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Introduction: Neonatal hyperbilirubinemia is common and remains a clinical concern in China. Since neonatal hyperbilirubinemia is linked to genetic factors, we aimed to identify the gene variants of the red blood cell membrane (RBCM) and evaluate the clinical risk factors in Chinese neonates with hyperbilirubinemia. Methods: 117 hyperbilirubinemia neonates (33 cases of moderate hyperbilirubinemia and 84 cases of severe hyperbilirubinemia) and 49 controls with normal bilirubin levels were selected as our study subjects. A customized 22-gene panel with next-generation sequencing (NGS) was designed to characterize genetic variations among the neonates. Sanger sequencing was used to verify the accuracy of the NGS. The clinical risk factors and potential effects of genetic variations in neonates with hyperbilirubinemia were subsequently assessed. Results: After data filtering, suspected pathogenic variants of UGT1A1, SLCCO1B1, and RBCM-associated gene were identified in neonates, the combined numbers of RBCM-associated gene variants were found to have differences between the hyperbilirubinemia group and the controls (p = 0.008), they were also different between severe hyperbilirubinemia and moderate hyperbilirubinemia (p = 0.008), and were correlated with an increased risk of hyperbilirubinemia (odds ratio = 9.644, p = 0.006). The UGT1A1-rs4148323 variant in neonates with hyperbilirubinemia was significantly increased as compared with the controls (p < 0.001). However, there was no statistical difference for the SLCO1B1-rs2306283 variant between the hyperbilirubinemia group and the controls. In addition, breastfeeding contributed to an increased risk of hyperbilirubinemia. Conclusion: Our study highlights that the RBCM-related gene variants are an underestimated risk factor, which may play an important role in developing hyperbilirubinemia in Chinese newborns.

Gastrointestinal stromal tumors (GIST) are mostly seen in the stomach. Clinical data on GISTs ≤ 2 cm with 5 mitosis/50 HPFs are limited. This study aimed to analyze small GISTs with high histological grades to gain a more comprehensive understanding of their clinical characteristics with long-term follow-up.This was a nested cohort study of patients with gastric GISTs ≤ 2 cm and 5 mitosis/50 HPFs. Individuals with endoscopically resected gastric specimens diagnosed as GISTs between January 2008 and July 2019 were enrolled. We analyzed baseline clinicopathological characteristics, perioperative characteristics, risk of recurrence, and metastasis during follow-up.A total of 55 patients diagnosed with gastric GISTs ≤ 2 cm and 5 mitosis/50 HPFs were enrolled. The mean tumor size was 1.6 ± 0.4 cm (median 1.7 cm, range 0.8-2.0 cm). ESD was performed in 33 patients (60.0%) and EFTR in 22 patients (40.0%). Mean mitotic figures were 8.9/50 HPFs. Postoperative bleeding in one patient (1.8%) was the only severe adverse event. The mean follow-up period was 61.2 ± 33.9 months (median 53 months, range 13-133 months). Five patients (5/55, 9.1%) received additional therapies, including partial gastrectomy and adjuvant Imatinib. Only two patients (2/55, 3.6%) showed signs of recurrence. We observed no significant difference regarding baseline clinical characteristics and recurrence among GISTs with mitosis 10/50 HPF and ≥ 10/50 HPF. No patient had signs of metastasis during follow-up.Endoscopic resection of gastric GISTs ≤ 2 cm with 5 mitosis/50 HPFs has a low risk of recurrence and metastasis in the long term. Endoscopic resection of GISTs is safe and feasible.

Background: The interaction between gut microbiota and innate immunity plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors (TLRs) defending against microbial invasion and initiating downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of IBD is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism. Methods: MyD88 inhibitor (TJ-M2010-5, TJ5) were used to investigate the effect of MyD88 suppression on acute DSS-induced colitis. Disease activity index, colon length, histological score and inflammatory cytokines were examined to evaluate the colitis severity. The RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism. Results: In the acute DSS-colitis model, the colitis severity was not alleviated in TJ5-treated mice, though the significantly lower of MyD88 expression and NF-κB activation were exhibited compared with control mice. Meanwhile, the 16S rDNA sequencing and RNA transcriptome analysis showed a higher abundance of intestinal Proteobacteria and an up-regulation of NOD-like receptors (NLRs) signaling pathway in colitis mice after MyD88 suppression. Further blockade of the NLR signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ5 ameliorated the disease severity that was not improved by solely MyD88 inhibition. The downregulated NLR signaling pathway after broad-spectrum antibiotics treatment suggested that the MyD88 suppressionassociated dysbiosis may stimulate intestinal inflammation via NLR signaling pathway. Conclusion: Our study revealed that the suppression of MyD88 may be associated with unfavorable changes in the gut microbiota composition and lead to immune activation mediated by NLRs, which may play an important role in modulating intestinal inflammation.

