BackgroundPulmonary fibrosis (PF) is an irreversible and lethal lung disease characterized by progressive scarring lacking safe and effective treatment options. Recent studies have underscored the role of macrophage polarization in fibrotic progression, yet the role of kynurenine (Kyn), a metabolite of tryptophan (Trp), in macrophages during PF progression remains elusive.MethodsLiquid Chromatography-tandem Mass Spectrometry (LC-MS) analysis was used to detect tryptophan metabolism changes in the serum of PF patients and control subjects. Macrophage-specific Ido1 or Ahr deletion mice was utilized to explored the role of Kyn in the bleomycin-induced fibrotic mouse model and ChIP sequence was employed to elucidate the mechanism by which Kyn inhibits pro-fibrotic macrophage activation.ResultsWe identified Kyn, Trp levels and Kyn/Trp ratio (KTR) were notably elevated in the serum of patients with different types of PF and these alterations were inversely correlated with lung function. Although such elevation might appear pathogenic, our functional studies demonstrate that Kyn exerts protective effects in PF, akin to brain natriuretic peptide in heart failure. Macrophage-specific deletion of Ido1 or aryl hydrocarbon receptor (AhR, the receptor of Kyn) exacerbated bleomycin-induced PF, while exogenous Kyn supplementation mitigated disease severity. Mechanistically, Kyn bound to the AhR, facilitating its nuclear translocation, where it promoted Slc39a10 transcription to increase the intracellular levels of zinc ion, thereby inhibiting profibrotic macrophage differentiation. Intriguingly, pirfenidone was noted with high potency to suppress Kyn production and our studies demonstrated that administration of Kyn along with pirfenidone effectively enhanced the therapeutic efficacy against PF.ConclusionsIn summary, these findings reveal a previously unrecognized Kyn-AhR-SLC39A10-Zn2+ signaling axis that governs macrophage polarization in PF, and unveiled the importance of Trp metabolism in PF pathogenesis, which could be novel therapeutic strategies against PF.

Neutrophilic asthma, characterized by the relative accumulation of neutrophils in the airways, constitutes a distinct endotype of asthma resistant to corticosteroid and associated with severe and uncontrolled cases. Milk fat globule-EGF factor 8 (MFGE8) is a soluble glycoprotein functioning in phagocytosis, tissue repair, angiogenesis, and the regulation of neutrophil activity. However, the role of this glycoprotein in neutrophilic asthma has not been thoroughly investigated. MFGE8 concentrations were assessed in asthmatic patients with various endotypes. Utilizing an ovalbumin (OVA)/complete Freund’s adjuvant (CFA)-induced mouse model of neutrophilic asthma, we investigated the critical roles of MFGE8 in neutrophilic asthma in MFGE8-knockout (Mfge8−/−) mice by assessment of H E/PAS staining, bronchoalveolar lavage (BAL) cell counting, and lung function tests. Bioinformatic analyses were conducted to determine downstream functions, and mechanistic experiments were performed on primary cultures of neutrophils isolated from the mouse’s lungs. Recombinant MFGE8 was administered to the mice to evaluate its therapeutic effects. Our results demonstrated that MFGE8 is expressed in neutrophils, and its protein levels are significantly reduced in the sputum supernatant of patients suffering from neutrophilic and paucigranulocytic asthma. Mfge8−/− mice exacerbated airway neutrophil infiltration, mucus secretion, and hyperresponsiveness. Further mechanistic studies, involving gene sequencing of sputum cells and lung tissue biopsies of asthmatic patients from GEO databases, identified neutrophil extracellular traps (NETs) as the critical factor in the progression of neutrophilic asthma. MFGE8 was shown to inhibit the formation of NETs (NETosis) through interaction with integrin β3. The absence of MFGE8 or the application of integrin β3 inhibitor was found to enhance NETosis and promote the release of pro-inflammatory cytokines via NLRP3-Caspase-1 pathway. Upstream mechanism indicated that USP14 mediated the ubiquitination of MFGE8 and participated in the development of NETosis. Moreover, recombinant MFGE8 was observed to effectively mitigate neutrophilic airway inflammation. This study underscored the significance of the MFGE8/integrin β3 axis in ameliorating NETosis and neutrophilic airway inflammation, suggesting MFGE8 as a potential therapeutic target for neutrophilic asthma. Not applicable.

