ABSTRACT
Supersolid, an exotic quantum state of matter that consists of particles forming an incompressible solid structure while simultaneously showing superfluidity of zero viscosity1, is one of the long-standing pursuits in fundamental research2,3. Although the initial report of 4He supersolid turned out to be an artefact4, this intriguing quantum matter has inspired enthusiastic investigations into ultracold quantum gases5-8. Nevertheless, the realization of supersolidity in condensed matter remains elusive. Here we find evidence for a quantum magnetic analogue of supersolid-the spin supersolid-in the recently synthesized triangular-lattice antiferromagnet Na2BaCo(PO4)2 (ref. 9). Notably, a giant magnetocaloric effect related to the spin supersolidity is observed in the demagnetization cooling process, manifesting itself as two prominent valley-like regimes, with the lowest temperature attaining below 100 mK. Not only is there an experimentally determined series of critical fields but the demagnetization cooling profile also shows excellent agreement with the theoretical simulations with an easy-axis Heisenberg model. Neutron diffractions also successfully locate the proposed spin supersolid phases by revealing the coexistence of three-sublattice spin solid order and interlayer incommensurability indicative of the spin superfluidity. Thus, our results reveal a strong entropic effect of the spin supersolid phase in a frustrated quantum magnet and open up a viable and promising avenue for applications in sub-kelvin refrigeration, especially in the context of persistent concerns about helium shortages10,11.
ABSTRACT
A single insulin receptor (InR) gene has been identified and extensively studied in model species ranging from nematodes to mice. However, most insects possess additional copies of InR, yet the functional significance, if any, of alternate InRs is unknown. Here, we used the wing-dimorphic brown planthopper (BPH) as a model system to query the role of a second InR copy in insects. NlInR2 resembled the BPH InR homologue (NlInR1) in terms of nymph development and reproduction, but revealed distinct regulatory roles in fuel metabolism, lifespan, and starvation tolerance. Unlike a lethal phenotype derived from NlInR1 null, homozygous NlInR2 null mutants were viable and accelerated DNA replication and cell proliferation in wing cells, thus redirecting short-winged-destined BPHs to develop into long-winged morphs. Additionally, the proper expression of NlInR2 was needed to maintain symmetric vein patterning in wings. Our findings provide the first direct evidence for the regulatory complexity of the two InR paralogues in insects, implying the functionally independent evolution of multiple InRs in invertebrates.
Subject(s)
Evolution, Molecular , Gene Expression Regulation, Developmental , Hemiptera/genetics , Insect Proteins/genetics , Receptor, Insulin/genetics , Wings, Animal/metabolism , Adaptation, Physiological/genetics , Animals , Base Sequence , CRISPR-Cas Systems , Energy Metabolism/genetics , Gene Dosage , Gene Editing/methods , Hemiptera/anatomy & histology , Hemiptera/growth & development , Hemiptera/metabolism , Insect Proteins/metabolism , Longevity/genetics , Nymph/genetics , Nymph/growth & development , Nymph/metabolism , Phenotype , Receptor, Insulin/metabolism , Signal Transduction , Starvation/genetics , Starvation/metabolism , Wings, Animal/anatomy & histology , Wings, Animal/growth & developmentABSTRACT
Wing polymorphism is an evolutionary feature found in a wide variety of insects, which offers a model system for studying the evolutionary significance of dispersal. In the wing-dimorphic planthopper Nilaparvata lugens, the insulin/insulin-like growth factor signaling (IIS) pathway acts as a 'master signal' that directs the development of either long-winged (LW) or short-winged (SW) morphs via regulation of the activity of Forkhead transcription factor subgroup O (NlFoxO). However, downstream effectors of the IIS-FoxO signaling cascade that mediate alternative wing morphs are unclear. Here we found that vestigial (Nlvg), a key wing-patterning gene, is selectively and temporally regulated by the IIS-FoxO signaling cascade during the wing-morph decision stage (fifth-instar stage). RNA interference (RNAi)-mediated silencing of Nlfoxo increase Nlvg expression in the fifth-instar stage (the last nymphal stage), thereby inducing LW development. Conversely, silencing of Nlvg can antagonize the effects of IIS activity on LW development, redirecting wing commitment from LW to the morph with intermediate wing size. In vitro and in vivo binding assays indicated that NlFoxO protein may suppress Nlvg expression by directly binding to the first intron region of the Nlvg locus. Our findings provide a first glimpse of the link connecting the IIS pathway to the wing-patterning network on the developmental plasticity of wings in insects, and help us understanding how phenotypic diversity is generated by the modification of a common set of pattern elements.
