Wolfberry genome database: integrated genomic datasets for studying molecular biology.

Wolfberry, also known as goji berry or Lycium barbarum, is a highly valued fruit with significant health benefits and nutritional value. For more efficient and comprehensive usage of published L. barbarum genomic data, we established the Wolfberry database. The utility of the Wolfberry Genome Database (WGDB) is highlighted through the Genome browser, which enables the user to explore the L. barbarum genome, browse specific chromosomes, and access gene sequences. Gene annotation features provide comprehensive information about gene functions, locations, expression profiles, pathway involvement, protein domains, and regulatory transcription factors. The transcriptome feature allows the user to explore gene expression patterns using transcripts per kilobase million (TPM) and fragments per kilobase per million mapped reads (FPKM) metrics. The Metabolism pathway page provides insights into metabolic pathways and the involvement of the selected genes. In addition to the database content, we also introduce six analysis tools developed for the WGDB. These tools offer functionalities for gene function prediction, nucleotide and amino acid BLAST analysis, protein domain analysis, GO annotation, and gene expression pattern analysis. The WGDB is freely accessible at https://cosbi7.ee.ncku.edu.tw/Wolfberry/. Overall, WGDB serves as a valuable resource for researchers interested in the genomics and transcriptomics of L. barbarum. Its user-friendly web interface and comprehensive data facilitate the exploration of gene functions, regulatory mechanisms, and metabolic pathways, ultimately contributing to a deeper understanding of wolfberry and its potential applications in agronomy and nutrition.

Diploid and tetraploid genomes of Acorus and the evolution of monocots.

Monocots are a major taxon within flowering plants, have unique morphological traits, and show an extraordinary diversity in lifestyle. To improve our understanding of monocot origin and evolution, we generate chromosome-level reference genomes of the diploid Acorus gramineus and the tetraploid Ac. calamus, the only two accepted species from the family Acoraceae, which form a sister lineage to all other monocots. Comparing the genomes of Ac. gramineus and Ac. calamus, we suggest that Ac. gramineus is not a potential diploid progenitor of Ac. calamus, and Ac. calamus is an allotetraploid with two subgenomes A, and B, presenting asymmetric evolution and B subgenome dominance. Both the diploid genome of Ac. gramineus and the subgenomes A and B of Ac. calamus show clear evidence of whole-genome duplication (WGD), but Acoraceae does not seem to share an older WGD that is shared by most other monocots. We reconstruct an ancestral monocot karyotype and gene toolkit, and discuss scenarios that explain the complex history of the Acorus genome. Our analyses show that the ancestors of monocots exhibit mosaic genomic features, likely important for that appeared in early monocot evolution, providing fundamental insights into the origin, evolution, and diversification of monocots.

PbABCG1 and PbABCG2 transporters are required for the emission of floral monoterpenes in Phalaenopsis bellina.

Terrestrial plants emit volatiles into the atmosphere to attract both pollinators and the enemies of herbivores, for defense. Phalaenopsis bellina is a scented orchid species in which the main scent components are monoterpenes, including linalool and geraniol, and their derivatives. Here, we investigated whether ABC transporters are involved in floral scent emission. We carried out whole-genome identification of ABC transporter-related genes using four floral transcriptomics libraries of P. bellina. We identified 86 ABC subfamily G genes related to terpenoid transport. After comparing the gene expression patterns of P. bellina with that of Phalaenopsis aphrodite subsp. formosana, a scentless species, followed by gene-to-gene correlation analysis, PbABCG1 and PbABCG2 were selected. The temporal expression of both PbABCG1 and PbABCG2 was highly correlated with that of the key enzyme PbGDPS and the major transcription factor PbbHLH4 in monoterpene biosynthesis, with optimal expression on day 5 post-anthesis. Spatial gene expression analysis showed that PbABCG1 was highly expressed in sepals, whereas PbABCG2 was expressed in the lip. Subcellular localization with a GFP fusion protein revealed that both PbABCG1 and PbABCG2 are cytoplasmic membrane proteins. Co-downregulation of PbABCG1 and PbABCG2 using both double-strand RNA interference and tobacco rattle virus-based gene silencing led to a significant decrease in monoterpene emission, accompanied by an increase in the internal monoterpene pools. Furthermore, ectopic expression of PbABCG1 and PbABCG2 in an ABC16- mutant yeast strain rescued its tolerance to geraniol. Altogether, our results indicate that PbABCG1 and PbABCG2 play substantial roles in monoterpene transport/emission in P. bellina floral scent.

