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Background and Aim Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes. Methods Meta-analyses of observational studies that examined the associations between inflammatory bowel disease and the risk of adverse health outcomes in PubMed, EMBASE, and Web of Science were screened. Results This umbrella review identified 25 meta-analyses, which yielded 123 effect estimates for 60 unique putative health outcomes. Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes, including multiple cancers, cardiovascular disease, adverse pregnancy outcomes, adverse oral outcomes, and other adverse events. Moreover, inflammatory bowel diseases caused greater harm to health based on the presented evidence. However, none of the evidence was classified as “high” quality, only 15% was classified as “moderate,” and 65% of outcomes were rated as “very low.” Conclusion Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes and further studies should be conducted to draw firmer conclusions.

Background Current studies on the number of removed lymph nodes (LNs) and their prognostic value in small-bowel neuroendocrine tumors (SBNETs) are limited. This study aimed to clarify the prognostic value of removed LNs for SBNETs. Methods SBNET patients without distant metastasis from 2004 to 2017 in the SEER database were included. The optimal cutoff values of examined LNs (ELNs) and negative LNs (NLNs) were calculated by the X-tile software. Propensity score matching (PSM) was done to match patients 1:1 on clinicopathological characteristics between the two groups. The Kaplan-Meier method with log-rank test and multivariable Cox proportional-hazards regression model were used to evaluate the prognostic effect of removed LNs. Results The cutoff values of 14 for ELNs and 9 for NLNs could well distinguish patients with different prognoses. After 1:1 PSM, the differences in clinicopathological characteristics between the two groups were significantly reduced (all P > 0.05). Removal of more than one LN significantly improved the prognosis of the patients (P < 0.001). The number of lymphatic metastasis in the sufficiently radical resection group (SRR, 3.74 ± 3.278, ELN > 14 and NLN > 9) was significantly more than that in the insufficiently radical resection group (ISRR, 2.72 ± 3.19, ELN < 14 or NLN < 9). The 10-year overall survival (OS) of the SRR was significantly better than that of the ISRR (HR = 1.65, P = 0.001, 95% CI: 1.24–2.19). Conclusion Both ELNs and NLNs can well predict the OS of patients. Systematic removal of more than 14 LNs and more than 9 NLNs can increase the OS of SBNET patients.

BACKGROUND The number of negative lymph nodes (NLNs) and tumor size are associated with prognosis in rectal cancer patients undergoing surgical resection. However, little is known about the prognostic significance of the NLN count after adjusting for tumor size. AIM To assess the prognostic impact of the log odds of NLN/tumor size (LONS) in rectal cancer patients. METHODS Data of patients with stage I–III rectal cancer were extracted from the Surveillance, Epidemiology, and End Results Program database. These patients were randomly divided into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to determine the prognostic value of the LONS. The optimal cutoff values of LONS were calculated using the "X-tile" program. Stratified analysis of the effect of LONS on cancer-specific survival (CSS) and overall survival (OS) were performed. The Kaplan-Meier method with the log-rank test was used to plot the survival curve and compare the survival data among the different groups. RESULTS In all, 41080 patients who met the inclusion criteria were randomly divided into a training cohort (n = 28775, 70%) and a validation cohort (n = 12325, 30%). Univariate and multivariate analyses identified the continuous variable LONS as an independent prognostic factor for CSS [training cohort: Hazard ratio (HR) = 0.47, 95% confidence interval (CI): 0.44–0.51, P < 0.001; validation cohort: HR = 0.46, 95%CI: 0.41-0.52, P < 0.001] and OS (training cohort: HR = 0.53, 95%CI: 0.49-0.56, P < 0.001; validation cohort: HR = 0.52, 95%CI: 0.42-0.52, P < 0.001). The X-tile program indicated that the difference in CSS was the most significant for LONS of -0.8, and the cutoff value of -0.4 can further distinguish patients with a better prognosis in the high LONS group. Stratified analysis of the effect of the categorical variable LONS on CSS and OS revealed that LONS was also an independent predictor, independent of pN stage, pT stage, tumor-node-metastasis stage, site, age, sex, the number of examined lymph nodes, race, preoperative radiotherapy and carcinoembryonic antigen level. CONCLUSION LONS is associated with improved survival of rectal cancer patients independent of other clinicopathological factors.

The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle–Ottawa–Scale. Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn’s disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.

To investigate the effect of laparoscopic surgery in colorectal cancer (CRC) patients with natural orifice specimen extraction (NOSE) on the recovery and quality of life (QOL) of patients.Ninety-two eligible patients were randomly assigned into two groups: the traditional laparoscopy group (L group,A total of 46 patients in each group were enrolled in this study. The general data and surgery-related indicators were comparable between the two groups (all

Background Fish contains a variety of essential nutrients, which may contribute to multiple health benefits in humans. Conversely, it also may contain contaminants, resulting in confusion over the health impact of fish consumption. Scope and approach To assess the strength and validity of associations between fish intake and multiple health outcomes. We performed an umbrella review of systematic reviews and meta-analyses in humans. Key findings and conclusions: Of the 55 unique outcomes in the identified 89 systematic reviews and meta-analyses, fish consumption did more benefit than harm for a variety of health outcomes with largest risk reduction at 2 to 4 servings per week. Dose-response analyses revealed that every 20 g/d (approximately one serving/week) increment could decrease 2%–7% risk of coronary heart disease mortality, cardiovascular disease mortality, all-cause mortality, stroke, myocardial infarction, acute coronary syndrome, heart failure, gastrointestinal cancer, metabolic syndrome, dementia and Alzheimer's disease. Beneficial associations were also found for cancers, atopic, musculoskeletal, gastrointestinal and ophthalmologic outcomes. Caution is warranted for potential allergy or contamination when advising during pregnancy and young children. Fish intake appears generally safe in this umbrella review with largest risk reduction for a range of health outcomes at two to four servings per week, and seems more beneficial than harmful. High-quality prospective studies are needed.

BackgroundMatrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its expression pattern and function in tongue cancer is not clear.MethodsThe expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on the proliferation, apoptosis, migration, invasion of tongue cancer cells was tested in appropriate ways after MMP7 siRNA knockdown or overexpression. The effect of MMP7 on lymph node metastasis in vivo was analyzed using a high-metastasis orthotopic nude mouse tongue transplanted tumour model.ResultsWe found markedly elevated expression of MMP7 in human TSCC specimens compared with their respective paired nontumour tissues, and this high expression was correlated with the patients’ lymph node metastasis. Furthermore, the results of molecular functional assays confirmed that MMP7 promotes cell proliferation, migration and invasion of TSCC cells. Knockdown of MMP7 inhibited lymph nodes metastasis in vivo.ConclusionsMMP7 plays an oncogenic role in carcinogenesis and metastasis of tongue cancer, and may serve as a potential therapeutic target for tongue cancer.

The development of novel approaches for the treatment of gastric cancer is of utmost importance. Taxifolin (Tax) has been reported to possess biological activities against a number of types of cancer. The objective of the present study was to examine the effects of Tax on gastric cancer and to explore its potential mechanisms of action. For this purpose, AGS and NCI-N87 cells, as well as BALB/c mice with gastric cancer cell-derived tumors were treated with Tax. Cell Counting Kit-8 and colony formation assays were performed to detect cell viability and proliferation, respectively. Wound-healing and Transwell assays were also conducted to determine the cell migratory and invasive abilities, respectively. Western blot analysis was performed to determine protein expression in vitro and in vivo. The results revealed that Tax significantly inhibited the viability, proliferation, migration and invasion of gastric cancer cells through the aryl hydrocarbon receptor (AhR)/cytochrome P450 1A1 (CYP1A1) signaling pathway. SB203580, an AhR agonist, partly abolished the inhibitory effects of Tax on gastric cancer cell viability, proliferation, migration and invasion. In addition, Tax also suppressed tumor growth in vivo. Collectively, the present study demonstrated that Tax significantly suppressed the tumor characteristics of gastric cancer. Tax may thus prove to be a potential therapeutic strategy for gastric cancer.

Observational studies have reported an association between metabolic syndrome (MetS) and colorectal cancer risk with inconsistent risk estimates. We conducted this meta-analysis to evaluate the risk of colorectal cancer in individuals with MetS. PubMed, Embase, and Web of Science were searched for related studies from database inception to 21 January 2021. Risk estimates for colorectal cancer were extracted from individual articles and pooled using a fixed-effect or random-effect model according to the heterogeneity. MetS was significantly associated with a higher risk of colorectal cancer in both sexes (relative risk [RR] 1.36, 95% confidence interval [CI] 1.26–1.47, P

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) used for super obesity (SO) and super super obesity (SSO) remain controversial. The meta-analysis was to summarize the evidence. We searched in MEDLINE and PubMed for studies concerning RYGB and SG for SO or SSO and pooled complication, percentage excess weight loss (%EWL), and resolution of comorbidities. Twelve studies were identified. RYGB achieved higher %EWL at 12 months, but no significant difference at 24 months. Resolution of diabetes mellitus and dyslipidemia reached a statistical significance; however, there was no significant difference in hypertension. RYGB was superior in %EWL for SSO and SO at 12 months. However, regarding at 24 months, RYGB was equal to SG, which is from a meta-analysis and cannot be seen as a definitive conclusion.

Purpose: Preoperative platelet-to-monocyte ratio (PLR), albumin and hemoglobin are suggested prognostic indicators in various malignancies. However, the prognostic values of PLR, albumin and hemoglobin remain elusive. The objective of the present study was to evaluate the prognostic values of PLR, albumin and hemoglobin in stage I-III colon cancer. Patients and methods: A total of 312 patients with non-metastatic colon cancer undergoing curative resection were enrolled in this study. The prognostic values of PLR, albumin and hemoglobin were identified by receiver operating characteristics, and univariate and multivariate analyses. Results: Univariate analysis revealed that preoperative PLR, albumin and hemoglobin were significantly associated with overall survival (OS) and that preoperative PLR and albumin were significantly associated with progression-free survival (PFS). Multivariate analysis revealed that preoperative PLR was significantly associated with OS. Conclusion: Reduced preoperative PLR was significantly associated with better OS in patients with stage I-III colon cancer. Preoperative PLR was an independent prognostic indictor for OS in patients with colon cancer undergoing curative resection.

Plasmid-mediated antimicrobial resistance has emerged as one of the principal global issues, posing significant threats to public health. Herein, we reported a mobile tigecycline resistance mechanism Tet(X4) on both plasmid and chromosome in Escherichia coli strains from migratory birds in China. Besides tigecycline, these tet(X4)-positive strains also exhibited elevated MICs to the FDA newly approved tetracycline antibiotics, eravacycline (4 µg/ml) and omadacycline (8 µg/ml). Worrisomely, the tet(X4)-carrying plasmids and chromosome also shared high homology with the plasmids from human. Taken together, Tet(X4) represents another emerging antimicrobial threat and collective efforts from different sectors are needed to control its further spread.

