Objective:To investigate the expression characteristics of mucin 5B (MUC5B) protein and programmed cell death factor 4 (PDCD4) protein in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram model for prognosis prediction.Methods:Clinical data of 100 patients who underwent radical surgical resection and were diagnosed as ICC by postoperative pathology from September 2009 to September 2020 in the Third Affiliated Hospital of Wenzhou Medical University were retrospectively selected, including 46 males and 54 females, aged (56.9±12.2) years old. Immunohistochemistry was used to detect the expression of MUC5B and PDCD4 protein in 100 cases of ICC and corresponding adjacent tissues respectively, and the relationship between them and clinicopathological factors of ICC patients was analyzed. Univariate and multivariate Cox regression analysis were performed to analyze the influencing factors on postoperative prognosis of ICC patients. The nomogram model was constructed using rms package and performed internal verification.Results:The positive expression rate of MUC5B protein in ICC was 76.0% (76/100), which was higher than that in para-cancer tissues 27.0%(27/100), and the difference was statistically significant ( χ2=11.33, P=0.015). While the positive expression rate of PDCD4 protein in ICC was 21.0%(21/100), which was lower than that in normal tissues 73.0% (73/100), and the difference was statistically significant ( χ2=15.57, P=0.007). Multivariate Cox regression analysis showed that ICC patients with carbohydrate antigen 19-9>37 kU/L, tumor length>5 cm, tumor TNM stage Ⅱ/Ⅲ, tumor medium/low differentiation, MUC5B positive expression, and PDCD4 negative expression had a high risk of short survival after resection (all P<0.05). The nomogram model was constructed based on the above indicators, and the C-index was 0.801. The postoperative survival calibration curve showed that the high predictive survival fit of the nomogram model, and the area under the receiver operating characteristic curve was 0.862. Conclusions:Positive expression of MUC5B protein and negative expression of PDCD4 protein in ICC tissue suggest poor prognosis of ICC patients. The nomogram model constructed on the basis of MUC5B and PDCD4 protein is well distinguished and has ideal predictive efficacy.

Objective:To evaluate the effects of hemoclips on preventing delayed bleeding for early gastric cancer (EGC) after endoscopic submucosal dissection (ESD).Methods:Clinical data of 459 patients who underwent ESD for EGC in Beijing Friendship Hospital from June 2013 to August 2020 were collected retrospectively. Patients were divided into group A (hemoclip group, n=162) and group B (non-hemoclip group, n=297) according to whether preventive hemostatic clip treatment was performed after resection. Delayed bleeding within 2 weeks after ESD was observed. Univariate analysis and subgroup analysis were conducted for the delayed bleeding incidence and clinicopathological features. Results:Delayed bleeding incidences of group A and group B were 3.1% (5/162) and 8.1% (24/297) with significant difference between the two groups ( χ2=4.418, P=0.036). Subgroup analysis showed that there were significant differences in the delayed bleeding incidence between the two groups when the diameter of the tumor >20 mm [3.5% (2/57) VS 15.3% (13/85), χ2=5.016, P=0.025], the tumor located in the lower part of the stomach [1.0% (1/97) VS 10.4% (20/192), χ2=8.425, P=0.004], and the depth of tumor invasion was M/SM1 [3.2% (5/157) VS 8.1% (23/285), χ2=4.072, P=0.044]. There were no significant differences in the delayed bleeding incidence between group A and group B when the diameter of the tumor ≤20 mm, the tumor located in the upper/medial part of the stomach and the depth of tumor invasion was SM2 ( P>0.05). Conclusion:Hemoclips can prevent delayed bleeding after ESD for EGC, which is mainly observed in a tumor of diameter >20 mm, located in the lower part of the stomach and M/SM1 tumor invasion. It has little effect on the prevention when the tumor diameter ≤20 mm and located in the upper/medial part of the stomach.

