OBJECTIVES:Postdiagnosis physical activity is an important component of healthy lifestyle in cancer survivors. In this study, we aimed to explore the association between intensity and duration of physical activity measured by wearable accelerometers and mortality among pan-cancer survivors. METHODS:A prospective cohort study involving cancer survivors (n = 11,708) from UK Biobank was performed. All participants had thorough physical activity data that was measured by wrist-worn accelerometers. Restricted cubic splines and multivariate Cox proportional hazards models were employed to assess the dose-response associations between physical activity time at varying intensities and both all-cause and cancer-specific mortality. RESULTS:During a median follow-up of 8.9 years, a total of 983 deaths occurred, including 656 cancer-related deaths. Multivariate models identified significant dose-response associations between moderate to vigorous-intensity physical activity (MVPA) time and mortality. Hazard ratios (HRs) for all-cause mortality were 0.64 (95% CI, 0.54-0.76), 0.61 (95% CI, 0.51-0.74) and 0.52 (95% CI, 0.42-0.66) in participants with MVPA time of 272-407, 407-579 and ≥579 min per week, respectively. HRs for cancer-specific mortality were 0.71 (95% CI, 0.58-0.88), 0.69 (95%CI, 0.55-0.87) and 0.61 (95%CI, 0.47-0.81) for the aforementioned groups. Similar patterns were observed for moderate-intensity physical activity but not for light-intensity physical activity. Survival benefits of active physical activity were pronounced in cancers from multiple organs. CONCLUSIONS:Active physical activity substantially reduced all-cause mortality in pan-cancer survivors and cancer-specific mortality in cancer survivors of specific sites. However, the benefits were significant only when intensity of physical activity reached moderate to vigorous level.

Metabolic abnormalities contribute to the pathogenesis of obesity and its complications. Yet, the understanding of the interactions between critical metabolic pathways that underlie obesity remains to be improved, in part owing to the lack of comprehensive metabolomics studies that reconcile data from both hydrophilic and lipophilic metabolome analyses that can lead to the identification and characterization of key signaling networks. Here, the study conducts a comprehensive metabolomics analysis, surveying lipids and hydrophilic metabolites of the plasma and omental adipose tissue of obese individuals and the plasma and epididymal adipose tissue of mice. Through these approaches, it is found that a significant accumulation of ceramide due to inhibited sphingolipid catabolism, while a significant reduction in the levels of uridine monophosphate (UMP), is critical to pyrimidine biosynthesis. Further, it is found that UMP administration restores sphingolipid homeostasis and can reduce obesity in mice by reversing obesity-induced inhibition of adipocyte hypoxia inducible factor 2a (Hif2α) and its target gene alkaline ceramidase 2 (Acer2), so as to promote ceramide catabolism and alleviate its accumulation within cells. Using adipose tissue Hif2α-specific knockout mice, the study further demonstrates that the presence of UMP can alleviate obesity through a HIF2α-ACER2-ceramide pathway, which can be a new signaling axis for obesity improvement.

Background Colorectal cancer (CRC) has been a leading cause of cancer-associated death worldwide. Several promising targeted therapies for CRC treatment, like anti-EGFR antibody, while the unforeseen non-responders limit its clinical application. An imbalance of ceramides, the core metabolites involved in the sphingolipid metabolism, is found in CRC patients, while its role and underlying mechanism in CRC progression and treatment remains unclear. Methods A clinical cohort of 41 CRC patients was established for the identification of CRC-related lipid biomarkers. MC38 cell line, xenograft and AOM/DSS mouse models, and patient-derived CRC organoids were applied to explore the underlying mechanism. Another cohort of 32 CRC patients was established for patient-derived organoid culturing and screening for anti-EGFR therapy response. Results Based on lipidomic, VIP score analysis showed that several ceramide metabolites were the primary ones leading to clustering in non-tumor and tumor tissues of CRC patients (IDDF2024-ABS-0220-Figure 1 (A)). Of note, ceramide (d18:1/C26:0) (C26) was most significantly elevated in patients with advanced stages (IDDF2024-ABS-0220-Figure 1 (B,C)). Administration of C26 obviously enhanced the proliferation of human CRC organoids both in morphology and as shown in EdU staining (IDDF2024-ABS-0220-Figure 1 (D)). To figure out the key ceramide-related enzyme involved in CRC progression, we set up the LC-MS-based enzyme screening method. Based on that, we found that CERS3 activity was significantly activated in CRC (IDDF2024-ABS-0220-Figure 2 (A)), and its mRNA expressions were positively correlated to C26 levels (IDDF2024-ABS-0220-Figure 2 (B)). Genetically modification of CERS3 also influenced the proliferation of human CRC organoids (IDDF2024-ABS-0220-Figure 2 (C,D)). In terms of mechanism, C26 was found to activate PI3K/AKT signaling pathway as a ligand of EGFR to promote CRC (IDDF2024-ABS-0220-Figure 3 (A-C)). Patient-derived CRC organoids were established with 32 patients for anti-EGFR therapy response screening (IDDF2024-ABS-0220-Figure 3 (D-E)), and CERS3 was proved to act as a biomarker in the evaluation of response to anti-EGFR therapy (IDDF2024-ABS-0220-Figure 3 (F)). Conclusions This study highlights that C26 produced by its synthetase CERS3 activates EGFR directly as a ligand, and acts as a potential targets for treating CRC and predicting the patient response to anti-EGFR therapies.