Green leafy vegetables (GLVs) are a key element of healthy eating patterns and are an important source of lutein. To clarify the evidence for associations between GLVs and lutein intake and multiple health outcomes, we performed a review. A total of 24 meta-analyses with 29 health outcomes were identified by eligibility criteria. Dose-response analyses revealed that, per 100 g/d GLV intake was associated with a decreased risk (ca. 25%) of all-cause mortality, coronary heart disease and stroke. Beneficial effects of GLV intake were found for cardiovascular disease and bladder and oral cancer. Dietary lutein intake was inversely associated with age-related macular degeneration, age-related cataracts, coronary heart disease, stroke, oesophageal cancer, non-Hodgkin lymphoma, metabolic syndrome, and amyotrophic lateral sclerosis. Caution was warranted for contamination with potentially pathogenic organisms, specifically Escherichia coli. GLV consumption and lutein intake therein are generally safe and beneficial for multiple health outcomes in humans.

Background Proximal gastrectomy with double-tract reconstruction (DTR) has been used for upper third gastric cancer as a function-preserving procedure. However, the safety and feasibility of laparoscopic proximal gastrectomy (LPG) with DTR remain uncertain. This study compared open proximal gastrectomy (OPG) with DTR and LPG with DTR for proximal gastric cancer. Methods Sixty-four patients who had undergone OPG with DTR and forty-six patients who had undergone LPG with DTR were enrolled in this case–control study. The clinical characteristics, surgical outcomes and postoperative nutrition index were analysed retrospectively. Results The operation time was significantly longer in the LGP group than in the OPG group (258.3 min vs 205.8 min; p = 0.00). However, the time to first flatus and postoperative hospital stay were shorter in the LPG group [4.0 days vs 3.5 days (p = 0.00) and 10.6 days vs 9.2 days (p = 0.001), respectively]. No significant difference was found between the two groups in the number of retrieved lymph nodes, complications or reflux oesophagitis. The nutrition status was assessed using the haemoglobin, albumin, prealbumin and weight levels from pre-operation to six months after surgery. No significant difference was found between the groups. Conclusion LPG with DTR can be safely performed for proximal gastric cancer patients by experienced surgeons.

Background Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The LUAD cells display increased aerobic glycolysis, which generates energy required for their survival and proliferation. Deregulation of Wnt/β-catenin signaling pathway induces the metabolism switching and oncogenesis in tumor cells. RING finger protein 115 (RNF115) is an E3 ligase for ubiquitin-mediated degradation. Although the oncogenic functions of RNF115 have been revealed in breast tumor cells, the effect of RNF115 on lung cancer is still not clear. Methods RNF115 expression and its correlation with the features of LUAD patients were analyzed by using public database and our own cohort. The functions of RNF115 in proliferation and energy metabolism in LUAD cells were explored by downregulating or upregulating RNF115 expression. Results We demonstrated that RNF115 was overexpressed in LUAD tissues and its expression was positively correlated with the poor overall survival of LUAD patients. Moreover, RNF115 overexpression inhibited LUAD cell apoptosis and promoted cellular proliferation and metabolism in LUAD cells. On the contrary, RNF115 knockdown displayed reverse effects. Furthermore, the underlying mechanism of the biological function of RNF115 in LUAD was through regulating Wnt/β-catenin pathway via ubiquitination of adenomatous polyposis coli (APC). Conclusion The current study reveals a close association between RNF115 expression and prognostic conditions in LUAD patients and the oncogenic roles of RNF115 in LUAD at the first time. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for lung cancer in future.

Background & aims: The strategy of increasing the postoperative enteral nutrition dose to the target goal has not yet been clarified. This study aimed to determine whether an immediate goal-dose enteral nutrition (IGEN) strategy is non-inferior to a gradual goal-dose enteral nutrition (GGEN) strategy in reducing infections in patients undergoing abdominal surgery involving the organs of the digestive system. Methods: This randomized controlled trial enrolled postoperative patients with nutritional risk screening 2002 scores ≥3 from 11 Chinese hospitals. Energy targets were calculated as 25 kcal/kg and 30 kcal/kg of ideal body weight for women and men, respectively. Patients were randomly assigned 1:1 to IGEN or GGEN group after enteral tolerance was confirmed (30% of the target on day 2). The IGEN group immediately started receiving 100% of the caloric requirements on day 3, while the GGEN group received 40% progressing to 80% of target on day 7. The primary endpoint was the infection rate until discharge, based on the intention-to-treat population. Results: A total of 411 patients were enrolled and randomized to the IGEN and GGEN groups, and five patients did not receive the allocated intervention. A total of 406 patients were included in the primary analysis, with 199 and 207 in the IGEN and GGEN groups, respectively. Infection was observed in 17/199 (8.5%) in the IGEN group and 19/207 (9.2%) in the GGEN group, respectively (difference, −0.6%; [95% confidence interval (CI), −6.2%–4.9%]; P = 0.009 for non-inferiority test). There were significantly more gastrointestinal intolerance events with IGEN than with GGEN (58/199 [29.1%] vs. 32/207 [15.5%], P < 0.001). All other secondary endpoints were non-significant. Conclusions: Among postoperative patients at nutritional risk, IGEN was non-inferior to GGEN in regards to infectious complications. IGEN was associated with more gastrointestinal intolerance events. It showed that IGEN cannot be considered to be clinically directive. ClinicalTrials.gov (#NCT03117348).