Hexokinase catalyzes the first rate-limiting step glycolysis. However, the roles of hexokinase 2 (HK2) in asthma remain incompletely understood. This study aimed to investigate metabolic alterations in asthma, focusing on the expression, function and regulation of HK2. In this study, non-targeted metabolomics analysis of 20 asthma patients and 15 healthy controls identified metabolic alterations in asthma, particularly in the glycolytic pathways. Consistently, HK2 expression was elevated in both asthma individuals and mice with allergic airway inflammation. Airway epithelium–specific HK2 knockdown and pharmacological inhibition with 2-deoxy-D-glucose (2-DG) significantly attenuated airway inflammation and hyperresponsiveness in mice induced by ovalbumin/ lipopolysaccharide. Mechanistic analyses demonstrated that HK2 regulates epithelial apoptosis and inflammation via interaction with peptidylprolyl isomerase F (PPIF), independent of voltage-dependent anion channel 1 (VDAC1). Asthma is associated with metabolic reprogramming, characterized by alterations in lipid and glucose metabolism. These findings establish HK2 plays a crucial role in asthma pathogenesis by promoting airway epithelial apoptosis and inflammation in asthma, suggesting its potential as a therapeutic target.

Idiopathic pulmonary fibrosis (IPF) is a deadly respiratory condition distinguished by gradual fibrotic restructuring and diminishing pulmonary capacity, with cellular senescence serving as a critical factor in its pathogenesis. This study investigated the function of Sine oculis homeobox homologue 1 (Six1), a transcription factor, in pulmonary fibrosis (PF) and assessed its therapeutic potential as a target. The expression of Six1 was reduced in type II alveolar epithelial cells (AECII) in both patients with IPF and mouse models of PF induced by bleomycin (BLM). Conditional overexpression of Six1 in AECII exacerbated fibrosis severity, as confirmed by histological analysis and impaired lung function. RNA sequencing indicated the involvement of Six1 in pathways related to immune response, inflammation, and cellular senescence. Mechanistic studies revealed that Six1 promotes cellular senescence in AECII by directly upregulating Tp53 transcription, a process mitigated by treatment with PFN-α, a Tp53 inhibitor. Inhibition of Six1 using the specific repressor NCGC00378430 (NCG) attenuated fibrotic changes and improved pulmonary function in both Six1-overexpressing and wild-type mice. These findings suggest that Six1 is a contributor to the progression of IPF by regulating AECII senescence, emphasizing the therapeutic potential of targeting Six1 to alleviate PF. This study underscores the necessity of exploring Six1 inhibitors further as promising candidates for treating IPF.

Abstract Background Asthma is a prevalent inflammatory lungs disease which poses a substantial global health and economic burden. Abnormal glucose metabolism in asthmatic patients has recently attracted much attention. As a key enzyme in glycolysis, the participation of Hexokinase 2(HK2) in the disease course of asthma has not been fully understudied. Methods In an asthma mouse model, the expression levels of Hexokinase 2 (HK2) were validated, and a mouse model with HK2 specifically knocked out in airway epithelial cells was created to investigate the role of HK2 in bronchial asthma. In vitro cellular experiments involved the overexpression and knockdown of HK2 to study its role and related mechanisms in airway epithelial cell death and airway inflammation in bronchial asthma. Results HK2 is found to have increased expression in both mouse asthma models, especially showing elevated expression in airway epithelial cells. Mice that specifically lacked HK2 in their airway epithelium were observed to be protected from cell death and inflammation during asthma. Moreover, airway epithelial cells treated with HK2 overexpression exacerbated cell death and elevated the expression of inflammatory interleukins, conversely after silencing HK2 in vitro, cell death and inflammatory interleukins expression were greatly improved. We further surmise that HK2 might be involved in the regulation of airway epithelial cell death and airway inflammation through PPIF and VDAC1. Furthermore, the treatment of mice with HK2 inhibitor, 2-DG, markedly attenuated the inflammatory cell infiltration in the pulmonary tissues. Conclusion HK2 plays a crucial role in the occurrence and progression of bronchial asthma, being involved in airway epithelial cell death and airway inflammation.

