LINC01116 modulates EMT process via binding with AGO1 mRNA in oesophageal squamous cell carcinoma.

Recent researches have uncovered that long non-coding RNAs (lncRNAs) are closely correlated with the development of different diseases, while biological functions and hidden molecular mechanisms of antisense lncRNAs in oesophageal squamous cell carcinoma (OSCC) remain unclear. Here, we identified upregulation of LINC01116 in RNA sequencing data, online database, and in OSCC and intraepithelial neoplasia (IEN) specimens. Functionally, LINC01116 facilitates OSCC advancement and metastasis in vitro and vivo. Mechanistically, elevated expression of LINC01116 in OSCC cells other than tumor stroma and cytoplasmic enables it to activate AGO1 expression via complementary binding with AGO1 mRNA to facilitate EMT process of OSCC.

Clinical First-Trimester Prediction Models for Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication that negatively impacts the health of both the mother and child. Early prediction of the risk of GDM may permit prompt and effective interventions. This systematic review and meta-analysis aimed to summarize the study characteristics, methodological quality, and model performance of first-trimester prediction model studies for GDM. METHODS: Five electronic databases, one clinical trial register, and gray literature were searched from the inception date to March 19, 2022. Studies developing or validating a first-trimester prediction model for GDM were included. Two reviewers independently extracted data according to an established checklist and assessed the risk of bias by the Prediction Model Risk of Bias Assessment Tool (PROBAST). We used a random-effects model to perform a quantitative meta-analysis of the predictive power of models that were externally validated at least three times. RESULTS: We identified 43 model development studies, six model development and external validation studies, and five external validation-only studies. Body mass index, maternal age, and fasting plasma glucose were the most commonly included predictors across all models. Multiple estimates of performance measures were available for eight of the models. Summary estimates range from 0.68 to 0.78 (I2 ranged from 0% to 97%). CONCLUSION: Most studies were assessed as having a high overall risk of bias. Only eight prediction models for GDM have been externally validated at least three times. Future research needs to focus on updating and externally validating existing models.

Endoscopic debulking resection with additive chemoradiotherapy: Optimal management of advanced inoperable esophageal squamous cell carcinoma.

BACKGROUND: There is no remedial strategy other than definitive chemoradiotherapy for patients with advanced esophageal squamous cell carcinoma (ESCC) who are not eligible to undergo surgical treatment. AIM: To introduce a novel therapy called endoscopic debulking resection (EdR) followed by additive chemoradiotherapy (CRT) and evaluate its efficacy and safety. METHODS: Advanced, inoperable ESCC patients between 1 January 2015 and 30 December 2019 were investigated retrospectively. Patients who received EdR followed by CRT were deemed the EdR + CRT group and those without CRT were deemed the EdR group. Overall survival (OS), progression-free survival (PFS), and adverse events were evaluated. RESULTS: A total of 41 patients were enrolled. At a median follow-up of 36 mo (range: 1-83), the estimated 1-, 2-, and 3-year cumulative OS rates of patients who underwent EdR plus additive CRT were 92.6%, 85.2%, and 79.5%, respectively, which were higher than those of patients who underwent EdR alone (1-year OS, 83.3%; 2-year OS, 58.3%; 3-year OS, 50%; P = 0.05). The estimated 2-year cumulative PFS rate after EdR + CRT was 85.7%, while it was 61.5% after EdR (P = 0.043). According to the univariate and multivariate Cox regression analyses, early clinical stage (stage ≤ IIB) and additive CRT were potential protective factors for cumulative OS. No severe adverse events were observed during the EdR procedure, and only mild to moderate myelosuppression and radiation pneumonia were observed in patients who underwent additive CRT after EdR. CONCLUSION: EdR plus CRT is an alternative strategy for selective advanced inoperable ESCC patients.

