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Abstract:
Upper gastrointestinal bleeding (UGIB), a common medical emergency, causes significant morbidity and mortality. Endoscopic evaluation and treatment remain the standard care in patients who can be hemodynamically stabilized. However, severe bleeding despite conservative medication treatment or medication combined with endoscopic intervention occurs in 5%-10% of patients, requiring interventional or surgical treatment. Endovascular embolization has emerged as an alternative to emergency operative intervention for high-risk patients with non-variceal UGIB and is now commonly considered the first-line therapy for refractory bleeding after endoscopic treatment. Child-Pugh class C or class B cirrhosis patients who have varicosity or active bleeding detected in endoscopy are at high risks for treatment failure, rebleeding, and death. A preemptive transjugular intrahepatic portosystemic shunt has been shown to reduce treatment failure and mortality significantly. Herein, we reviewed the current role of interventional treatment in the management of massive UGIB on the basis of years of clinical experience of the Department of Gastroenterology, West China Hospital, Sichuan University.

Abstract:
Lower gastrointestinal bleeding (LGIB) is a common clinical emergency. However, most of the published findings on LGIB were of retrospective or observational studies, and the relevant clinical guidelines and consensuses were not published until quite recently. In clinical practice, LGIB treatment is not as standardized as the treatment of upper gastrointestinal bleeding. Herein, on the basis of the latest clinical research findings on and guidelines for LGIB, we summarized and analyzed the existent diagnosis and treatment of LGIB from the perspectives of patient assessment and endoscopic, interventional and medication treatment, intending to provide more references to support the clinical practice.

Abstract:
Non-variceal upper gastrointestinal bleeding (NVUGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of varices. As a common clinical problem, NVUGIB entails a heavy burden on the healthcare system. In addition to endoscopic hemostasis, evaluation and treatment before and after endoscopy are also of critical importance for the clinical management of NVUGIB patients. In recent years, based on the rapid development of endoscopic technology and clinical management of NVUGIB, the research evidence and clinical guidelines have been updated internationally, while some clinical decisions remain controversial. In this article, we mainly reviewed and discussed the current status of NVUGIB patient management before, during, and after endoscopy, aiming to deepen the understanding of the disease for clinicians, and to promote standardized management of patients with NVUGIB.

Abstract:
Endoscopic submucosal dissection (ESD) has been widely used in the clinical treatment of early-stage and precancerous lesions of the digestive tract. Compared with traditional open surgery, the procedure has a number of advantages, including low postprocedural recurrence rate, the location and scope of lesions not posing much restrictions on the procedure, and quick patients recovery afterwards. The procedure has hence become one of the minimally-invasive procedures commonly performed with gastrointestinal endoscope. However, due to the influence of various factors, complications such as intraoperative and postoperative bleeding, perforation, electrocoagulation syndrome and lumen stenosis may occur. Delayed postoperative bleeding, in particular, may induce cardiovascular and other related diseases due to the insidious nature of its onset, resulting in serious consequences. It is critically important for the further development of ESD that we should acquire thorough understanding and mastery of the relevant influencing factors and preventive measures of delayed bleeding after ESD of early-stage gastrointestinal cancer. We herein summarized and discussed the latest research findings in the preventative and treatment measures.

Abstract:
  Objective  To evaluate the efficacy of three endoscopic therapies of isolated gastric varices (IGV) with modified tissue adhesive.   Methods   A retrospective analysis was conducted with the clinical data of 73 IGV patients who were treated between January 2008 and December 2019 at Beijing Ditan Hospital. Patient clinical data on age, sex, etiology, biochemistry findings, Child-Pugh classification, the type of spontaneous shunt, preoperative bleeding history, and the presence or absence of liver cancer were collected. The three therapies evaluated were endoscopic intravenous injection of tissue glue combined with lauromacrogol, endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, and endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. Their respective clinical treatment outcomes, including ectopic embolism rate, survival rate, rebleeding rate, amount of lauromacrogol and tissue glue used, the number of endoscopic clips used, and the number of times of the procedure the patient underwent, were evaluated.   Results   In the patient baseline data, Child-Pugh grade, preoperative thrombus formation, and the presence or absence of liver cancer, showed significant difference between the three therapies (P<0.05). There was no significant difference in the rates of ectopic embolism among the three methods (P>0.05), but no ectopic embolism occurred after endoscopic clip-assisted intravenous injection of tissue glue combined with lauromacrogol, or after endoscopic clip and LOOP-assisted intravenous injection of tissue glue combined with lauromacrogol. There was no significant difference in the survival rate, the rebleeding rate, amount of lauromacrogol and tissue glue used for the three therapies, but there was significant difference in the number of endoscopic clips used and the number of times the procedure was conducted within one year (P<0.05).   Conclusion   The two endoscopic therapies of intravenous injection of modified tissue glue, one assisted by clip and the other assisted by clip and LOOP, can help reduce the number of procedures IGV patients undergo within one year.

