The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective To explore the clinicopathological features and prognosis of the obstructive colorectal cancer (CRC).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 667 CRC patients who were admitted to the Beijing Friendship Hospital Affiliated to Capital Medical University between January 2013 and December 2015 were collected.The diagnosis and treatment of CRC patients were based on colon cancer and rectal cancer clinical practice guidelines in oncology(Version 2013) of the National Comprehensive Cancer Network (NCCN) and the 7th edition of the American Joint Committee on Cancer (AJCC) cancer staging manual and the future of TNM.CRC and clinical staging were confirmed by colonoscopy,biopsy pathology and CT or MRI examination.Patients selected laparoscopic surgery or open surgery according to their conditions,and then selectively underwent postoperative adjuvant therapy based on the results of pathological examination.Observation indicators:(1) diagnosis and treatment;(2) clinicopathological features;(3) prognosis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall and tumor-free survivals up to April,2017.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Count data were described as case and percentage,comparisons between groups were evaluated with the chi-square test.Ordinal data were analyzed using the nonparametric test.Results (1) Diagnosis and treatment:tumor locations of 677 patients:tumors located in the right hemicolon,left hemicolon and rectum were respectively detected in 213,312 and 142 patients.Preoperative clinical staging:3,47,300,298 and 19 patients were respectively detected in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ.Ninety-nine patients were complicated with intestinal obstruction,with an obstructive rate of 14.84％ (99/667),and 568 patients didn't have intestinal obstruction.Treatments of 667 patients:① Preoperative adjuvant treatment:17 non-obstructive CRC patients underwent preoperative adjuvant treatments and 650 didn't undergo preoperative adjuvant treatment.② Surgical treatment:389 and 278 patients underwent respectively open and laparoscopic surgeries,and 588 received radical resection and 79 received non-radical resection.(2) Clinicopathological features:of 99 obstructive CRC patients,tumors located in the right hemicolon,left hemicolon and rectum were respectively detected in 26,61 and 12 patients.Eighteen and 81 patients underwent respectively laparoscopic and open surgeries,including 21 with low-differentiated tumors,61 with moderate-differentiated tumors and 17 with high-differentiated tumors;71 patients received radical resection,with a number of lymph node dissected of 12±9,and 37,20 and 14 were respectively detected in stage N0,N1 and N2.Of 568 non-obstructive CRC patients,tumors located in the right hemicolon,left hemicolon and rectum were respectively detected in 187,251 and 130 patients.Two hundred and sixty and 308 patients underwent respectively laparoscopic and open surgeries,including 38 with low-differentiated tumors,420 with moderate-differentiated tumors and 110 with high-differentiated tumors;517 patients received radical resection,with a number of lymph node dissected of 15±8,and 338,155 and 24 were respectively detected in stage N0,N1 and N2.There were statistically significant differences in above indicators between obstructive CRC and non-obstructive CRC patients(x2=11.234,46.505,30.088,Z=-2.782,t=2.942,Z=-2.892,P＜0.05).(3) Prognosis:of 667 patients,584 were followed up for 18-52 months,with a median time of 36 months,including 88 with obstructive CRC (1,5,23,28 and 31patients were respectively in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ) and 469 with non-obstructive CRC (5,62,212,116 and 101 patients were respectively in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ).During the follow-up,56 obstructive CRC patients survived,including 1 in stage 0,4 in stage Ⅰ,15 in stage Ⅱ,17 in stage Ⅲ and 19 in stage Ⅳ,with an overall survival rate of 63.64％ (56/88),and overall survival rates in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ were respectively 1/1,4/5,65.22％(15/23),60.71％(17/28) and 61.29％ (19/31);38 had tumor-free survival,including 1 in stage 0,4 in stage Ⅰ,15 in stage Ⅱ,13 in stage Ⅲ and 5 in stage Ⅳ,with a tumor-free survival rate of 43.18％(38/88),and tumor-free survival rates in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ were respectively 1/1,4/5,65.22％ (15/23),46.43％ (13/28),16.13％ (5/31).Four hundred and forty-three non-obstructive CRC patients survived,including 5 in stage 0,58 in stage Ⅰ,181 in stage Ⅱ,106 in stage Ⅲ and 93 in stage Ⅳ,with an overall survival rate of 89.31％(443/496),and overall survival rates in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ were respectively 5/5,93.55％ (58/62),85.38％ (181/212),91.38％ (106/116) and 92.08％ (93/101);384patients had tumor-free survival,including 5 in stage 0,52 in stage Ⅰ,166 in stage Ⅱ,94 in stage Ⅲ and 67 in stage Ⅳ,with a tumor-free survival rate of 77.42％ (384/496),and tumor-free survival rates in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ were respectively 5/5,83.87％ (52/62),78.30％ (166/212),81.03％ (94/116) and 66.34％ (67/101).There were statistically significant differences in overall survival rate and tumor-free survival rate between obstructive CRC and non-obstructive CRC patients (x2 =39.626,43.707,P＜ 0.05).The subgroup analysis:there were statistically significant differences in stage Ⅱ,Ⅲ and Ⅳ overall survival rates between obstructive CRC and non-obstructive CRC patients (x2 =6.092,17.027,11.268,P＜0.05) and in stage Ⅲ and Ⅳ tumor-free survival rates (x2 =14.148,24.116,P＜ 0.05).Conclusion The obstructive CRC commonly locates in the left hemicolon,with complex clinicopathological features and low-differentiated tumors,meanwhile,there are lower radical rate and poor prognosis.