Biological and clinical implications of metastasis-associated circular RNAs in oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality as a result of early metastasis and poor prognosis. Metastasis is a multistep process, involving various signalling pathways. Circular RNAs (circRNAs) are a class of covalently closed noncoding RNAs, the aberrant expression of which is reported to be involved in several biological events, including cell transformation, proliferation, migration, invasion, apoptosis and metastasis. Several studies have reported interactions between circRNAs and metastasis-associated signalling pathways. The abundance, stability and highly specific expression of candidate circRNAs make them potential biomarkers and therapeutic targets in OSCC. In this review article, we comprehensively describe metastasis-related circRNAs and their interactions with epithelial-mesenchymal transition-associated molecules. We also describe the molecular mechanisms and clinical relevance of circRNAs in OSCC progression and metastasis.

New Iboga-Type Indole Alkaloids from Tabernaemontana divaricata.

Two hitherto unknown iboga-type indole alkaloids, namely (3R)-7,19-di-epi-3-methoxytabernoxidine (1) and (3R,19R)-19-hydroxy-3-(2-oxopropyl)voacangine (2), together with eight known alkaloids (3-10), were isolated from the twigs and leaves of Tabernaemontana divaricata. Their structures were established on the basis of spectroscopic data interpretation, single crystal X-ray diffraction analysis and circular dichroism spectrum.

A review and comparison of common maternal positions during the second-stage of labor.

The second-stage of labor is the most stressful part of childbirth process and the proper maternal position during this period is paramount for women's safe vaginal birth. Midwives play a pivotal role in managing maternal positions during the second-stage of labor. However, there is limited evidence to support an ideal maternal position during the second-stage of labor. Further, the difference between different maternal positions might not be apparent. This paper aims to review and compare the benefits and risks of common maternal positions during the second-stage of labor, thereby to provide midwives evidence-based practical guidelines.

Cerebral Blood Flow, Oxygen Delivery, and Pulsatility Responses to Oxygen Inhalation at High Altitude: Highlanders vs. Lowlanders.

Objective: To determine whether the acute cerebral hemodynamic responses to oxygen inhalation are impacted by race or acclimation to high altitude. Methods: Three groups of young healthy males, who were Tibetans (highlanders, n = 15) with lifelong exposure to high altitude, and Han Chinese (lowlanders) with five-year (Han-5 yr, n = 15) and three-day (Han-3 d, n = 16) exposures, participated in the study at an altitude of 3658 m. Cerebral blood flow velocity (CBFV) was recorded for three minutes prior to and during pure oxygen inhalation (2 L/min), respectively, using a transcranial color-coded duplex (TCCD) sonography at the middle cerebral artery (MCA). The blood draw and simultaneous monitoring of blood pressure (BP), heart rate (HR), and finger arterial oxygen saturation (SaO2) were also performed. Results: Values are Mean ± SEM. The three groups had similar demographic characteristics and HR responses, with the group differences (P < 0.05) found in hemoglobin concentration (16.9 ± 0.9, 18.4 ± 1.3, and 15.5 ± 1.0 gm/dL), baseline BPs and HR as expected. Both the Tibetans and Han-5yr groups presented blunted BP responses to O2-inhalation when compared to the Han-3d group; more interestingly, the Tibetans showed significantly reduced responses compared with Han-5yr and Han-3d in CBFV, cerebral oxygen delivery (COD), and pulsatility index (PI) as assessed by Δ%CBFV/ΔSaO2 (-1.50 ± 0.25 vs. -2.24 ± 0.25 and -2.23 ± 0.27, P = 0.049 and 0.048), Δ%COD/ΔSaO2 (-0.52 ± 0.27 vs. -1.33 ± 0.26 and -1.38 ± 0.28, P = 0.044 and 0.031), and Δ%PI (7 ± 2 vs. 16 ± 3 and 16 ± 3 %, P = 0.036 and 0.023), respectively. Conclusion: These findings provide evidence on the Tibetans trait of a distinct cerebral hemodynamic regulatory pattern to keep more stable cerebral blood flow (CBF), oxygen delivery, and pulsatility in response to oxygen inhalation as compared with Han Chinese, which is likely due to a genetic adaptation to altitude.

Motilimonas pumila sp. nov., isolated from the gut of sea cucumber Apostichopus japonicus.

