Humans ; Early Detection of Cancer ; Endoscopy ; Esophageal Neoplasms/epidemiology* ; Risk Factors ; Mass Screening

Background::Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort.Methods::Participants from the United Kingdom Biobank cohort (https://biobank.ndph.ox.ac.uk/) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn’s disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results::Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years’ follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HR Q4 vs. Q1 =1.36, 95% CI: 1.19-1.55, Ptrend <0.001), UC (HR Q4 vs. Q1 =1.25, 95% CI: 1.07-1.46, Ptrend=0.047), and CD (HR Q4 vs. Q1 =1.58, 95% CI: 1.26-1.97, Ptrend <0.001) after multivariable adjustment. Compared with non-NAFLD, NAFLD participants had a significantly higher risk of incident IBD (HR=1.13, 95% CI: 1.04-1.24) and CD (HR =1.36, 95% CI: 1.17-1.58). Conclusions::Higher degree of non-alcoholic fatty liver is associated with increased risk of incident IBD. Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatment of IBD.

Objective:To investigate the clinicopathological features of missed synchronous multiple early gastric cancer (SMEGC).Methods:Clinical and pathological data of 10 missed SMEGC patients in Beijing Friendship Hospital collected from January 2015 to December 2019 were reviewed for the clinicopathological and endoscopic features.Results:Ten missed SMEGC patients were all over 60 years old, and 6 of them were males. Six patients had family history of tumor and 6 had comorbidity (hypertension, diabetes, dyslipidemia, cardiovascular or cerebrovascular diseases). In terms of endoscopic and pathological manifestations, missed lesions of 6 cases were not smaller than the initial lesions, and more than half of the missed lesions had the same vertical location in the stomach (6/10), infiltration depth (8/10), histological classification (9/10), atrophic (8/10) and intestinal metaplasia (8/10) as the initial lesions.Conclusion:Physicians should be aware of the possibility of missed lesions during the first endoscopic treatment and the follow-up, especially at the same vertical location of the initial lesions in elderly males with family history of tumor and comorbidity.

Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions. In recent years, molecular glues have been widely used as protein degraders. In addition, however, molecular glues play a variety of vital roles, such as complex stabilization, interactome modulation and transporter inhibition, enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery. Since most molecular glues are identified serendipitously, exploration of their systematic discovery and rational design are important. In this review, representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization, homo-polymerization and hetero-dimerization according to their aggregation modes, and we attempt to elucidate their mechanisms of action. In particular, we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development: starting point, optimization and identification.

Objective:To study the clinical value of blood neutrophil gelatinase-associated lipocalin (NGAL) in the early diagnosis and prognostic evaluation of late-onset sepsis in very/extremely low birth weight infants (VLBWI/ELBWI).Method:From January 2017 to December 2019, VLBWI/ELBWI older than 3 days admitted to NICU of our hospital were prospectively enrolled in the study. The infants were assigned into suspected-sepsis group and non-infection (control) group according to their clinical symptoms and laboratory indicators. In the suspected-sepsis group, complete blood count, C-reactive protein (CRP), procalcitonin (PCT) and blood culture were examined on the 1st day of disease onset and blood NGAL was examined on the 1st day of disease onset, 3rd day of treatment and 2nd week of treatment. In the control group, blood NGAL was examined at the time of enrollment. The suspected-sepsis group was later assigned into sepsis group and non-sepsis infection group and the sepsis group was further assigned into mild sepsis group and severe sepsis group according to the severity of the disease. Blood NGAL levels between the sepsis group and the non-sepsis infection group on the 1st day of onset and the control group were compared. The dynamic changes of NGAL in the sepsis group and the non-sepsis infection group at different time points were compared and analyzed. ROC curve of NGAL level on the first day of onset predicting sepsis was drawn.Result:(1) On the 1st day of disease, the sepsis group (n=106) had higher level of NGAL compared with non-sepsis infection group (n=121) and the control group (n=84). Non-sepsis infection group had significantly higher level of NGAL compared with the control group ( P<0.05). (2) A gradual decrease of NGAL was found in both sepsis and non-sepsis infection group. Significantly higher level of NGAL in sepsis group was found comparing with non-sepsis infection group at different time points ( P<0.05). (3) For blood culture positive and negative patients in the sepsis group, no statistically significant differences existed in NGAL,CRP, PCT levels on the 1st day of disease onset ( P>0.05).(4) The NGAL level in the severe sepsis group was significantly higher than the mild sepsis group on the 1st day of disease onset ( P<0.05). However,CRP and PCT showed no differences between the two groups. (5) On the 1st day of disease onset, to establish the diagnosis of sepsis, the area under the ROC curve of NGAL level was 0.852. The sensitivity and specificity of cut-off value 205.25 ng/ml were 84.0% and 66.9%, respectively. Conclusion:The serum NGAL level is elevated in VLBWI/ELBWI with late-onset sepsis. The more severe the sepsis,the more elevated the NGAL level. NGAL has certain predictive value for late onset sepsis in VLBWI/ELBWI.

