Objective A feasible and stable mouse model of thoracic aortic dissection(TAD)combined with acute lung injury(ALI)was established using β-aminopropionitrile monofumarate(BAPN)1 g/(kg·d)administered in drinking water.The mouse model of TAD combined with acute lung injury(ALI)was established to provide a rational animal model to study TAD combined with ALI.Methods Forty-five SPF-grade 3-week-old C57BL/6J male mice were selected and randomly allocated to a CON group(normal dietary water;15 mice)or BAPN group(administration in sterile water at 1 g/(kg·d);30 mice)for 4 weeks.During the experimental period,the general condition and modeling rate of mice were observed.TAD model mice were validated,and the BAPN group was divided into TAD and non-TAD groups by measuring the maximum diameter of the thoracic aorta and HE staining of aortic tissues.HE pathological staining,the wet/dry weight(W/D)ratio,total protein level in bronchioalveolar lavage fluid(BALF),and interleukin(IL)-1 β,IL-6,and tumor necrosis factor-α(TNF-α)in BALF)were used to validate the TAD combined ALI model in mice.Results BAPN treatment significantly delayed the increase in body mass and water intake of mice.Compared with CON and non-TAD groups,the maximum diameter of the thoracic aorta of mice in the TAD group was significantly thickened(P＜0.05).HE staining of the aorta showed significant thickening of the middle aortic layer,and the structure of the aortic wall was damaged and disordered.HE staining of lung tissues showed significant interstitial edema and inflammatory exudation accompanied by enlargement of alveolar lumen,alveolar wall epithelial exfoliation and hyaline membrane formation,and a significant increase in the pathological scores of lung injury(P＜0.05).Total protein levels and expression of IL-1β,IL-6,and TNF-α in lung tissue,W/D ratio,and BALF were also significantly increased(P＜0.05),whereas no significant difference was observed in the above indexes between the other two groups.Conclusions A mouse model of thoracic aortic dissection combined with acute lung injury can be established by BAPN administration in drinking water.

Objective To discuss the clinical features,differential diagnosis and complication treatment of a patient with genetic visceral myopathy.Methods Medical history,physical examination and laboratory results of the patient were collected in detail.The pathology of previous surgery was reviewed.The patient's peripheral blood DNA was extracted and submitted for whole-exome sequencing.Subsequent Sanger sequencing was used to complete the pedigree verification of the mutation site.Results The patient was a young female presented with repeated in-complete intestinal obstruction since early childhood.She used to be misdiagnosed as Hirschsprung's disease for a long period and underwent multiple gastrointestinal segment resections.Her intestinal obstruction symptoms were temporarily relieved by surgeries,but severe diarrhea,mucus and bloody stools and malnutrition gradually occurred after the last operation.The patient had bacterial overgrowth in small intestinal tract and followed by intestinal op-portunistic infections secondary to chronic intestinal pseudo-obstruction.The symptoms improved after anti-infection and enteral element diet treatment.Further pathological consultation and whole-exome gene sequencing confirmed the diagnosis of visceral myopathy related to ATCG2 R148L mutation.Conclusions Patients with early onset of chronic intestinal pseudo-obstruction and have poor response to conventional treatment are recommended to perform genetic test.The patients with hereditary visceral myopathy are susceptible to opportunistic intestinal infection.At-tentions should also be paid to the prevention and treatment of complications to avoid unnecessary surgery.

Objective:Summarize and analyze the clinical features of immune checkpoint inhibitor (ICI)-related colitis.Methods:From January 2019 to September 2020, the clinical data of 8 patients with ICI-related colitis from Peking Union Medical College Hospital were retrospectively collected and including the onset of ICI-related colitis, clinical symptoms, endoscopic and pathological findings, treatment, comorbidities and resuming of ICI. Independent sample t test was used for statistical analysis. Results:Eight patients were all male, and the median age (range) was 66 years old (55 to 74 years old), 7 cases were diagnosed with stage Ⅳ lung cancer and 1 case was diagnosed with stage Ⅲc pyelo-carcinoma. Among 8 patients, 4 cases of ICI-related colitis occurred during combination of anti-programmed death-1 (PD-1) treatment and chemotherapy, 2 cases occurred during anti-PD-1 monotherapy after combination of anti-PD-1 treatment and chemotherapy, and 2 cases occurred after anti-PD-1 monotherapy. The median time (range) was 44 d (27 to 128 d) from initial anti-PD-1 treatment to the onset of ICI-related colitis and the median time (range) was 8 d (6 to 35 d) from last anti-PD-1 treatment to onset of ICI-related colitis. The ICI efficacy of 4 patients had partial response, 2 patients had stable disease, 1 patient had disease progression, and 1 patient′s condition was not assessed. All 8 patients had moderate to severe extensive colitis. The main clinical manifestation was diarrhea (5/8), 3 patients accompanied by abdominal pain. The endoscopic findings were diffuse mucosal erosion, accompanied by ulcer in 2 patients. The main pathologic findings were cryptitis or crypt abscess, accompanied by apoptosis in 2 patients. Eight patients were all treated with glucocorticoids, among them 2 patients were further treated with biologics, due to the insufficient efficacy of glucocorticoid treatment, 4 patients had opportunistic infections. The initial prednisone dose for patients with opportunistic infections and patients without opportunistic infections was (85.00±52.60) and (60.00±23.09) mg, respectively. The prednisone treatment course was (8.75±4.03) and (7.50±3.11) weeks, respectively, and the differences were not statistically significant (both P>0.05). The colitis relapsed in all 3 patients after resuming of ICI. Conclusions:ICI-related colitis had corresponding ICI treatment history and clinical, endoscopic, and histopathological features. Glucocorticoid is the main treatment, and it is prone to relapse after resuming of ICI.