Objective To evaluate the curative effect of trans-anal surgery vs.conventional laparoscopic surgery in treating sigmoid and high-rectum tumor.Methods From Jan 2014 to Mar 2017,100 patients in Beijing Friendship Hospital participated in this clinical study.45 patients underwent transanal surgery and 55 patients underwent conventional laparoscopic surgery.Results No significant difference was found between trans-anal surgery group and the traditional laparoscopic group in terms of operation time,blood loss,the use of analgesic drugs and the radical evaluation of tumor.While the postoperative pain scores in trans-anal surgery group (2.0 ± 1.0 vs.2.6 ± 1.0,t =2.9,P =0.005) were lower than those in the conventional group.The follow-up data showed one case of local tumor recurrence and one case of multiple peritoneal metastasis in the trans-anal surgery group,compared to two cases of liver metastasis and one case dying of pneumonia in the conventional laparoscopic group.The remaining cases were of no local recurrence,nor distant metastases or any critical complications.Conclusions Trans-anal surgery in the treatment of sigmoid and high-rectum tumor is safe,reliable and having the same clinical efficacy with conventional laparoscopic surgery.

Objective: To assess the incidence and independent risk factors for clinical anastomotic leakage (AL) in patients undergoing anterior resection (AR) or low anterior resection, (LAR) for rectal cancer. Methods: This was a retrospective case-control study of 550 patients with rectal cancer who underwent AR or LAR from April 2007 to March 2017 in Beijing Friendship Hospital, Capital Medical University. The relationship between the incidence of AL and clinicopathological manifestations was analyzed by Chi-squared test and Fisher exact test, and the independent risk factors of AL were analyzed using logistic regression analysis. AL is defined as a defect (including necrosis or abscess formation) of the intestinal wall at the anastomotic site, leading to a communication between the intra- and extra-luminal compartments. AL can be divided into three grades. Grade A anastomotic leakage results in no change in the management of patients, whereas grade B leakage requires active therapeutic intervention but is manageable without re-laparotomy. Grade C anastomotic leakage requires re-laparotomy. Results: AL was noted in 32 (5.8%) of 550 patients with rectal cancer who underwent AR or LAR, including 15 (46.9%) , 4 (12.5%) , and 13 patients (40.6%) with Grades A, B, and C, respectively. Five patients (0.9%, 5/550) died peri-operatively. AL- and non-AL-related deaths occurred in 3 (9.4%, 3/32, all cases were Grade C) and 2 patients (0.4%, 2/518) , respectively, with the two mortality rates being significant difference (P = 0.002) . Chi-squared test or Fisher exact test showed that the incidence of AL was associated with neoadjuvant chemoradiotherapy (P = 0.011) , intraoperative bleeding (≥100 ml) (χ² = 11.980, P = 0.001) , and tension-reducing suture of anastomosis (P = 0.015) . The results of logistic regression analysis showed that the independent risk factors of AL were neoadjuvant chemoradiotherapy (OR = 2.402, 95%CI: 1.004 - 5.749, P = 0.049) , intraoperative bleeding (≥100 ml) (OR = 2.971, 95%CI: 1.269 - 6.957, P = 0.012) and tension-reducing suture of anastomosis (OR = 2.304, 95%CI: 1.008 - 5.263, P = 0.048) . Conclusion The incidence of AL in patients undergoing AR for rectal cancer is 5.8%. The high-risk factors for AL are neoadjuvant chemoradiotherapy, intraoperative bleeding (≥100 ml) , and tension-reducing suture of anastomosis. Patients with these three risk factors have a high risk of AL rate, and a defunctioning stoma should be performed.