Abstract:
  Objective  To explore the diagnostic performance of blood urea nitrogen-to-creatinine (BUN/Cr) ratio in differentiating the site of gastrointestinal bleeding, and to assess the predictive value of early elevated BUN/Cr ratio for clinical outcomes in patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB).   Methods  The adult patients diagnosed with gastrointestinal bleeding who were hospitalized in the Department of Gastroenterology, Zhongshan Hospital, Xiamen University between May 2020 and May 2021 were retrospectively enrolled. According to the site of gastrointestinal bleeding, the patients were divided into the upper gastrointestinal tract group, the proximal small intestinal bleeding group, and the distal small intestinal and colonic bleeding group. According to the early dynamic changes of BUN/Cr ratio within 6-48 hours after admission, patients with ANVUGIB were divided into early dynamic elevated BUN/Cr ratio group and non-early dynamic elevated BUN/Cr ratio group. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of BUN/Cr ratio in differentiating the site of gastrointestinal bleeding and examine the predictive efficacy of early dynamic elevated BUN/Cr ratio after admission, Rockall scoring system, and the combined indicator of the two for estimating the primary clinical outcomes in ANVUGIB patients.   Results  A total of 266 patients were enrolled. Among them, 204 cases were in the upper gastrointestinal bleeding group, 15 cases were in the proximal small intestinal bleeding group, and 47 cases were in the distal small intestinal and colonic bleeding group. In the ANVUGIB patients, 16 were in the group with early dynamic elevated BUN/Cr ratio after admission, and 146 were in the group with non-early dynamic elevated BUN/Cr ratio after admission. The area under the ROC curve of the BUN/Cr ratio was 0.831 (95% CI: 0.780-0.874), the optimal cut-off value being 34.59 mg/g for differentiation between upper and lower gastrointestinal bleeding. The area under the ROC curve of the BUN/Cr ratio was 0.901 (95% CI: 0.798-0.963) and the optimal cut-off value was 19.27 mg/g for differentiation between proximal small intestinal bleeding and the distal small intestinal and colonic bleeding. The area under the ROC curve of the early dynamic elevated BUN/Cr ratio after admission was 0.806 (95% CI: 0.737-0.864) for predicting the primary clinical outcome in patients with ANVUGIB. The area under the ROC curve of the combined indicator included the early dynamic elevated BUN/Cr ratio after admission and the Rockall scoring system was 0.909 (95% CI: 0.854-0.949) for predicting the primary clinical outcome in patients with ANVUGIB.   Conclusion  The BUN/Cr ratio shows rather reliable diagnostic performance for identifying the site of gastrointestinal bleeding, and the early dynamic elevated BUN/Cr ratio after admission is a reliable indicator for predicting clinical outcomes in patients with ANVUGIB.

Abstract:
  Objective  To evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) in the treatment of acute non-variceal upper gastrointestinal bleeding (ANVUGIB), and to guide clinical practice and continue to optimize diagnosis and treatment strategies.  Methods  This retrospective study included 266 patients who underwent angiography due to ANVUGIB between March 2016 and March 2021. Data on the positive rate of angiography, the technical success rate and clinical success rate of TAE, and the rebleeding rate and the all-cause mortality within 30 days after TAE treatment were collected, and the influencing factors relevant to the above events were analyzed accordingly.  Results  All 266 patients completed angiography--the positive rate of angiography was 54.1% (144/266), the total technical success rate was 97.3% (217/223), the clinical success rate was 73.1% (155/212), and the rebleeding rate and all-cause mortality within 30 days were 26.9% (57/212) and 16.1% (35/217), respectively. This study found that shock index>1 (OR=5.950; 95% CI: 1.481-23.895; P=0.012), computed tomography angiography (CTA) positive result (OR=6.813; 95% CI: 1.643-28.252; P=0.008) and interval<24 h (OR=10.530; 95% CI: 2.845-38.976; P<0.001) were independent predictors of positive angiography. Shock index>1 (OR=2.544; 95% CI: 1.301-4.972; P=0.006) and INR>1.5 (OR=3.207; 95% CI: 1.381-7.451; P=0.007) were independent risk factors for rebleeding. Patients with postoperative bleeding (OR=3.174; 95% CI: 1.164-8.654; P=0.024) and patients with rebleeding after embolization (OR=34.665; 95% CI: 11.471-104.758; P<0.001) had a higher risk of death within 30 days.  Conclusion  TAE is safe and effective in the treatment of ANVUGIB. Patients with shock index>1 and positive CTA are more likely to be angiographic positive, and should undergo angiography as early as possible after bleeding. In addition, rebleeding after embolization deserves high attention.