The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell lines were used for investigating potential mechanisms. We found that GC with EBV-positive, MSI-H/dMMR, TMB-H or PIK3CA mutant subtype had enhanced efficacy of PD-L1/PD-1 blockades. Also, differentially expressed genes of these molecular subtypes shared the same gene signature and functional annotations related to immunity. Meanwhile, CIBERSORT identified that the overlapping landscapes of tumor-infiltrating immune cells in the four molecular subtypes were mainly M1-like macrophages (M1). The relationships between M1 and clinical characteristics, M1, and gene signatures associated with PD-1/PD-L1 blockades also revealed that M1 was associated with improved prognosis and required for the efficacy of PD-L1/PD-1 blockades in GC. We identified that tumor-infiltrating CD68+CD163− macrophages could represent M1 calculated by CIBERSORT in clinical application, and CXCL9, 10, 11/CXCR3 axis was involved in the mechanism of CD68+CD163− macrophages in the enhanced efficacy of PD-L1/PD-1 blockades. In conclusion, CD68+CD163− macrophages are required for the efficacy of PD-L1/PD-1 blockades and expand the applicable candidates in GC patients without the molecular subtypes.

Background Bariatric surgery could increase the risk of cholelithiasis, although it is unclear whether the incidence rates of cholelithiasis are similar after different bariatric procedures. Objectives To compare the incidence rates of cholelithiasis after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in people with obesity. Setting Meta-analysis of cohort studies. Methods We searched the PubMed and Web of Science databases for relevant studies before December 2020, and estimated the summary odds ratios (OR) and 95% confidence intervals (CI) using a random-effects model or fixed-effects model, according to the heterogeneity. Results In total, 8 cohort studies were included in this meta-analysis, and 94,855 and 106,844 participants received SG and RYGB, respectively. Compared with those receiving RYGB, the summary results showed that participants receiving SG had a 35% lower rate of cholelithiasis (OR, .65; 95% CI, .49–.86). Also, the participants receiving SG had a significantly lower incidence of cholecystectomy than those receiving RYGB (OR, .54; 95% CI, .30–.99). In a subgroup analysis, SG was associated with a significantly lower incidence of subsequent cholelithiasis than RYGB in both Western and non-Western countries. SG led to a significantly lower incidence of cholelithiasis than RYGB only when the follow-up was Conclusion Participants receiving SG had a significantly lower incidence of cholelithiasis than those receiving RYGB, particularly within the first 2 years after the bariatric surgery.

Objective: Lung cancer is often associated with hypercoagulability. Thromboelastography provides integrated information on clot formation in whole blood. This study explored the possible relationship between thromboelastography and lung cancer. Methods: Lung cancer was staged according to the Tumor, Node, and Metastasis (TNM) classification system. Thromboelastography parameters in different stages of disease were compared. The value of thromboelastography for stage prediction was determined by area under the receiver operating characteristic curve analysis. Results: A total of 182 patients diagnosed with lung cancer were included. Thromboelastography parameters, including kinetics time, α-angle, and maximum amplitude, differed significantly between patients with metastatic and limited lung cancers ( P < 0.05). Kinetics time was significantly reduced and maximum amplitude was significantly increased in patients with stage I and II compared with stage III and IV tumors ( P < 0.05). TNM stage was significantly negatively correlated with kinetics time ( r = −0.186), and significantly positively correlated with α-angle ( r = 0.151) and maximum amplitude ( r = 0.251) (both P < 0.05). The area under the curve for kinetics time in patients with stage I cancer was 0.637 ( P < 0.05) and that for α-angle in stage ≥ II was 0.623 ( P < 0.05). The areas under the curves for maximum amplitude in stage ≥ III and stage IV cancer were 0.650 and 0.605, respectively (both P < 0.05). Thromboelastography parameters were more closely associated with TNM stage in patients with lung adenocarcinoma than in the whole lung cancer population. Conclusion: This study identified the diagnostic value of thromboelastography parameters for determining tumor stage in patients with lung cancer. Thromboelastography can be used as an independent predictive parameter for lung cancer severity.

The recent emergence of plasmid-mediated tigecycline resistance gene tet(X) has challenged the clinical effectiveness of tigecycline as a last-resort treatment option. During 2017-2018, 336 fecal samples from sick ducks, pigs, chickens and geese in Guangdong, China, were screened for tet(X)-positive Acinetobacter baumannii strains. Their activities on tetracyclines were determined by microbiological degradation and mass spectrometry, followed by susceptibility testing, sequence typing, gene transfer, molecular location and genomic DNA sequencing analyses. A total of 10 tet(X)-positive A. baumannii strains were isolated from ducks and chickens, including eight plasmid-borne tet(X5)-positive and two chromosomal tet(X6)-positive isolates. All of them exhibited good degradation activities on tetracyclines by hydroxylation at C11a and were multidrug-resistant to tigecycline, tetracycline, florfenicol, ciprofloxacin and trimethoprim/sulfamethoxazole. Genetically, they belonged to two sequence types (ST355, n = 8; ST1980, n = 2) that were consistent with their pulsotypes, revealing a clonal spread of ST355 A. baumannii. An ISCR2- or IS26-mediated tet(X) transposition structure, homologous to those of clinical A. baumannii strains, was also identified and ISCR2 could transfer tet(X5) into the recipient Acinetobacter baylyi ADP1 at a frequency of (1.8 ± 0.3)×10-6. Therefore, more efforts are needed to evaluate the clinical impact of these tigecycline resistance genes.