BACKGROUND:The treatment of hepaticojejunal anastomotic strictures in patients with surgically altered anastomosis is challenging. Endoscopic ultrasound (EUS)-guided biliary drainage is being established as a feasible biliary drainage procedure. How can oblique-viewing endoscopic ultrasound (OV-EUS) safely reach the treatment area in the afferent limb for EUS-guided hepaticojejunostomy? This is a key, meaningful, and challenging question.METHODS:A unique case of an OV-EUS-guided hepaticojejunostomy performed in a patient with severe stenotic hepaticojejunal anastomosis was reported, and the relevant literatures were reviewed.RESULTS:There are only 3 previous case reports of EUS-guided transanastomotic drainage using OV-EUS. The above 3 cases reported did not elaborate on the key treatment details of the procedure. Especially how can the OV-EUS safely reach the treatment area in the afferent limb?CONCLUSIONS:For patients with severe anastomotic stricture, when the retrograde or antegrade guide wire cannot pass through the stenosis to establish biliary drainage, OV-EUS can safely reach the treatment area in the afferent limb under the guidance of a fluoroscopic view and a guide wire. Thus, an OV-EUS-guided hepaticojejunostomy can be achieved.

Patients with eosinophilic asthma react well to conventional treatment of asthma while individualized therapy for non-eosinophilic endotypes have yet to be developed. Dysregulated sphingosine metabolites are associated with the pathophysiology of different asthma endotypes with their receptors involved. However, whether the sphingosine-1-phosphate receptor 4 (S1PR4) contributes to disease progression of asthma remains underappreciated. In this study, we demonstrated that sphingosine metabolism was disturbed in asthma while it could not be used to distinguish between different endotypes of asthma. S1PR4, a vital receptor of bioactive sphingosine metabolites and mainly expressed in macrophages, exhibited lower expression both in patients and experimental mice with neutrophilic airway inflammation. Additionally, S1pr4 deficiency aggravated the OVA/LPS-induced pulmonary inflammation in mice along with a significant up-regulation in M1 macrophage activation. Mechanistic studies showed that S1PR4 was strongly connected to bioactive oxylipins concurrent with bounding to formyl peptide receptor 2 to influence the phosphorylation of JNK and contributed to the macrophage M1 program, which in turn secreted amounts of inflammatory cytokines associated to the inflammatory response of neutrophilic asthma. Furthermore, treating mice with S1PR4 agonist CYM50308 was characterized by less pulmonary inflammatory infiltration. Our research indicates S1PR4 a promising therapeutic target for non-eosinophilic phenotypes of asthma.

Dysregulation of type II alveolar epithelial cells (AECII) plays a vital role in the initiation and development of pulmonary fibrosis (PF). Dachshund homolog 1 (Dach1), frequently expressed in epithelial cells with stem cell potential, controls cell proliferation, apoptosis, and cell cycle in tissue development and disease process. In this study, we demonstrated that the lungs collected from PF patients and mice of Bleomycin (BLM)-treated were characterized by low expression of Dachshund homolog 1 (Dach1), especially in AECII. Dach1 deficiency in the alveolar epithelium exacerbated PF in BLM-treated mice, as evidenced by reduced pulmonary function and increased expression of fibrosis markers. Rather, treatment with lung-specific overexpression of Dach1 alleviated histopathological damage, lung compliance, and fibrosis in BLM-treated mice. Moreover, overexpression of Dach1 could inhibit epithelial apoptosis in vitro. Conversely, primary AECII with Dach1 depletion were more susceptible to apoptosis in vivo. Mechanically, Dach1 combined with C-Jun protooncogene selectively bound to the promoter of B-cell lymphoma 2 interacting mediators of cell death (Bim), by which it repressed Bim expression and alleviated epithelial apoptosis. Taken together, our data support that Dach1 in AECII contributes to the progression of PF and may be a viable target for the prevention and treatment of PF.

