Objective:To summarize and analyze the clinical characteristics of patients with Crohn′s disease (CD) complicated with small intestinal cancer (SBC) .Methods:Clinical data of patients with CD complicated with SBC treated in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine from May 2018 to September 2022 were collected and analyzed retrospectively, including general data, clinical features (lesion location, disease behavior and complications, etc.), CD-related history, tumor features, diagnosis, treatment and prognosis. The cases of CD complicated with SBC published in PubMed database up to March 2022 were searched, and the literatures were reviewed and summarized.Results:There were 7 patients with CD complicated with SBC in our hospital, including 5 males and 2 females. Of the 7 patients, 6 patients were small intestinal adenocarcinoma and 1 patient was high-grade intraepithelial neoplasia. All the lesions involved ileum with stenosis. Tumors in only 2 cases of tumors were found by imaging examination. Before the diagnosis of SBC, the drugs and duration of CD-related treatment were different in 7 patients. SBC was mainly treated by surgery, supplemented by chemotherapy and CD-related treatment. No tumor recurrence was found in 5 patients after treatment, 1 patient had tumor recurrence 7 months after operation, and suspected tumor recurrence 3 years after the second operation. One patient ws lost during follow-up. Seven literatures were retrieved.Conclusion:Most of the patients with CD complicated with PBC are male, and ileal involvement is more common. Small intestinal adenocarcinoma and lymphoma are the most common tumor types. The ability of imaging examination to detect CD-SBC is limited.

Objective:To summarize and analyze the clinical characteristics of patients with Crohn′s disease (CD) complicated with small intestinal cancer (SBC) .Methods:Clinical data of patients with CD complicated with SBC treated in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine from May 2018 to September 2022 were collected and analyzed retrospectively, including general data, clinical features (lesion location, disease behavior and complications, etc.), CD-related history, tumor features, diagnosis, treatment and prognosis. The cases of CD complicated with SBC published in PubMed database up to March 2022 were searched, and the literatures were reviewed and summarized.Results:There were 7 patients with CD complicated with SBC in our hospital, including 5 males and 2 females. Of the 7 patients, 6 patients were small intestinal adenocarcinoma and 1 patient was high-grade intraepithelial neoplasia. All the lesions involved ileum with stenosis. Tumors in only 2 cases of tumors were found by imaging examination. Before the diagnosis of SBC, the drugs and duration of CD-related treatment were different in 7 patients. SBC was mainly treated by surgery, supplemented by chemotherapy and CD-related treatment. No tumor recurrence was found in 5 patients after treatment, 1 patient had tumor recurrence 7 months after operation, and suspected tumor recurrence 3 years after the second operation. One patient ws lost during follow-up. Seven literatures were retrieved.Conclusion:Most of the patients with CD complicated with PBC are male, and ileal involvement is more common. Small intestinal adenocarcinoma and lymphoma are the most common tumor types. The ability of imaging examination to detect CD-SBC is limited.

This study aims to investigate the effect of transmembrane protein angiotensin converting enzyme 2 (ACE2) on the prognosis of breast cancer and its potential mechanism.Public databases were used to analyze ACE2 expression and its relationship with clinicopathological features and prognosis of breast cancer patients, combined with in vitro experiments to analyze the mechanism of action and immune relevance of ACE2 in breast cancer.Results showed that the expression of ACE2 in breast cancer tissues was significantly lower than that in normal breast tissues, and that its expression was negatively correlated with age, M stage and N1mi stage of breast cancer patients (P < 0.05).Patients with Luminal type breast cancer with high ACE2 expression had poor prognosis, while in the triple-negative breast cancer (TNBC) subtype, ACE2 showed different prognostic significance.In addition, ACE2 is closely associated with the metabolic and immune microenvironment of tumor tissue.In vitro experiments have shown that ACE2 is lowly expressed in MDA-MB-231 cells and may inhibit cell progress by downregulating matrix metalloproteinase 2（MMP2）.The results suggest that the low expression of ACE2 in breast cancer is closely associated with patient prognosis as well as metabolic and immune microenvironment, and that ACE2 may inhibit TNBC cell progress through the MMP2 pathway.

