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Background: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a stroke prevention strategy in patients with nonvalvular atrial fibrillation (NVAF), and these patients were required to receive antithrombotic therapy post-procedure. However, the optimal antithrombotic strategy after LAAO remains controversial. This study explored the safety and efficacy of different antithrombotic strategies after LAAO through a network comparison method.Methods: We systematically searched the MEDLINE, Embase, and Cochrane Library databases for studies that reported the interested efficacy and safety outcomes (stroke, device-related thrombus (DRT), and major bleeding) of different antithrombotic strategies [DAPT (dual antiplatelet therapy), DOACs (direct oral anticoagulants), and VKA (vitamin k antagonist)] in patients who had experienced LAAO. Pairwise comparisons and network meta-analysis were performed for the interested outcomes. Risk ratios (RRs) with their confidence intervals (CIs) were calculated using a random-effects model. The rank of the different strategies was calculated using the surface under the cumulative ranking curve (SUCRA).Results: Finally, 10 observational studies involving 1,674 patients were included. There was no significant difference in stroke, DRT, and major bleeding among the different antithrombotic strategies (DAPT, DOACs, and VKA). Furthermore, DAPT ranked the worst in terms of stroke (SUCRA: 19.8%), DRT (SUCRA: 3.6%), and major bleeding (SUCRA: 6.6%). VKA appeared to be superior to DOACs in terms of stroke (SUCRA: 74.9% vs. 55.3%) and DRT (SUCRA: 82.3% vs. 64.1%) while being slightly inferior to DOACs in terms of major bleeding (SUCRA: 71.0% vs. 72.4%).Conclusion: No significant difference was found among patients receiving DAPT, DOACs, and VKA in terms of stroke, DRT, and major bleeding events after LAAO. The SUCRA indicated that DAPT was ranked the worst among all antithrombotic strategies due to the higher risk of stroke, DRT, and major bleeding events, while VKAs were ranked the preferred antithrombotic strategy. However, DOACs are worthy of consideration due to their advantage of convenience.

ObjectiveIn patients with hydrocephalus, laparoscopy significantly improved ventriculoperitoneal shunt (VPS) outcomes. However, abdominal complications still occur, which require revision surgeries. In this study, we aimed to examine whether laparoscopy-assisted VPS with two-point fixation (LAVPS-TPF) has better outcomes than those of VPS (open-VPS) and laparoscopy-assisted VPS with no fixation (LAVPS-NF).MethodsWe retrospectively reviewed clinical records of 105 open-VPS, 40 LAVPS-NF, and 49 LAVPS-TPF cases from 2015 to 2020. Data including body mass index, etiology, abdominal surgery history, Glasgow coma scale (GCS), operation time, in-hospital days, shunt failure, complications, and modified Rankin scores were analyzed, as well as subgroups of patients with history of abdominal surgery, GCS scores, and revision surgeries.ResultsThe LAVPS-TPF group demonstrated decreased shunt failure rates at 12 months (2.04%) compared to those of the open-VPS group (14.29%, P = 0.020) and reduced abdominal shunt-related complications (P = 0.004 vs. open-VPS and LAVPS-NF) and shunt revisions. In the LAVPS-TPF group with abdominal history (n = 51), 12-month shunt failure rates (P = 0.020 vs. open-VS), repair frequency (P = 0.020 vs. open-VS), and abdominal complications (P = 0.003 and 0.006 vs. open-VS and LAVPS-NF) were reduced. In the LAVPS-TPF group with GCS scores of 13–15 (n = 152), shunt failure rates at 12 months, abdominal complications, and revision frequency were decreased (P