We aim to evaluate the efficacy and safety of endoscopic radial incision (ERI) versus endoscopic balloon dilation (EBD) treatment of naïve, recurrent, and refractory benign esophageal anastomotic strictures.One hundred and one ERI, 145 EBD, and 42 ERI combined with EBD sessions were performed in 136 consecutive patients with benign esophageal anastomotic stricture after esophagectomy at Zhongshan Hospital from January 2016 to August 2021. Baseline characteristics, operational procedures, and clinical outcomes data were retrospectively evaluated. Parameters and recurrence-free survival (RFS) were compared between ERI and EBD in patients with naïve or recurrent or refractory strictures. Risk factors for re-stricture after ERI were identified using univariate and multivariate analyses.Twenty-nine ERI versus 68 EBD sessions were performed for naïve stricture, 26 ERI versus 60 EBD for recurrent strictures, and 46 ERI versus 17 EBD for refractory stricture. With comparable baseline characteristics, RFS was greater in the ERI than the EBD group for naïve strictures (P = 0.0449). The ERI group had a lower 12-month re-stricture rate than the EBD group (37.9% vs 61.8%, P = 0.0309) and a more prolonged patency time (181.5 ± 263.1 vs 74.5 ± 82.0, P = 0.0233). Between the two interventions, recurrent and refractory strictures had similar RFS (P = 0.0598; P = 0.7668). Multivariate analysis revealed initial ERI treatment was an independent predictive factor for lower re-stricture risk after ERI intervention (odds ratio = 0.047, P = 0.001). Few adverse events were observed after ERI or EBD (3.0% vs 2.1%, P = 0.6918).ERI is associated with lower re-stricture rates with better patency and RFS compared with EBD for naive strictures.

Pulmonary fibrosis is a major cause of the poor prognosis of acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) is an indispensable life-saving intervention for ARDS, it may cause the remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 is a mechanosensitive ion channel that is known to play a role in regulating diverse physiological processes, but whether Piezo1 is necessary for MV-exacerbated ARDS-associated pulmonary fibrosis remains unknown.This study aimed to explore the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis.Human lung epithelial cells were stimulated with hydrochloric acid (HCl) followed by mechanical stretch for 48 h. A two-hitmodel of MV afteracidaspiration-inducedlunginjuryin mice was used. Mice were sacrificed after 14 days of MV. Pharmacological inhibition and knockout of Piezo1 were used to delineate the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. In some experiments, ATP or the ATP-hydrolyzing enzyme apyrase was administered.The stimulation of human lung epithelial cells to HCl resulted in phenotypes of epithelial-mesenchymal transition (EMT), which were enhanced by mechanical stretching. MV exacerbated pulmonary fibrosis in mice exposed to HCl. Pharmacologicalinhibitionorknockout of Piezo1 attenuated the MV-exacerbated EMT process and lung fibrosis in vivo and in vitro. Mechanistically, the observed effects were mediated by Piezo1-dependent CaOur findings identify a key role for Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis that is mediated by increased ATP release in lung epithelial cells. Inhibiting Piezo1 may constitute a novelstrategyfor the treatment of MV-exacerbated ARDS-associated pulmonary fibrosis.

To summarize the endoscopic and clinicopathological features of gastric adenocarcinoma of the fundic gland type(GA-FGs), and to evaluate the safety and efficacy of endoscopic submucosal dissection(ESD) for GA-FGs.From September 2017 to August 2021, patients treated with endoscopic resection and with pathological confirmed diagnosis of GA-FGs were included. Lymph node or distal metastasis was excluded before endoscopic resection. Medical records were retrospectively reviewed to obtain information regarding patient demographics, clinicopathological features, tumor characteristics, complete resection rate and complications. All patients underwent regular follow-up to evaluate for any local recurrence or distant metastasis.15 patients were included in this study, among which 11 were males and 4 were females. The average age of the patients was 56.9±10.7 years. Lesions were found at upper third(n=13,86.7%)or middle third(n=2,13.3%) of the stomach. The average size was 9.1±4.8mm. Lesions presented as flat elevated type with erosion on top(n=7,46.7%), depression type with pale color(n=5,33.3%) or submucosal tumor-like(SMT-like) appearance type(n=3,20%), macroscopiclly. 14(93.3%) patients reached en bloc resection, 13 (86.7%)patients had complete resection, and 11(73.3%) patients got curative resection, respectively. 9(60%)of the lesions had submucosal invasion. One patient accepted additional surgery. No local recurrence or metastasis was detected during follow-up.GA-FGs present with various endoscopic features. ESD appears to be a safe and effective choice for early-stage GA-FGs. This article is protected by copyright. All rights reserved.

Esophageal squamous cell carcinoma (ESCC) causes aggressive and lethal malignancies with extremely poor prognoses, and accounts for about 90% of cases of esophageal cancer. Neuropilin and tolloid-like 2 (NETO2) protein coding genes have been associated with various human cancers. Nevertheless, little information is reported about the phenotypic expression and its clinical significance in ESCC progression. Here, our study found that NETO2 expression in ESCC patients was associated with tumor clinical stage and lymph node metastasis status. Gain-of-function and loss-of-function analyses showed that NETO2 stimulated ESCC cell proliferation while suppressing apoptosis in vitro and enhanced tumor growth in vivo. Moreover, knockdown of NETO2 significantly inhibited migration and invasion in combination with regulation of epithelial-mesenchymal transition (EMT) related markers. Mechanistically, overexpression of NETO2 increased the phosphorylation of ERK, PI3k/AKT, and Nuclear factor erythroid-2-related factor 2(Nrf2), whereas silencing NETO2 decreased the phosphorylation of these targets. Our data suggest that Nrf2 was a critical downstream event responsible for triggering the PI3K/AKT and ERK signaling pathways and plays a crucial role in NETO2-mediated tumorigenesis. Taken together, NETO2 acts as an oncogene and might serve as a novel therapeutic target or prognostic biomarker in ESCC patients.