BACKGROUND: Endoscopic biopsy can underestimate gastric malignancies as low-grade intraepithelial neoplasia (LGIN). Definitively diagnosed LGIN would progress. This study aimed to evaluate predictive factors to identify malignancies misdiagnosed as LGIN by biopsy and LGIN at high risk of progression. METHODS: The clinical records of patients diagnosed with gastric LGIN by endoscopic biopsy who underwent at least two endoscopies during the first year of follow-up between 2007 and 2017 were retrospectively collected. Three endoscopists reviewed photographs of the initial endoscopy, described lesion characteristics, and made endoscopic diagnoses. Logistic regression was used to analyze predictors to identify malignancies underestimated as LGIN. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of these predictors. Patient clinical outcomes of follow-up >1 year were collected. Kaplan-Meier estimates with log-rank tests and Cox proportional hazards regression were used to analyze predictors of progression. RESULTS: Overall, 48 of 182 (26.4%) patients were proven to have malignancies. A single lesion, a large lesion size, and marked intestinal metaplasia (IM) were independent predictors of initially misdiagnosed malignancies. The area under the curve of these predictors was 0.871, with a sensitivity of 68.7% and specificity of 92.5%. Twelve of 98 patients (12.2%) progressed during the 33-month median follow-up period. A whitish appearance, irregular margins, marked IM, and histological diagnosis of LGIN more than twice within the first year were predictors for progression. CONCLUSIONS Lesions diagnosed as LGIN by biopsy with marked IM and other predictors above should be prudently treated for high potential to be malignancies or progress. Endoscopic follow-up with repeated biopsies within the first year is recommended.
Biopsy ; Carcinoma in Situ ; Endoscopy ; Humans ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/diagnosis*

Objective:To investigate the effect and mechanism of short-chain fatty acids (SCFAs) on the side-effect of tacrolimus on blood glucose.Methods:The C57BL/6 mice were treated with tacrolimus orally (10 mg/kg, tacrolimus group), tacrolimus plus 150 mmol/L sodium butyrate and isovalerate mixed solution (SCFAs group), broad-spectrum antibiotics (antibiotic group), and tacrolimus plus broad-spectrum antibiotics (tac&abx group). After 8 weeks intervention, the fasting blood glucose (FBG), oral glucose tolerance test (OGTT), hemoglobin A1C (HbA1c) were tested as indicators of glucose metabolism, and the gut microbiota, SCFAs concentration in the ileocecal, serum glucagon-like peptide-1 (GLP-1), fasting serum insulin, and GLP-1 expression in intestinal mucosa were performed for intestinal-glucose metabolism mechanism.Results:The FBG and HbA1c were significantly increased in tacrolimus group[(7.31±0.97)mmol/L, (8.34±1.12)%] than control group [(5.23±0.30)mmol/L, (4.32±0.80)%, all P<0.05], which remained normal in antibiotic group [(4.92±0.31)mmol/L, (5.61±0.98)%)], tac&abx group[(5.95±0.37)mmol/L, (4.56±0.26)%] and SCFAs groups [(5.87±0.68)mmol/L, (5.07±1.79)%]. The OGTT in the tacrolimus group showed glucose tolerance impairment, while other groups remained normal. The ileocecal butyric acid and isovaleric acid concentrations in the tacrolimus group were (722.3±262.2) μg/g and (10.0±5.1)μg/g, lower than the control group[ (1 321.3±165.5) μg/g, (19.7±3.6)μg/g, P<0.05]. The above acids in the SCFAs group remained normal as in the control group [(1 375.7±451.6) μg/g, (24.5±11.5)μg/g)]. The fasting serum insulin in the tacrolimus group decreased significantly to (3.2 ± 0.6)mIU/L, compared with control[ (4.4±0.9) mIU/L]and SCFAs groups [(7.0±1.1) mIU/L]. The GLP-1 test indicated a significant decrease in the tacrolimus group[ (4.7±2.9)pg/ml, P<0.05] compared with the SCFAs group and control group [(42.5±19.9) pg/ml, (33.1±9.1) pg/ml]. Conclusions:Tacrolimus affects glucose metabolism through the SCFAs-associated GLP-1 pathway in the intestine, and oral supplementation with mixed SCFAs provides a new insight for the prevention and treatment of tacrolimus-induced hyperglycemia in transplant recipients.