Subject(s)
Forkhead Box Protein O1/metabolism , Hemiptera/metabolism , Insect Proteins/metabolism , Somatomedins/metabolism , Wings, Animal/growth & development , Animals , Forkhead Box Protein O1/genetics , Gene Expression Regulation, Developmental/genetics , Gene Knockout Techniques , Gene Ontology , Gene Silencing , Hemiptera/genetics , Hemiptera/growth & development , High-Throughput Nucleotide Sequencing , Insect Proteins/genetics , Introns , Phenotype , Protein Binding , RNA Interference , Somatomedins/genetics , Spatio-Temporal Analysis , Wings, Animal/metabolismABSTRACT
BACKGROUND AND AIMS: Reintervention modalities after myotomy failure in achalasia patients have yet to be established. The efficacy and safety of salvage peroral endoscopic myotomy (POEM) for treatment of achalasia after myotomy failure were evaluated in the study. METHODS: Between August 2011 and August 2021 at the Endoscopy Center of Zhongshan Hospital, 219 achalasia patients who had previously undergone a myotomy underwent a salvage POEM and were thus retrospectively enrolled in this study. After propensity score matching (PSM), operation-related parameters were compared between the salvage POEM group and the naïve POEM group. Subgroup analysis was performed between patients with previous Heller myotomy (HM) and patients with previous POEM. RESULTS: With similar baseline characteristics between both groups after PSM, the salvage POEM group presented with shorter tunnel length (11.8 ± 2.2 cm vs 12.8 ± .9 cm, P < .0001) and myotomy length (9.8 ± 2.0 cm vs 10.4 ± 1.0 cm, P < .0001) than the naïve POEM group. No significant differences were found in procedure-related adverse events between patients of salvage POEM and naïve POEM. The primary outcome of treatment success occurred in 175 of 193 patients (90.7%) in the salvage POEM group versus 362 of 374 patients (96.8%) in the naïve POEM group (P = .0046). At a 2- and 5-year follow-up, significantly higher rates of clinical failures were observed in the previous HM subgroup than in the previous POEM subgroup (P = .0433 and P = .0230, respectively). CONCLUSIONS: Salvage POEM after a previous myotomy failure, especially after a POEM failure, is a promising treatment option because it has a durable clinical relief rate.
Subject(s)
Digestive System Surgical Procedures , Esophageal Achalasia , Heller Myotomy , Myotomy , Humans , Esophageal Achalasia/surgery , Retrospective StudiesABSTRACT
Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.
Subject(s)
Chikungunya Fever , Chikungunya virus , Animals , Humans , Molecular Docking Simulation , Chikungunya Fever/drug therapy , Antiviral Agents/metabolism , Virus ReplicationABSTRACT
BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is a promising endoscopic technique for achalasia. We aimed to establish a regression model and develop a simple nomogram to predict the technical difficulty of POEM in a single center with large volume cases. METHODS: 3385 achalasia patients treated with POEM were included, and the technical difficulty was systemically evaluated. All of them were randomized into the training cohort (n = 1693) or internal validation cohort (n = 1692). Then, the prediction model and nomogram were proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. RESULTS: Of 3385 patients, technical difficulty happened in 417 (12.32%) cases. In the training stage, six factors were weighted based on the ß coefficient from the regression model, including age, disease duration, sigmoid esophagus, mucosal edema, submucosal fibrosis, and tunnel length. The patients were categorized into low-risk (< 0.1), medium-risk (0.1-0.25), and high-risk (> = 0.25) groups. Our score model performed satisfying discrimination with the areas under the receiver-operating characteristic curve (AUC) of 0.743 (95% confidence interval (CI), 0.701-0.785) and calibration with goodness of fit in the Hosmer-Lemeshow test (P = 0.088) in internal validation. CONCLUSIONS: The prediction model and nomogram demonstrated good performance in predicting the technical difficulty of POEM.