Background There is still no consensus on the preferred endoscopic therapy for small bowel angioectasias (SBAs). The aim of this study was to evaluate effectiveness and safety of endoscopic injection sclerotherapy (EIS) for treating recurrent bleeding of SBAs. Methods Sixty-six adult patients diagnosed with SBAs by capsule endoscopy (CE) or double-balloon enterscopy (DBE) examinations were enrolled in this retrospective study from September 2013 to September 2021. The patients were divided into an EIS group (35 cases) and a control group (31 cases) according to whether they underwent EIS treatment. Clinical characteristics, medical histories, lesion characteristics, main laboratory indicators, treatments, and outcomes were collected. The rates of re-bleeding, re-admission, and red blood cell (RBC) transfusion were compared between different groups after discharge. The rates of hospitalization and RBC transfusion were compared between before admission and after discharge in both groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were used in the multivariate logistic regression analysis to assess relative factors for re-bleeding. Results All the rates of re-bleeding, re-admission and RBC transfusion after discharge in the EIS group were significantly lower than those in the control group (all P < 0.05). The rates of hospitalization and RBC transfusion after discharge were significantly lower than those before admission in the EIS group (both P < 0.05), while those did not reach significant differences in the control group (both P > 0.05). Multivariate logistic regression analysis showed that RBC transfusion before admission (OR, 5.655; 95% CI, 1.007–31.758, P = 0.049) and multiple lesions (≥ 3) (OR, 17.672; 95% CI, 2.246–139.060, P = 0.006) were significant risk factors of re-bleeding, while EIS treatment (OR, 0.037; 95% CI, 0.005–0.260, P < 0.001) was a significant protective factor. No endoscopic adverse events were observed during hospitalization and none of the enrolled patients died within 12 months after discharge. Conclusion EIS treatment had good effectiveness and safety for treating recurrent bleeding of SBAs, which could be considered as one of the first-line endoscopic treatment options for SBAs.

BackgroundTo analyze the diversity in endoscopic manifestations of Meckel's diverticulum (MD) in adults by using balloon-assisted enteroscopy (BAE) and supply more information on the application of BAE.MethodsA retrospective study was carried out on adult patients diagnosed with MD by BAE in two tertiary general hospitals in China, from May 2007 to September 2021. The patients were divided into a small bowel bleeding (SBB) group and a control group according to their main symptoms. Clinical charts and endoscopic images were reviewed, analyzed, and summarized.ResultsSingle diverticulum in the ileum and double-lumen sign were observed in all patients. The SBB group consisted of 51 patients, among which 35 cases of ulcerative lesions, 9 cases of erosive lesions, 9 cases of active bleeding/blood clots, and 4 cases of lumps inside the diverticulum were observed respectively. Majority of ulcerative lesions were inside the diverticulum (23/35). A circumferential stricture inside the diverticulum was discovered in 11 cases, and ulcerative lesions tended to occur at this structure (10/11). In the control group consisting of 15 patients, 1 case of erosive lesions at the orifice edge was observed. The percentage of patients with MD-associated ulcerative lesions was significantly higher in the SBB group than that in the control group (p < 0.001).ConclusionsThe endoscopic manifestations of MD in adults are extraordinarily complex and connected with the patients' primary symptoms. The internal features of MD should be regarded as crucial observational objectives in adult patients.

AbstractBackground To evaluate the outcomes of endoscopic sphincterotomy (EST) combined with endoscopic papillary large balloon dilation (EPLBD) for removing stones from large common bile duct (CBD) and identify the risk factors for stone recurrence. Methods After reviewing 69 patients with large CBD stones, 44 were included in the group treated with EST combined with EPLBD (ESLBD) and 25 patients were in included in the EPLBD group. The clinical data of both groups, including success rates of removing large CBD stones, complications, hospital stay and total costs of hospitalization were compared. In addition, the risk factors for stone recurrence were explored. Results The ESLBD and EPLBD groups showed similar success rates of stone clearance (97.27% vs 96.00%). However, the use of lithotripsy and the incidence of post-endoscopy pancreatitis (PEP) were higher in the EPLBD group. The recovery time and total costs of hospitalization were also lower in the ESLBD group. No serious complications were identified in our study, such as hemorrhage, perforation and death; and no significant differences in infection, procedural time, hospital stay and procedural costs of groups. Multiple logistic regression analysis showed that lithotripsy and maximum transverse diameter of the CBD stone were independent risk factors for stone recurrence. Conclusions ESLBD was superior to EPLBD alone for removing large CBD stones. In addition, the maximum transverse diameter of CBD stone and lithotripsy were independent risk factors for associated with stone recurrence.