Objective:To analyze the clinicopathological features of de novo early colorectal cancer and to evaluate the efficacy of endoscopic treatment.Methods:Patients with de novo early colorectal cancer who underwent endoscopic resection in Beijing Friendship Hospital, Capital Medical University from June 2020 to May 2022 were enrolled. The baseline data, endoscopic manifestations, treatment methods, postoperative pathological results and prognosis of the patients were collected retrospectively.Results:A total of 33 patients with de novo early colorectal cancer were enrolled with the age of 62.67 ± 8.62 years, and the male to female ratio was 7.25∶1. The long diameter of lesions was 0.96 ± 0.36 cm. The lesion morphology was mainly superficial phenotype (type 0-Ⅱ), accounting for 72.7% (24/33). Endoscopic submucosal dissection (ESD) was performed in 29 cases and endoscopic mucosal resection (EMR) was performed in 4 cases. Postoperative pathology showed that 11 cases (33.3%) were well differentiated tubular adenocarcinoma, of which the superficial submucosal layer was invaded in 2 cases. Twenty cases (60.6%) were moderately differentiated tubular adenocarcinoma, of which the superficial submucosa layer was invaded in 5 cases and the deep submucosa layer in 15 cases. Two cases (6.1%) were moderately-poorly differentiated tubular adenocarcinoma, where the deep submucosa layer was invaded in both. There was significant correlation between the depth of invasion and the degree of differentiation ( P<0.001), and moderately and moderately-poorly differentiated lesions were more likely to invade the deep submucosa layer. The en bloc resection rate was 100.0% (33/33), the complete resection rate was 97.0% (32/33), and the curative resection rate was 42.4% (14/33). Among the 19 patients who did not achieve curative resection, 13 patients received supplementary surgical treatment. No tumor residue or lymph node metastasis was found in the postoperative pathology. All patients were followed up for 3-25 months, and no signs of local recurrence or metastasis were found. Conclusion:Most de novo early colorectal cancers are superficial phenotype under endoscopy. The pathology is mainly moderately differentiated tubular adenocarcinoma. Endoscopic resection of de novo early colorectal cancer shows encouraging short-term efficacy.

This study aimed to investigate the efficacy and safety of apatinib plus programmed cell death protein 1 (PD-1) blockades for patients with metastatic colorectal cancer (CRC) who were refractory to the standard regimens. In this retrospective study, patients with metastatic CRC who received apatinib plus PD-1 blockades in clinical practice were included. The initial dosage of apatinib was 250 mg or 500 mg, and PD-1 blockades were comprised of camrelizumab, sintilimab and pembrolizumab. Efficacy and safety data were collected through the hospital’s electronic medical record system. From October 2018 to March 2022, a total of 43 patients with metastatic CRC were evaluated for efficacy and safety. The results showed an objective response rate of 25.6% (95% CI, 13.5%-41.2%) and a disease control rate of 72.1% (95% CI, 56.3%-84.7%). The median progression-free survival (PFS) of the cohort was 5.8 months (95% CI, 3.81-7.79), and the median overall survival (OS) was 10.3 months (95% CI, 5.75-14.85). The most common adverse reactions were fatigue (76.7%), hypertension (72.1%), diarrhea (62.8%), and hand-foot syndrome (51.2%).Multivariate Cox regression analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status and location of CRC (left or right-side) were independent factors to predict PFS of patients with metastatic CRC treated with the combination regimen. Consequently, the combination of apatinib and PD-1 blockades demonstrated potential efficacy and acceptable safety for patients with treatment-refractory metastatic CRC. This conclusion should be confirmed in prospective clinical trials subsequently.

Objective:To evaluate the efficacy and safety of rubber band traction-assisted endoscopic submucosal dissection (ESD).Methods:A total of 49 patients with rectal endocrine tumor who underwent ESD at Beijing Friendship Hospital Affiliated to Capital Medical University from January 2016 to December 2019 were reviewed. Thirty-two patients who underwent traditional ESD from January 2016 to May 2018 were assigned to the non-traction group. Seventeen patients who underwent the operation with a rubber band as auxiliary traction from June 2018 to December 2019 were assigned to the traction group. Basic information, ESD procedure time, complications were compared between the two groups.Results:There were no significant differences in age, gender or lesion size between the traction group and the non-traction group ( P>0.05). The ESD operation time of the traction group was significantly shorter than that of the non-traction group (13.76±5.71 min VS 22.99±10.32 min, t=-3.408, P=0.001). There were no postoperative complications in the traction group, but 3 cases of perforation occurred in the non-traction group. There was no significant difference in the incidence of perforation between the two groups ( P=0.542). Conclusion:Rubber band traction can safely improve the efficiency of ESD.

Acute cholecystitis is a common acute abdominal disease, and it can be classified into grade Ⅰ (mild), grade Ⅱ (moderate), and grade Ⅲ (severe) based on severity. Gallbladder drainage is an important treatment method for patients with severe disease conditions and a high surgical risk. Percutaneous transhepatic gallbladder drainage is commonly used in clinical practice and has a clinical success rate of more than 65%. With the development of endoscopic technology, some centers in China and globally have begun to apply endoscopic gallbladder drainage to the management of acute cholecystitis. This article introduces the methods of gallbladder drainage commonly used in clinical practice, such as percutaneous hepatic gallbladder drainage, endoscopic ultrasound-guided gallbladder drainage, endoscopic transpapillary gallbladder drainage, as well as the progress in endoscopic interventional treatment of acute cholecystitis in recent years.