BackgroundTriglyceride-glucose (TyG) index, a novel surrogate marker of insulin resistance, has been demonstrated to be significantly associated with cardiovascular disease. It remains indistinct regarding the association between TyG index and non-culprit coronary plaque characteristics in patients following acute coronary syndrome (ACS).MethodsThe present study retrospectively recruited patients who were diagnosed with ACS and underwent non-culprit optical coherence tomography (OCT) examination. The study population was divided into 2 groups based on the median of TyG index, which was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting blood glucose (FBG) (mg/dL)/2]. The non-culprit plaque characteristics were determined by interpreting OCT images in accordance with the standard of previous consensus.Results110 patients (54.8 ± 12.1 years, 24.5% female) with 284 non-culprit plaques were included in the current analysis. TyG index was closely associated with high-risk plaque characteristics. Elevated TyG index was consistent to be an independent indicator for thin-cap fibroatheroma (TCFA) [odds ratio (OR) for per 1-unit increase 4.940, 95% confidence interval (CI) 1.652–14.767, P = 0.004; OR for taking lower median as reference 2.747, 95% CI 1.234–7.994, P = 0.011] and ruptured plaque (OR for per 1–unit increase 7.065, 95% CI 1.910–26.133, P = 0.003; OR for taking lower median as reference 4.407, 95% CI 1.208–16.047, P = 0.025) in fully adjusted model. The predictive value of TyG index for TCFA and ruptured plaque was moderate–to–high, with the area under the receiver operating characteristic curve (AUC) of 0.754 and 0.699 respectively. The addition of TyG index into a baseline model exhibited an incremental effect on the predictive value for TCFA, manifested as an increased AUC (0.681, 95% CI 0.570–0.793 vs. 0.782, 95% CI 0.688–0.877, P = 0.042), and significant continuous net reclassification improvement (0.346, 95% CI 0.235–0.458, P < 0.001) and integrated discrimination improvement (0.221, 95% CI 0.017–0.425, P = 0.034). TyG index failed to play an incremental effect on predicting ruptured plaque.ConclusionTyG index, which is simply calculated from fasting TG and FBG, can be served as an important and independent risk predictor for high-risk non-culprit coronary plaques in patients following ACS.

BackgroundProprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been documented with significantly reduction in LDL cholesterol levels and cardiovascular events. However, evidence regarding the impact of PCSK9 inhibitors on coronary calcification is limited.MethodsEligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard statin therapy. Calcium score based on coronary computed tomographic angiography at baseline and follow up were compared.ResultsCompared with baseline levels, LDL cholesterol were significantly decreased in both groups, while the absolute reduction of LDL cholesterol levels were higher in patients treated with alirocumab (1.69 ± 0.52 vs. 0.92 ± 0.60, P < 0.0001). Additionally, patients in alirocumab group demonstrated a significant reduction of Lp(a) levels, whereas it was not observed in the standard statin group. Notably, greater increases in the percentage changes of CAC score (10.6% [6.3–23.3] vs. 2.9% [−6.7–8.3]; P < 0.0001) were observed in the statin group compared to the alirocumab group. Consistently, CAC progression was significantly lower in the alirocumab group than in the standard statin group (0.6 ± 2.2% vs. 2.7 ± 2.3%; P = 0.002).ConclusionsStudy indicated that administration of the PCSK9 inhibitors to statins produced significantly lower rate of CAC progression in patients with coronary artery disease. Further studies with CAC progression and their clinical outcomes are needed.Trial RegistrationClinicalTrials.gov, Identifier: NCT04851769.

BackgroundFollow-up guidelines for serrated polyps (SPs) are mainly based on factors such as histology and size with limited evidence. The underlying genomic mechanism of SPs in relation to recurrence risks is utterly unknown.MethodsWe applied targeted next-generation sequencing (NGS) approach on two groups of SPs [polyp-relapsed SPs (PRSPs) vs. polyp-free SPs (PFSPs)] based on the surveillance outcomes to compare differences of DNA variants in 71 colorectal cancer-associated genes. A multicenter validation cohort was established longitudinally from 2016 to 2019 to confirm the relevant results.ResultsAmong the 96 NGS samples, at least one mutant after filtration was detected in 90 samples (94%). Molecular profiling presented BRAF, KRAS, and APC as top 3 mutated genes. FBXW7, MSH2, and ERBB2 might be recurrence-relevant, while DMD, BRCA1, and BRCA2 might be negatively correlated with recurrence. Notably, ERBB2 mutants (R678Q and V842I) (n = 5) had higher risks of polyp recurrence than the wild types (n = 85), with a median polyp-free interval of 15 months compared to 26 months [P < 0.001; hazard ratio (HR) = 4.9; 95% confidence interval (CI) = 1.9–12.8]. Furthermore, a multicenter cohort composed by 321 SPs verified that ERBB2-mutated SPs had increased risks of polyp recurrence (P < 0.001; HR = 3.7; 95% CI = 2.3–6.0) and advanced neoplastic lesion (ANL) recurrence (P < 0.001; HR = 10.0; 95% CI = 2.7–36.9) compared with wild-type SPs, respectively.ConclusionsOur results are emphasizing that SP individuals with ERBB2 mutants are at higher risks of subsequent colorectal neoplasms. ERBB2 mutants might work as facilitated markers for prediction of high-risk SPs and might implicate a potential mechanism in the serrated pathway to colorectal carcinoma (CRC).