A facultatively anaerobic and Gram-negative bacterium, designated strain PLHSC7-2T, was isolated from the gut of sea cucumber Apostichopusjaponicus that had been collected from the coastal area of Yantai, China. The cells were rod-shaped and motile by means of polar flagella. The novel isolate grew optimally at 28-30 °C, in the presence of 2.0-3.0 % (w/v) NaCl and at pH 7.0-7.5. The sole respiratory quinone was Q-8 and the major fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C17 : 0. The predominant polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain PLHSC7-2T was phylogenetically affiliated with the genus Motilimonas, and exhibited sequence similarity of 96.2 % toMotilimonas eburnea YH6T. The DNA G+C content was 45.5 mol%. On the basis of phenotypic , phylogenetic and genetic distinctiveness, strain PLHSC7-2T (=MCCC 1K03522T=KCTC 62589T) was classified as a novel species within the genus Motilimonas, for which the name Motilimonas pumila sp. nov. is proposed.

Carboxylicivirga sediminis sp. nov., isolated from coastal sediment.

A yellow-pigmented bacterial strain (JR1T) isolated from a sediment sample was subjected to a taxonomic study, based on phenotypic, genetic and physiological characterization. Here, we describe the cultivation and characteristics of strain JR1T, a novel member of the genus Carboxylicivirga in the family Marinilabiliaceae. Cells of strain JR1T were rod-shaped, Gram-stain-negative, non-motile and facultatively anaerobic. The temperature range for growth was 15-42 °C (optimum, 33 °C) and the pH range for growth was pH 6.0-8.5 (optimum, pH 7.0-7.5). Growth occurred in the presence of 0.0-10.0 % (w/v) NaCl (optimum 2.0-3.0 %). 16S rRNA gene sequence analysis produced results with 97.4 % similarity to Carboxylicivirga taeanensisMEBiC 08903T, 96.8 % similarity to Carboxylicivirga mesophilaMEBiC 07026T, 94.9 % similarity to Carboxylicivirga linearis FB218T and 94.6 % similarity to Carboxylicivirga flava Q15T. The DNA G+C content was 42.3 mol% and the major fatty acids were iso-C15 : 0, C15 : 0, anteiso-C15 : 0, C17 : 1ω6c and iso-C17 : 0-3OH. The major polar lipids detected were phosphatidylethanolamine and two unidentified lipids; the major respiratory quinone detected was MK-7. The results of the phenotypical, phylogenetic and biochemical analyses between the study strain and some related type strains indicated that this strain represent a novel species of the genus Carboxylicivirga within the family Marinilabiliaceae, for which the name Carboxylicivirga sediminis sp. nov. is proposed. The type strain is JR1T (=MCCC 1K03323T=KCTC 52869T).

Endosulfan induces apoptosis by activating the negative regulation pathway of cell cycle and death receptor pathway in spermatogenic cells.

The male reproductive toxicity of endosulfan has been proved. Nevertheless, the underlying molecular mechanisms of the apoptosis caused by endosulfan in spermatogenic cells remains poorly understood. In order to investigate the reproductive toxicity mechanism caused by endosulfan, there were four groups, which had eight Wistar male rats randomly assigned to them, and the rats in different groups received different doses of endosulfan for a period of 21 days. GC-1 spermatogenic cell lines were divided into four groups, and each group was exposed to different doses of endosulfan for 24 hours. The results of this research showed that endosulfan decreased the cell viability, damaged cell membranes and induced apoptosis in spermatogenic cells. Endosulfan had obviously activated the protein expression of PKC-δ, p53, p21cip1, p27kip1, Fas, FasL, Caspase-8, Caspase-3, and inhibited the expression of E2F-1. Endosulfan also induced oxidative stress and DNA damage in spermatogenic cells. The results of this research suggested that endosulfan could lead to E2F-1-induced apoptosis of spermatogenic cells by activating the negative regulation factors of the cell cycle, and endosulfan might cause apoptosis by death receptor pathway, causing oxidative stress.

Effects of race and sex on cerebral hemodynamics, oxygen delivery and blood flow distribution in response to high altitude.