Colorectal cancer is a heterogeneous disease which can be divided into proximal colon cancer, distal colon cancer and rectal cancer according to the anatomical location of the tumor. Each anatomical location of colorectal cancer exhibits distinct characteristics in terms of incidence, clinical manifestations, molecular phenotypes, treatment, and prognosis. Notably, proximal colon cancer differs significantly from cancers of other anatomical subsites. An increasing number of studies have highlighted the presence of unique tumor biological characteristics in proximal colon cancer. Gaining a deeper understanding of these characteristics will facilitate accurate diagnosis and treatment approaches.

Silibinin is a kind of flavonoid extracted from the dried ripe fruit of Silybum marianum,a plant of compositae. It has a variety of pharmacological activities and can effectively prevent and treat diabetes and its complications. This paper reviews the research progress on the mechanism of silibinin in the prevention and treatment of diabetes and its complications. It is found that silibinin can prevent and treat diabetes by up-regulating the expression of estrogen receptor-α,activating the duodenum-brain-liver axis pathway and stabilizing the protein structure. It can prevent and cure the nervous system diseases of diabetes by activating glucagon-like peptide-1 receptor/protein kinase A signal pathway and inhibiting the hyperphosphorylation of tau protein. It can prevent and treat diabetic retinopathy by down-regulating the expression and activity of pro-inflammatory,pro-oxidative factors and histone deacetylase 6. It can prevent diabetic nephropathy by activating protein kinase B signal pathway and reducing the level of transforming growth factor-β1,and prevent and treat diabete’s obesity by inhibition of hepatobiliary transporter CD36 expression,and suppressing nuclear factor-κB pathway and its downstream expression of pro-inflammatory cytokines（tumor necrosis factor-αand interleukin-1β）,etc.

OBJECTIVE:The clinical and biological characteristics of colorectal cancer have been found to differ depending on the anatomic site of the cancer. However, for Chinese patients, there is limited information on the proportion of cases at each site and the related features. In this study, we explored the location, distribution and other features of colorectal cancers at each anatomic site in Chinese patients. METHODS:We conducted a hospital-based study using hospitalization summary reports from 10 Peking University-affiliated hospitals from 2014 to 2018; the reports covered a total of 2,097,347 hospitalizations. Incident cases were chosen as the study population, and their epidemiological features were further analyzed. RESULTS:A total of 20,739 colorectal cancer patients were identified. Rectum was the most common location (48.3%) of the cancer, whereas the proportions of patients with distal and proximal colon cancer were 24.5% and 18.6%, respectively. Patients with rectal cancer were predominantly male and were the youngest for all anatomical sites (each P<0.001). The highest proportion of emergency admissions, the longest hospital stays and the highest hospitalization costs were found in patients with proximal colon cancer (each P<0.001). The proximal colon cancer subgroup included the highest proportions of patients with medical histories of cholecystectomy, cholecystolithiasis and/or gallbladder polyps and appendectomy (P=0.009, P<0.001 and P<0.001, respectively). The distal colon cancer subgroup included the highest proportions of patients with medical histories of diabetes and hypertension (P<0.001, respectively). CONCLUSIONS:The patterns of colorectal cancer observed in this study differ from those reported for Western patients and show a significantly higher proportion of patients with rectal cancer. Different epidemiological features were also found based on anatomic sites. Further studies based on tumor location should be conducted to facilitate more accurate screening and treatment.