Background The recent emergence and dissemination of high-level mobile tigecycline resistance Tet(X) challenge the clinical effectiveness of tigecycline, one of the last-resort therapeutic options for complicated infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens. Although tet(X) has been found in various bacterial species, less is known about phylogeographic distribution and phenotypic variance of different genetic variants. Methods Herein, we conducted a multiregional whole-genome sequencing study of tet(X)-positive Acinetobacter isolates from human, animal, and their surrounding environmental sources in China. The molecular and enzymatic features of tet(X) variants were characterized by clonal expression, microbial degradation, reverse transcription, and gene transfer experiments, while the tet(X) genetic diversity and molecular evolution were explored by comparative genomic and Bayesian evolutionary analyses. Results We identified 193 tet(X)-positive isolates from 3846 samples, with the prevalence ranging from 2.3 to 25.3% in nine provinces in China. The tet(X) was broadly distributed in 12 Acinetobacter species, including six novel species firstly described here. Besides tet(X3) (n = 188) and tet(X4) (n = 5), two tet(X5) variants, tet(X5.2) (n = 36) and tet(X5.3) (n = 4), were also found together with tet(X3) or tet(X4) but without additive effects on tetracyclines. These tet(X)-positive Acinetobacter spp. isolates exhibited 100% resistance rates to tigecycline and tetracycline, as well as high minimum inhibitory concentrations to eravacycline (2–8 μg/mL) and omadacycline (8–16 μg/mL). Genetic analysis revealed that different tet(X) variants shared an analogous ISCR2-mediated transposon structure. The molecular evolutionary analysis indicated that Tet(X) variants likely shared the same common ancestor with the chromosomal monooxygenases that are found in environmental Flavobacteriaceae bacteria, but sequence divergence suggested separation ~ 9900 years ago (7887 BC), presumably associated with the mobilization of tet(X)-like genes through horizontal transfer. Conclusions Four tet(X) variants were identified in this study, and they were widely distributed in multiple Acinetobacter spp. strains from various ecological niches across China. Our research also highlighted the crucial role of ISCR2 in mobilizing tet(X)-like genes between different Acinetobacter species and explored the evolutionary history of Tet(X)-like monooxygenases. Further studies are needed to evaluate the clinical impact of these mobile tigecycline resistance genes.

BackgroundGrowing evidence has proposed prognostic value of immune infiltration in gastrointestinal stromal tumors (GISTs). Therefore, we aimed to develop a novel immune-based prognostic classifier (IPC) to help better stratify and predict prognosis of GISTs.MethodsThe gene expression profiles of 22 immune features of GISTs were detected from GEO dataset. The IPC was constructed using the LASSO Cox regression model and validated in a cohort including 54 patients with complete resection of localized primary GISTs via immunohistochemistry process. The performance assessment of the IPC was estimated, then compared with conventional risk prognostic criteria.ResultsThe IPC was established based on 4 features: CD8, CD8/CD3, CD68, CD163/CD68 and validated to be an independent predictor of RFS for GISTs (HR 5.2, 95%CI 1.99-13.65). Significant differences were found between low- and high-IPC group in 5-year RFS (92.6% vs 48.1%, p < 0.001). Using the IPC, the high-risk group of the Modified NIH classification was split into two groups in 5-year RFS (low-IPC vs high-IPC, 85.7% vs 30.0%, p < 0.001). The IPC showed a higher net benefit than both “treat all” or “treat none” methods for the threshold probability within a range of 0-0.62 and exhibited a performance (AUC 0.842) superior to modified NIH classification (AUC 0.763).ConclusionThe IPC was effective to predict RFS after complete resection of localized primary GISTs, adding prognostic value to the routine clinical prognostic criteria. Prospective studies are needed to further validate the analytical accuracy and practicability of the IPC in estimating prognosis of GISTs.

Background: A growing body of evidence has pointed to the prognostic value of immune infiltration in gastrointestinal stromal tumors (GISTs). Thus, we aimed to develop a novel immune-based prognostic (IP) nomogram for better prognosis prediction of GISTs. Methods: Gene expression profiles of 22 immune features of GISTs were extracted from the GEO dataset. The immunoscore (IS) was constructed using the LASSO Cox regression model and validated in 54 GISTs via immunohistochemistry. The IP nomogram integrating IS and clinicopathological factors was constructed. The performance of the IP nomogram was evaluated and compared with conventional risk prognostic criteria. Results: The IS was established based on 4 features: CD8, CD8/CD3, CD68, CD163/CD68. Significant differences were observed between the low- and high-IS groups in the 5-year RFS (93.9% vs. 33.3%, p

The emergence of novel plasmid-mediated high-level tigecycline resistance genes tet(X) in the Enterobacteriaceae has increased public health risk for treating severe bacterial infections. Despite growing reports of tet(X)-positive isolates detected in animal sources, the epidemiological association of animal- and environment-derived isolates with human-derived isolates remains unclear. Here, we performed a comprehensive analysis of tet(X4)-positive Escherichia coli isolates collected in a hospital in Guangdong province, China. A total of 48 tet(X4)-positive E. coli isolates were obtained from 1001 fecal samples. The tet(X4)-positive E. coli isolates were genetically diverse but certain strains that belonged to ST48, ST10, and ST877 etc. also have clonally transmitted. Most of the tet(X4) genes from these patient isolates were located on conjugative plasmids that were successfully transferred (64.6%) and generally coexisted with other antibiotic resistance genes including aadA, floR, blaTEM and qnrS. More importantly, we found the IncX1 type plasmid was a common vector for tet(X4) and was prevalent in these patient-derived strains (31.3%). This plasmid type has been detected in animal-derived strains from different species in different regions demonstrating its strong transmission ability and wide host range. Furthermore, phylogenetic analysis revealed that certain strains of patient and animal origin were closely related indicating that the tet(X4)-positive E. coli isolates were likely to have cross-sectorial clonal transmission between humans, animals, and farm environments. Our research greatly expands the limited epidemiological knowledge of tet(X4)-positive strains in clinical settings and provides definitive evidence for the epidemiological link between human-derived tet(X4)-positive isolates and animal-derived isolates.