本文报道1例经内镜逆行胰胆管造影术中特殊胆总管穿孔病例，该病例在穿孔部位、分型、引起胆总管穿孔的器械等方面，均属罕见。

BACKGROUND:Dilated cardiomyopathy type 2A (DCM2A, MIM: #611880) is a rare autosomal recessive heart disease leading to heart failure and sudden cardiac death. However, the causative role of TNNI3 in DCM2A is still questioned due to few cases reported and the conflicting molecular biological evidence. METHODS:Trio whole-exome sequencing (trio-WES) was performed in a Chinese family with dilated cardiomyopathy. Sanger sequencing and real-time quantitative PCR were used to confirm the variants identified. Expression outcome caused by the synonymous mutation was validated by minigene splicing analyses. RESULTS:The one-year-old girl presented severe left ventricular enlargement and significantly reduced left ventricular systolic function and she died of respiratory and heart failure soon after her diagnosis. Trio-WES revealed a compound heterozygous variants of TNNI3, a novel c.24G＞A (p.Ala8Ala) (NM_000363.4) in exon 2 and a deletion of entire gene. Minigene splicing analyses showed it led to an intron retention (c.24 + 1_24 + 45ins) by intron 2 cryptic splicing. CONCLUSIONS:Our study describes and characterizes a synonymous mutation in TNNI3 gene, supporting the clinical diagnosis of an autosomal recessive DCM. Our study emphasizes the importance of functional analysis to assess the potential pathogenicity of synonymous mutations, especially when the synonymous variants are not annotated as benign.

目的:探索内镜下球囊扩张术联合胆道细胞刷检应用于胆管癌的诊断价值。方法:单中心前瞻性研究，本研究在华中科技大学同济医学院附属武汉市中心医院进行，总结2018年1月-2020年1月期间影像学(CT或MRI)提示胆管恶性狭窄可能或原因不明胆管狭窄并同意行内镜逆行胰胆管造影诊治的患者的临床资料及随访情况。所纳入研究患者均行内镜下胆管狭窄球囊扩张术，并于球囊扩张前后分别进行细胞刷检术，扩张前留取病理组织为对照组样本，扩张后留取病理组织为试验组样本。试验组、对照组样本经同一名病理专业副主任医师阅片后提出病理诊断意见。若有癌细胞或显著异型细胞发现提示刷检阳性。若未见癌细胞或异型细胞则提示刷检阴性。阴性患者中结合临床仍高度考虑胆管癌且同意手术，术后大体标本证实为恶性的考虑刷检假阴性；难以判断胆管癌患者经随访2个月有进展考虑刷检假阴性。2个月随访无进展，暂考虑胆管良性狭窄可能。应用优势性检验(McNemar检验)分析试验组与对照组之间是否存在差异。结果:共纳入符合条件的研究病例39例，男性26例，女性13例，年龄(68.0±5.2)岁。经细胞学检测、手术病理及临床随访最终明确诊断胆管癌35例。对照组刷检阳性17例，细胞刷检敏感率48.6%(17/35)，试验组刷检阳性26例，细胞刷检敏感率74.2%(26/35)。另外有2例患者对照组刷检阳性，试验组刷检阴性。合计对照组及试验组刷检阳性共28例，细胞刷检敏感率80.0%(28/35)，两组比较差异有统计学意义( P<0.05)。 结论:内镜下球囊扩张术联合细胞刷检可提高胆管癌的病理诊断灵敏度，球囊扩张前后分别进行细胞刷检可提高诊断灵敏度。