To assess racial, sexual, and regional differences in cerebral hemodynamic response to high altitude (HA, 3658 m). We performed cross-sectional comparisons on total cerebral blood flow (TCBF = sum of bilateral internal carotid and vertebral arterial blood flows = QICA + QVA), total cerebrovascular resistance (TCVR), total cerebral oxygen delivery (TCOD) and QVA/TCBF (%), among six groups of young healthy subjects: Tibetans (2-year staying) and Han (Han Chinese) at sea level, Han (2-day, 1-year and 5-year) and Tibetans at HA. Bilateral ICA and VA diameters and flow velocities were derived from duplex ultrasonography; and simultaneous measurements of arterial pressure, oxygen saturation, and hemoglobin concentration were conducted. Neither acute (2-day) nor chronic (>1 year) responses showed sex differences in Han, except that women showed lower TCOD compared with men. Tibetans and Han exhibited different chronic responses (percentage alteration relative to the sea-level counterpart value) in TCBF (-17% vs. 0%), TCVR (22% vs. 12%), TCOD (0% vs. 10%) and QVA/TCBF (0% vs. 2.4%, absolute increase), with lower resting TCOD found in SL- and HA-Tibetans. Our findings indicate racial but not sex differences in cerebral hemodynamic adaptations to HA, with Tibetans (but not Han) demonstrating an altitude-related change of CBF distribution.

Endosulfan inhibiting the meiosis process via depressing expressions of regulatory factors and causing cell cycle arrest in spermatogenic cells.

Endosulfan is a persistent organic pollutant and widely used in agriculture as a pesticide. It is present in air, water, and soil worldwide; therefore, it is a health risk affecting especially the reproductive system. The aim of this study was to evaluate the toxicity of endosulfan in the reproductive system. To investigate the effect of endosulfan on meiosis process, 32 rats were divided into four groups, treated with 0, 1, 5, and 10 mg/kg/day endosulfan, respectively, and sacrificed after the 21 days of treatments. Results show that endosulfan caused the reductions in sperm concentration and motility rate, which resulted into an increased in sperm abnormality rate; further, endosulfan induced downregulation of spermatogenesis- and oogenesis-specific basic helix-loop-helix transcription factor (Sohlh1) which controls the switch on meiosis in mammals, as well cyclin A1, cyclin-dependent kinases 1 (CDK1), and cyclin-dependent kinases 2 (CDK2). In vitro, endosulfan induced G2/M phase arrest in the spermatogenic cell cycle and caused proliferation inhibition. Moreover, endosulfan induced oxidative stress and DNA damage in vivo and vitro. The results suggested that endosulfan could inhibit the start of meiosis by downregulating the expression of Sohlh1 and induce G2/M phase arrest of cell cycle by decreasing the expression of cyclin A1, CDK1, and CDK2 via oxidative damage, which inhibits the meiosis process, and therefore decrease the amount of sperm.

EVALUATION OF THE ACUTE AND SUBCHRONIC TOXICITY OF Aster tataricus L. F.