Objective:To investigate the relationship between anti-Helicobacter pylori antibody(Hp-IgG)and anti-aquaporin 4 antibody which are in neuromyelitis optica(NMO)and multiple sclerosis(MS).Methods: Serum specimens were collected from the 33 patients with MS,7 patients with NMO,and 35 health examination cases.Hp-IgG were detected by enzyme-linked immunosorbent assasy and anti-aquaporin 4 antibody were detected by cell based assay respectively.The positive rate of Hp-IgG and anti-aquaporin 4 antibody were analyzed,and the difference of Hp-IgG positive rate was compared between patients with Hp-IgG positive and negative.Results: Serum Hp-IgG positive rate of MS,NMO and normal control groups were 69.70％,85.71％ and 42.86％ respectively with a significant statistically difference of Hp-IgG(P<0.05).Positive rate of serum anti HP-IgG antibody in MS group,NMO group and normal control were significantly different(P<0.05);but there was no statistical significant difference of anti HP-IgG antibody positive rate between MS group and NMO group(P>0.05).Serum anti AQP4 antibody positive rate of MS,NMO and normal control groups were 4.2％,85.71％ and 0％ respectively with a significant statistically difference of anti AQP4 antibody(P<0.05).The positive rates of anti HP-IgG which were in MS patients and NMO patients with positive anti AQP4 antibody were 72.73％,the positive rates of anti HP-IgG which were in MS patients and NMO patients with negative anti AQP4 antibody were 79.31％,the difference was not statistically significant(P>0.05).Conclusion: HP infection is a risk factor for the occurrence of MS and NMO,but not associated with MS and NMO patients with anti AQP4 antibodies.

Objective:To evaluate immune response of murine peritoneal macrophage challenging by methicillin-resistant S.aureus(MRSA)after pretreatment with Pam3Csk4(TLR2 agonist).Methods: Murine peritoneal macrophage was pretreated with Pam3Csk4(1 μg/ml).Following pretreatment 12 h later,heat-killed MRSA( HK-MRSA) was added and incubated for another 2 or 6 hours.The protein and mRNA level of TNF-α, IL-6 and IL-1 were determined by ELISA and Q-PCR, respectively.To estimate phagocytosis of macrophage,HK-MRSA/MSSA labeled with FITC( FITC-HK-MRSA/MSSA) were added to well and incubated for 30 min.After washing 5 times with PBS,intracellular FITC-HK-MRSA was detected by flow cytometry.To estimate antimicrobal activity of macrophage,live MRSA and MSSA were added to well and incubated at indication time,the CFU of s.aureus was estimated via a 10-fold serial dilution on agar media.cDNA was further quantitative assessed using primers for mouse FCR-Ⅰ,FCR-Ⅲ,CR-1,CR-3,iNOS and LL37 by Q-PCR .Results: Compared with saline-pretreated cell, the protein and mRNA level of TNF-α, IL-6 and IL-1 were markely reduced, respectively.However, both the phagocytosis and antimicrobal activity to S.aureus were significantly increased in macrophages pretreated with Pam3Csk4.Further study found that the macrophages had higher FCR-Ⅰ,FCR-Ⅲ,CR-1,CR-3,iNOS and LL37 expression at 6 h and 12 h post-stimulation Pam3Csk4.Conclusion: The results suggest that Pam3Csk4 could activate murine antimicrobal activity of peritoneal macrophage challenging by methicillin-resistant Saureus via increasing opsonophagocytosis in depended antibodies, complements manners.The results suggest Pam3Csk4 probably be a novel immunotherapy candidate against MRSA.

OBJECTIVETo verify the clinical safety of complete mesocolic excision (CME) and manufacture pathological large slices.

