620 cell lines, were prepared for this study. The transfected HCT-116 cells were divided into the miR-27a mimics, miR-27a-NC, anti-miR-27a, blank, Lv-SFRP1, Lv-NC, and miR-27a mimics + Lv-SFRP1 groups. RT-qPCR was performed to detect the expressions of miR-27a and SFRP1 mRNA. A dual-luciferase reporter assay was conducted to examine the effect of miR-27a on SFRP1. Western blotting was used to measure the expressions of the SFRP1, ß-catenin, GSK-3ß, p-ß-catenin, p-GSK-3ß, c-Myc and cyclin D1 proteins. MTT, soft agar clone formation and Transwell chamber assays were performed to detect cell proliferation and invasion. RESULTS: Compared with normal tissues and cells, colon cancer tissues and cells demonstrated significantly higher expression of miR-27a, but lower expressions of SFRP1 mRNA and protein. MiR-27a negatively regulated the expression of SFRP1 mRNA. SFRP1 was also found to be a target gene of miR-27a. In the miR-27a mimic group, the proliferation and invasiveness of colon cancer cells were significantly increased, while the expressions of GSK-3 ß and p-ß-catenin were remarkably down-regulated; in contrast, the expressions of p-GSK-3ß, -catenin, c-Myc and cyclin D1 were up-regulated. While the proliferation and invasiveness of colon cancer cells in the anti-miR-27a and Lv-SFRP1 groups were decreased, the expressions of GSK-3ß and p-ß-catenin were elevated, and the expressions of p-GSK-3ß, ß-catenin, c-Myc and cyclin D1 were decreased. CONCLUSION: These findings indicated that miR-27a could promote the proliferation and invasiveness of colon cancer cells by targeting SFRP1 through the Wnt/ß-catenin signaling pathway.
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Neoplasias do Colo/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Via de Sinalização Wnt , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagomirs/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação para Baixo , Feminino , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Células HCT116 , Células HT29 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Adulto Jovem , beta Catenina/metabolismoRESUMO
The Tibetan Plateau supplies water to nearly 2 billion people in Asia, but climate change poses threats to its aquatic microbial resources. Here, we construct the Tibetan Plateau Microbial Catalog by sequencing 498 metagenomes from six water ecosystems (saline lakes, freshwater lakes, rivers, hot springs, wetlands and glaciers). Our catalog expands knowledge of regional genomic diversity by presenting 32,355 metagenome-assembled genomes that de-replicated into 10,723 representative genome-based species, of which 88% were unannotated. The catalog contains nearly 300 million non-redundant gene clusters, of which 15% novel, and 73,864 biosynthetic gene clusters, of which 50% novel, thus expanding known functional diversity. Using these data, we investigate the Tibetan Plateau aquatic microbiome's biogeography along a distance of 2,500 km and >5 km in altitude. Microbial compositional similarity and the shared gene count with the Tibetan Plateau microbiome decline along with distance and altitude difference, suggesting a dispersal pattern. The Tibetan Plateau Microbial Catalog stands as a substantial repository for high-altitude aquatic microbiome resources, providing potential for discovering novel lineages and functions, and bridging knowledge gaps in microbiome biogeography.
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Microbiota , Humanos , Tibet , Microbiota/genética , Lagos , Rios , ÁguaRESUMO
The spatial pattern and driving mechanism of biodiversity along elevational gradients are key topics in ecology. However, it is still unclear whether the multidimensional diversity of different types of organisms shows a similar response to elevation changes. Here, we measured the species and phylogenetic diversity of plants, bacteria, fungi, and microbial functional groups (nitrifiers, denitrifiers, methanogens, and methanotrophs) in 36 wetland sites on the Qinghai-Tibetan Plateau. The results showed that both species and phylogenetic diversity of plants, bacteria, and fungi exhibited a significant elevational gradient, in direct contrast to no significant diversity changes observed for denitrifiers, methanogens, and methanotrophs along the same altitude gradient. Our findings suggest that elevation and temperature were more likely to associate with the diversity of plants, bacteria, and fungi than the diversity of microbial functional groups, with important implications for assessing the effect of ongoing climate warming on biodiversity in Qinghai-Tibetan alpine wetlands.