Tigecycline serves as one of the antibiotics of last resort to treat multidrug-resistant (including carbapenem-resistant) pathogens. However, the recently emerged plasmid-mediated tigecycline resistance mechanism, Tet(X), challenges the clinical efficacy of this class of antibiotics. In this study, we detected 180 tet(X)-harboring Acinetobacter isolates (8.9%, n = 180) from 2,018 samples collected from avian farms and adjacent environments in China. Eighteen tet(X)-harboring isolates (10.0%) were found to cocarry the carbapenemase gene bla(NDM-1), mostly from waterfowl samples (94.4%, 17/18). Interestingly, among six Acinetobacter strains, tet(X) and bla(NDM-1) were found to colocalize on the same plasmids. Moreover, whole-genome sequencing (WGS) revealed a novel orthologue of tet(X) in the six isolates coharboring tet(X) and bla(NDM-1). Inverse PCR suggested that the two tet(X) genes form a single transposable unit and may be cotransferred. Sequence comparison between six tet(X)- and bla(NDM-1)-coharboring plasmids showed that they shared a highly homologous plasmid backbone even though they were isolated from different Acinetobacter species (three from Acinetobacter indicus, two from Acinetobacter schindleri, and one from Acinetobacter lwoffii) from various sources and from different geological regions, suggesting the horizontal genetic transfer of a common tet(X)- and bla(NDM-1)-coharboring plasmid among Acinetobacter species in China. Emergence and spread of such plasmids and strains are of great clinical concern, and measures must be implemented to avoid their dissemination.

Recently, a novel plasmid-mediated tigecycline resistance mechanism, Tet(X4), has raised a global antimicrobial resistance concern (1, 2).….

BACKGROUND The contemporary risk classification criteria of gastrointestinal stromal tumors (GISTs) may still have room to improve. The aim of our research was to analyze the impact factors for GIST patients' relapse-free survival (RFS). Furthermore, we explore whether gastrointestinal (1) bleeding will be a valuable indicator to predict GIST patients' prognosis. MATERIAL AND METHODS R0 resection GISTs patients were retrospectively enrolled during an 8-year period at West China Hospital of Sichuan University, and all patients' data were from the WCHSU-GIST database. Of a total of 333 GIST patients, 164 patients had GI bleeding. Univariate analysis and Cox regression analysis were used to calculate the survival and recurrence rates. RESULTS Compared with non-GI-bleeding patients, GI-bleeding patients had a shorter relapse-free survival (RFS, P=0.003), but among the different risk groups, GI bleeding only affected the RFS rate of the high-risk group. A Cox regression analysis illustrated that tumor site (P

The duration of adjuvant imatinib for high-risk patients with gastrointestinal stromal tumors (GISTs) is still controversial. Therefore, we retrospectively analyzed the data of high-risk patients with GISTs to investigate the appropriate duration. All 185 patients were divided into 4 groups: 3 years (Group D). The mean recurrence-free survival (RFS) in Groups A, B, and C were 44.3, 62.1, and 86.8 months, respectively (P P = 0.009). The 5-year RFS in Groups A, B, C, and D was 15%, 26%, 83%, and 100%, respectively (P P P P

We read with interest the study by Axelrad et al 1 which reported that Crohn’s disease (CD) and UC were associated with nearly ninefold and twofold increased risk of small bowel cancer (SBC), respectively. However, there were also two observational studies2 3 suggesting that UC was not associated with risk of SBC. Because epidemiological studies about IBD and risk of SBC were controversial, to better understand this issue, we conducted this meta-analysis. We searched the PubMed and Web of Science for relevant studies published before 1 June 2020. We included observational studies investigating the associations between IBD and risk of SBC (including adenocarcinoma, neuroendocrine tumour and sarcoma) and reporting the HR, OR or other measures of association. The pooled OR and 95% CIs were estimated with random-effect model when the significant …

We read with interest the study by Zhang et al 1 which investigated the associations between oral antibiotic use and risk of colorectal cancer (CRC). The study included 166 057 participants and found that antibiotic use was associated with an increased risk of colon cancer but a reduced risk of rectal cancer. We also noticed another study by Armstrong et al 2 reporting that patients prescribed antibiotics in up to 15 years preceding diagnosis were associated with a higher risk of CRC. However, the study by Armstrong et al did not analyse the risk of colon cancer and rectal cancer, respectively. Considering current studies about antibiotic use and risk of CRC were inconsistent, we conducted this meta-analysis. The PubMed and Web of Science were …

We read with interest the study by Cheung et al 1 reporting that long-term use of proton pump inhibitors (PPIs) was associated with an increased risk of gastric cancer (GC) in participants after Helicobacter pylori eradication. Considering PPIs were widely used for the treatment of acid-related disorders, and previous studies about PPIs use and risk of GC did not have a consistent result. To better understand this issue, we conducted this meta-analysis that investigated the associations between long-term PPIs use and risk of GC. We searched the PubMed, Embase and Web of Science for potential studies published before March 2018. …

BACKGROUND: Visceral obesity is associated with diabetogenic and atherogenic abnormalities, including insulin resistance and increased risk for cardiometabolic diseases and mortality. Rodent lipectomy studies have demonstrated a causal link between visceral fat (VF) and insulin resistance, yet human omentectomy studies have failed to replicate this metabolic benefit, perhaps owing to the inability to target the mesentery. OBJECTIVES: We aimed to demonstrate that safe and effective removal of mesenteric fat (MF) can be achieved in obese insulin-resistant baboons using tissue liquefaction technology (TLT). SETTING: Southwest National Primate Research Center, San Antonio, Texas. METHODS: TLT has been developed to enable Mesenteric Visceral Lipectomy (MVL) to be safely performed without disturbing the integrity of surrounding nerves and vessels in the mesentary. Following an initial MVL optimization study (n=3), we then performed MVL (n=4) or Sham surgery (n=2) in a cohort of insulin-resistant baboons, and the metabolic phenotype was assessed via hyperinsulinemic-euglycemic clamps at baseline and 6 wks later. RESULTS: MVL led to a 75% improvement in glucose disposal at 6 wks follow-up (p=0.01). Moreover, despite removing only an average of 430 g of MF (~1% of total body mass), MVL led to a 14.4% reduction in total body weight (p=0.001). Thus, these data demonstrate that MF can be safely targeted for removal by TLT in a non-human primate, leading to substantial metabolic improvements, including reversal of insulin resistance and weight loss. CONCLUSIONS: These data provide the first demonstration of successful adipose tissue removal from the mesentery in a mammal. Importantly, we have demonstrated that when MVL is performed in obese, insulin resistant baboons, insulin resistance is reversed and significant weight loss occurs. Therefore, trials performing MVL in humans with abdominal obesity and related metabolic sequelae should be explored as a potential clinical tool to ameliorate insulin resistance and treat type 2 diabetes.