Background: Malnutrition has been shown to be associated with adverse cardiovascular outcomes in many patient populations.Aims: To investigate the prognostic significance of malnutrition as defined by nutritional risk index (NRI) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and whether NRI could improve the GRACE score based prognostic models.Methods: This study applied NRI among 1,718 patients with ACS undergoing PCI. Patients were divided into three nutritional risk groups according to their baseline NRI: no nutritional risk (NRI ≥ 100), mild nutritional risk (97.5 ≤ NRI

Gut microbiota plays important roles in several metabolic processes, such as appetite and food intake and absorption of nutrients from the gut. It is also of great importance in the maintenance of the health of the host. However, much remains unknown about the functional mechanisms of human gut microbiota itself. Here, we report the identification of one anticancer gut bacterial strain AD16, which exhibited potent suppressive effects on a broad range of solid and blood malignancies. The secondary metabolites of the strain were isolated and characterized by a bioactivity-guided isolation strategy. Five new compounds, streptonaphthalenes A and B (1-2), pestaloficins F and G (3-4), and eudesmanetetraiol A (5), together with nine previously known compounds, were isolated from the effective fractions of AD16. Structures of the new compounds were established by 1D and 2D NMR and MS analysis, and the absolute configurations were determined by the CD method. The analysis of network pharmacology suggested that 3, 2, and 13 could be the key components for the anti-NSCLC activity of AD16. In addition to the PI3K–Akt signaling pathway, the proteoglycans in cancer pathway could be involved in the anti-NSCLC action of AD16.

Background: Visceral adiposity index (VAI), a surrogate marker of adiposity and insulin resistance, has been demonstrated to be significantly related to cardiovascular disease. It remains indistinct whether VAI predicts adverse prognosis after percutaneous coronary intervention (PCI) for patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and type 2 diabetes mellitus (T2DM).Methods: A total of 798 participants who met the enrollment criteria were finally brought into this study. VAI was determined by waist circumference, body mass index, fasting triglyceride, and high-density lipoprotein cholesterol as previously reported. Adverse prognosis included all-cause death, non-fatal myocardial infarction, non-fatal ischemic stroke, and ischemia-driven revascularization, the composite of which was defined as the primary endpoint.Results: Higher VAI maintained as a significant and independent risk predictor for the primary endpoint, regardless of the adjustment for the various multivariate models [hazard ratio (95% CI) for fully adjusted model: 2.72 (2.02–3.68), p < 0.001]. The predictive value of VAI was further confirmed in sensitivity analysis where VAI was taken as a continuous variate. There was a dose-response relationship of VAI with the risk of the primary endpoint (p for overall association < 0.001). Moreover, the ability of VAI on the prediction of the primary endpoint was consistent between subgroups stratified by potential confounding factors (all p for interaction > 0.05). VAI exhibited a significant incremental effect on risk stratification for the primary endpoint beyond existing risk scores, expressed as increased Harrell's C-index, significant continuous net reclassification improvement, and significant integrated discrimination improvement.Conclusion: VAI is a significant indicator for predicting worse prognosis and plays an important role in risk stratification among patients with NSTE-ACS and T2DM undergoing elective PCI. The present findings require further large-scale, prospective studies to confirm.

Guidelines have differed in their opinion regarding the indications for endoscopic resection of gastric-neuroendocrine neoplasms (g-NENs) and duodenal-NENs (d-NENs). We examined the association between size and lymph node metastasis (LNM) to identify candidates most suitable for endoscopic resection. We identified 706 patients with T1/T2 g-NENs and 621 patients with T1/T2 d-NENs from the SEER database. The prevalence of LNM and risk factors associated with LNM were analyzed. LNM was present in 8.1% of patients with gastroduodenal neuroendocrine tumors (NETs) and 31.6% of patients with neuroendocrine carcinomas (NECs). Multivariate logistic regression indicated that tumor size >10mm, greater invasion depth, and poor differentiation were independently associated with LNM. In addition, the percentage of g-NETs invading submucosa with LNM increased with tumor size (≤10 mm,3.9%;11–20 mm,8.6%;>20 mm,16.1%). However, in contrast to the low LNM risk in patients with small g-NETs (≤10 mm), we found that LNM rate exceeded 5% even for patients with small submucosal-infiltrating d-NETs. Among patients with nodal-negative g-NETs, the cause specific survival (CSS) was similar for those who received surgical resection and endoscopic resection. Among patients with d-NETs, the CSS was better for those who received endoscopic resection. In conclusion, patients with d-NETs had a higher probability of LNM than those with g-NETs. Endoscopic resection can be utilized for curative treatment of submucosa-infiltrating g-NETs and intramucosal d-NETs when the size is 10 mm or less. These results reinforce the need to search for LNM in lesions that are larger than 10 mm.