Abstract:
  Objective  To summarize the clinical characteristics and treatment experience of gastric primary lymphoma with acute upper gastrointestinal bleeding as the primary manifestation, and to provide support for clinical treatment.  Methods  Information on gastric primary lymphoma patients admitted to the Department of Gastroenterology, West China Hospital of Sichuan University between January 2010 and March 2021 for acute upper gastrointestinal bleeding was retrospectively collected. Data on endoscopic morphology, tumor staging, pathology typing, severity of bleeding, risks of rebleeding, treatment and inhospital prognosis were documented and analyzed.   Results  A total of 25 patients with a mean age of 57.2 years were included in the study, all of whom presented clinically with melena (100%), 9 (36%) had hematemesis, and 6 (24%) was accompanied with abdominal pain. Twenty, or 80%, of the gastric lymphoma patients with bleeding as the primary manifestation showed endoscopically a tumor-forming phenotype (Yao Classification), mostly involving the middle and lower parts of the gastric body (44% and 32%, respectively). After conservative treatment with medication, rebleeding occurred in 4 patients during hospitalization. One of them required endoscopic hemostasis, two required surgical resection to stop the bleeding, and one decided not to undergo any further treatment. Only one patient died from infection and no death resulted directly from severe bleeding.   Conclusion  Gastric primary lymphoma presenting acute upper gastrointestinal bleeding as the sole clinical manifestation rarely occurs, but when the condition does occur, it shows a wide range of endoscopic involvement. It has a higher risk of rebleeding, and endoscopic or surgical treatment may be attempted when conservative medication treatment for acute upper gastrointestinal bleeding fails.

Abstract:
  Objective   To study the virulence variation of enterovirus 71 (EV71) during thermal adaptive evolution, providing references for the prevention and control of the EV71-related hand, foot and mouth disease.   Methods   Parental strains and thermal-adapted strains originating from EV71 sibling strains (lineage #100 and #101) were used for plaque assay validation, CCK-8 cytotoxicity experiment, and host proteomics studies after Vero cell infection. Plaque morphology and cell inhibition rate of the viral strains were obtained. Mass spectrometry was used to examine and analyze the functions of proteins that were differential expressed in the host cells.   Results   Plaque morphology variation was found only in the heat-adapted strain of lineage #101. Increase in cell inhibition rate was observed in all the thermal-adapted strains, but the amount of increase varied in different strains. According to the results of clustering analysis and principal component analysis, after infection of Vero cells, the host cell protein profile of the heat-adapted strains was similar to that of the parental strains and the host cell protein profile of cold-adapted strains was similar to that of cell-adapted strains. It showed that 500 kinds of proteins presented inter-group difference in their expression, with 239 kinds being up-regulated proteins and 261 being down-regulated. The function of the up-regulated proteins were related to post-translational protein modification, while the functions of the down-regulated proteins were related to SRP-dependent cotranslational protein translocation/targeting to membrane and retrograde protein transport.  Conclusion   Virulence variations of enterovirus 71 may accompany thermal adaptive evolution, but its mechanism of action still awaits further investigation.

Abstract:
  Objective  To investigate the expression and role of programmed death ligand-1 (PD-L1) in a mouse model of necrotizing enterocolitis (NEC).  Methods  A total of 20 wild-type C57BL/6J mice were randomly assigned to the control and the model groups. Mice in the control group were breastfed, while mice in the model group were given lipopolysaccharide, formula feeding, hypoxia, and cold stimulation for NEC induction. Then, the intestines of the mice were collected in order to assess the pathological changes through HE staining, to examine PD-L1 expression and localization with immunofluorescence co-localization, and to evaluate intestinal PD-L1 expression with Western blot. Peripheral blood was collected for flow cytometry to examine leukocyte subpopulations and their PD-L1 expression. On the other hand, 14 PD-L1 (+/+) mice and 14 PD-L1 (−/−) mice were randomly divided into their respective genotype control groups and model groups. The same induction method as was already mentioned was adopted for the model groups. The intestines of the mice were collected for HE staining to evaluate the pathological change and peripheral blood was collected to examine the expression of inflammatory factors.   Results  The NEC mouse model was successfully constructed. PD-L1 was widely expressed in enterocytes and inflammatory cells in the mouse intestines and in T cells, monocytes, and neutrophils in peripheral blood. The expression of PD-L1 in NEC mouse intestines increased in comparison with that of the control group. In the peripheral blood of NEC mice, the proportion of T cells and monocytes and their PD-L1 expression showed no significant changes compared with those of the control group, while the proportion of neutrophils and their PD-L1 expression increased by about 140% and 150%, respectively, in comparison with those of the control group (P<0.05). According to the results of the PD-L1 gene mouse experiment, the control groups of PD-L1 (+/+) mice and PD-L1 (−/−) mice showed no significant difference in their intestinal conditions and serum inflammatory factor levels, while the PD-L1 (−/−) NEC mouse had worse intestinal pathological changes and increased mean pathological scores compared with those of PD-L1 (+/+) NEC mouse (P<0.05). In addition, serum interleukin (IL)-10 in PD-L1 (−/−) NEC mouse decreased by about 44% compared with that of PD-L1 (+/+) NEC mice, and chemokine (C-X-C motif) ligand 1/IL-6/IL-1β all increased by more than 25% (all P<0.05).   Conclusion  PD-L1 is widely expressed in inflammatory cells and enterocytes in mice. Knocking out PD-L1 aggravates the degree of NEC inflammation and intestinal pathological changes. PD-L1 plays a protective role by reducing inflammation in the pathogenesis of NEC, the mechanism of which may be related to the regulation of neutrophils/enterocytes.