Scope The aim of this article is to conduct an umbrella review to study the strength and validity of associations between tea consumption and diverse health outcomes. Methods and results Meta-analyses of observational studies examining associations between tea consumption and health outcomes in all human populations and settings are screened. The umbrella review identifies 96 meta-analyses with 40 unique health outcomes. Tea consumption shows greater benefits than harm to health in this review. Dose-response analyses of tea consumption indicates reduced risks of total mortality, cardiac death, coronary artery disease, stroke, and type 2 diabetes mellitus with increment of two to three cups per day. Beneficial associations are also found for several cancers, skeletal, cognitive, and maternal outcomes. Harmful associations are found for esophageal and gastric cancer when the temperature of intake is more than 55-60 °C. Conclusion Tea consumption, except for very hot tea, seems generally safe at usual levels of intake, with summary estimates indicating the largest reduction for diverse health outcomes at two to three cups per day. Generally, tea consumption seems more beneficial than harmful in this umbrella review. Randomized controlled trials are further needed to understand whether the observed associations are causal.

The systemic inflammation plays a crucial role in carcinogenesis and cancer progression. Pretreatment lymphocyte-to-monocyte ratio (LMR) has been suggested to be associated with clinical outcomes in various malignancies. To evaluate the prognostic significance of pretreatment LMR on gastric cancer, we conducted a comprehensive literature search in PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov (Prospero Registration No. CRD42018087263). This meta-analysis included all studies evaluating the prognostic significance of pretreatment LMR on gastric cancer. The main outcome measures included overall survival (OS), progression-free survival (PFS), and the relationship between LMR and clinicopathological features. In total, 11 studies (12 cohorts) enrolling 14,262 patients with gastric cancer were included. The pooled estimates showed that elevated pretreatment LMR was significantly associated with better OS (hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.58–0.83) and better PFS (HR: 0.71, 95% CI: 0.44–0.99). The elevated LMR was also significantly associated with young patients, female, low level of carcinoembryonic antigen (CEA), low level of carbohydrate antigen 19-9 (CA19-9), stage I–II, small tumor size, absence of lymph node metastasis, absence of vascular invasion, and absence of perineural invasion. In conclusion, the elevated pretreatment LMR predicted the better clinical outcomes in patients with gastric cancer.

Objectives Although targeted therapy has revolutionized the treatment of gastrointestinal stromal tumours (GIST), it is almost never curative in GIST, and resistance commonly develops. One potential strategy is to combine targeted therapy with immunotherapy. Materials and methods We first studied Programmed cell death 1 ligand 1 (PD‐L1) expression and tumour‐infiltrating T cells (TILs) in GIST. IFN‐γ was used to induce the upregulation of PD‐L1 expression in GIST‐882 cells, a well‐known GIST cell line. CD8+ T‐cell apoptosis was determined by flow cytometry. The PI3K/Akt/mTOR levels in CD8+ T cells were examined by Western blotting. Results PD‐L1 expression was an independent factor of poor prognosis in GIST and resulted in exhausted T cells in the TILs population or the blood. Then, we found that PD‐L1 blockade alone could not increase tumour cell apoptosis in GIST. The apoptosis rate of CD8+ T cells was higher when T cells were cultured with PD‐L1+ GIST‐882 cells (GIST‐882 cells with high PD‐L1 expression) than when T cells were cultured with control GIST‐882 cells. However, when the PD‐L1 blockade was used, the apoptosis rates of the CD8+ T cells in the two groups became similar. Then, Western blotting showed the PI3K/Akt/mTOR levels of the CD8+ T cells rescued by the PD‐1/PD‐L1 blockade were higher than those of the CD8+ T cells not treated with the PD‐1/PD‐L1 blockade. Conclusions PD‐L1 expression was an independent poor prognosis factor in GIST. PD‐1/PD‐L1 blockade rescued exhausted CD8+ T cells in GIST via the PI3K/Akt/mTOR signalling pathway. In GIST, PD‐1/PD‐L1 not only function as predictive biomarkers but also improve current therapies as treatment targets.

Gastrointestinal stromal tumor (GIST) is a common sarcoma of gastrointestinal tract (GIT) with high metastatic and recurrence rates, but the proteomic features are still less understood. Here we performed systematic quantitative proteome profiling of GIST from 13 patients classified into very low/low, intermediate and high risk subgroups. An extended cohort of GIST (n = 131) was used for immunohistochemical validation of proteins of interest. In total, 9177 proteins were quantified, covering 55.9% of the GIT transcriptome from The Human Protein Altas. Out of the 9177 quantified proteins, 4930 proteins were observed in all 13 cases with 517 upregulated and 187 downregulated proteins in tumorous tissues independent of risk stage. Pathway analysis showed that the downregulated proteins were mostly enriched in metabolic pathway, whereas the upregulated proteins mainly belonged to spliceosome pathway. In addition, 131 proteins showed differentially expressed patterns among GIST subgroups with statistical significance. The 13 GIST cases were classified into 3 subgroups perfectly based on the expression of these proteins. The intensive comparison of molecular phenotypes and possible functions of quantified oncoproteins, tumor suppressors, phosphatases and kinases between GIST subgroups was carried out. Immunohistochemical analysis of the phosphatase PTPN1 (n = 117) revealed that the GIST patients with high PTPN1 expression had low chances of developing metastasis. Collectively, this work provides valuable information for understanding the inherent biology and evolution of GIST.