Background: Aging is a strong risk factor and an independent prognostic factor in idiopathic pulmonary fibrosis (IPF). In this study, we aimed to conduct a comprehensive analysis based on gene expression profiles for the role of aging in pulmonary fibrosis. Method: Four datasets (GSE21411, GSE24206, GSE47460, and GSE101286) for patients with clinical IPF and one dataset for bleomycin (BLM)-induced pulmonary fibrosis (BIPF) mouse model (GSE123293) were obtained from Gene Expression Omnibus (GEO). According to different age ranges, both patients with IPF and BIPF mice were divided into young and aged groups. The differently expressed genes (DEGs) were systemically analyzed using Gene Ontology (GO) functional, Kyoto Encyclopedia of Genes and Genomes (KEGG), and hub genes analysis. Finally, we verified the role of age and core genes associated with age in vivo. Results: Via the expression profile comparisons of aged and young patients with IPF, we identified 108 aging-associated DEGs, with 21 upregulated and 87 downregulated. The DEGs were associated with "response to glucocorticoid," "response to corticosteroid," and "rhythmic process" in GO biological process (BP). For KEGG analysis, the top three significantly enriched KEGG pathways of the DEGs included "IL-17 signaling pathway," "Mineral absorption," and "HIF-1-signaling pathway." Through the comparisons of aged and young BIPF mice, a total number of 778 aging-associated DEGs were identified, with 453 genes increased and 325 genes decreased. For GO and KEGG analysis, the DEGs were enriched in extracellular matrix (ECM) and collagen metabolism. The common DEGs of patients with IPF and BIPF mice were enriched in the BP category, including "induction of bacterial agglutination," "hyaluronan biosynthetic process," and "positive regulation of heterotypic cell-cell adhesion." We confirmed that aged BIPF mice developed more serious pulmonary fibrosis. Finally, the four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) were verified in vivo. Conclusion: This study provides new insights into the impact of aging on pulmonary fibrosis. We also identified four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) related to the development of pulmonary fibrosis.

Objective: To investigate and analyze the relevant risk factors for hemophagocytic lymphohistiocytosis (HLH) in children with severe adenovirus pneumonia (SAP). Methods: A retrospective study of children with SAP was performed in 30 cases developing HLH and 94 cases not developing HLH from December 2018 to August 2019. The binary logistic regression analysis was used to identify risk factors that were significantly associated with the development of HLH after the univariate analysis, and the receiver operating characteristic (ROC) curve was performed to find out the cut-off value for the significant relevant factors. Results: Two factors were associated with the development of HLH, which were the length of fever (OR = 1.331, 95%CI: 1.002-1.769) and triglycerides (TG) (OR = 17.345, 95%CI: 1.358-221.538). The cut-off value of the length of fever was 12.5 days, and the cut-off value of TG was 3.02 mmol/L. Conclusion: Children with SAP who had a duration of fever over 12.5 days and the TG level over 3.02 mmol/L are more likely to develop HLH.

目的:探索内镜下球囊扩张术联合胆道细胞刷检应用于胆管癌的诊断价值.方法:单中心前瞻性研究2018年1月至2020年1月华中科技大学同济医学院附属武汉中心医院经影像学(CT或MRI)提示胆管恶性狭窄可能或原因不明胆管狭窄并同意逆行胰胆管造影(endoscopic retrograde cholangiopancreatography,ERCP)诊治的患者临床资料及随访情况.所纳入研究患者均行内镜下胆管狭窄球囊扩张术,并于球囊扩张前后分别进行细胞刷检术,扩张前后留取病理设为对照组及试验组.若有癌细胞或显著异形细胞发现提示刷检阳性,若未见癌细胞或异形细胞则提示刷检阴性.阴性患者中结合临床仍高度考虑胆管癌同意手术且术后证实胆管癌者或者难以判断胆管癌的患者经随访2个月有进展者均考虑刷检假阴性.应用优势性检验(McNemar检验)分析两种诊断方法之间是否存在显著性差异.结果:共纳入符合条件的研究病例39例,其中男性26例,女性13例,平均年龄(68.0±5.2)岁.经细胞学检测、手术病理及临床随访最终明确诊断胆管癌35例.对照组刷检阳性17例,细胞刷检灵敏度48.6％(17/35),试验组刷检阳性26例,细胞刷检灵敏度74.2％(26/35).另外有2例患者对照组刷检阳性,试验组刷检阴性.合计对照组及试验组刷检阳性共28例,细胞刷检灵敏度80.0％(28/35),两组比较差异有统计学意义(P<0.05).结论:内镜下球囊扩张术联合细胞刷检可提高胆管癌的病理诊断灵敏度,球囊扩张前后分别进行细胞刷检可提高诊断灵敏度,且操作比较简单,值得临床推广.