Objective To explore the etiological characteristics of severe hyperbilirubinemia in full-term newborns of eastern Guangdong. Methods Full-term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed. The etiology was determined according to the laboratory results and clinical manifestations. Results Among 1602 full-term newborns with hyperbilirubinemia in Chaozhou area, 32.20% (580/1602) was severe hyperbilirubinemia, including 213 newborns with TSB levels reaching the recommended exchange transfusion levels and 52 cases diagnosed with prolonged jaundice. Among the causes of severe hyperbilirubinemia, neonatal hemolysis accounted for 15.17%, infection accounted for 10.17%, G6PD deficiency accounted for 9.13%, and the coexistence of multiple etiologies accounted for 6.55%, unknown etiology accounted for 50.00%. ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy. 94 severe hyperbilirubinemia newborns were tested for UGT1A1*6 variant (rs4148323, c.211G > A, p.Arg71Gly,), 9 cases were 211 G to A homozygous variant, 37 cases were 211 G to A heterozygous variant, and 48 cases were wild genotypes. Conclusion The main cause for severe hyperbilirubinemia and bilirubin encephalopathy were the hemolytic disease of the newborn, G6PD deficiency and infection. UGT1A1 gene variant was also a high risk factor for neonatal hyperbilirubinemia. Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.

Polysaccharide from Grifola frondosa is an excellent metal-ion chelating agent owing to its distinctive structure and outstanding functional activities. Our previous research has successfully synthesized novel organic chromium derived from the chelation ofG. frondosapolysaccharide-chromium (III) [GFP-Cr(III)]. The purpose of present research was to reveal the hypoglycemic and hypolipidemic mechanism of GFP-Cr(III), and its relationship with the modulation of intestinal microflora. Successful fabrication of GFP-Cr(III) was verified by thermogravimetric analysis (TGA), powder X-ray diffraction (XRD) and 1H NMR spectrum.The hypoglycemic and hypolipidemic effects were examined using type 2 diabetic mice induced by a high-fat diet (HFD) and streptozocin (STZ). Results indicated that GFP-Cr(III) intervention improved abnormal serum biochemical indicators (triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose), inhibited lipid accumulation and steatosis in the liver. Metagenomic analysis revealed that GFP-Cr(III) treatment produced obvious changes on the intestinal microflora in T2DM mice. Thecorrelationnetwork analysis further revealed that the serum and hepatic lipid profiles were positively correlated with Streptococcus and Enterococcus, but negatively correlated with Enterorhabdus, Ruminococcaceae-UCG-011, Coriobacteriaceae and Micrococcaceae. Meanwhile, oral administration with GFP-Cr(III) regulated the mRNA expression related to glucose and lipid metabolism. These results of present study suggest that GFP-Cr(III) could be used as potential functional food ingredients for the amelioration of hyperglycemia and hyperlipidemia.

Lactobacillus plantarum FZU3013, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorders of lipid metabolism. This study aimed to investigate the role of L. plantarum FZU3013 in improving non-alcoholic fatty liver (NAFL) associated with hyperlipidemia in mice fed a high-fat diet. The results indicated that L. plantarum FZU3013 intervention significantly reduced the HFD-induced body weight gain and the abnormal levels of serum total triglycerides (TG), total cholesterol (TC) and low-density lipoprotein (LDL-C), and inhibited the excessive accumulation of liver lipids. In addition, L. plantarum FZU3013 also promoted the excretion of bile acids through feces. Metagenomic and multivariate statistical analysis revealed that L. plantarum FZU3013 made significant structural changes in the intestinal microbiome of the mice fed with HFD, in particular by modulating the relative abundance of some function related microbial phylotypes. Furthermore, ultra-performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. plantarum FZU3013 had a significant regulatory effect on the composition of liver metabolites in hyperlipidemic mice, especially on the levels of some important biomarkers involved in the pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Moreover, L. plantarum FZU3013 regulated the mRNA expression levels of the genes responsible for liver lipid and cholesterol metabolism. L. plantarum FZU3013 intervention increased the hepatic mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and the bile salt export pump (BSEP), suggesting enhanced bile acid synthesis and excretion from the liver. These findings present new evidence supporting that L. plantarum FZU3013 has the potential to improve lipid metabolism disorders through modulating specific intestinal microbial phylotypes and regulating hepatic lipid metabolism related genes, therefore it could be used as a potential functional food for the prevention of NAFL and hyperlipidemia.

Two new diterpenoids, 12,15-di

Two new diterpenoids, 12,15-di-O-acetylhypargenin B (1) and taiwanin F-12-O-β-D-glucopyranoside (2), one new monoterpenoid, (S)-7-methyl-3-methyleneoct-6-ene-1,2-diyl diacetate (3), together with eight known compounds (4−11), were obtained from the twigs and leaves of Nageia fleuryi Hickel. The structures of the new compounds were elucidated by extensive spectroscopic techniques including HR-ESI-MS and 1 D and 2 D NMR experiments. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 1 and 11 exhibited strong inhibitory activity on LPS-stimulated production of NO in RAW 264.7 murine macrophages, while compounds 1, 3, and 5 showed significant quinone reductase inducing activity in Hepa 1c1c7 murine hepatoma cells. Moreover, compounds 7 and 8 showed inhibitory activity against the proliferation of the human prostate carcinoma DU145 cells.

Paeoniae Radix Alba is the dried root of Paeonia lactiflora, which was first recorded in the Shennong's Classic of Materia Medica and listed as the top grade. It is a common blood-tonifying herb, and its chemical components are mainly monoterpenes and their glycosides, triterpenes, flavonoids and so on. Modern research has demonstrated that Paeoniae Radix Alba has the activities of anti-inflammation, pain easing, liver protection, and anti-oxidation, and thus it is widely used in clinical practice and has broad development prospects. In this paper, the research progress on the chemical composition, pharmacological effects, and quality control of Paeoniae Radix Alba were summarized. On this basis, the Q-markers of Paeoniae Radix Alba were predicted from the aspects of mass transfer and traceability, chemical composition specificity, and availability and measurability of chemical components, which will provide a scientific basis for the quality evaluation of Paeoniae Radix Alba.