Subject(s)
Digestive System Surgical Procedures , Esophageal Achalasia , Myotomy , Humans , Colon, Sigmoid , Esophageal Achalasia/surgery , NomogramsABSTRACT
The homeotic complex gene Abdominal-B (Abd-B) is involved in regulating the development of posterior abdomens and has been extensively studied in holometabolous insects. However, the function of Abd-B in hemimetabolous insects is not fully understood. Here, we functionally characterize an Abd-B homologue in the brown planthopper (BPH), Nilaparvata lugens. The full-length cDNA of the N. lugens Abd-B homologue (NlAbd-B) is 2334 nt, with an open reading frame of 1113 bp. NlAbd-B has the highest expression level at the egg stage relative to the nymphal and adult stages and is mainly expressed in the fourth to the ninth abdominal segment of embryos. RNA interference (RNAi)-mediated knockdown of NlAbd-B in nymphs disrupted the development of genitalia both in females and males and caused a genitalia-to-leg transformation. Parental RNAi of NlAbd-B in both female and male adults caused an extra abdominal segment in offspring nymphs, while parental RNAi of the N. lugens abdominal-A homologue in both female and males adults led to embryos with leg-like appendages on the second to the eighth abdominal segment. These findings suggest that NlAbd-B plays a pivotal role in genital development and posterior abdominal patterning and thus highlight the conservational role of Abd-B in holometabolous and hemimetabolous insects.
Subject(s)
Hemiptera , Abdomen , Animals , Female , Hemiptera/physiology , Male , Nymph/genetics , Nymph/metabolism , Open Reading Frames , RNA InterferenceABSTRACT
BACKGROUND AND AIM: Developments of endoscopic techniques brought the possibility of endoscopic resection for gastrointestinal stromal tumors (GISTs) of larger sizes. We aim to compare safety and short-term outcomes between endoscopic and laparoscopic resections of gastric GISTs with a diameter of 2-5 cm. METHODS: This is a single-center, retrospective cohort study. The clinical data, perioperative conditions, and the adverse events of patients who underwent endoscopic or laparoscopic resection for gastric GIST of 2-5 cm in Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were retrospectively reviewed. RESULTS: A total of 346 patients were reviewed; 12 patients who failed to accomplish the planned procedure were excluded; 182 underwent laparoscopic resection; and 152 underwent endoscopic resection. Significant differences exist in the tumor size between the laparoscopic group (3.43 ± 0.86 cm) and the endoscopic group (2.78 ± 0.73 cm) (P < 0.01). Compared with laparoscopic resection, endoscopic resection was associated with faster recovery (P < 0.01), shorter hospital stays (P < 0.01), and lower cost (P < 0.01). The incidence of Clavien-Dindo grade II-V adverse events in the endoscopic group (3/152) was significantly lower than that in the laparoscopic group (12/182) (P = 0.04). After a propensity score matching analysis, the endoscopic group showed similar incidences of complications with the laparoscopic group, while the advantages over laparoscopic resection in postoperative hospital stay, time to first oral intake, and hospitalization expenses remained significant (P < 0.01). CONCLUSIONS: Endoscopic resection is a safe and cost-effective method for 2-5 cm of gastric GISTs compared with laparoscopic resection.