It is currently difficult for pathologists to diagnose pancreatic cancer (PC) using biopsy specimens because samples may have been from an incorrect site or contain an insufficient amount of tissue. Thus, there is a need to develop a platform-independent molecular classifier that accurately distinguishes benign pancreatic lesions from PC. Here, we developed a robust qualitative messenger RNA signature based on within-sample relative expression orderings (REOs) of genes to discriminate both PC tissues and cancer-adjacent normal tissues from non-PC pancreatitis and healthy pancreatic tissues. A signature comprising 12 gene pairs and 17 genes was built in the training datasets and validated in microarray and RNA-sequencing datasets from biopsy samples and surgically resected samples. Analysis of 1,007 PC tissues and 257 non-tumor samples from nine databases indicated that the geometric mean of sensitivity and specificity was 96.7%, and the area under receiver operating characteristic curve was 0.978 (95% confidence interval, 0.947–0.994). For 20 specimens obtained from endoscopic biopsy, the signature had a diagnostic accuracy of 100%. The REO-based signature described here can aid in the molecular diagnosis of PC and may facilitate objective differentiation between benign and malignant pancreatic lesions.

Background: N6-methyladenosine (m6A) RNA methylation, associated with cancer initiation and progression, is dynamically regulated by the m6A RNA regulators. However, its role in liver carcinogenesis is poorly understood.Methods: Three hundred seventy-one hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas database with sequencing and copy number variations/mutations data were included. Survival analysis was performed using Cox regression model. We performed gene set enrichment analysis to explore the functions associated with different HCC groups. Finally, we used a machine-learning model on selected regulators for developing a risk signature (m6Ascore) The prognostic value of m6Ascore was finally validated in another two GEO datasets.Results: We demonstrated that 11 m6A RNA regulators are significantly differentially expressed among 371 HCC patients stratified by clinicopathological features (P

Lung cancer (LC) is one of the most serious malignant tumors, which has the fastest growing morbidity and mortality worldwide. A role of the lung microbiota in LC pathogenesis has been analyzed, but a comparable role of the gut microbiota has not yet been investigated. In this study, the gut microbiota of 30 LC patients and 30 healthy controls were examined via next-generation sequencing of 16S rRNA and analyzed for diversity and biomarkers. We found that there was no decrease in significant microbial diversity (alpha diversity) in LC patients compared to controls (P observed = 0.1422), while the composition (beta diversity) differed significantly between patients and controls (phylum [stress = 0.153], class [stress = 0.16], order [stress = 0.146], family [stress = 0.153]). Controls had a higher abundance of the bacterial phylum Actinobacteria and genus Bifidobacterium, while patients with LC showed elevated levels of Enterococcus. These bacteria were found as possible biomarkers for LC. A decline of normal function of the gut microbiome in LC patients was also observed. These results provide the basic guidance for a systematic, multilayered assessment of the role of the gut microbiome in LC, which has a promising potential for early prevention and targeted intervention.

Regarding rubber tree plantations, researchers lack a basic understanding of soil microbial communities; specifically, little is known about whether or not soil microbial variation is correlated with succession in these plantations. In this paper, we used high-throughput sequencing of the 16S rRNA gene to investigate the diversity and composition of the soil bacterial communities in a chronosequence of rubber tree plantations that were 5, 10, 13, 18, 25, and 30 years old. We determined that: (1) Soil bacterial diversity and composition show changes over the succession stages of rubber tree plantations. The diversity of soil bacteria were highest in 10, 13, and 18 year-old rubber tree plantations, followed by 30 year-old rubber tree plantations, whereas 5 and 25 year-old rubber tree plantations had the lowest values for diversity. A total of 438,870 16S rDNA sequences were detected in 18 soil samples from six rubber tree plantations, found in 28 phyla, 66 classes, 139 orders, 245 families, 355 genera, and 645 species, with 1.01% sequences from unclassified bacteria. The dominant phyla were Acidobacteria, Proteobacteria, Chloroflexi, Actinobacteria, and Verrucomicrobia (relative abundance large than 3%). There were differences in soil bacterial communities among different succession stages of rubber tree plantation. (2) Soil bacteria diversity and composition in the different stages was closely related to pH, vegetation, soil nutrient, and altitude, of which pH, and vegetation were the main drivers.