OrchidBase 5.0: updates of the orchid genome knowledgebase.

Containing the largest number of species, the orchid family provides not only materials for studying plant evolution and environmental adaptation, but economically and culturally important ornamental plants for human society. Previously, we collected genome and transcriptome information of Dendrobium catenatum, Phalaenopsis equestris, and Apostasia shenzhenica which belong to two different subfamilies of Orchidaceae, and developed user-friendly tools to explore the orchid genetic sequences in the OrchidBase 4.0. The OrchidBase 4.0 offers the opportunity for plant science community to compare orchid genomes and transcriptomes and retrieve orchid sequences for further study.In the year 2022, two whole-genome sequences of Orchidoideae species, Platanthera zijinensis and Platanthera guangdongensis, were de novo sequenced, assembled and analyzed. In addition, systemic transcriptomes from these two species were also established. Therefore, we included these datasets to develop the new version of OrchidBase 5.0. In addition, three new functions including synteny, gene order, and miRNA information were also developed for orchid genome comparisons and miRNA characterization.OrchidBase 5.0 extended the genetic information to three orchid subfamilies (including five orchid species) and provided new tools for orchid researchers to analyze orchid genomes and transcriptomes. The online resources can be accessed at https://cosbi.ee.ncku.edu.tw/orchidbase5/.

Impact of ventilator settings during venovenous extracorporeal membrane oxygenation on clinical outcomes in influenza-associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

Background: Patients with influenza-associated acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (vv-ECMO) support have a high mortality rate. Ventilator settings have been known to have a substantial impact on outcomes. However, the optimal settings of mechanical ventilation during vv-ECMO are still unknown. Methods: This multicenter retrospective cohort study was conducted in the intensive care units (ICUs) of three tertiary referral hospitals in Taiwan between July 2009 and December 2019. It aims to describe the effect of ventilator settings during vv-ECMO on patient outcomes. Results: A total of 93 patients with influenza receiving ECMO were screened. Patients were excluded if they: were receiving venoarterial ECMO, died within three days of vv-ECMO initiation, or were transferred to the tertiary referral hospital >24 hours after vv-ECMO initiation. A total of 62 patients were included in the study, and 24 (39%) died within six months. During the first three days of ECMO, there were no differences in tidal volume (5.1 vs. 5.2 mL/kg, p = 0.833), dynamic driving pressure (15 vs. 14 cmH2O, p = 0.146), and mechanical power (11.3 vs. 11.8 J/min, p = 0.352) between survivors and non-survivors. However, respiratory rates were significantly higher in non-survivors compared with survivors (15 vs. 12 breaths/min, p = 0.013). After adjustment for important confounders, a higher mean respiratory rate of >12 breaths/min was still associated with higher mortality (adjusted hazard ratio = 3.31, 95% confidence interval = 1.10-9.97, p = 0.034). Conclusions: In patients with influenza-associated ARDS receiving vv-ECMO support, we found that a higher respiratory rate was associated with higher mortality. Respiratory rate might be a modifiable factor to improve outcomes in this patient population.

Genomes of leafy and leafless Platanthera orchids illuminate the evolution of mycoheterotrophy.

To improve our understanding of the origin and evolution of mycoheterotrophic plants, we here present the chromosome-scale genome assemblies of two sibling orchid species: partially mycoheterotrophic Platanthera zijinensis and holomycoheterotrophic Platanthera guangdongensis. Comparative analysis shows that mycoheterotrophy is associated with increased substitution rates and gene loss, and the deletion of most photoreceptor genes and auxin transporter genes might be linked to the unique phenotypes of fully mycoheterotrophic orchids. Conversely, trehalase genes that catalyse the conversion of trehalose into glucose have expanded in most sequenced orchids, in line with the fact that the germination of orchid non-endosperm seeds needs carbohydrates from fungi during the protocorm stage. We further show that the mature plant of P. guangdongensis, different from photosynthetic orchids, keeps expressing trehalase genes to hijack trehalose from fungi. Therefore, we propose that mycoheterotrophy in mature orchids is a continuation of the protocorm stage by sustaining the expression of trehalase genes. Our results shed light on the molecular mechanism underlying initial, partial and full mycoheterotrophy.