METHODSA prospective analysis clinical data of 85 right colon cancer in patients by the same group of surgeons at the Department of General Surgery, Beijing Friendship Hospital, Capital Medical University from January 2012 to December 2013 which were divided into two groups: CME group (n=39) and traditional radical operation group (n=46) by surgical approach. CME group and control group were compared the differences of clinic and pathologic variables, precise tissues morphometry, lymph nodes harvest, mesocolic area and so on. By comparison to operation time, blood loss, postoperative complications, flatus restoring time, drainage removal time and length of stay, the security of CME was analyzed. Statistical methods included independent sample t-test, Wilcoxon rank sum test and χ(2) test. In order to manufacture pathological large slices, the CME operation specimens were fixed. The large slices were stained by routine HE staining to detection of circumferential resection margin.

RESULTSMean number of total lymph nodes was increased obviously in CME group (26.8±1.9 vs. 23.2±3.4, t=4.261, P=0.000). Mean number of lymph nodes of stage Ⅰ, Ⅱ were different between two groups (25.8±3.6 vs. 18.2±4.5, 26.8±7.7 vs. 24.9±6.2, t=8.776, 2.802, P=0.000). The positive lymph nodes of CME group was higher than control group (4(7) vs. 1.5(2), P=0.032), above all with statistically significant difference. Comparing CME group with the control group, there were the larger area of mesentery ((15 555±1 263) mm(2) vs. (12 493±1 002) mm(2,) t=12.456, P=0.000), the greater distance between the tumor and the high vascular tie ((116±22) mm vs. (82±11) mm, t=9.295, P=0.000), the greater distance between the normal bowel and the high vascular tie ((92±17) mm vs. (74±10) mm, t=8.132, P=0.000) of CME, with statistically significant difference. There were no statistically significant differences from operation safety when CME group was compared with the control group. The pathological large slices of colon cancer were prepared successfully and dyed evenly than those large slices were used to observe whether the lymph tube and lymph node metastasis inside the mesocolon. Existence of direct tumor invasion could be confirmed by investigating the large slices. Cancer embolus in intravascular and micro infiltration in mesocolon also could be found.

CONCLUSIONSCME operation can get the standard excision according the mesocolic area and integrity, as well as to harvest the maximum number of lymph node. The clinical application of CME is safe and does not increase the risk of operation. Circumferential resection margins can be detected by pathological large slices.

Colectomy ; Colonic Neoplasms ; surgery ; Device Removal ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Mesocolon ; surgery ; Operative Time ; Postoperative Complications ; Prospective Studies

Objective To explore the distribution change and antimicrobial resistance of pathogens causing catheter associat‐ed urinary tract infection in ICU .Methods 500 cases of patients received by emergency department ICU in our hospital from 2012 April~ 2014 June were collected ,urine samples were collected by closed drainage bag after indwelling catheter in 3 ,7 ,14 ,21ds .By culture ,separation ,purification ,screening and identification and antimicrobial disc diffusion experiments ,distribution changes and resistantance of pathogens causing catheter related infections were analyzed .Results 358 strains were found in catheter associated urinary tract infections ,in which 175 strains were Gram‐positive bacteria ,mainly were Staphylococcus aureus (48 .57% ) and en‐terococci (46 .86% ) ,137 were Gram‐negative bacteria ,mainly were E .coli (56 .93% ) ,46 fungi ,mainly were Candida albicans (47 .83% );Gram‐positive bacteria showed a decreasing trend ,while Gram‐negative bacteria increased every year;resistance rates of Staphylococcus aureus and enterococci to penicillins ,cephalosporins and quinolones were more than 50% ;Escherichia coli and Kleb‐siella pneumoniae had strong resistance to penicillins ,cephalosporins and quinolones ;resistance rate of Pseudomonas aeruginosa to ampicillin ,sulbactam and ampicillin cefazolin up to 100% .Conclusion Escherichia coli is the major pathogens causing ICU catheter associated urinary tract infections;pathogens resistance are strong ,clinical monitoring should be strengthened .