BACKGROUND: Aster tataricus L. f. is used as a traditional Chinese drug to relieve cough and asthma symptoms and to eliminate phlegm. However, Aster tataricus L. f. possesses toxicity, and little systematic research has been conducted on its toxic effects in the laboratory. METHODS AND MATERIALS: The acute group was administered 75% alcohol extract of Aster tataricus L. f. in a single dose. A subchronic toxicity study was performed via daily oral administration of Aster tataricus L. f. at a dose of 0.34 g/kg body weight in SD rats. The rats were divided into six groups: a petroleum ether extract (PEA) group, an ethyl acetate extract (EEA) group, an n-butyl alcohol extract (NEA) group, a remaining lower aqueous phases (REA) group, a 75% alcohol extract (AEA) group and a control group. Quantitative measurements of cytokines were obtained by fluorescence with a laser scanner using a Cy3 equivalent dye. RESULTS: The LD50 of the 75% alcohol extract of Aster tataricus L. f. was 15.74 g/kg bw. In the subchronic toxicity study, no significant differences were observed among groups in relative organ weights, urine traits, liver antioxidase levels, or cytokine levels. However, significant sporadic differences were observed in body weight gains, haematology indices, biochemistry values, and histopathology features in PEA, EEA group. In addition, sporadic changes in other groups in measures such as WBC, MCHC, CK, ALP, AST, ALT, LDH, T-BIL, LDL-C, HDL-C, and TC were observed. CONCLUSION: The toxicity study showed that Aster tataricus L. f. can produce toxic effects, mainly on the liver; much less on the heart. The LD50 was 15.74 g/kg BW in mice, and the subchronic toxicity study, used a dosage of 0.34 g/kg/d.BW, showed that the toxic components of Aster tataricus L. f. were mainly concentrated in the petroleum ether fraction, followed by the ethyl acetate fraction, the n-butyl alcohol fraction, the lower aqueous phase and the 75% ethanol extracts. Abbreviations: PEA, petroleum ether extract of Aster tataricus L. f.; EEA, ethyl acetate extract of Aster tataricus L. f.; NEA: n-butyl alcohol extract of Aster tataricus L. f.; REA: lower aqueous phases of Aster tataricus L. f.; AEA, 75% alcohol extract of Aster tataricus L. f.; WBC, white blood cell; RBC, red blood cell, PLT, platelet; HCT, haematocrit; MCV, mean corpuscular volume; HGB, haemoglobin; MCH, mean corpuscular haemoglobin; MCHC, mean corpuscular haemoglobin concentration; CREA, creatinine; LDH, lactate dehydrogenase; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; T-BIL, total bilirubin; ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase; TP, total protein; ALB, albumin; Glu, glucose; TC, total cholesterol; TG, triglycerides; CK, creatine kinase; GSH, Glutathione; MDA, malondialdehyde; T-SOD, total superoxide dismutase; TNF, tumour necrosis factor; IFN, interferon; MCP, monocyte chemotactic protein C.

The complete mitochondrial genome of Cynoglossus joyneri (Teleostei: Pleuronectiformes).

The complete mitochondrial genome of a commercially important sea fish Cynoglossus joyneri was sequenced and annotated. The 16,941 bp-long genome contained 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a control region. Phylogenetic analysis indicated that C. joyneri is a sister group with C. sinicus and C. bilineatus, and corroborated the proposed paraphyly of Cynoglossus genus.

Biologics for the prevention of postoperative Crohn's disease recurrence: A systematic review and meta-analysis.

AIM: To evaluate the efficacy and safety of biologics in the prevention of postoperative recurrence of Crohn's disease. METHODS: Published papers and conference literatures were screened for suitable studies. The main outcome measures were clinical, endoscopic recurrence and adverse events. RESULTS: Seven controlled trials met the inclusion criteria for this meta-analysis. At one year postoperation, the biologic therapies showed significant preventative effects in clinical recurrence (RR=0.36, 95% CI: 0.16-0.79; P=0.01), endoscopic recurrence (RR=0.16, 95% CI: 0.07-0.34; P<0.01) and severe endoscopic recurrence (RR=0.17, 95% CI: 0.04-0.71; P=0.02) when compared with the control arms. Similarly, two years postresection, the use of biologics significantly reduced the risk of clinical, endoscopic and severe endoscopic recurrence relative to the controls. Although the biologic agents were not more effective than azathioprine in preventing clinical recurrence (P=0.14), they were more effective in preventing endoscopic recurrence (RR=0.09, 95% CI: 0.02-0.47; P<0.01). Moreover, administration of the biologics was not associated with any significant difference in the rate of adverse events (RR=1, 95% CI: 0.75-1.34; P=0.99) or severe adverse events (RR=1.03, 95% CI: 0.33-3.26; P=0.96) when compared with controls. CONCLUSION: Biologics are superior to azathioprine and traditional therapies and are not associated with increased adverse events in the postoperative treatment of Crohn's disease.

MicroRNA-1290 promotes esophageal squamous cell carcinoma cell proliferation and metastasis.