Prognostic value of computed tomographic findings in acute respiratory distress syndrome and the response to prone positioning.

BACKGROUND: Prone positioning enables the redistribution of lung weight, leading to the improvement of gas exchange and respiratory mechanics. We aimed to evaluate whether the initial findings of acute respiratory distress syndrome (ARDS) on computed tomography (CT) are associated with the subsequent response to prone positioning in terms of oxygenation and 60-day mortality. METHODS: We retrospectively included patients who underwent prone positioning for moderate to severe ARDS from October 2014 to November 2020 at a medical center in Taiwan. A semiquantitative CT rating scale was used to quantify the extent of consolidation and ground-glass opacification (GGO) in the sternal, central and vertebral regions at three levels (apex, hilum and base) of the lungs. A prone responder was identified by a 20% increase in the ratio of arterial oxygen pressure (PaO2) to the fraction of oxygen (FiO2) or a 20 mmHg increase in PaO2. RESULTS: Ninety-six patients were included, of whom 68 (70.8%) were responders. Compared with nonresponders, responders had a significantly greater median dorsal-ventral difference in CT-consolidation scores (10 vs. 7, p = 0.046) but not in CT-GGO scores (- 1 vs. - 1, p = 0.974). Although dorsal-ventral differences in neither CT-consolidation scores nor CT-GGO scores were associated with 60-day mortality, high total CT-GGO scores (≥ 15) were an independent factor associated with 60-day mortality (odds ratio = 4.07, 95% confidence interval, 1.39-11.89, p = 0.010). CONCLUSIONS: In patients with moderate to severe ARDS, a greater difference in the extent of consolidation along the dependent-independent axis on CT scan is associated with subsequent prone positioning oxygenation response, but not clinical outcome regarding survival. High total CT-GGO scores were independently associated with 60-day mortality.

Extracorporeal Membrane Oxygenation in Immunocompromised Patients With Acute Respiratory Distress Syndrome-A Retrospective Cohort Study.

Objective: Although the negative impact of immunosuppression on survival in patients with acute respiratory distress syndrome (ARDS) treated by extracorporeal membrane oxygenation (ECMO) is well known, short-term outcomes such as successful weaning rate from ECMO and subgroups benefit most from ECMO remain to be determined. The aims of this study were (1) to identify the association between immunocompromised status and weaning from ECMO in patients of ARDS, and (2) to identify subgroups of immunocompromised patients who may benefit from ECMO. Methods: This retrospective cohort study enrolled patients who received ECMO for ARDS from 2010 to 2020. Immunocompromised status was defined as having a hematological malignancy, active solid tumor, solid organ transplant, or autoimmune disease. Results: This study enrolled 256 ARDS patients who received ECMO, of whom 68 were immunocompromised. The multivariable analysis showed that immunocompromised status was not independently associated with failure to wean from ECMO. In addition, the patients with an autoimmune disease (14/24, 58.3%) and organ transplantation (3/3, 100%) had a numerically higher weaning rate from ECMO than other immunocompromised patients. For causes of ARDS, most patients with pulmonary hemorrhage (6/8, 75%) and aspiration (5/9, 55.6%) could be weaned from ECMO, compared to only a few of the patients with interstitial lung disease (2/9, 22.2%) and sepsis (1/4, 25%). Conclusions: Immunocompromised status was not an independent risk factor of failure to wean from ECMO in patients with ARDS. For patients with pulmonary hemorrhage and aspiration-related ARDS, ECMO may be beneficial as bridge therapy.

Real-world effectiveness of second-line Afatinib versus chemotherapy for the treatment of advanced lung squamous cell carcinoma in immunotherapy-naïve patients.