Subject(s)
Gastrointestinal Stromal Tumors , Laparoscopy , Stomach Neoplasms , Gastrectomy/adverse effects , Gastrectomy/methods , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Length of Stay , Retrospective Studies , Stomach Neoplasms/pathology , Treatment OutcomeABSTRACT
BACKGROUND AND AIMS: We aimed to establish a predictive model and develop a simple risk-scoring system (Zhongshan POEM Score) to help clinicians to characterize high-risk patients for clinical failure after peroral endoscopic myotomy (POEM). METHODS: A total of 1538 patients with achalasia treated with POEM with available follow-up data were included in this study and were randomly classified to the training cohort (n = 769) or internal validation cohort (n = 769). A risk-scoring system was developed using multivariate Cox regression analysis in the training cohort. The system was then internally validated by survival analysis in the validation cohort. RESULTS: During a median follow-up time of 42 months, 109 patients had clinical failure. In the training stage, 3 risk factors for clinical failure were weighted with point values: previous treatment (2 points), intraprocedural mucosal injury (2 points for type I and 6 points for type II), and clinical reflux (3 points). The patients were categorized into low-risk and high-risk groups. In the validation stage, Kaplan-Meier curves differed significantly between the 2 groups. Patients in the high-risk group had a significantly higher risk of clinical failure than those in the low-risk group (hazard ratio, 3.99; 95% confidence interval, 2.31-6.91; P < .001). Satisfactory discrimination and calibration were shown. CONCLUSIONS: This risk-scoring system demonstrated good performance in predicting clinical failure in patients who underwent POEM.
Subject(s)
Esophageal Achalasia/etiology , Esophageal Achalasia/surgery , Esophageal Sphincter, Lower/surgery , Myotomy/adverse effects , Natural Orifice Endoscopic Surgery/adverse effects , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Risk Assessment , Survival Analysis , Treatment FailureABSTRACT
BACKGROUND: Peroral endoscopic myotomy (POEM) is a safe and effective approach for achalasia. However, the safety, feasibility, perioperative and long-term efficacy in treating geriatric patients has not been well evaluated. METHODS: Data of 2367 patients diagnosed with achalasia and treated with POEM in the Endoscopy Center, Zhongshan Hospital, Fudan University from August 2010 to December 2017 were retrospectively reviewed. Last follow-up was in December 2018. Propensity score matching based on baseline characteristics was used to adjust for confounding. With a caliper of 0.01 in propensity scoring, 139 patients aged ≥ 65 years were matched at a 1:2 ratio with 275 patients aged < 65 years. Perioperative complications and long-term outcomes were compared between the two groups. RESULTS: After propensity score matching, the two groups had similar baseline clinical characteristics and distribution of propensity scores. The mean age was 70.22 years in geriatric patients and 42.02 in younger patients. Technical failure occurred in one geriatric and one non-geriatric patients (p = 0.485). The procedural time in geriatric patients was similar to younger patients [50 (interquartile range (IQR) 36-76) vs. 50 (IQR 36-70) min, p = 0.398]. There were also no significant differences in major perioperative adverse events (2.88% vs. 2.18%, p = 0.663) and hospitalization length (median 3 vs. 3 days, p = 0.488). During a median follow-up period of 41 months (IQR 26-60), mean decrease in Eckardt score and pressure of the LES were 6.63 and 11.9 mmHg in geriatric patients, which were similar to the change in non-geriatric patients (6.49 and 11.6 mmHg, p = 0.652 and 0.872, respectively). Clinical reflux occurred in 23.53% geriatric patients and 21.59% non-geriatric patients (p = 0.724). 5-year success rate of 92.94% was achieved in geriatric patients and 92.61% in younger patients (log-rank p = 0.737). CONCLUSIONS: POEM is a safe and reliable treatment in geriatric achalasia patients with confirmed short-term and long-term efficacy compared with those in non-geriatric patients.