Objective: This study aimed to test associations between type 2 diabetes mellitus (T2DM) and metabolites in urea cycle including arginine, citrulline and ornithine. Methods: This study used a hospital-based cross-sectional study design. We retrieved medical notes of 401 in-patients with onset of T2DM within 2 years and 1,522 healthy subjects who attended annual physical examination. All cases were admitted to a tertiary care center in Jinzhou, China from May 2015 to August 2016. Binary logistic regression analyses were performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Results: Patients with T2DM had higher arginine, and lower ornithine than control subjects. Levels of citrulline were similar in two groups. Arginine was positively associated with T2DM (ORs: 1.20, 1.17-1.23) while ornithine was negatively associated with T2DM (OR: 0.89, 0.88-0.91). After adjustment for other amino acids and traditional risk factors, these associations were still significant and persistent for arginine and ornithine. The association between citrulline and T2DM was not significant. Their ratios of pairs of two amino acids were associated with increased risk of T2DM. After adjustment for other ratios of amino acids, effect size for T2DM remained significant. Further adjustment for traditional risk factors did not lead to large changes (ORs: 1.78, 1.20-2.65 for the ratio of arginine to ornithine; ORs: 1.59, 1.37-1.86 for the ratio of citrulline to ornithine, respectively) except the ratio of arginine to citrulline. Conclusions: Plasma levels of amino acids related to urea cycle and their ratios of these amino-acids were associated with T2DM in Chinese adults.

介入性超声是指在实时超声影像学监测和引导下,将特制的针具、导管导丝、消融电极等器械或造影剂引入人体,对病变进行诊断和治疗的过程,是超声与介入学融合而成的交叉学科. 1974年Pedersen等[1]在超声引导下进行第一例肾造瘘术,标志着介入性超声治疗的开始. 由于这种治疗方法能够实时监测诊断及治疗的全过程,不仅安全简便,而且定位精准,取材满意,并发症较少,目前已用于全身多系统组织器官的穿刺活检及射频消融治疗,而且建立了诊疗规范[2] ,部分应用已经写入治疗指南[3] ,成为介入治疗学的重要分支[4]. 但是囿于我国当前的临床教育水平及教学能力,介入性超声的发展仍然比较缓慢,而从业医师的学历、临床经验、技术水平也参差不齐,因此,探讨介入超声专科医师培训的模式,建立相应的培养体系和操作技术规范,对提高我国相关专业技术水平具有重要意义.

目的 探讨超声引导下经皮经肝胆囊穿刺引流(percutaneous transhepatic gallbladder drainage,PTGBD)治疗高手术风险的急性胆囊炎的安全性、有效性及近期疗效.方法 回顾性分析2016年1月～2017年4月超声引导PTGBD治疗的高手术风险急性胆囊炎20例的临床资料.年龄58～94岁,平均83.1岁,胆囊急性炎症均为Ⅲ级,ASA分级Ⅲ级及以上.结果 均顺利完成穿刺.术后并发症3例(15％),均为穿刺管脱出,无死亡.术后饮食恢复中位时间2(1～5)d;住院中位时间7(5～21)d.穿刺后41(30～58)d拔除引流管.结论 超声引导PTGBD是高手术风险急性胆囊炎的安全、有效的替代急诊胆囊切除或胆囊造瘘术的治疗方法.

Objective To evaluate the effect and feasibility of simulation teaching on the acquisition and retention of basic surgical clinic skills for eight-year medical program.Methods 46 clinical medical students of eight-year medical program in 2012 grade in Peking University Third Hospital were randomized to a simulation training (experimental group) or a traditional teaching (control group) for surgical skill training curriculum during a period of 3 weeks.Students were tested with objective structured assessment of technical skills (OSATS) scoring system after training and 1 year later.Results 46 students completed all models training and post-training assessments.OSATS scores were higher in experimental group compared with control group (t=9.194,P=0.001).After 1 year,this effect persisted with OSATS scores still being significantly higher in experimental group (t =14.140,P=0.001).The simulation teaching method was approved by most of students through the questionnaire survey.Conclusions Simulation teaching improves technical efficiency.Retesting can further evaluate advantages of simulation teaching.

Background: To summarize the characteristics of cystic pancreatic adenocarcinoma, and to improve the general understanding of the imaging and pathologic features, and other pancreatic cystic diseases are compared for differential diagnosis.