Objective:To evaluate the treatment persistence and long-time safety of infliximab (IFX) in the real-world in Chinese patients with Crohn′s disease (CD).Methods:From January 2009 to December 2021, at Sir Run Run Shaw Hospital, School of medicine, Zhejiang University, the clinical data of 1 309 patients with CD and treated with IFX were retrospectively analyzed, which included baseline data (gender, age at diagnosis, follow-up time, etc.), usage of IFX (the duration of treatment and situation of discontinuation) and adverse effects of IFX. Kaplan-Meier method was used to calculate the rate of consistent use of IFX and Cox regression was performed to analyze the influencing factors of treatment persistence. The chi-square test was used to analyze the associations between different factors and safety outcomes.Results:Among 1 309 patients, 936 (71.5%) were male, age at diagnosis was 28.7 years (28.1 years, 29.3 years). The follow-up time was 3.9 years (3.7 years, 4.0 years). The longest time of IFX treatment was 9.4 years. During the follow-up period, a total of 421 (32.2%) patients discontinued use of IFX and the sustained use of IFX at year 1, 3, 5 and 10 were 84.0%, 65.8%, 56.7% and 30.9% respectively. The results of Cox regression analysis revealed that patients with perianal lesions had an increased rate of sustained use of IFX ( HR(95% confidence interval) 0.75 (0.61, 0.92), P=0.006), while patients with adverse reactions had a decreased rate of sustained use of IFX ( HR(95% confidence interval) 1.23(1.01, 1.50), P=0.038). A total of 445 patients experienced adverse events, with an incidence rate of 34.0% (445/1 309). The acute infusion reaction was the most common side with an incidence rate of 13.7% (179/1 309), of which the rate of severe acute infusion reaction was 2.8% (5/1 309). The rate of infection was 10.5% (138/1 309), among which the rate of severe infection was 2.6% (34/1 309), and the rate of special pathogens infection was 5.5% (72/1 309). The rate of tuberculosis infection was 1.0% (13/1 309), and the most common affected site was the lungs (10 cases). The incidence of skin lesions (non-allergic, non-infectious and non-tumor skin) was 6.9% (90/1 309). The incidence of tumor was 1.1% (14/1 309). Patients who discontinued IFX due to adverse reactions accounted for 20.7% (92/445) of the patients with adverse reactions, among them patients who discontinued IFX due to acute infusion reaction, infections, neoplasms, delayed infusion reaction, skin lesions, abnormal liver function, hematological disorder, acute pancreatitis, joint pain and seizure accounted for 47.8% (44/92), 18.5% (17/92), 8.7% (8/92), 6.5% (6/92), 5.4% (5/92), 5.4% (5/92), 3.3% (3/92), 2.2% (2/92), 1.1% (1/92) and 1.1% (1/92), respectively. Among 14 patients with tumor, 11 were malignant tumors, 1 case of chronic leukemia was related with IFX. Multi-round of IFX treatment increased the risk of acute infusion reaction and severe acute infusion reaction, combination of immunosuppressants decreased the risk of liver injury, and IFX treatment for more than 1 year increased the risk of skin lesions ( χ2=6.16, 11.30, 18.20 and 9.47; P=0.013, =0.001, <0.001, =0.002). Conclusions:The rate of constant use of IFX is relatively high in Chinese Crohn′s disease patients. The long-term safety is good. Clinicians should pay more attention on the safety of patients receiving multiple rounds and long courses of IFX treatment.

Objective:To summarize the clinical characteristics of ulcerative colitis (UC) with primary sclerosing cholangitis (PSC) .Methods:The clinical characteristics, diagnosis and treatment of 6 UC patients with PSC admitted to Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine from May 2017 to May 2022 were analyzed retrospectively. Meanwhile "ulcerative colitis", "primary sclerosing colangitis" were used as retrieval words to search associated literatures from CNKI, Wanfang Data, and PubMed databases as of August 2022. Relevant literatures were reviewed and summarized.Results:There were 6 UC patients complicated with PSC, included 4 males and 2 females. Four UC cases were diagnosed before PSC and other 2 cases were diagnosed simultaneously. Six cases were all extensive colonic type (E3), 2 patients were rectal sparing, and 4 patients had backwash ileitis. Five patients had elevated alkaline phosphatase (AKP) levels. All the patients received oral treatment with ursodeoxycholic acid (UDCA). Two patients with concurrent cholangiocarcinoma died within one year of follow-up. A total of 75 relevant literatures were retrieved.Conclusions:Patients with UC complicated with PSC are often diagnosed with UC before PSC, and PSC is often discovered due to abnormal liver function. The main clinical manifestations include jaundice, abdominal pain and diarrhea, and some may be accompanied by symptoms such as fever, vomiting, and fatigue. There are clinical characteristics such as elevated AKP, pancolitis, rectal sparing, and backwash ileitis. UC complicated with PSC is more likely to develop cholangiocarcinoma.