BACKGROUND: Limited treatment options exist for relapsed advanced lung squamous cell carcinoma (SCC), leading to poor outcomes compared with adenocarcinoma. This study aimed to investigate the efficacy of second-line afatinib versus chemotherapy in patients with advanced lung SCC who progressed after first-line chemotherapy. METHODS: In this retrospective, multisite cohort study, we recruited patients with initial locally advanced or metastatic lung SCC from four institutes in Taiwan between June 2014 and October 2020. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: The present study enrolled 108 patients: 19 received second-line afatinib, and 89 received second-line chemotherapy. The median ages were 71 and 67 years, respectively. PFS was significantly longer among patients who received afatinib than among those who received chemotherapy (median 4.7 months [95% confidence interval (CI), 0.1-7.5] vs. 2.6 months [95% CI, 0.9-6.7]; hazard ratio (HR) 0.53 [95% CI 0.32-0.88], p = 0.013). Compared with the chemotherapy group, OS was longer in the afatinib group but did not reach significance (median 16.0 months [95% CI, 6.1-22.0] vs. 12.3 months [6.2-33.9]; HR 0.65 [95% CI 0.38-1.11], p = 0.112). CONCLUSIONS: Afatinib offered a longer PFS and comparable OS to chemotherapy in advanced lung SCC patients in a real-world setting, it may be considered as a 2nd line alternative treatment choice for immunotherapy unfit advanced lung SCC patients.

OrchidBase 4.0: a database for orchid genomics and molecular biology.

BACKGROUND: The Orchid family is the largest families of the monocotyledons and an economically important ornamental plant worldwide. Given the pivotal role of this plant to humans, botanical researchers and breeding communities should have access to valuable genomic and transcriptomic information of this plant. Previously, we established OrchidBase, which contains expressed sequence tags (ESTs) from different tissues and developmental stages of Phalaenopsis as well as biotic and abiotic stress-treated Phalaenopsis. The database includes floral transcriptomic sequences from 10 orchid species across all the five subfamilies of Orchidaceae. DESCRIPTION: Recently, the whole-genome sequences of Apostasia shenzhenica, Dendrobium catenatum, and Phalaenopsis equestris were de novo assembled and analyzed. These datasets were used to develop OrchidBase 4.0, including genomic and transcriptomic data for these three orchid species. OrchidBase 4.0 offers information for gene annotation, gene expression with fragments per kilobase of transcript per millions mapped reads (FPKM), KEGG pathways and BLAST search. In addition, assembled genome sequences and location of genes and miRNAs could be visualized by the genome browser. The online resources in OrchidBase 4.0 can be accessed by browsing or using BLAST. Users can also download the assembled scaffold sequences and the predicted gene and protein sequences of these three orchid species. CONCLUSIONS: OrchidBase 4.0 is the first database that contain the whole-genome sequences and annotations of multiple orchid species. OrchidBase 4.0 is available at http://orchidbase.itps.ncku.edu.tw/.

Corrigendum to "Comparative analysis of Phytophthora genomes reveals oomycete pathogenesis in crops" [Heliyon 7 (2) (February 2021) e06317].

[This corrects the article DOI: 10.1016/j.heliyon.2021.e06317.].

Wolfberry genomes and the evolution of Lycium (Solanaceae).

Wolfberry Lycium, an economically important genus of the Solanaceae family, contains approximately 80 species and shows a fragmented distribution pattern among the Northern and Southern Hemispheres. Although several herbaceous species of Solanaceae have been subjected to genome sequencing, thus far, no genome sequences of woody representatives have been available. Here, we sequenced the genomes of 13 perennial woody species of Lycium, with a focus on Lycium barbarum. Integration with other genomes provides clear evidence supporting a whole-genome triplication (WGT) event shared by all hitherto sequenced solanaceous plants, which occurred shortly after the divergence of Solanaceae and Convolvulaceae. We identified new gene families and gene family expansions and contractions that first appeared in Solanaceae. Based on the identification of self-incompatibility related-gene families, we inferred that hybridization hotspots are enriched for genes that might be functioning in gametophytic self-incompatibility pathways in wolfberry. Extremely low expression of LOCULE NUBER (LC) and COLORLESS NON-RIPENING (CNR) orthologous genes during Lycium fruit development and ripening processes suggests functional diversification of these two genes between Lycium and tomato. The existence of additional flowering locus C-like MADS-box genes might correlate with the perennial flowering cycle of Lycium. Differential gene expression involved in the lignin biosynthetic pathway between Lycium and tomato likely illustrates woody and herbaceous differentiation. We also provide evidence that Lycium migrated from Africa into Asia, and subsequently from Asia into North America. Our results provide functional insights into Solanaceae origins, evolution and diversification.