Background The role of resistant starch (RS) in glucose, insulin, insulin resistance or sensitivity, and lipid parameters have been reported in several studies and remained controversial. A pooled analysis which assessed these parameters has not been performed. Thus, we conducted a meta-analysis to sum up existing evidence about the issue. Methods We searched in MEDLINE and PUBMED for studies that were published before November 2018. Meta-analysis of diabetics and nondiabetics trials were performed by use of a random-effects model. Results A total of 13 case–control studies that included 428 subjects with body mass index ≥25 were identified. RS supplementation reduced fasting insulin in overall and stratified (diabetics and nondiabetics trials) analysis (SMD = –0.72; 95% CI: –1.13 to –0.31; SMD = –1.26; 95% CI: –1.66 to –0.86 and SMD = –0.64; 95% CI: –1.10 to –0.18, respectively), and reduced fasting glucose in overall and stratified analysis for diabetic trials (SMD = –0.26; 95% CI: –0.5 to –0.02 and SMD = –0.28; 95% CI: –0.54 to –0.01, respectively). RS supplementation increased HOMA-S% (SMD = 1.19; 95% CI: 0.59–1.78) and reduced HOMA-B (SMD =–1.2; 95% CI: –1.64 to –0.77), LDL-c concentration (SMD =–0.35; 95% CI: –0.61 to −0.09), and HbA1c (SMD = –0.43; 95% CI: –0.74 to –0.13) in overall analysis. Conclusions This meta-analysis has provided evidence that RS supplementation can improve fasting glucose, fasting insulin, insulin resistance and sensitivity, especially for diabetic with overweight or obesity. However, owing to potential sophistication, individual difference and composition of intestinal microbiota, this result should be carefully taken into account.

Lycopene is a potent lipophilic antioxidant in tomato. We aim to clarify the evidence for associations between tomato and lycopene and multiple health outcomes. Umbrella review of meta-analyses and systematic reviews was performed in humans. A total of 174 articles were searched, 17 articles with 20 health outcomes were identified by eligibility criteria. Tomato intake was inversely associated with all-cause mortality, coronary heart disease mortality, cerebrovascular disease mortality, prostate cancer, and gastric cancer. Dietary lycopene intake or serum lycopene was inversely associated with all-cause mortality, prostate cancer, stroke, cardiovascular disease, metabolic syndrome, and male infertility. Caution was warranted for potential allergy and pollution. The quality of the vast majority of evidence by GRADE was low or very low with the remaining six as moderate. The intake of tomato or lycopene was generally safe and beneficial for multiple health outcomes in humans. But the quality of the evidence was not high.

Background Recently, a nickel–titanium (NiTi) memory-shape device has been successfully used in gastrointestinal anastomosis. The aim of this study was to investigate the feasibility and safety of the device. Methods Four databases, reference lists, and the World Health Organization International Clinical Trials Registry Platform were systematically searched for randomized controlled trials assessing the clinical efficacy of a NiTi memory-shape device compared with that of a stapler in gastrointestinal or colorectal anastomosis. Results Seven randomized controlled trials regarding the use of compression anastomosis clips (CACs) were enrolled for meta-analysis. The use of CACs was associated with a significant reduction in hospital duration (mean = −0.88 d; 95% confidence interval [CI], −1.38 to −0.38), the time to flatus (mean = −0.36 d; 95% CI, −0.08 to −0.04), and the start of oral intake (mean = −0.45 d; 95% CI, −0.83 to −0.06), as well as a nonsignificant change in postoperative complications and mortality. These clinical outcomes did not significantly change with the use of compression anastomosis rings. Conclusions Colonic anastomosis with a CAC is likely to reduce hospital duration, time to flatus, and the start of oral intake without influencing mortality or postoperative complications and may be a safe and preferable choice in colonic anastomosis. Further well-designed trials should be performed to determine the safety and efficacy of the newly developed compression anastomosis ring in both ileocolic and colorectal anastomosis.

The association between coffee and colorectal adenoma risk remains controversial. We conducted a meta-analysis of cohort and case–control studies to sum up the existing proof about this matter. We searched Pubmed, Medline, and Embase for studies published before 1 September 2018 on coffee consumption and colorectal adenoma in any language. The different ORs were calculated for cohort and case–control studies in this study, and we use a random-effects model to aggregate the relative risks of individual studies and conduct dose response, heterogeneity, and publication bias. A total of 8 studies (6 case–control studies, 2 cohort studies) were identified, including 7090 subjects. In a summary analysis of all studies, high coffee intake (compared the highest with the lowest categories) was associated with a reduced risk of colorectal adenoma (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.55–0.90). The results of subgroup analysis of adenoma location were similar with the pooled analysis, except for rectal adenoma. In the dose–response meta-analysis study, the estimated total odds ratio for increasing coffee consumption by 150 ml per day (about one cup) was 0.91 (95% CI = 0.87–0.95). The meta-analysis demonstrates possible evidence that increased coffee intake is related to a reduced risk of colon adenoma. However, because of latent confusion and different exposure classification, this finding should be carefully considered.