Subject(s)
Digestive System Surgical Procedures/methods , Esophageal Achalasia/surgery , Natural Orifice Endoscopic Surgery/methods , Adult , Aged , Digestive System Surgical Procedures/adverse effects , Esophageal Achalasia/mortality , Female , Gastroesophageal Reflux/etiology , Humans , Length of Stay , Male , Middle Aged , Myotomy/adverse effects , Natural Orifice Endoscopic Surgery/adverse effects , Postoperative Complications/etiology , Propensity Score , Retrospective Studies , Treatment OutcomeABSTRACT
This study aims to elucidate the mechanisms by which microRNA-143-5p (miR-143-5p) targets runt-related transcription factor 2 (Runx2) in the differentiation of dental pulp stem cells (DPSCs) into odontoblasts, through regulating the osteoprotegerin receptor activator of the nuclear factor-κB ligand (OPG/RANKL) signaling pathway. Following transfection, DPSCs were divided into blank, control, miR-143-5p mimics, miR-143-5p inhibitors, miR-143-5p inhibitors + siRunx2 and siRunx2 groups. Alkaline phosphatase (ALP) activity and mineralized nodules were detected using ALP kit and alizarin red staining. Quantitative reverse transcriptase real time PCR (qRT-PCR) was conducted to measure mRNA expressions of miR-143-5p, Runx2, OPG, and RANKL. Western blotting was used to assess protein expression of odontoblast differentiation-related proteins. Transwell assay and an extracellular matrix (ECM) adhesion cell assay were employed to examine cell migration and cell adhesion. Compared with the blank group, the miR-143-5p mimics and siRunx2 groups showed decreased ALP activity, decreased mineralized nodules and displays of calcium. Fewer migrated cells, weakened cell adhesion, decreased protein expression of dentin phosphoprotein (DPP), dentin sialoprotein (DSP), dentin matrix protein 1 (DMP1), osteopontin (OPN), bone sialoprotein (BSP), osteocalcin (OCN), OPG and Runx2, and increased RANKL protein expressions were observed. Additionally, opposite results were observed in the miR-143-5p inhibitors group, demonstrating that down-regulated miR-143-5p promotes the differentiation of DPSCs into odontoblasts by enhancing Runx2 expression via the OPG/RANKL signaling pathway. Based on findings in this study, it is postulated that the enhancement of Runx2 expression via the regulation of the OPG/RANKL signaling pathway could be a beneficial approach for dental pulp regeneration. J. Cell. Biochem. 119: 536-546, 2018. © 2017 Wiley Periodicals, Inc.
Subject(s)
Cell Differentiation , Core Binding Factor Alpha 1 Subunit/metabolism , Dental Pulp/metabolism , MicroRNAs/metabolism , Odontoblasts/metabolism , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Signal Transduction , Stem Cells/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Dental Pulp/cytology , Female , Humans , Male , MicroRNAs/genetics , Odontoblasts/cytology , Osteoprotegerin/genetics , RANK Ligand/genetics , Stem Cells/cytologyABSTRACT
BACKGROUND AND OBJECTIVES: Frequently aberrant expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) have been observed in several human cancers. In this retrospective study, we aimed at investigating the prognostic significance of CK7 and CK19 in intrahepatic cholangiocarcinoma (ICC). METHODS: Immunohistochemistry was performed to assess CK7 and CK19 expression on tissue microarrays in training cohort enrolling 214 ICC patients and validation cohort comprising 108 ICC patients. Kaplan-Meier analysis, Cox's proportional hazards regression, and nomogram were applied to evaluate the prognostic significance of both CKs. RESULTS: Both CK7 and CK19 expression were significantly up-regulated in ICC compared to their non-tumor counterparts, and positively correlated with aggressive tumor phenotypes, like lymph node metastasis and larger tumor size. Furthermore, high expression of either CK7 or CK19 predicted a significantly dismal postoperative survival. Integrated analysis of CK7 and CK19 expression was identified as a better indicator for survival probability. Notably, the nomogram integrating CK7/CK19 index had a perfect prognostic performance as compared with current staging systems. The results were further confirmed in the validation cohort. CONCLUSIONS: CK7/CK19 index was an independent adverse prognostic factor for ICC patients' survival, and may be helpful to improve postoperative risk stratification and individualized treatment strategies.