Objective To explore the safety and feasibility of pure transanal total mesorectal excision (pure-TaTME)combination with intersphincteric resection (ISR) for ultra-low rectal cancer.Methods The patient with ultra-low rectal cancer,who had been treated with pure-TaTME and ISR,was screened carefully by colonoscopy,cndorectal ultrasound and MRI examination.A purse suture closure of the rectal lumen at the level of tumor's inferior edge was done transanally.The cut-line was made vertically to the anal canal at the level of dentate line,and further ISR procedure was performed upright into the pelvic floor.Then pure-TaTME was performed.The specimen was pulled down transanally and removed.A colo-anal anastomosis was made by use of circle stapler.Results The operation time was 350 min and the volume of blood loss was 200 mL.The length of the specimen was about 18 cm with intact mesorectum.The distal resection margin was 1.0 cm below the inferior edge of tumor.The circumferential resection margin (CRM) was negative.The pathological cancer staging was T1N0M0.Totally 32 lymph nodes had been retrieved without positive node.The postoperative recovery of patient was good without any evidence of infection and anastomotic leakage.Defecation function was acceptable and no tumor relapse was detected after a follow-up of 24 months.Conclusion The operation of pure-TaTME combined with ISR is safe,which provides a feasible option for the surgical treatment of the low or ultra-low rectal cancer.The long-term outcome need to be identified by further clinical study.

AIMTo explore the safety, feasibility and short-term outcomes of laparoscopic-assisted transanal total mesorectal excision (La-TaTME) of middle-low rectal carcinoma.MATERIALS AND METHODSThis retrospective research collected and analyzed the clinical data of 19 patients diagnosed with middle and low rectal carcinoma who underwent La-TaTME from August 2015 to February 2017.RESULTSNo case was converted to laparotomy. In none of the enrolled cases, did the circumferential resection margin test positive by histopathology examination. Also, there was no detected residual tumor at the proximal and distal resection margins. The rate of postoperative morbidity was 15.8% (Clavien-Dindo grade 2). During the follow-up period, no local recurrence or metastasis was observed.CONCLUSIONLa-TaTME is a safe alternative to standard laparoscopic TME in middle-low rectal carcinoma when operated by an experienced colorectal surgeon. However, large-scaled randomized multi-centered comparative trials are still needed to further test its oncological effectiveness.

This study investigates survival of patients diagnosed with pancreatic neuroendocrine tumor with liver metastases based on local treatment on the primary tumor. Patients diagnosed with stage IV PNET between 2010 and 2014 were identified from the Surveillance Epidemiology and End Results database. Cancer-Specific Survival and Overall Survival were examined. A total of 191 patients with pancreatic neuroendocrine tumor with liver metastases were included in this analysis. There were 47 patients (24.6%) who received surgical resection and 144 (75.4%) who did not. Patients with N1 stage was more likely to be treated with surgical resection. The results showed that surgical resection of primary tumor was associated with Cancer-Specific Survival (p = 0.028) and Overall Survival (p = 0.025) benefit. Not receiving surgery, being unmarried and N1 stage are factors associated with poor survival. This study reveals that local treatment on the primary benefits both Cancer-Specific Survival and Overall Survival in PNET patients with LM. This may be suggestive for the management on this patient population.

目的 探讨腹腔镜下切除原发性腹膜后肿瘤的安全性及手术效果.方法 回顾性分析2006年1月至2015年12月期间于北京大学第三医院普通外科接受腹腔镜切除手术的52例原发性腹膜后肿瘤患者的临床资料.结果 52例患者中,21例患者(40.3％)的肿瘤与大血管关系密切,31例患者(59.7％)的肿瘤远离大血管.2例(3.8％)早期病例在手助下完成,2例(3.8％)因肿瘤与大血管粘连致密中转开腹手术.平均手术时间为171.4 min(60～520 min);平均切口长度为2.8 cm(1～15 cm);术中平均出血量为86.4 mL(10～1 150 mL),其中2例输血;术后平均饮食恢复时间为1.5d(1～5d);术后平均住院时间为4.9 d(1～16 d).围手术期均无严重并发症及死亡病例.术后47例获访,平均随访时间为62个月(4～120个月).随访期间,3例腹膜后脂肪肉瘤患者复发,1例黏液性外周神经鞘瘤患者复发,均行再次手术切除,余无复发及转移病例;非肿瘤相关死亡3例.结论 腹腔镜下能够安全地切除毗邻腹腔大血管的原发性腹膜后肿瘤.