Huge improvement has been made in the diagnosis and treatment of endoscopic ultrasonography (EUS) and more doctors have begun to focus on this subject with the increased level of EUS. Beijing Friendship Hospital has built a comprehensive system for the teaching method and process which include basic information screening of trainee and standardized training of perceiving and operating ability. There were 3 grades training of computer simulation, animal simulation and operation on real patients. During the first month of training, trainees accepted training with computer simulator for at least 100 hours, and underwent animal simulator during the second month, then underwent EUS on the real patients under supervision of instructors during the third month. By doing this, residents can master the technique of treatment and diagnosis of EUS in a safer and better way.

Objective To analyze the possible influencing factors of postoperative bleeding after endoscopic submucosal dissection and endoscopic mucosal resection ( ESD/EMR) for early gastric cancer. Methods Clinical data of patients receiving ESD/EMR for the diagnosis of early gastric cancer at the Endoscopy Center of Beijing Friendship Hospital from January 2013 to May 2018, including demographic information ( age, gender and history ) , endoscopic lesion characteristics ( tumor size, location and morphology) and postoperative pathological features ( differentiated types and invasive depth) were collected to analyze the effects of these factors on bleeding after ESD/EMR. Results A total of 195 patients with early gastric cancer were included in the study and 9 cases ( 4. 6％) had postoperative bleeding. The medication history of clopidogrel and main lesion sizes were statistically different between postoperative bleeding group and non-bleeding group ( P=0. 018 and P=0. 034 ) . Multivariate analysis showed a history of clopidogrel ( OR=10. 223, 95％CI:1. 143-91. 468, P= 0. 038 ) , multiple lesions ( OR= 6. 412, 95％CI:1. 123-36. 616, P=0. 037) and lesions sizes of larger than 2 cm ( OR=6. 718, 95％CI:1. 130-39. 935, P=0. 036) were possible risk factors for postoperative bleeding. Survival analysis showed of higher postoperative bleeding risks in patients with the history of clopidogrel ( P<0. 001) and lesions sizes of more than 2 cm ( P=0. 022) . Conclusion More attention should be paid to the risk of ESD/EMR postoperative bleeding in early gastric cancer patients with medication history of clopidogrel and multiple large lesions.

Objective To investigate the dynamic changes of soluble urokinase-type plasminogen activator receptor (suPAR) and its predictive value in late-onset sepsis in the newborn.Method To collect the data of neonates aged 7 days and older,who were diagonsed to have infections.They were admitted to neonatal intensive care unit of our Hospital from January 2014 to January 2015.The group of sepsis and nonseptic group were assigned according to the diagnostic criteria of sepsis,and a control group was selected without infection.Blood cultures were collected in patients on the first day when infection was identified and the serum suPAR and CRP were measured on the first day,fourth day and tenth day respectively.The controls were tested with suPAR and CRP when infection was excluded.The levels of blood suPAR and CRP in the three groups were compared and the receiver-operating characteristic curve was performed according to serum suPAR level of neonates with sepsis on the first day.Result A total of 65 infants with infections (40 were septic and 25 were non-septic) were enrolled in this study and 20 patients were selected as control group.There were significant differences in serum suPAR and CRP levels between the patients with and without infection (P ＜ 0.001).The level of suPAR in the survivors of the sepsis group was significantly decreased as time went by,and the difference was statistically significant on the 10th day compared with the 1 st day [9.3 (8.2,13.1) ng/ml vs.18.9 (14.8,24.7) ng/ml,P ＜ 0.05].The level of CRP increased first initially and then decreased with time,while the highest level was on the 4th day and the difference was statistically significant compared with the 10th day [19.0 （ 6.8,56.4) mg/L vs.6.4 (2.5,12.0) mg/L,P ＜ 0.05].The levels of serum suPAR and CRP in non-sepsis group were not significantly different (P ＞ 0.05).There were no deaths in the sepsis group and the non-septic group,but the levels of suPAR between survivals and deaths in the infection groups were statistically significant [15.4(10.6,21.6) ng/ml vs.22.6 (15.4,31.9) ng/ml,Z =-2.063,P =0.039].The area under the receiver-operating characteristic curve of serum suPAR was 0.955 (95％ CI 0.906 ～ 1.000,P ＜0.001),and the sensitivity was 90％ and the specificity was 100％ when the suPAR level was 10.9 ng/ml.Conclusion Early elevated serum suPAR levels were prominently related to the severity of neonatal late-onset sepsis.The level of first day suPAR has a high sensitivity and specificity in the prognosis of sepsis and can be helpful to predict the prognosis.