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River ecological health assessments are the premise for protecting river biodiversity and curbing river water environment deterioration. To explore the river ecosystem health status and its response mechanism to water environmental factors in the middle reaches of the Yarlung Zangbo River, phytoplankton samples were collected during July and October 2021, and water environmental factors were measured. The phytoplankton species were identified, and their cell abundance and biomass were calculated. The phytoplankton integrity index was constructed to evaluate the ecological health status of the river. The temporal and spatial distribution characteristics of water environmental factors and phytoplankton community, as well as the correlation between P-IBI value and community parameters and water environmental factors were analyzed. The results showed that the difference in water environmental factors was not evident in time but was significant in space. The average cell abundance and biomass of phytoplankton were in the order of wet season>dry season and main stream>tributaries. Diatoms dominated the community, and pH and WT were the major water environmental factors driving the spatial and temporal distributions of phytoplankton. The ecological health status of the middle reaches of the Yarlung Zangbo River was "healthy to sub-healthy." The river health status was better than that of the dry season, and that of the tributaries was better than that of the main stream. EC, TUR, WT, NO3--N, and NH4+-N were the major water environmental factors affecting the ecological health status of the river reach, which could be affected by the direction and rate of phytoplankton community succession. It is involved in and affects the process of material circulation and energy flow of the river ecosystem, thereby driving the ecological health of the middle reaches of the Yarlung Zangbo River.
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Ecossistema , Rios , Água , Biomassa , Nível de Saúde , FitoplânctonRESUMO
Alpine wetland is a natural laboratory for studying the Earth's third polar ecosphere. Protist communities are key components of wetland ecosystems which are extremely vulnerable to environmental change. It is of great importance to study the protist community in relation to environment, which might be the key to understand the ecosystem of the alpine wetlands under global change. In this study, we investigated the composition of protist communities across the Mitika Wetland, a unique alpine wetland hosting tremendous endemic diversity. Using 18S rRNA gene high-throughput sequencing, we evaluated how protist taxonomic and functional group composition is structured by seasonal climate and environmental variation. We found a high relative abundance of Ochrophyta, Ciliophora, and Cryptophyta, each of which showcased a unique spatial pattern in the wet and dry seasons. The proportion of consumers, parasites and phototrophs groups were stable among the functional zones and also between the seasons, with consumers dominating communities in terms of richness, while phototrophic taxa dominated in terms of relative abundance. Protist and each functional group were rather regulated by deterministic than stochastic processes, with water quality having a strong control on communities. Salinity and pH were the most important environmental factors at shaping protistan community. The protist co-occurrence network dominated by the positive edge indicating the communities resisted extreme environmental conditions through close cooperation, and more consumers were determined as the keystones in wet season and more phototrophic taxa in dry season. Our results provided the baseline of the protist taxonomic and functional group composition in the highest wetland, and highlighted environmental selections drive protist distribution, implying the alpine wetland ecosystem are sensitive to climate changes and human activities.
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Ecossistema , Áreas Alagadas , Humanos , Biodiversidade , Qualidade da Água , AltitudeRESUMO
Eukaryotic microorganisms play an important role in the biogeochemical cycles of rivers. Dynamic hydrological processes in rivers are thought to influence the assembly processes of eukaryotic microbes, as well as affecting local geomorphology. These processes have not been extensively studied for eukaryotic river microbes in extreme environments on the Tibetan Plateau. This study used 18S rDNA gene amplification sequencing, a neutral community model, and a null model to analyze the spatial and temporal dynamics and assembly processes of eukaryotic microbial communities in the middle reaches of the Yarlung Zangbo River. We conducted analyses across wet and dry seasons, as well as varying altitudinal gradients. Our results showed that the diversity, structure, and taxonomic composition of eukaryotic microbial communities varied more with altitude than season, and the diversity of the communities first increased, then decreased, with increasing elevation. Distance-decay analysis showed that the correlation between eukaryotic microbial communities and environmental distance was stronger than the correlation between the microbial communities and geographical distance. Deterministic processes (homogeneous selection) dominated the construction of eukaryotic microbial communities, and water temperature, pH, and total phosphorus were the primary environmental factors that influenced the construction of eukaryotic microbial communities. These results expand our understanding of the characteristics of eukaryotic microbial communities in rivers on the Tibetan Plateau and provide clues to understanding the mechanisms that maintain eukaryotic microbial diversity in extreme environments.