This study investigated Grifola frondosa active substances extracted from low-concentration (55%) ethanol (GF55) and their role in regulating glucose and lipid metabolism disorders (GLMDs). The main components of GF55 were identified as fatty acids and coumarins by UPLC-Q-TOF-MS/MS After the intervention of GF55, the serum and liver lipid level, aspartate transaminase, alanine aminotransferase, free fatty acid, total superoxide dismutase, glutathione peroxidase, liver histopathological and key genes, short-chain fatty acids and intestinal flora changed. Compared with HFD, GF55 treatment up-regulated the expressions of protein kinase B, glucokinase, adenine monophosphate-activated protein kinase-α and cholesterol 7-α hydroxylase, down-regulated the expressions of stearoyl-CoA desaturase 1, acetyl-CoA carboxylase and sterol regulatory element-binding transcription factor-1c at the mRNA and protein levels (P

BACKGROUND Recently, thymectomy using minimally invasive approaches has been increasing with the development of robotic video-assisted thoracoscopic surgery (R-VATS). Although multimodal approach is effective for robot assisted thymectomy, it is necessary to determine the approach (left, right or subxiphoid) associated with the least complications. METHODS An electronic retrieval from PubMed, Embase, Web of Science, GreyNet International and The Cochrane Library. The single-arm meta-analysis was performed to compare the rate of complications of right- and left-side approaches by R-VATS. RESULTS A total of 21 studies including 930 patients were identified. The pooled incidence of total complications was 12.2% (confidence interval: 10.0%-14.8%) for all studies. The overall complication rate was 17.3% for the right-side compared with 7.4% for the left side (P

Submucosal tunneling endoscopic resection (STER) has been widely applied for esophageal submucosal tumors. This large volume study aims to provide a standard landscape of STER-related AEs for reference.1701 patients with esophageal SMTs undergoing STER were included at Zhongshan Hospital, Fudan University. Data of clinical characteristics and adverse events were collected and analyzed in depth. Adverse events were recorded by ASGE lexicon and graded by ASGE grading/Clavien-Dindo system. Risk factors for major AEs were analyzed by univariate and multivariate logistic regression.Three hundred and twenty (18.8%) patients with 962 cases of adverse events were observed. Accordingly, 84 (5.0%) were classified as major AEs (moderate and severe) by ASGE grading and 37 (2.2%) were classified as major AEs (grades III-V) by Clavien-Dindo grading. First 1 year operation, distance 6 cm from incision to tumor, piecemeal resection, partially extraluminal location, mucosal injury, and operation time 60 min were included in the risk score model for major AEs of STER, with 57.1% sensitivity and 87.5% specificity.STER was a safe procedure for diagnosis and treatment of esophageal SMTs with a total 18.8% incidence of AEs, among which only 5.0% were major AEs requiring therapeutic measurements.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may manifest as neonatal hyperbilirubinemia, is the most prevalent erythrocytic enzyme-related disease in the world.Objective: To investigate the association between neonatal hyperbilirubinemia and co-inheritance of G6PD deficiency and 211 G to A variation of UGT1A1 in Chaozhou city of eastern Guangdong province, the effects of G6PD deficiency and UGT1A1 gene variant on the bilirubin level were determined in neonates with hyperbilirubinemia.Method: The activity of G6PD was assayed by an auto-bioanalyzer. PCR and flow-through hybridization were used to detect 14 common G6PD mutations in G6PD deficient neonates. 211 G to A variation of UGT1A1 was determined by PCR and sequencing. The data of neonatal peak bilirubin was collected and analyzed retrospectively.Results: 74 cases of the 882 hyperbilirubinemia neonates were G6PD deficiency (8.39%) while 12 cases of the 585 non-hyperbilirubinemia neonates (control group) were G6PD deficiency (2.05%). The rate of G6PD deficiency in the hyperbilirubinemia group was higher than that of the control group. Moreover, the peak bilirubin in the G6PD-deficient group of hyperbilirubinemia neonates was 334.43±79.27μmol/L, higher than that of the normal G6PD group of hyperbilirubinemia neonates (300.30±68.62 μmol/L). The most common genotypes of G6PD deficiency were c.1376G>T and c.1388G>A, and the peak bilirubin of neonates with these two variants were 312.60±71.81μmol/L and 367.88±75.79 μmol/L, respectively. The bilirubin level of c.1388G>A was significantly higher than that of c.1376G>T. Among the 74 hyperbilirubinemia neonates with G6PD deficiency, 6 cases were 211 G to A homozygous mutation (bilirubin levels 369.55±84.51 μmol/L), 27 cases were 211 G to A heterozygous mutation (bilirubin levels 341.50±63.21 μmol/L), and 41 cases were wild genotypes (bilirubin levels 324.63±57.52 μmol/L). Conclusion: The rate of G6PD deficiency in hyperbilirubinemia neonates was significantly higher than that of the non-hyperbilirubinemia neonates in Chaozhou. For the hyperbilirubinemia group, neonates with G6PD deficiency had a higher bilirubin level compared to those with normal G6PD. For hyperbilirubinemia neonates with G6PD deficiency, there was a declining trend of bilirubin levels among 211 G to A homozygous mutation, heterozygous mutation, and wild genotype, but there was no significance statistically among the three groups.