Objective:To determine the accuracy and influencing factors for endoscopic ultrasound (EUS) in predicting the invasive depth of early gastric cancer (EGC).Methods:A retrospective analysis was conducted on data of patients with EGC who were staged T1 with EUS and were treated at Beijing Friendship Hospital from January 2014 to August 2020. The consistency between the invasive depth determined by EUS and postoperative pathology were compared, and the accuracy, the sensitivity and the specificity of EUS were calculated. Logistic regression model was used for univariate and multivariate analysis to explore the relevant factors that affected the accuracy of EUS.Results:A total of 380 lesions were included. While 301 intramucosal (T1a) lesions and 79 submucosal (T1b) lesions were detected with EUS, postoperative pathology diagnosed 320 T1a lesions and 60 T1b lesions. The accuracy of EUS in predicting the invasive depth of EGC was 77.1% (293/380), the sensitivity and the specificity were 83.4% (267/320) and 43.3% (26/60) respectively. Multivariate analysis indicated that the lesions located in the upper 1/3 of the stomach ( OR=2.272, 95% CI: 1.266-4.080, P=0.006), ≥20 mm in size ( OR=2.013, 95% CI: 1.200-3.377, P=0.008) and poorly differentiated cancer ( OR=2.090, 95% CI: 1.018-4.294, P=0.045) were the independent risk factors affecting the accuracy of EUS. Poorly differentiated EGC ( OR=4.046, 95% CI: 1.737-9.425, P=0.001) was the risk factor for over-staging of EUS. Conclusion:EUS is useful in predicting the invasive depth of EGC. Factors affecting the accuracy of EUS include location in the upper 1/3 of the stomach, ≥20 mm in size and poorly differentiated EGC. Additionally, poor differentiation is the risk factor for over-staging of EUS.

OBJECTIVE：To investigate the improvement effect of Tiarella polyphylla ethanol extract （TPME）on CCl 4-induced hepatic fibrosis in mice ，and to explore its possible mechanism preliminarily. METHODS ：Totally 60 male Kunming mice were randomly divided into normal group ，model group ，positive control group （colchicine 0.1 mg/kg），TPME low-dose ，medium-dose and high-dose groups （250，500，1 000 mg/kg）according to body weight ，with 10 mice in each group. Except for normal group ， other groups were given 20％ CCl4 olive oil solution intraperitoneally to induce hepatic fibrosis ，twice a week ，for consecutive 8 weeks. From the fifth week after modeling ，administration groups were given relevant medicine intragastrically ，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 4 weeks. Twelve hours after last administration ，the liver weight of mice in each group was measured and the liver index was calculated. The serum contents of ALT，AST，SOD，MDA，PC-Ⅲ，C-Ⅳ，LN，TNF-α and IL- 6 were determined. Western blot assay was used to detect the protein expression of α-SMA，TGF-β1 and Smad 3 in liver tissue. HE and Masson staining were used to observe the pathological changes of hepatic tissue. RESULTS ：Compared with normal group ，the liver index ，the activities of ALT and AST and the contents of MDA ， LN，PC- Ⅲ ，C- Ⅳ ，LN，TNF-α and IL- 6 in serum were increased significantly ， while the activity of SOD was 6011） decreased significantly in model group （P＜0.01）；the protein expression of α-SMA，TGF-β1 and Smad 3 in liver tissues were hfjsznd8@126.com increased significantly （P＜0.01）. Obvious fibrosis lesions was observed in liver tissue. Compared with model group ，the live indexes ，the activities of ALT and AST ，the contents of MDA，PC-Ⅲ，C-Ⅳ，LN，TNF-α and IL-6 in serum were decreased significantly in positive control group and TPME groups ， while the activities of SOD were increased significantly （P＜0.05 or P＜0.01）. The protein expression of α-SMA，TGF-β1 and Smad3 in liver tissue were decreased significantly （P＜0.05 or P＜0.01），and liver fibrosis was improved to different extent. Compared with TPME low-dose group ，the contents of PC- Ⅲ，LN and IL- 6 in serum ，protein expression of TGF-β1 and Smad 3 in liver tissue were decreased significantly in TPME high-dose group （P＜0.05）. CONCLUSIONS ：TPME can improve hepatic fibrosis induced by CCl 4 in mice ，the mechanism of which may be associated with the inhibition of collagen synthesis and oxidative stress，the reduction of inflammatory factors ，and the down-regulation of the expression α-SMA and relative proteins of TGF-β1/ Smad signal pathway.