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Eucariotos , Rios , Estações do Ano , Células Eucarióticas , TemperaturaRESUMO
Hot springs are some of the most special environments on Earth. Many prokaryotic and eukaryotic microbes have been found to live in this environment. The Himalayan geothermal belt (HGB) has numerous hot springs spread across the area. Comprehensive research using molecular techniques to investigate eukaryotic microorganisms is still lacking; investigating the composition and diversity of eukaryotic microorganisms such as protists in the hot spring ecosystems will not only provide critical information on the adaptations of protists to extreme conditions, but could also give valuable contributions to the global knowledge of biogeographic diversity. In this study, we used high-throughput sequencing to illuminate the diversity and composition pattern of protist communities in 41 geothermal springs across the HGB on the Tibetan Plateau. A total of 1238 amplicon sequence variants (ASVs) of protists were identified in the hot springs of the HGB. In general, Cercozoa was the phylum with the highest richness, and Bacillariophyta was the phylum with the highest relative abundance in protists. Based on the occurrence of protist ASVs, most of them are rare. A high variation in protist diversity was found in the hot springs of the HGB. The high variation in protist diversity may be due to the different in environmental conditions of these hot springs. Temperature, salinity, and pH are the most important environmental factors that affect the protist communities in the surface sediments of the hot springs in the HGB. In summary, this study provides the first comprehensive study of the composition and diversity of protists in the hot springs of the HGB and facilitates our understanding of the adaptation of protists in these extreme habitats.
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BACKGROUND: Tension pneumoperitonium is a rare complication during bronchoscopy that can cause acute respiratory and hemodynamic failure, with fatal consequences. Isolated pneumoperitonium during bronchoscopy usually results from ruptures of the abdominal viscera that need surgical repair. Non-surgical pneumoperitoneum (NSP) refers to some pneumoperitoneum that could be relieved without surgery and only by conservative therapy. However, the clinical experience of managing tension pneumoperitonium during bronchoscopy is limited and controversial. CASE SUMMARY: A 51-year-old female was admitted to our hospital for cough with bloody sputum of seven days. On the 8th day of her admission, a bronchoscopy was arranged for bronchial-alveolar lavage to detect possible pathogens in the lower respiratory tract, as oxygen was delivered via a 12 F nasopharyngeal cannula, approximately 5-6 cm from the tip of the catheter, with a flow rate of 5-10 L/min. After four minutes of bronchoscopy, the patient suddenly vomited 20 mL of water, followed by severe abdominal pain, while physical examination revealed obvious abdominal distension, as well as hardness and tenderness of the whole abdomen, which was considered pneumoperitonium, and the bronchoscopy was terminated immediately. A computer tomography scan indicated isolated tension pneumoperitonium, and abdominal decompression was performed with a drainage tube, after which her symptoms were relieved. A multidisciplinary expert consultation discussed her situation and a laparotomy was suggested, but finally refused by her family. She had no signs of peritonitis and was finally discharged 5 d after bronchoscopy with a good recovery. CONCLUSION: The possibility of tension pneumoperitonium during bronchoscopy should be guarded against, and given its serious clinical consequences, cardiopulmonary instability should be treated immediately. Varied strategies could be adopted according to whether it is complicated with pneumothorax or pneumomediastinum, and the presence of peritonitis. When considering NSP, conservative therapy maybe a reasonable option with good recovery. An algorithm for the management of pneumoperitonium during bronchoscopy is proposed, based on the features of the case series reviewed and our case reported.
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BACKGROUND: The prevalence of chronic kidney disease (CKD) at high altitude is not known. We conducted a population-based survey in Tibet to identify the prevalence and associated risk factors of CKD in subjects living at altitudes of > 3500 m. METHODS: One thousand two hundred and eighty-nine Tibetans (≥ 18 years) from four districts of Lhasa city (altitude 3658 m) and eight villages of Dangxiong County (altitude 4200 m) were interviewed and tested for haematuria, albuminuria and estimated glomerular filtration rate (eGFR). RESULTS: The adjusted prevalence of hypertension, albuminuria, haematuria and reduced eGFR were 38.8% (95% CI: 36.2-41.5%), 16.2% (95% CI: 14.1-18.2%), 3.9% (95% CI: 2.8-4.9%) and 2.1% (95% CI: 1.3-2.9%), respectively. Both the presence of hypertension and the presence of albuminuria were strongly and independently associated with hyperuricaemia and elevated haematocrit. CONCLUSIONS: This is the first population-based epidemiological study of CKD in the Tibetan population. We found a higher prevalence of CKD and associated high prevalence of albuminuria, hypertension, hyperuricaemia and high haematocrit in the Tibetan population. The present study indicates the urgent need to develop comprehensive strategies targeted at reducing the CKD burden in this area and may lead to a better understanding of CKD in high-altitude populations.