The approach to paraoesophageal structures and lesions via the oesophagus was initiated by the introduction of peroral endoscopic myotomy (POEM), followed by peroral endoscopic removal of tumours within the muscular layer. We now report a case which suggests that the next step, that is, to remove paraoesophageal tumours not related to the oesophageal wall, would also be possible. This is the case of a 66-year-old male patient with a 4.0×2.0×1.5 cm benign schwannoma from the recurrent laryngeal nerve bulging into the proximal oesophagus, which we removed via a POEM tunnel. The postoperative course was uneventful. Further controlled studies have to show which lesions may be suitable for this expanded approach and also confirm the safety and feasibility of this technique which can be regarded as much less invasive than operative minimal invasive alternatives. Due to the complicated anatomy of the mediastinum, mediastinal masses represent a heterogeneous group of tumours.1 2 Characteristic location of the mass establishes a useful differential diagnosis that aids in planning the diagnostic evaluation. Video-assisted thoracoscopic surgery and conventional open surgery are the currently available treatments for these patients with benign lesions in whom removal is considered to be indicated, also for clarification of the diagnosis.3–5 Traditional surgical approach can be associated with substantial trauma, slower recovery, higher complication rate and decreased postoperative quality of life. To overcome these disadvantages, we report on a novel technique, transoesophageal endoscopic surgery, for treating mediastinal tumours. This technique takes advantage of the submucosal tunnelling technique popularised by natural orifice translumenal endoscopic surgery (NOTES). NOTES stimulated with the development of POEM and submucosal tunnelling endoscopic resection (STER), the submucosal or ‘third space’ endoscopy combining minimal invasive surgery and endoscopy. Here we present a rare case of schwannoma originated from the recurrent laryngeal nerve, which we removed via transoesophageal endoscopic surgery …

Polysaccharide from Ganoderma lucidum is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel G. lucidum polysaccharide‑chromium (III) [GLP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GLP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 5.71 mg/mL, pH 6.36, temperature 66.4 °C and time 2.0 h, respectively. The pH was the most significant factor, followed by reaction temperature and CrCl3 concentration. Under the optimal conditions, the experimental chelation rate was 94.17 ± 1.0% for GLP-Cr(III) complex, which agreed closely with the predicted value (94.60%). Fourier transform infrared (FT-IR) spectroscopy revealed that the primary sites of chromium (III)-binding in G. lucidum polysaccharide were O H and C O groups, which induce the morphology change from flat sheet to rough surface. Meanwhile, according to the result of X-ray diffraction (XRD), the crystal degree of GLP was disappeared after chelation with Cr(III). The presence of a “blind zone” in the 1H NMR spectrum obviously indicated the binding of Cr(III) to GLP. Additionally, the effects of GLP-Cr(III) complex on hyperglycemia and hyperlipidemia in high fructose and fat diet-induced pre-diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in mice supplemented with GLP-Cr(III) complex (50 mg/kg day) were significantly lower than the model group (P

Nickel-cobalt (Ni-Co) oxide nanocages were synthesized by etching the cobalt-based metal-organic framework (Co-MOF) with nickel nitrate in an isopropyl alcohol solution. The dodecahedral Co-MOF (300 nm in size) was composed of micropores, while the Ni-Co oxide nanocages gained additional mesopores and macropores. Both Co-MOF and Ni-Co oxide electrodes in KOH behaved more like the nondiffusion-controlled pseudocapacitor through the surface adsorption/desorption with a concomitant faradaic charge-transfer reaction. In the presence of ferrocyanide/ferricyanide redox electrolyte, both nondiffusion- and diffusion-controlled currents contributed equally to the current response of Ni-Co oxide electrode at lower scan rates. Nondiffusion-limited processes governed the charge-storage behavior of Ni-Co oxide electrode at faster scan rates. The Ni-Co oxide electrode with redox electrolyte showed high specific capacities of 810 and 496 C g−1 at the charge/discharge current densities of 10 and 50 A g−1, respectively, much greater than that electrode without redox electrolyte (384 and 348 C g−1). Ni-Co oxide electrode with highly porous nanocages could provide large electrolyte/electrode interface to store more charges and short pathways to expedite the transport of electron and ion, showing a noticeable increase in its electrochemical performance compared with Co-MOF electrode.