OBJECTIVETo investigate the correlation between intrahepatic eovalently closed circular (ccc)DNA of hepatitis B virus (HBV) and pathogen-and patient-related parameters.

METHODSUltrasound-guided liver biopsies were obtained from 60 patients with chronic HBV infection. Levels of intrahepatic HBV cccDNA and serum HBV DNA were measured by quantitative fluorescence PCR. Level of serum hepatitis B surface antigen (HBsAg) was measured by chemiluminescence immunoassay. Clinical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (AKP), albumin, globulin (GLO), white blood cell, platelet, prothrombin-international normalized ratio, were measured by standard assay. Demographic information was recorded.The correlation between intrahepatic HBV cccDNA and pathogen-and patient-related parameters was assessed.

RESULTSIntrahepatic HBV cccDNA level was negatively correlated with age, GLO, ALT and grade of necroinflammation. Patients with age of 30 years or more showed significantly higher level of HBV cccDNA level than patients under 30 years-old (7.44±0.58 and 5.66±1.35; t=7.157, P less than 0.001). Intrahepatic HBV cccDNA level was positively correlated with serum HBV DNA level (r=0.916, P less than 0.001) and serum HBsAg level (r=0.727, P less than 0.001). The median ratio of HBV cccDNA to HBV DNA was 1.18, and of HBV cccDNA to HBsAg was 1.67.

CONCLUSIONIntrahepatic HBV cccDNA levels decrease with age, level of ALT, level of GLO and grade of liver necroinflammation, but increase with level of serum HBV DNA and level of serum HBsAg. To a certain extent, serum HBV DNA and serum HBsAg levels may be a sufficient marker of intrahepatic HBV cccDNA levels.

Age Distribution ; Alanine Transaminase ; Aspartate Aminotransferases ; Biomarkers ; DNA, Circular ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Real-Time Polymerase Chain Reaction ; Serologic Tests

Objective To provide the basis for clinical treatment and prevention of Stenotrophomonas maltophilia infection ,ana‐lyze the characteristics of the bacteria infection and drug‐resistant strains of the area children .Methods Statistical analysis of 52 ca‐ses detected Stenotrophomonas maltophilia culture positive patients clinical data from September 2011 to September 2012 ,and the antibiotic susceptibility test results .Results Clinical data analysis showed that patients infected with Stenotrophomonas maltophilia had no difference on age and gender ,in the detection department was given priority to with of NICU and PICU ,82 .7% of infected children with SMA had a history of invasive procedures ,95 .92% of children with SMA had a history of penicillium carbon alkene drug use ,infection SMA patients in hospital for a long time with an average of (22 .3 ± 19 .0) days .Laboratory data analysis showed that Stenotrophomonas maltophilia main detection in sputum specimen type (63 .5% ) ,four kinds of commonly used clinical drug re‐sistance was higher ,sulfa drugs up to 21 .9% .Conclusion Stenotrophomonas maltophilia infection in children is closely related to carbapenem drug use and the invasive operation ,drug resistance in severe cases ,the rational use of antibiotics are crucial to treat‐ment .