The ancestral duplicated DL/CRC orthologs, PeDL1 and PeDL2, function in orchid reproductive organ innovation.

Orchid gynostemium, the fused organ of the androecium and gynoecium, and ovule development are unique developmental processes. Two DROOPING LEAF/CRABS CLAW (DL/CRC) genes, PeDL1 and PeDL2, were identified from the Phalaenopsis orchid genome and functionally characterized. Phylogenetic analysis indicated that the most recent common ancestor of orchids contained the duplicated DL/CRC-like genes. Temporal and spatial expression analysis indicated that PeDL genes are specifically expressed in the gynostemium and at the early stages of ovule development. Both PeDLs could partially complement an Arabidopsis crc-1 mutant. Virus-induced gene silencing (VIGS) of PeDL1 and PeDL2 affected the number of protuberant ovule initials differentiated from the placenta. Transient overexpression of PeDL1 in Phalaenopsis orchids caused abnormal development of ovule and stigmatic cavity of gynostemium. PeDL1, but not PeDL2, could form a heterodimer with Phalaenopsis equestris CINCINNATA 8 (PeCIN8). Paralogous retention and subsequent divergence of the gene sequences of PeDL1 and PeDL2 in P. equestris might result in the differentiation of function and protein behaviors. These results reveal that the ancestral duplicated DL/CRC-like genes play important roles in orchid reproductive organ innovation.

Comparative analysis of Phytophthora genomes reveals oomycete pathogenesis in crops.

The oomycete genus Phytophthora includes devastating plant pathogens that are found in almost all ecosystems. We sequenced the genomes of two quarantined Phytophthora species-P. fragariae and P. rubi. Comparing these Phytophthora species and related genera allowed reconstruction of the phylogenetic relationships within the genus Phytophthora and revealed Phytophthora genomic features associated with infection and pathogenicity. We found that several hundred Phytophthora genes are putatively inherited from red algae, but Phytophthora does not have vestigial plastids originating from phototrophs. The horizontally-transferred Phytophthora genes are abundant transposons that "transmit" exogenous gene to Phytophthora species thus bring about the gene recombination possibility. Several expansion events of Phytophthora gene families associated with cell wall biogenesis can be used as mutational targets to elucidate gene function in pathogenic interactions with host plants. This work enhanced the understanding of Phytophthora evolution and will also be helpful for the design of phytopathological control strategies.

Orchid Bsister gene PeMADS28 displays conserved function in ovule integument development.

The ovules and egg cells are well developed to be fertilized at anthesis in many flowering plants. However, ovule development is triggered by pollination in most orchids. In this study, we characterized the function of a Bsister gene, named PeMADS28, isolated from Phalaenopsis equestris, the genome-sequenced orchid. Spatial and temporal expression analysis showed PeMADS28 predominantly expressed in ovules between 32 and 48 days after pollination, which synchronizes with integument development. Subcellular localization and protein-protein interaction analyses revealed that PeMADS28 could form a homodimer as well as heterodimers with D-class and E-class MADS-box proteins. In addition, ectopic expression of PeMADS28 in Arabidopsis thaliana induced small curled rosette leaves, short silique length and few seeds, similar to that with overexpression of other species' Bsister genes in Arabidopsis. Furthermore, complementation test revealed that PeMADS28 could rescue the phenotype of the ABS/TT16 mutant. Together, these results indicate the conserved function of Bsister PeMADS28 associated with ovule integument development in orchid.

Genome-Wide Identification of YABBY Genes in Orchidaceae and Their Expression Patterns in Phalaenopsis Orchid.