BACKGROUND Four-liter polyethylene glycol (PEG) solutions are effective for bowel cleansing, but their large volume might hinder patient compliance. Due to the unique features of Asians, 4 L PEG might be a suboptimal bowel preparation in predominantly ethnically Asian countries. In view of this, a balance should be achieved between the volume and effectiveness. The ideal bowel cleansing regimen for a colonoscopy has yet to be determined in a Chinese population. AIM To compare the cleansing efficacy of 3 L PEG plus simethicone with 4 L PEG. METHODS A total of 291 patients were randomly allocated to two groups: Group 1 (n = 145) received 4 L split-dose PEG (4-P); group 2 (n = 146) received 3 L split-dose PEG plus simethicone (3-PS). Bowel-cleansing efficacy was evaluated by endoscopists using the Boston bowel preparation scale (BBPS) and the bubbles score. RESULTS Although there were no significant differences in the total BBPS score or the adequate rate of bowel preparation between the two groups, the BBPS score of the right-side colon was significantly higher in the 3-SP group (2.37 ± 0.54 vs 2.21 ± 0.78; P = 0.04). Moreover, the use of simethicone significantly reduced bubbles in all colon segments (P < 0.001). The mean withdrawal time was significantly shorter in the 3-PS group (8.8 ± 3.4 vs 9.6 ± 2.3; P = 0.02). Furthermore, significantly more proximal adenomas were detected in the 3-PS group (53.6% vs 45.7%; P = 0.03). In addition, the proportions of patients with nausea and bloating were significantly lower in the 3-SP group (P < 0.01 for both). More patients in the 3-PS group expressed willingness to repeat the bowel preparation (87.7% vs 76.6%, P = 0.01). CONCLUSION Three-liter PEG shows satisfactory bowel cleansing despite the decrease in dosage, and addition of simethicone with better bubble elimination and enhanced patient acceptance offers excellent potential impact on the detection of proximal adenomas in Chinese patients.

Autophagy and apoptosis are two major modes of cell death. A balanced interplay between both is vital for phagocytic clearance of apoptotic testicular cells. Here, generating a SD rats model-treated with cadmium (Cd) to mimic environmental exposure on human, we show that autophagy and apoptosis present synchronous change trends in Cd-induced testicular injury/self-recovery. Further, the cross-talk of autophagy and apoptosis is investigated in four testicular cell lines (GC-1/GC-2/TM3/TM4 cells) respectively. Results reveal that Cd-exposure for five consecutive weeks induces reproductive toxicity in male rats. After one cycle of spermatogenesis within 8 weeks without Cd, toxic effects are ameliorated significantly. In vitro, we find that PI3K inhibitor 3-MA regulates apoptosis by inhibiting autophagy with mTOR-independent pathway in Cd-treated testicular cells. Conclusively, cross-talk between autophagy and apoptosis regulates testicular injury/recovery induced by Cd via PI3K with mTOR-independent pathway.

Background Although several randomized controlled trials (RCTs) have shown that the addition of simethicone to polyethylene glycol (PEG) can improve bowel preparation, whether PEG plus simethicone had a beneficial role in the adenoma detection rate (ADR) during a colonoscopy has yet to be confirmed. The aim of this study was to clarify whether adding simethicone to a PEG solution could improve the effectiveness of the ADR. Methods The PubMed, EMBASE, and Cochrane Library databases were searched for articles published prior to November 2018. The primary outcomes included the ADR and the polyp detection rate (PDR). The secondary endpoints included the efficacy of the colon preparation, procedure-related parameters, adverse events and willingness to repeat preparation. The odds ratios (ORs) and mean difference (MD) with 95% confidence intervals (CIs) were pooled for discrete and continuous variables. The subgroup analyses and sensitivity analyses were performed. Results Eighteen studies were eligible. Although there was no significant difference in the overall ADR (OR =1.03, 95% CI: 0.89–1.18, P=0.73) between the groups with or without simethicone, a significant effect of simethicone for small adenomas ( Conclusions In summary, we believe that the addition of simethicone to PEG is a promising bowel preparation method for colonoscopy in clinical practice among Asian populations. Additional large clinical trials are necessary to validate our results.