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Albuminúria/epidemiologia , Hematúria/epidemiologia , Hipertensão/epidemiologia , Falência Renal Crônica/epidemiologia , Adulto , Albuminúria/etiologia , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Hematúria/etiologia , Humanos , Hipertensão/etiologia , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Tibet/epidemiologiaRESUMO
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is biologically and clinically heterogeneous. Due to lack of gene expression signatures for risk and prognosis stratification of CRC, identifying novel molecular biomarkers and therapeutic targets may potentially improve CRC prognosis and treatment. RNF180 has been shown to play key contributions to the development of several types of cancers. In the current study, we investigate its role in CRC. In this study, we show that RNF180 expression was significantly downregulated in human CRC tumors and cell lines. Overexpression of RNF180 in CRC cells markedly inhibited cell viability and induced cell apoptosis, while depletion of RNF180 dramatically enhanced cell survival. Moreover, WISP1 was found to be the critical downstream molecule that mediated the tumor suppressive effects of RNF180. Mechanistically, RNF180 ubiquitinated WISP1, resulting in WISP1 downregulation and ultimately leading to suppression of CRC tumor growth in patient-derived xenograft (PDX) mouse models. Last, 5-FU and RNF180 had synergetic effect on the apoptosis induction and tumor growth inhibition. Our findings revealed a crucial role of RNF180 in suppressing tumor growth by ubiquitinating WISP1 in CRC.
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OBJECTIVE: A network meta-analysis was performed to compare the short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer. METHODS: Randomized controlled trials of different chemotherapy regimens for advanced gastric cancer were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the odds ratio and draw surface under the cumulative ranking curves of different chemotherapy regimens in advanced gastric cancer. RESULTS: The results of surface under the cumulative ranking curves showed that S-1 and capecitabine regimens were better than fluorouracil. As for multi-drug combination regimens, the disease control rate of cisplatin + capecitabine, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + capecitabine regimens were relatively better, while fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Additionally, the overall response ratio of cisplatin + capecitabine, paclitaxel + fluorouracil, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + fluorouracil regimens were relatively better, while the disease control rate of fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Furthermore, the results of cluster analysis demonstrated that cisplatin + capecitabine, etoposide + cisplatin + capecitabine, S-1 + paclitaxel and S-1 + irinotecan chemotherapy regimens had better disease control rate and overall response ratio for advanced gastric cancer patients. CONCLUSION: This network meta-analysis clearly showed that multi-drug combination chemotherapy regimens based on capecitabine and S-1 might be the best chemotherapy regimen for advanced gastric cancer.
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Capecitabina/uso terapêutico , Fluoruracila/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Capecitabina/farmacologia , Combinação de Medicamentos , Fluoruracila/farmacologia , Humanos , Metanálise em Rede , Ácido Oxônico/farmacologia , Neoplasias Gástricas/patologia , Tegafur/farmacologiaRESUMO
OBJECTIVE: A network meta-analysis was conducted comparing the short-term efficacies of 16 targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer (CRC). RESULTS: Twenty-seven RCTs were ultimately incorporated into this network meta-analysis. Compared with chemotherapy alone, bevacizumab + chemotherapy, panitumumab + chemotherapy and conatumumab + chemotherapy had higher PR rate. Bevacizumab + chemotherapy, cetuximab + chemotherapy, panitumumab + chemotherapy, trebananib + chemotherapy and conatumumab + chemotherapy had higher ORR rate in comparison to chemotherapy alone. Furthermore, bevacizumab + chemotherapy had higher DCR rate than chemotherapy alone. The results of our cluster analysis showed that chemotherapy combined with bevacizumab, cetuximab, panitumumab, conatumumab, ganitumab, or brivanib + cetuximab had better efficacies for the treatment of advanced/metastatic CRC in comparison to chemotherapy alone. MATERIALS AND METHODS: Electronic databases were comprehensively searched for potential and related randomized controlled trials (RCTs). Direct and indirect evidence were incorporated for evaluation of stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR) and overall response ratio (ORR) by calculating odds ratio (OR) and 95% confidence intervals (CI), and using the surface under the cumulative ranking curve (SUCRA). CONCLUSIONS: These results indicated that bevacizumab + chemotherapy, panitumumab + chemotherapy, conatumumab + chemotherapy and brivanib + cetuximab + chemotherapy may have better efficacies for the treatment of advanced/metastatic CRC.