Hong Qu glutinous rice wine (HQGRW), as one of the most typical representatives of Chinese rice wine, is generally brewed from glutinous rice by adding two traditional wine fermentation starters-Hong Qu (HQ) and Bai Qu (BQ). The objective of this study was to determine the microbial communities and volatile metabolites of different traditional fermentation starters for HQGRW, and elucidate the potential correlation between microbiota and volatile metabolites. Both heatmap and principal component analysis (PCA) revealed the significant variances in volatile profiles among different wine starters. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that both of bacterial and fungal communities varied significantly in different starters. HQ was dominated mainly by bacteria of Bacillus ginsengihumi (20.17%), Pantoea sp. (10.39%), Elizabethkingia sp. (5.52%), Streptococcus sp. (5.03%) Brevundimonas sp. (3.03%), Rickettsia prowazekii (2.94%), Thermus thermophilus (2.54%), Bacillus amyloliquefaciens (1.48%), Bacillus aryabhattai (1.42%); fungi of Monascus purpureus (39.7%), Aspergillus niger (27.35%), Xeromyces bisporus (8.39%), Aspergillus penicillioides (6.89%), Aspergillus flavus (2.33%) and Pichia farinose (0.79%). By contrast, BQ contained much higher proportions of bacteria of Lactococcus lactis (10.45%), Lactobacillus brevis (9.99%), Pediococcus pentosaceus (8.29%), Weissella paramesenteroides (6.69%), Lactobacillus fermentum (4.83%), Gluconobacter thailandicus (3.93%), Lactobacillus alimentarius (3.59%), fungi of Rhizopus arrhizus (31.47%), Saccharomycopsis fibuligera (27.86%), Aspergillus niger (20.81%), Issatchenkia orientalis (3.79%), Saccharomycopsis malanga (3.15%), Clavispora lusitaniae (2.29%), Candida tropicalis (1.47%), Saccharomyces cerevisiae (1.11%) and Rhizopus microsporus (0.57%). Furthermore, core functional microbiota that might contribute to volatile flavour development was explored through Spearman's correlation-based network analysis. Lactobacillus brevis, Lactobacillus alimentarius, Lactobacillus plantarum and Aspergillus niger were found to be strongly associated with acid compounds (FDR adjusted P 0.01), while Pichia sp., Candida sp., Monascus purpureus, Lactobacillus brevis and Lactobacillus alimentarius were positively correlated with concentrations of aromatic esters associated with fruity and floral notes (FDR adjusted P 0.01), implying that these microorganisms might make significant contributions to the flavour of rice wine. These findings demonstrated that the aromatic quality of HQGRW may be critically influenced by the microbiota in traditional fermentation starters. To conclude, this study would contribute to the development of novel defined starter cultures for improving the aromatic quality of HQGRW.

Polysaccharide from Grifola frondosa is one of the best metal-ion chelating agents because of its structural characteristics and excellent functional activities. In this study, we synthesized and characterized a novel Grifola frondosa polysaccharide-chromium (III) [GFP-Cr(III)] complex. Response surface methodology (RSM) was used to optimize the reaction conditions for the maximum chelation rate of GFP-Cr(III) complex. The optimal reaction conditions obtained from RSM were as follows: concentration of CrCl3 6.97 mg/mL, pH 7.75 and temperature 71.73 °C, respectively. The pH was the most significant factor, followed by reaction temperature and concentration of CrCl3. Under the deduced optimal conditions (CrCl3 7.0 mg/mL, pH 7.7 and temperature 70.0 °C), the experimental chelation rate was 28.01% ± 0.18% for GFP-Cr(III) complex, which agreed closely with the predicted value (27.61%). Fourier transform infrared (FTIR) spectroscopy revealed that the primary sites of chromium (III)-binding in polysaccharides were O H and C N groups, leading to the structure of GFP-Cr(III) complex was loose than the original polysaccharide. Nevertheless, Cr(III) did not make a fundamental change in the structure of GFP when comparing the FTIR spectra of GFP and GFP-Cr(III) complex. Additionally, the effects of GFP-Cr(III) complex on hyperglycemia and hyperlipidemia in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were also investigated. Results showed that the serum total cholesterol (TC), total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting blood glucose levels and glucose tolerance in diabetic mice fed a high-fat diet (HFD) supplemented with GFP-Cr(III) complex (900 mg/kg day) were significantly lower than the diabetic group (P

Livestock farms are a propagating source of antibiotic resistance genes (ARGs) via the discharge of animal waste carrying resistant bacteria. Groundwater is widely used in traditional livestock farming. However, there is little available information on ARGs in pumped well water. To investigate the dissemination of ARGs in well water and to assess the impact of rainfall on ARGs, the abundance and diversity of ARGs on a long-term co-livestock feedlot farm where both pig and fish farming is conducted were analysed during the dry and wet seasons in this study, and twenty ARGs were detected. The total concentrations of the target ARGs (∑ARGs) in piggery wastewater and fishponds were approximately 109 copies/mL and 106 copies/mL, respectively. The wastewater treatment plant at this farm failed to avoid ARG contamination, and the biogas digester and lagoon treatment showed low abilities to eliminate ∑ARGs. The open operation mode of the lagoon and fishpond facilitated the dissemination of ARGs, which was assisted by the nearby stream, especially in the wet season. Additionally, the tetracycline resistance gene tetB showed the highest levels among the target ARGs in well water, which were higher in the wet season than the dry season. Affected by rainfall, the concentrations of ARGs in the samples rose, and the correlation between surface water and groundwater increased. These results suggested that both the surface water and the well water in the livestock farming area harboured serious ARGs contamination, which could pose ecological risks and cause food safety problems.

The purpose of this study was to assess the potential effects of polysaccharides from edible mushroom Grifola frondosa (GFP) on lipid metabolic disorders and gut microbiota dysbiosis, and elucidate their possible regulatory mechanisms on lipid and cholesterol metabolism in high-fat diet (HFD)-exacerbated hyperlipidemic and hypercholesterolemic rats. Results showed that oral administration of GFP markedly alleviated dyslipidaemia through decreasing the serum levels of total triglycerides, total cholesterol, and free fatty acids, and significantly suppressing hepatic lipid accumulation and steatosis. Besides, the excretion of fecal bile acids was also promoted by oral administration of GFP. Metagenomic analysis revealed that GFP supplementation (400 mg kg-1 day-1) resulted in significant structure changes on gut microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. Key microbial phylotypes responding to GFP intervention were identified to strongly correlate with the lipid metabolism disorder associated parameters using the correlation network based on Spearman's correlation coefficient. Serum and hepatic lipid profiles were found positively correlated with Clostridium-XVIII, Butyricicoccus and Turicibacter, but negatively correlated with Helicobater, Intestinimonas, Barnesiella, Parasutterella, Ruminococcus and Flavonifracter. Moreover, GFP treatment (400 mg kg-1 day-1) regulated the mRNA expression levels of the genes responsible for hepatic lipid and cholesterol metabolism. Oral supplementation of GFP markedly increased the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acid (BA) synthesis and excretion from the liver. These findings illustrated that GFP could ameliorate lipid metabolic disorders through modulating specific gut microbial phylotypes and regulating hepatic lipid and cholesterol metabolism related genes, and therefore could be used as a potential functional food ingredient for the prevention or treatment of hyperlipidemia.