Objective To investigate the imaging features and the treatments of ischemic cerebrovascular disease with unruptured intracranial aneurysms.Methods The clinical data of 23 patients of ischemic cerebrovascular disease with unruptured intracranial aneurysms ( unruptured group) and 147 patients of hemorrhagic cerebrovascular with ruptured intracranial aneurysms ( ruptured group) were retrospectively analyzed.Results There were no statistical significances between the two groups baselines such as age, gender, hypertension, diabetes, hyperlipidemia, heart disease, smoking, drinking alcohol (all P>0.05).There were 16 patients (69.6%) with single intracranial aneurysm and 7 patients (30.4%) with multi-intracranial aneurysms in the unruptured group, and the number of intracranial aneurysms were 34.There were 125 patients (85%) with single intracranial aneurysm and 22 patients ( 15%) with multi-intracranial aneurysms in the ruptured group, and the number of intracranial aneurysms were 170.There was no statistical significance of single aneurysm and multi-aneurysms percentage between the two groups (P>0.05).The maximum aneurysm diameter and the percentage of large aneurysms, dissecting aneurysms of the unruptured group were significantly greater than the ruptured group; and the percentage of small-middle aneurysms and saccular aneurysms were significantly smaller than the ruptured group ( all P<0.05 ) .In the unruptured group, 5 cases were treated with intervention treatment and 1 case was treated with aneurysm clip surgery, all of which recovered well after surgery;6 cases were treated with Plavix antiplatelet therapy, 5 cases were treated with Aspirin antiplatelet therapy, cerebrovascular disease events were not found of which followed-up for 6 months;6 cases were not taken antiplatelet therapy, and 1 case of which followed-up and occurred cerebral infarction.In the ruptured group, 46 cases were treated with intervention treatment, 2 cases of which were died;101 cases were treated with aneurysm clip surgery, 6 cases of which were died.Conclusions Small-middle aneurysms are more commonly occurred in patients of ischemic cerebrovascular disease with unruptured intracranial aneurysm, however, the maximum aneurysm diameter of which is significantly bigger than patiehts of hemorrhagic cerebrovascular with ruptured intracranial aneurysms.Most of unruptured aneurysms which had duty relationship with cerebral ischemic events are dissecting aneurysms and saccular aneurysms.Intervention treatment of unruptured intracranial aneurysms is relatively safe and effective.

Objective:To investigate therapeutic mechanism of immunoglobulin Yolk (IgY) against tumour necrosis factor alpha ( TNF-α) and interleukin-1 beta ( IL-1β) in guinea pigs with allergic rhinitis.Methods: Hartley guinea pigs were randomly divided into the control group (group C,n=17),the allergic rhinitis model group (group M,n=27),the 0.1%anti-TNF-αand IL-1βIgY treating group (group Z1,n=21) and the fluticasone propionate treating group (group Z2,n=21).The allergic rhinitis model in guinea pigs was established using ovalbumin.After treatment for 2 h,4 h,8 h,nose and bronchial lung were lavaged using 0.9%saline, the nasal lavage fluid (NLF) and bronchoalveolar lavage fluid (BALF) were collected,the precipitated cells were stained using Wright′s,the nasal mucosa and lung tissues were stained using methylene blue and eosin (HE),and TNF-α,IL-1β,IL-5 and IL-33 in nasal mucosa and lung tissues were stained using immunohistochemistry.Results:There were a large amount of eosinophils and more serious inflammation responses in nasal mucosa in the M group compared with the Z 1 and Z2 groups.In the lung tissues,there were more alveolar tube damage ,pulmonary interstitial edema ,interval thickening ,thickening of bronchial smooth muscle and inflammation cell in-filtration in the M group compared with the Z 1 and Z2 groups.The eosinophils ,lymphocytes and neutrophils were significantly decreased in NLF and BALF in the Z1 and Z2 groups compared with the M group (P<0.05).The expressions of IL-1βand TNF-αfrom 2 h to 8 h and IL-5 and IL-33 from 4 h to 8 h significantly decreased in the nasal mucosa and lung tissues in the Z 1 group compared with the M group ( P<0.05 ).Conclusion:The allergic rhinitis in guinea pigs accompany with the allergic asthma.The inhibitory capacity of anti-TNF-αand IL-1βIgY on pathological responses in guinea pigs with allergic rhinitis may be due to the significant decrease in the infiltration of eosinophils and the expressions of inflammatory cytokines in the nasal mucosas and lung tissues .