Objective:To explore the endoscopic features of early gastric cancer (EGC) related to non-curative endoscopic resection, and to construct an assessment model to quantify the risk of non-curative resection.Methods:From August 2006 to October 2019, 378 lesions that underwent endoscopic resection and were diagnosed pathological as EGC in the Department of Gastroenterology, Peking Union Medical College Hospital were included in this case-control study.Seventy-eight (20.6%) non-curative resection lesions were included in the observation group, and 234 lesions which selected from 300 lesions of curative resection were included in the control group according to the difference of operation year ±1 with the observation group, and the ratio of 1∶3 of the observation group to the control group. Univariate and multivariate logistic regression analysis were performed to explore the risk factors for non-curative resection. The independent risk factor with the minimum β coefficient was assigned 1 point, and the remaining factors were scored according to the ratio of their β coefficient to the minimum. A predictive model was established to analyze the 378 lesions.The non-curative resection rates of lesions of different scores were calculated. Results:Univariate analysis showed that the lesion diameter, the location, redness, ulcer or ulcer scar, fold interruption, fold entanglement, and invasion depth observed with endoscopic ultrasonography (EUS) were associated with non-curative resection of EGC lesions ( P<0.05), and contact or spontaneous bleeding may be associated with non-curative resection ( P=0.068). Multivariate logistic regression analysis showed that submucosal involvement (VS confined to the mucosa: β=0.901, P=0.011, OR=2.46, 95% CI: 1.23-4.92), lesion diameter of 3-<5 cm (VS <3 cm: β=0.723, P=0.038, OR=2.06, 95% CI: 1.04-4.09), lesion diameter of ≥5 cm (VS <3 cm: β=2.078, P=0.003, OR=7.99, 95% CI: 2.02-31.66), location in the upper 1/3 of the stomach (VS lower 1/3: β=1.540, P<0.001, OR=4.66, 95% CI: 2.30-9.45), and fold interruption ( β=2.287, P=0.008, OR=1.93, 95% CI: 0.95-3.93) were independent risk factors for non-curative resection of EGC lesions. The factor of lesion diameter of 3-<5 cm and submucosal involvement were assigned 1 point respectively, location in the upper 1/3 of the stomach was assigned 2 points, diameter of ≥5 cm and fold interruption were assigned 3 points respectively, and other factors were assigned 0 point. Then the analysis of 378 lesions showed that the probability of non-curative resection at ≥2 points was 41.9% (37/93), 4 times as much as that at 0 [11.5% (25/217)]. Conclusion:EGC lesions with diameter ≥3 cm, located in the upper 1/3 of the stomach, interrupted folds or submucosal involvement are highly related to non-curative resection. The predictive model based on these factors achieves satisfactory efficacy, but it still needs further validation in larger cohorts.

Objective:To analyze clinical characteristics and monitor microbiome changes in patients with anti-PD-1 associated colitis.Methods:Two patients with non-small cell lung cancer who developed colitis after treated with anti-PD-1 antibodies were retrospectively analyzed in Peking Union Medical College Hospital from January 2019 to January 2020. The clinical symptoms, endoscopic and pathological manifestations, as well microbiome changes were analyzed and compared during pre-treatment, post-treatment and relapse.Results:The main clinical manifestations included diarrhea, elevated inflammatory indicators, colonic mucosal diffuse hyperemic edema with erosion by endoscopy. Changes in the structure of crypts were common pathological characteristics. Glucocorticoids were effective agents, which achieved clinical remission and mucosal healing. The microbiome composition of OTUs was different. After glucocorticoid treatment, the alpha diversity Observed species, Shannon, Simpson, Chao1, ACE indexes all decreased. The Firmicutesdecreased with Bacteroidetesincreasing in phylum level; while the Bacteroides increased with Ruminococcaceaedecreasing in genus level. Lactobacilluswas the potentially beneficial genus. Conclusion:Patients developing anti-PD-1 associated colitis have characteristic clinical and pathological manifestations. Glucocorticoids are effective treatment. The fecal microbiome diversity, relative abundance of major phylum and genus have changed after treatment.