Subject(s)
Bile Duct Neoplasms/pathology , Biomarkers, Tumor/metabolism , Cholangiocarcinoma/pathology , Hepatectomy/mortality , Keratin-19/metabolism , Keratin-7/metabolism , Nomograms , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/surgery , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Period , Prognosis , Retrospective Studies , Survival RateSubject(s)
Carcinoma, Neuroendocrine , Endoscopic Mucosal Resection , Esophageal Neoplasms , Carcinoma, Neuroendocrine/diagnostic imaging , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/surgery , Epithelial Cells/pathology , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Humans , Hyperplasia/pathologySubject(s)
Appendectomy , Endoscopic Mucosal Resection , Humans , Dogs , Animals , Gastroscopy , Gastric Mucosa/surgery , Treatment OutcomeABSTRACT
UNLABELLED: Hepatocellular carcinoma (HCC) is the third-most lethal cancer worldwide. Understanding the molecular pathogenesis of HCC recurrence and metastasis is the key to improve patients' prognosis. In this study, we report that protein tyrosine phosphatase receptor S (PTPRS) is significantly down-regulated in nearly 80% of HCCs, and its expression negatively correlates with aggressive pathological features, such as larger tumor size and advanced stage. In addition, PTPRS deficiency is independently associated with shorter survival and increased recurrence in patients, although 16.7% of HCCs show intratumor heterogeneous expression of PTPRS. Restoration of wild-type, but not mutant, PTPRS expression significantly inhibits HCC cell migration and invasion in vitro as well as lung metastasis in vivo, whereas knockdown of its expression significantly promotes invasion and metastasis. Notably, PTPRS-regulated HCC invasiveness is accompanied by typical changes of epithelial-mesenchymal transition (EMT). Moreover, PTPRS forms a complex with epithermal growth factor receptor (EGFR) and regulates its tyrosine residues' phosphorylation. Ectopic expression of EGFR reverses the metastasis-inhibiting effects of PTPRS, whereas silencing of EGFR or inhibiting phosphorylation of key molecules in EGFR downstream pathways reinhibits EMT and metastasis caused by PTPRS down-regulation. Meanwhile, promoter hypermethylation of PTPRS is frequently detected in HCC samples and cell lines. Treatment with a demethylation agent, 5-aza-2'-deoxycytidine, recovers PTPRS expression in a dose-dependent manner. CONCLUSIONS: Epigenetic inactivation of PTPRS may increase phosphorylation and activity of EGFR signaling to promote EMT and metastasis in HCC.
Subject(s)
Carcinoma, Hepatocellular/secondary , Down-Regulation , Epithelial-Mesenchymal Transition , ErbB Receptors/physiology , Liver Neoplasms/pathology , Neoplasm Metastasis , Receptor-Like Protein Tyrosine Phosphatases, Class 2/physiology , Humans , Receptors, Growth Factor , Tumor Cells, CulturedABSTRACT
A possible association between multiple drug resistance 1 gene (MDR1) polymorphisms and the risk of developing hepatocellular carcinoma (HCC) is currently under debate, and evidence from various epidemiological studies has yielded controversial results. To derive a more precise estimation of the association between MDR1 polymorphisms and HCC risk, the present meta-analysis was performed. A total of 8 studies containing 11 cohorts with 4407 cases and 4436 controls were included by systematic literature search of EMBASE, PubMed, Web of Science, and CNKI. All polymorphisms were classified as mutant/wild-type alleles. In particular, the variation type, functional impact, and protein domain location of the polymorphisms were assessed and used as stratified indicators. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the association. Overall, our results suggested that the mutant alleles of the MDR1 gene were associated with a significantly increased risk for HCC under all genetic models (allelic model: OR = 1.28, 95 % CI = 1.20-1.36, P < 0.001; dominant model: OR = 1.27, 95 % CI = 1.16-1.38, P < 0.001; recessive model: OR = 1.59, 95 % CI = 1.36-1.85, P < 0.001). Furthermore, increased risks for HCC were also revealed in stratified analyses by ethnicity, sample size, and quality scores of cohorts as well as variation type, functional impact, and protein domain location of polymorphisms. In conclusion, the present meta-analysis suggested that the presence of MDR1 mutant alleles might be a risk factor for HCC.