The purpose of our study was to analyze and compare the spino cranial angle (SCA) in patients with degenerative cervical spondylolisthesis (DCS) and asymptomatic controls and to determine whether SCA could help diagnose DCS.We enrolled 50 patients diagnosed with DCS (4.3%) from among 1168 patients and the same number of asymptomatic participants as the control group by using cervical radiographs. Both groups underwent cervical radiographs and computed tomography at the same time. Various sagittal parameters were measured on computed tomography in a standardized supine position and compared with the asymptomatic control group. The Spearman correlation coefficient was applied to test the correlation among the sagittal parameters in the DCS group. Multivariate logistic regression analysis and receiver operating characteristic curve analysis were performed to determine whether SCA could help predict DCS.Fifty patients were enrolled in the DCS group, and 50 asymptomatic participants were included in the control group. The SCA was significantly lower for the DCS group than for the control group (76.84 ± 7.48 degrees vs. 82.47 ± 8.06 degrees, P0.001), and the T1 slope (T1s) was significantly greater for the DCS group than for the control group (27.29 ± 7.84 degrees vs. 22.28 ± 6.43 degrees, P = 0.001). Except for SCA and T1s, no other parameters showed significant differences. The SCA on the computed tomography scan was significantly correlated with the values of the T1s (r = -0.890, P0.001), cervical lordosis (r = -0.437, P = 0.002), C2-C7 sagittal vertical axis (r = 0.397, P = 0.004), and thoracic inlet angle (r = -0.565, P0.001). Multivariate logistic regression analysis and receiver operating characteristic curve analysis showed that both a lower SCA and a higher T1s could be risk factors for DCS, and an SCA of79.1 degrees demonstrated significant diagnostic value for the detection of DCS.Patients in the DCS group had a lower SCA and a higher T1s. Both a lower SCA and a higher T1s could be risk factors for DCS, and an SCA of79.1 degrees demonstrated significant diagnostic value for the detection of DCS.

Background Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder causing muscle weakness and characterized by a defect in synaptic transmission at the neuromuscular junction. The pathogenesis of this disease remains unclear. We aimed to predict the key signaling pathways of genetic variants and miRNAs in the pathogenesis of MG, and identify the key genes among them. Methods We searched published information regarding associated single nucleotide polymorphisms (SNPs) and differentially-expressed miRNAs in MG cases. We search of SNPs and miRNAs in literature databases about MG, then we used bioinformatic tools to predict target genes of miRNAs. Moreover, functional enrichment analysis for key genes was carried out utilizing the Cytoscape-plugin, known as ClueGO. These key genes were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then a miRNA-target gene regulatory network was established to screen key genes. Results Five genes containing SNPs associated with MG risk were involved in the inflammatory bowel disease (IBD) signaling pathway, and FoxP3 was the key gene. MAPK1, SMAD4, SMAD2 and BCL2 were predicted to be targeted by the 18 miRNAs and to act as the key genes in adherens, junctions, apoptosis, or cancer-related pathways respectively. These five key genes containing SNPs or targeted by miRNAs were found to be involved in negative regulation of T cell differentiation. Conclusions We speculate that SNPs cause the genes to be defective or the miRNAs to downregulate the factors that subsequently negatively regulate regulatory T cells and trigger the onset of MG.

BACKGROUND Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune-mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. METHODS We collected information from forty-seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty-seven age- and sex-matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. KEY RESULTS Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF-s1 (P

Background and Aims. Gastric peroral endoscopic myotomy (G-POEM) has been regarded as a novel and minimally invasive therapy for refractory gastroparesis. This study reports the long-term outcomes and possible predictive factors for successful outcomes after G-POEM in an Asian population. Methods. This is a retrospective single-centre study of 16 patients who underwent G-POEM for refractory gastroparesis from August 2016 to October 2017. This study included 11 males and 5 females; in addition, 13 patients had postsurgical gastroparesis, and 3 patients had diabetes. The patients included had severe and refractory gastroparesis, as indicated by a Gastroparesis Cardinal Symptom Index (GCSI) score ≥20, and evidence of a delay on gastric emptying scintigraphy (GES). The primary outcome parameter was an assessment of the long-term clinical efficacy of the procedure. The secondary outcome parameter was the detection of possible predictive factors for success and the determination of cut-off values for such predictors. Results. Technical success was achieved in 100% of the patients, with a mean procedure time of 45.25±12.96 min. The long-term clinical response was assessed in all patients during a median follow-up of 14.5 months. Clinical success was achieved in 13 (81.25%) patients. There was a significant reduction in the GCSI scores and GES values after the procedure compared to the baseline values, with P values of ≤30 had a high sensitivity and a negative predictive value (NPV) of 100% for predicting a successful procedure. GES (half emptying time ≤221.6 min and 2-hour retention ≤78.6%) had a high specificity and a positive predictive value (PPV) of 100%. Conclusions. G-POEM is a safe and effective treatment option with a long-term efficacy of 81.6%. GCSI and GES could serve as good predictive measures.