人最宝贵的是生命，把生命照顾好，维护生命的圣洁，是上天赋予每位身穿白大衣，救死扶伤的医生的神圣使命。作为一名医生，平时接触最多的是患者，对我们而言，患者是个弱势群体，需要我们能够设身处地为患者排忧解难，与患者心连心，尽职工作，尽责做事。让患者在我们悉心的医治下早日康复是我们义不容辞的责任。

BACKGROUND:Pancreatic neuroendocrine tumors (pNETs) are a type of tumors with the characteristics of easy metastasis and recurrence. Till date, the risk factors affecting the prognosis are still in the debate. In this study, several risk factors will be discussed combined with our cases and experience.METHODS:Thirty-three patients diagnosed as pNETs were enrolled and the clinical features, blood tests, pathological features, surgical treatment, and follow-up data of these patients were collected and analyzed.RESULTS:In this study, operation time of G3 cases was longer than G1/G2 cases (P = 0.017). The elevated level of tumor markers such as AFP, CEA, Ca125, and Ca19-9 may predict easier metastasis, earlier recurrence, and poor prognosis (P = 0.007). The presence of cancer embolus and nerve invasion increases along with the TNM stage (P = 0.037 and P = 0.040), and the incidence of positive surgical margin increased (P = 0.007). When the presence of nerve invasion occurs, the chance of cancer embolus and lymph node metastasis also increases (P = 0.016 and P = 0.026).CONCLUSIONS:pNETs were tumors with the features of easy recurrence and metastasis and many risk factors could affect its prognosis such as the elevated levels of tumor markers and the presence of nerve invasion, except some recognized risk factors. If one or more of these factors existed, postoperative treatments may be needed to improve prognosis.

Objective To investigate the R1 rate of pancreaticoduodenectomy in patients with pancreatic head cancer,and to discuss its significance in clinical practice.Methods From November 2011 to March 2012,a single team in our hospital performed radical pancreaticoduodenectomy on 28 patients with pancreatic head cancer by using standardized pathological protocol(SP group).Specimens were collected from the resection margin of the pancreatic neck,common bile duct,stomach/jejunum,as well as the circumferential soft margins(the SMV groove,nucinate process margin and posterior surface).R1 margin was defined as the margins with tumor cells presented at the surface.A group of patients,who received radical pancreaticoduodenectomy without using standardized pathological protocol from February 2009 to November 2010 for pancreatic head cancer by a same team,were set as a control group.The R1 rate was compared between the groups.Results The R1 rate was 53.6%(15/28) in the SP group,which was significantly higher than the control(13.2%,5/38,χ2=12.467,P=0.000).The SMV groove and uncinate process margins were the most affected margins(9/15,60.0% and 8/15,53.3%),in 33.3% of the patients(5/15),both the margins were involved.Conclusions Standardized technique for obtaining pancreatoduodenectomy specimens can significantly rise the R1 rate on the resection margin,so that to provide accurate pathological information.The uncinate process and SMV groove should be resected radically to decrease R1 rate.The SMV shall be resected when necessary.

1Department of Surgery, Peking University Third Hospital, Beijing, China 2Department of Pathology, Peking University Third Hospital, Beijing, China [email protected]

Objective To evaluate the diagnosis and treatment of the primary retroperitoneal tumor based on experience with 30 cases. Methods The clinical manifestations,image examinations and operations of 30 cases with primary retroperitoneal tumor that were diagnosed and treated in our department from January 2007 to July 2009 were Retrospectively analyzed and discussed. Results Of the 30 cases,8 were male and 22 were female,the age range was 15~82 years,average 44.8 years.Nine of the cases were asymptomatic,7 had abdominal pain or fullness,4 had back pain,5 had abdominal mass,4 had lower extremity pain or numbness,and 1 case had body weight loss.All the 30 cases were treated with surgical operations,14 received laparoscopic surgery and the rest laparotomy.The average operation time was 205 minutes.There were no major complications in any of the patients.Twenty-seven cases were followed-up for an average of 18 months. Conclusion The image examinations are the main methods to detect the primary retroperitoneal tumors and the operations to remove the tumor are the main treatment.For benign or less malignant neoplasmas,laparoscopic surgery can be attempted.