Objective:To summarize the clinical characteristics of patients with ulcerative colitis (UC) who developed joint manifestations after receiving vedolizumab (VDZ) .Methods:Patients with UC who developed joint manifestations after receiving VDZ at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from November 2020 to October 2021 were retrospectively included. Cases previously reported in the literature were revieved.Results:Four patients with UC were included, none of whom had extraintestinal manifestations previously. After receiving VDZ, four patients developed joint pain, and three had polyarticular involvement. Three patients had elevated C-reactive protein (CRP) and ultrasonography indicated joint effusion. No one discontinued due to the worsening of arthropathy and the joint manifestations all improved after treatment.Conclusion:Arthropathy may be induced after receiving VDZ, manifesting as elevated CRP, joint effusion, and bone marrow edema. After treatment with nonsteroidal anti-inflammatory drugs, glucocorticoids, immunosuppressants, or biological agents, most of the patients had a favorable prognosis.

Objective:To summarize the clinical characteristics of ulcerative colitis (UC) with primary sclerosing cholangitis (PSC) .Methods:The clinical characteristics, diagnosis and treatment of 6 UC patients with PSC admitted to Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine from May 2017 to May 2022 were analyzed retrospectively. Meanwhile "ulcerative colitis", "primary sclerosing colangitis" were used as retrieval words to search associated literatures from CNKI, Wanfang Data, and PubMed databases as of August 2022. Relevant literatures were reviewed and summarized.Results:There were 6 UC patients complicated with PSC, included 4 males and 2 females. Four UC cases were diagnosed before PSC and other 2 cases were diagnosed simultaneously. Six cases were all extensive colonic type (E3), 2 patients were rectal sparing, and 4 patients had backwash ileitis. Five patients had elevated alkaline phosphatase (AKP) levels. All the patients received oral treatment with ursodeoxycholic acid (UDCA). Two patients with concurrent cholangiocarcinoma died within one year of follow-up. A total of 75 relevant literatures were retrieved.Conclusions:Patients with UC complicated with PSC are often diagnosed with UC before PSC, and PSC is often discovered due to abnormal liver function. The main clinical manifestations include jaundice, abdominal pain and diarrhea, and some may be accompanied by symptoms such as fever, vomiting, and fatigue. There are clinical characteristics such as elevated AKP, pancolitis, rectal sparing, and backwash ileitis. UC complicated with PSC is more likely to develop cholangiocarcinoma.

Objective:To summarize the clinical characteristics of patients with ulcerative colitis (UC) who developed joint manifestations after receiving vedolizumab (VDZ) .Methods:Patients with UC who developed joint manifestations after receiving VDZ at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from November 2020 to October 2021 were retrospectively included. Cases previously reported in the literature were revieved.Results:Four patients with UC were included, none of whom had extraintestinal manifestations previously. After receiving VDZ, four patients developed joint pain, and three had polyarticular involvement. Three patients had elevated C-reactive protein (CRP) and ultrasonography indicated joint effusion. No one discontinued due to the worsening of arthropathy and the joint manifestations all improved after treatment.Conclusion:Arthropathy may be induced after receiving VDZ, manifesting as elevated CRP, joint effusion, and bone marrow edema. After treatment with nonsteroidal anti-inflammatory drugs, glucocorticoids, immunosuppressants, or biological agents, most of the patients had a favorable prognosis.

There are diverse pathogenic factors for intestinal inflammation, but the process of activated immune response is similar. Ubiquitination, a widespread mechanism of protein post-translational modification in cells, plays a regulatory role in signal transduction, transcriptional regulation and protein kinase activation. Ubiquitination of proteins involving in immune inflammation signaling pathways determines the balance between inflammatory mediators and anti-inflammatory factors, thus affects the progression and outcome of intestinal inflammation. This article reviews the ubiquitination modification of protein, which will help to deeply understand the pathophysiological process of intestinal inflammation, and provide a theoretical reference for the research and development of targeted new drugs in precision therapy.

There are diverse pathogenic factors for intestinal inflammation, but the process of activated immune response is similar. Ubiquitination, a widespread mechanism of protein post-translational modification in cells, plays a regulatory role in signal transduction, transcriptional regulation and protein kinase activation. Ubiquitination of proteins involving in immune inflammation signaling pathways determines the balance between inflammatory mediators and anti-inflammatory factors, thus affects the progression and outcome of intestinal inflammation. This article reviews the ubiquitination modification of protein, which will help to deeply understand the pathophysiological process of intestinal inflammation, and provide a theoretical reference for the research and development of targeted new drugs in precision therapy.