The identification of optimal methylation biomarkers to achieve maximum diagnostic ability remains a challenge. The present study aimed to elucidate the potential molecular mechanisms underlying osteosarcoma (OS) using DNA methylation analysis. Based on the GSE36002 dataset obtained from the Gene Expression Omnibus database, differentially methylated genes were extracted between patients with OS and controls using t‑tests. Subsequently, hierarchical clustering was performed to segregate the samples into two distinct clusters, OS and normal. Gene Ontology (GO) and pathway enrichment analyses for differentially methylated genes were performed using the Database for Annotation, Visualization and Integrated Discovery tool. A protein‑protein interaction (PPI) network was established, followed by hub gene identification. Using the cut‑off threshold of ≥0.2 average β‑value difference, 3,725 unique CpGs (2,862 genes) were identified to be differentially methylated between the OS and normal groups. Among these 2,862 genes, 510 genes were differentially hypermethylated and 2,352 were differentially hypomethylated. The differentially hypermethylated genes were primarily involved in 20 GO terms, and the top 3 terms were associated with potassium ion transport. For differentially hypomethylated genes, GO functions principally included passive transmembrane transporter activity, channel activity and metal ion transmembrane transporter activity. In addition, a total of 10 significant pathways were enriched by differentially hypomethylated genes; notably, neuroactive ligand‑receptor interaction was the most significant pathway. Based on a connectivity degree >90, 7 hub genes were selected from the PPI network, including neuromedin U (NMU; degree=103) and NMU receptor 1 (NMUR1; degree=103). Functional terms (potassium ion transport, transmembrane transporter activity, and neuroactive ligand‑receptor interaction) and hub genes (NMU and NMUR1) may serve as potential targets for the treatment and diagnosis of OS.

Antibiotic resistance genes (ARGs) are emerging micropollutants with environmental persistence. Aquaculture environments are considered as potential reservoirs for ARGs pollution and horizontal gene transfer (HGT). This study analyzed water and sediment from eight culture ponds (integrated culture: duck-fish pond; monoculture: duck pond and fish pond) and a control pond (without any aquaculture activity) in Zhongshan, South China. Seventeen types of ARGs were detected in all ponds, which conferring resistance to four classes of antibiotics including tetracycline ( tet A, tet B, tet C, tet E, tet G, tet L, tet A-P, tet M, tet O, tet S, tet W and tet X), AmpC beta-lactamase products ( EBC and FOX ), sulfonamide ( sul 1 and sul 2) and erythromycin ( erm A), with class 1 integron ( intI 1) as motility gene. The total concentrations of detected ARGs in culture pond water were much higher than control (about 1.6–4.0 times). Integrated culture showed lowest absolute abundance of ∑ARGs in water (3.686 × 10 7 copies mL −1 ) and the highest in sediment (4.574 × 10 8 copies g −1 ). Monoculture ponds showed higher relative abundance of ∑ARGs both in water (fish pond: 0.5149) and sediment (duck pond: 0.4919). As the main contributor to the ARGs abundance and significant correlations with ∑ tet , ∑ARGs and intI 1 ( P tet A was suggested to be a potential indicator for the abundance of tetracycline resistance genes in these classes of aquaculture modes in the Pearl River Delta. This study provides a case for the ARGs abundance in aquaculture and as a reference for the upcoming health risk assessment in aquatic environment.

BackgroundAberrant expression of ubiquitin-specific peptide 22 (USP22) has been detected in various cancers. This study aimed to investigate the role of USP22 and the underlying mechanism in human gastric cancer.MethodsThe expression pattern of USP22 in human gastric cancer was detected in a tissue microarray containing 88 pairs of gastric cancer tissue and adjacent normal tissue samples from patients with primary gastric cancer using immunohistochemical staining. The correlation of USP22 expression with clinical characteristics of patients, as well as their prognostic values in the overall survival of patients, were evaluated. USP22-overexpressing SGC7901 and USP22-silencing AGS cells were used to explore the role of USP22 in gastric cancer cell behavior in vitro and in vivo. Chromatin immunoprecipitation was performed to identify differentially expressed genes induced by USP22 overexpression. Western blot analysis was conducted to detect the activation of RAS/ERK and PI3K/AKT signaling in USP22-overexpressing SGC7901 cells and xenograft tumor tissues. Knockdown of RAS activator son of sevenless 1 (SOS1) was performed to investigate the role of SOS1 in USP22-regulated gastric cancer cell behavior and RAS signaling both in vitro and in vivo.ResultsUSP22 protein expression was significantly increased in human gastric cancer tissues, compared with adjacent normal tissues, and was positively correlated with local tumor stage. Gain- and loss-of-function assays showed that USP22 promoted gastric cancer cell growth and cell cycle transition while suppressing apoptosis in vitro. Consistent results were observed in a xenograft mouse model. Chromatin immunoprecipitation revealed that the overexpression of USP22 induced the upregulation of RAS activator son of sevenless 1 (SOS1) in SGC7901 cells. Western blot analysis showed that USP22 overexpression also induced activation of the RAS/ERK and PI3K/AKT pathways in SGC7901 cells and xenograft tumor tissues. Furthermore, SOS1 silencing could reverse the effects of USP22 on gastric cancer cell behavior and RAS signaling both in vitro and in vivo.ConclusionsOur results suggest that USP22 acts as an oncogene in gastric cancer in a SOS1-dependent manner, identifying the USP22/SOS1/RAS axis as a potential therapeutic target in gastric cancer.