The plant YABBY transcription factors are key regulators in the lamina development of lateral organs. Orchid is one of the largest families in angiosperm and known for their unique floral morphology, reproductive biology, and diversified lifestyles. However, nothing is known about the role of YABBY genes in orchids, although biologists have never lost their fascination with orchids. In this study, a total of 54 YABBY genes, including 15 genes in CRC/DL, eight in INO, 17 in YAB2, and 14 in FIL clade, were identified from the eight orchid species. A sequence analysis showed that all protein sequences encoded by these YABBY genes share the highly conserved C2C2 zinc-finger domain and YABBY domain (a helix-loop-helix motif). A gene structure analysis showed that the number of exons is highly conserved in the same clades. The genes in YAB2 clade have six exons, and genes in CRC/DL, INO, and FIL have six or seven exons. A phylogenetic analysis showed all 54 orchid YABBY genes could be classified into four major clades, including CRC/DL, INO, FIL, and YAB2. Many of orchid species maintain more than one member in CRC/DL, FIL, and YAB2 clades, implying functional differentiation among these genes, which is supported by sequence diversification and differential expression. An expression analysis of PhalaenopsisYABBY genes revealed that members in the CRC/DL clade have concentrated expressions in the early floral development stage and gynostemium, the fused male and female reproductive organs. The expression of PeINO is consistent with the biological role it played in ovule integument morphogenesis. Transcripts of members in the FIL clade could be obviously detected at the early developmental stage of the flowers. The expression of three genes, PeYAB2,PeYAB3, and PeYAB4, in the YAB2 clade could be revealed both in vegetative and reproductive tissues, and PeYAB4 was transcribed at a relatively higher level than that of PeYAB2 and PeYAB3. Together, this comprehensive analysis provides the basic information for understanding the function of the YABBY gene in Orchidaceae.

Author Correction: The Apostasia genome and the evolution of orchids.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Changes in albuminuria during the spontaneous breathing trial: A prospective observational study.

BACKGROUND: We hypothesized urine albumin concentration may detect the early increasing cardiac load during the spontaneous breathing trial (SBT). The purpose of our study is to determine whether the changes in urine albumin concentration before and after the SBT correlate with SBT outcome. METHODS: This prospective observational study was conducted from January 2013 to September 2013. Patients receiving endotracheal tube intubation due to acute respiratory failure were included. Urine albumin concentration was measured upon admission to the intensive care unit, before and after the SBT. RESULTS: A total of 211 patients with respiratory failure were screened. Finally, 69 patients were included for analysis. Among the 69 patients received the SBT, 61 patients passed the SBT while 8 patients didn't. Urine albumin concentration upon admission was 251.00 ± 108.21 mg/g in the SBT success group and 260.87 ± 77.95 mg/g in the SBT failure group (p = 0.97). The mean percent change in urine albumin concentration during the SBT was significantly higher in the SBT failure group (+58.44%) than in the SBT success group (+13.11%) (p = 0.02). Univariable and multivariable logistic regression model showed that the difference of urine albumin concentration before and after the SBT correlated significantly with SBT failure (adjusted OR:1.04, p = 0.01). CONCLUSION: This open label pilot study demonstrates the significant association of the changes in urine albumin concentration with SBT outcome. Further study is warranted to investigate the predictive value of urine albumin concentration.

Association of IL-6 -174G>C (rs1800795) polymorphism with cervical cancer susceptibility.

Interleukin-6 (IL-6) is a multifunctional cytokine that has been implicated in the etiology of cancer. Several case-control studies have been conducted to assess the association of IL-6 -174G>C (rs1800795) polymorphism with the risk of cervical cancer, yet with conflicting conclusions. To derive a more precise estimation of the relationship, we performed this meta-analysis updated to June 2018. A total of seven original publications were identified covering IL-6 -174G>C (rs1800795) polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the relationship strengths. Statistically significant relationship was observed between IL-6 -174G>C polymorphism and cervical cancer risk (OR = 0.61, 95% CI: 0.40-0.94 for GG vs. CC, and OR = 0.77, 95% CI: 0.64-0.93 for G vs. C). Moreover, the significant association was found among Asians (OR = 0.46, 95% CI: 0.29-0.75 for GG vs. CC, and OR = 0.70, 95% CI: 0.57-0.89 for G vs. C); hospital-based subgroup (OR = 0.53, 95% CI: 0.38-0.72 for GG vs. CC, and OR = 0.73, 95% CI: 0.61-0.87 for G vs. C); and Hardy-Weinberg equilibrium ≤0.05 (OR = 0.56, 95% CI: 0.37-0.86 for GG vs. GC, and OR = 0.66, 95% CI: 0.47-0.93 for G vs. C). This meta-analysis showed the evidence that the IL-6 -174G>C polymorphism was a low-penetrance susceptibility variant for cervical cancer. Further large-scale case-control studies are needed to confirm these results.