Objective:To investigate the clinicopathological characteristics and the risk factors of lymph node metastasis(LNM) of undifferentiated early gastric cancers(EGCs) in elderly patients.Methods:The elderly patients(≥65 years old) who underwent radical gastrectomy with lymph node dissection and were diagnosed as having EGCs in Peking Union Medical College Hospital from January 2010 to August 2019 were included. The clinicopathological characteristics of undifferentiated EGCs(namely signet ring cell EGCs and poorly differentiated EGCs) were compared with those of differentiated EGCs, and the risk factors for LNM of undifferentiated EGCs in the elderly patients were analyzed with logistic regression.Results:Data of 165 elderly EGCs patients were reviewed, including 82 undifferentiated EGCs (11 signet ring cell and 71 poorly differentiated) and 83 differentiated EGCs. The overall LNM incidence was 9.1% (15/165) in elderly EGCs patients, 4.8% (4/83) and 13.4% (11/82) in differentiated and undifferentiated EGCs, respectively. Of all undifferentiated EGCs, the LNM incidence in poorly differentiated EGCs was 15.5%(11/71), and none of 11 signet ring cell EGCs had LNM. Depth of tumor invasion( P=0.019), tumor size( P=0.006), combination of ulceration( P=0.006), depressed gross type( P=0.003) were found to be associated with LNM in elderly undifferentiated EGCs patients under univariate analysis. Multivariate analysis revealed that submucosal invasion( OR=11.98, 95% CI: 1.17-122.84, P=0.037) and tumor size >2 cm ( OR=11.95, 95% CI: 1.88-76.07, P=0.009) were independent risk factors for LNM in elderly undifferentiated EGCs patients. All elderly undifferentiated EGCs patients who met the criteria for expanded indications had no LNM. Conclusion:Submucosal invasion and tumor size >2 cm are independent risk factors for LNM in elderly undifferentiated EGCs patients. The elderly EGCs patients who met the criteria for expanded indications are suitable for endoscopic submucosal dissection.

Objective    To evaluate the prognosis of interventional treatment with covered stent graft for retrograde Stanford type A aortic dissection and intramural hematoma by single-arm meta-analysis. Methods    Related studies on treating retrograde Stanford type A aortic dissection and intramural hematoma with covered stent graft were retrieved from the databases by computer, including PubMed, EMbase, The Cochrane Library, Wanfang Data, VIP, CNKI and CBM, from inception to January 2020. Literatures were screened by researchers step by step according to the predefined inclusion and exclusion criteria. Quality of the enrolled literatures was evaluated, and data were extracted from the included studies. Afterwards, single-arm meta-analysis was carried out by the R3.6.3 software. Results    A total of 12 English and 5 Chinese studies were included, which were all case series, and the quality of all literatures was moderate evaluated by Newcastle-Ottawa Scale (NOS). After analyzing the clinical prognosis of 260 patients, the 30-day mortality was 6% (95%CI 0.04 to 0.11, P=0.97), the late mortality was 8% (95%CI 0.05 to 0.14, P=0.78), the incidence of endoleak was 21% (95%CI 0.16 to 0.29, P=0.06), the incidence of stroke was 5% (95%CI 0.03 to 0.09, P=0.99), the incidence of new aortic dissection was 7% (95%CI 0.04 to 0.11, P=0.96), the incidence of dissection progression was 10% (95%CI 0.07 to 0.16, P=0.24), and the absorption rate of intramural hematoma was 84% (95%CI 0.37 to 1.00, P<0.01). Conclusion    Interventional treatment with covered stent graft for retrograde Stanford type A aortic dissection and intramural hematoma can obtain good early treatment results for some patients, and can be used as a safe and effective treatment for aged patient with high risk who cannot tolerate surgery. Endoleak, stroke and new aortic dissection are the early serious complications of this method.

Mucor infection is rarely reported in non-immunocompromised population, especially in isolated gastrointestinal tracts. IgG₄-related diseases (IgG₄-RD) have been recognized in recent years, but secondary causes of IgG₄ elevation should be differentiated. We reported a young man with duodenal mass and ulcer and high serum IgG₄ level. Histological biopsy of the mass revealed positive mucor mycelium and infiltration of IgG₄ positive plasma cells. Serum IgG₄ decreased to normal range after surgical resection and systemic antifungal treatment. This case suggests that isolated mucor mycosis infection can develop in the digestive tract and mimics as IgG₄-related disease.