Objective:To observe the relationship between autophagy regulation activity of chromosome 19 open reading frame 5 (C19ORF5) and malignant degree of colorectal cancer and chemosensitivity of paclitaxel.Methods:The tumor tissues and normal adjacent tissues of 141 colorectal cancer patients from 2015 to 2017 in the Second Affiliated Hospital of Harbin Medical University were selected. The expressions of C19ORF5 protein and mRNA were detected by immunohistochemistry and timed quantitative polymerase chain reaction. The correlation between C19ORF5 protein regulating autophagy activity and malignancy of colorectal cancer was analyzed. All 141 patients received postoperative chemotherapy, among whom 91 patients received conventional chemotherapy (capecitabine combined with oxaliplatin, conventional chemotherapy group), and 50 patients received conventional chemotherapy combined with paclitaxel (paclitaxel group). Six course of treatment was treated in both groups.Results:Autophagosomes could been seen under transmission electron microscopy. C19ORF5 protein was pale yellow to tan granules, and was expressed in the cytoplasm. The C19ORF5 protein staining intensity of cancer tissue was significantly stronger than that of normal tissue, and the staining intensity of stage Ⅱ was significantly higher than that of stage Ⅳ. The high expression rate of C19ORF5 protein in patients with stage Ⅰ to Ⅱ was significantly higher than that in patients with stage Ⅲ to Ⅳ: 83.3% (25/30) vs. 17.1% (19/111), and there was statistical difference ( P<0.01). The expression of C19ORF5 mRNA in cancer tissues was significantly higher than that in normal tissues: 1.17 ± 0.45 vs. 0.82 ± 0.29, and there was statistical difference ( P<0.05). The expression level of C19ORF5 protein in cancer tissue was related to tumor stage, carcinoembryonic antigen and liver metastasis ( P<0.01 or <0.05); the expression level of C19ORF5 protein in cancer tissue was not related to lymph node metastasis ( P>0.05). Of the 91 cases in conventional chemotherapy group, chemotherapy was effective in 70 cases (76.9%) and ineffective in 21 cases (23.1%). Of 50 cases in paclitaxel group, it was effective in 42 cases (84.0%) and ineffective in 8 cases (16.0%). There was no statistical difference in effective rate between 2 groups ( P>0.05). In conventional chemotherapy group, there was no significant difference in serum C19ORF5 protein expression levels between cancer tissues before and after chemotherapy in effective patients and ineffective patients ( P>0.05); there was no significant difference in serum C19ORF5 protein expression levels between effective patients and ineffective patients after chemotherapy ( P>0.05). In paclitaxel group, the expression level of C19ORF5 protein in cancer tissues before chemotherapy was significantly higher than that in serum C19ORF5 protein after chemotherapy: 0.9 ± 0.3 vs. 0.5 ± 0.2, the expression level of serum C19ORF5 protein in patients with effective chemotherapy was significantly lower than that in ineffective patients: 0.5 ± 0.2 vs. 0.8 ± 0.2, and there were statistical differences ( P<0.05). Conclusions:The high expression of C19ORF5 protein can increase the autophagy activity of colorectal cancer tissue; C19ORF5 protein regulates autophagy activity and is negatively correlated with the malignant degree of colorectal cancer; C19ORF5 protein may increase the sensitivity of paclitaxel chemotherapy by enhancing autophagy activity.

Objective:To investigate the independent predictors for malignancy in colorectal laterally spreading tumors (LSTs) by therapeutic endoscopy.Methods:Data of consecutive patients with colorectal LSTs who underwent endoscopic treatment in Beijing Friendship Hospital between June 2013 and March 2019 were collected for retrospective analysis. Patients′ gender, age, body mass index, smoking history, and endoscopic and histological results were reviewed. Univariate analysis was used to identify the associated factors for malignancy of colorectal LSTs. Factors with statistical significance in univariate analysis were used in multivariate logistic regression to determine the independent predictors.Results:A total of 323 patients with 341 colorectal LSTs were involved in the study. The rate of malignancy was highest in non-granular pseudo depressed (NG-PD) subtype [85.48% (53/62)], followed by granular nodular mixed (G-NM) subtype [76.97% (117/152)]. Both of the above rates were significantly higher than that of granular homogenous (G-H) subtype [29.51% (18/61), P<0.001] and non-granular flat elevated (NG-FE) subtype [24.24% (16/66), P<0.001]. Univariate analysis showed that NG-PD subtype ( P<0.001, OR=18.40, 95% CI: 7.46-45.42), G-NM subtype ( P<0.001, OR=10.45, 95% CI: 5.30-20.58), rectosigmoid location ( P<0.001, OR=2.33, 95% CI: 1.47-3.69) and size ≥2 cm ( P<0.001, OR=2.60, 95% CI: 1.60-4.00) associated with malignancy for colorectal LSTs. In multivariate logistic regression, NG-PD subtype ( P<0.001, OR=17.51, 95% CI: 7.06-43.43), G-NM subtype ( P<0.001, OR=8.25, 95% CI: 4.07-16.73) and size ≥2 cm ( P=0.032, OR=1.80, 95% CI: 1.05-3.08) remained to be independent predictors. Conclusion:LSTs of NG-PD subtype, G-NM subtype or size ≥2 cm are high risk factors of malignancy, in which cases, en bloc resection is required.