AIM: To investigate the biological role of miR-1290 in esophageal squamous cell carcinoma (ESCC) progression and invasion and the underlying mechanism. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate miR-1290 expression in ESCC tissue samples. The roles of miR-1290 in cell proliferation, migration and invasion were identified using miR-1290 mimic-transfected cells. In addition, the regulatory effect of miR-1290 on suppressor of cancer cell invasion (SCAI) was evaluated using qRT-PCR, Western blot analysis and a dual luciferase reporter assay. RESULTS: miR-1290 was significantly upregulated in ESCC tissue samples compared with normal adjacent tissues (9.213 ± 1.150 vs 1.000 ± 0.0), (P < 0.01). Upregulation of miR-1290 was associated with tumor differentiation (P = 0.021), N classification (P = 0.006) and tumor-node-metastasis stage (P = 0.021) in ESCC patients. Moreover, ectopic miR-1290 expression potently promoted ESCC cell growth (P < 0.01), migration (P < 0.01) and invasion (P < 0.01) in vitro. miR-1290 overexpression in ESCC cell lines decreased SCAI expression at the translational level and reduced SCAI-driven luciferase-reporter activity (P < 0.01). CONCLUSION: Our findings suggested that miR-1290 may play an oncogenic role in cellular processes of ESCC.

Enteric microbiota leads to new therapeutic strategies for ulcerative colitis.

Ulcerative colitis (UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition (termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrate-producing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractive approach for UC therapy. Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC. Such therapies include fecal microbiota transplantation, probiotics, prebiotics, antibiotics, helminth therapy, and dietary polyphenols, all of which can alter the abundance and composition of the enteric microbiota. Although there have been many large, randomized controlled clinical trials assessing these treatments, the effectiveness and safety of these bacteria-driven therapies need further evaluation. This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review.

Inflammatory bowel disease (IBD) is believed to develop via a complex interaction between genetic, environmental factors and the mucosal immune system. Crohn's disease and ulcerative colitis are two major clinical forms of IBD. MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNA molecules, and evolutionary conserved in animals and plants. It controls protein production at the post-transcriptional level by targeting mRNAs for translational repression or degradation. MiRNAs are important in many biological processes, such as signal transduction, cellular proliferation, differentiation and apoptosis. Considerable attention has been paid on the key role of miRNAs in autoimmune and inflammatory disease, especially IBD. Recent studies have identified altered miRNA profiles in ulcerative colitis, Crohn's disease and inflammatory bowel disease-associated colorectal cancer. In addition, emerging data have implicated that special miRNAs which suppress functional targets play a critical role in regulating key pathogenic mechanism in IBD. MiRNAs were found involving in regulation of nuclear transcription factor kappa B pathway (e.g., miR-146a, miR-146b, miR-122, miR-132, miR-126), intestinal epithelial barrier function (e.g., miR-21, miR-150, miR-200b) and the autophagic activity (e.g., miR-30c, miR-130a, miR-106b, miR-93, miR-196). This review aims at discussing recent advances in our understanding of miRNAs in IBD pathogenesis, their role as disease biomarkers, and perspective for future investigation and clinical application.

Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis.

AIM: To investigate the efficacy of adding prokinetics to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD). METHODS: PubMed, Cochrane Library, and Web of Knowledge databases (prior to October 2013) were systematically searched for randomized controlled trials (RCTs) that compared therapeutic efficacy of PPI alone (single therapy) or PPI plus prokinetics (combined therapy) for GERD. The primary outcome of those selected trials was complete or partial relief of non-erosive reflux disease symptoms or mucosal healing in erosive reflux esophagitis. Using the test of heterogeneity, we established a fixed or random effects model where the risk ratio was the primary readout for measuring efficacy. RESULTS: Twelve RCTs including 2403 patients in total were enrolled in this study. Combined therapy was not associated with significant relief of symptoms or alterations in endoscopic response relative to single therapy (95%CI: 1.0-1.2, P = 0.05; 95%CI: 0.66-2.61, P = 0.44). However, combined therapy was associated with a greater symptom score change (95%CI: 2.14-3.02, P < 0.00001). Although there was a reduction in the number of reflux episodes in GERD [95%CI: -5.96-(-1.78), P = 0.0003] with the combined therapy, there was no significant effect on acid exposure time (95%CI: -0.37-0.60, P = 0.65). The proportion of patients with adverse effects undergoing combined therapy was significantly higher than for PPI therapy alone (95%CI: 1.06-1.36, P = 0.005) when the difference between 5-HT receptor agonist and PPI combined therapy and single therapy (95%CI: 0.84-1.39, P = 0.53) was excluded. CONCLUSION: Combined therapy may partially improve patient quality of life, but has no significant effect on symptom or endoscopic response of GERD.