Development and validation of a prognostic prediction model for patients with stage Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features / 中华外科杂志

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

Thirty years' changes of the strategy of lateral lymph node dissection in low rectal cancer: treatment experience and prognostic analysis of 289 cases in one single center / 中华胃肠外科杂志

Objective: The surgical indications, resection extent and management principle of lateral lymph node dissection (LLND) in lower rectal cancer have been controversial between Eastern and Western countries. This study aims to provide a theoretical basis for the rational implementation of LLND by reviewing the changes of LLND strategy over the past 30 years in a single-center, and analyzing prognostic factors for the survival outcomes of patients with lateral lymph node metastasis (LLNM). Methods: A retrospective observational study was performed. Clinical data of 289 patients with rectal cancer who received LLND at the Department of General Surgery of Peking University First Hospital from 1990 to 2019 were collected. Patients were divided into three groups based on decades. There were 89 cases in 1990-1999 group, 92 cases in the 2000-2009 group, and 108 cases in the 2010-2019 group. Data analyzed: (1) patient baseline data; (2) surgery and postoperative recovery; (3) lateral lymph node dissection; (4) postoperative survival and prognosis of patients with positive lateral lymph nodes. The surgical methods and pathological results of LLND were compared between groups, and the prognostic risk factors of patients with LLNM were analyzed. Results: A total of 289 patients underwent radical resection with LLND' accounting for 6.3% of the 4542 patients with rectal cancer during the same period in our hospital. Except decade-by-decade increase in tumors with distance from anal verge ≤ 7 cm, the proportion of ulcerated tumors, and the proportion of neoadjuvant radiochemotherapy, the differences in other baseline data were not statistically significant among 3 decade groups (all P>0.05). The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2490), χ(2)=40.159, P<0.001]. The proportion of laparoscopic surgery and unilateral LLND increased, while the mean operative time, intraoperative blood loss, surgical complications above grade III and postoperative hospital stay decreased decade by decade. These 289 patients completed a total of 483 lateral dissections, including 95 cases of the unilateral dissection and 194 cases of the bilateral dissection. The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2510), P<0.001]. The median number of dissected lymph nodes in the internal iliac artery and obturator regions increased (2 vs. 3 vs. 3, P<0.001), but those in the common iliac and external iliac regions decreased significantly (4 vs. 3 vs. 2, P=0.014). A total of 71 patients with LLNM were identified. The rate of LLNM in the 2010-2019 group was significantly higher than that in the previous two groups [37.0% (40/108) vs. 16.9% (15/89) vs. 17.4% (16/92), P=0.001]. The patients with LLNM showed a poorer overall survival (OS) and disease-free survival (DFS) compared with negative lateral lymph nodes (P<0.001). There were statistically significant differences in 5-year OS rate (30.9% vs. 27.2% vs. 0, P=0.028) and 5-year DFS rate (28.3% vs. 16.0% vs. 0, P=0.038) among patients with only internal iliac lymph node metastasis, patients with only obturator lymph node metastasis, and patients with external iliac or common iliac lymph node metastasis. Multivariate analysis of prognostic factors showed that external iliac or common iliac lymph node metastasis was an independent risk factor for OS (HR=1.649, 95%CI: 1.087-2.501) and DFS (HR=1.714, 95%CI: 1.173-2.504) in patients with LLNM (all P<0.05) . The OS and DFS were not significant different in patients with LLNM among 3 decade groups. Conclusions: In the past decade, the proportion of LLND in rectal cancer has decreased significantly. However, LLNM rate has been significantly increased due to preoperative imaging assessments focusing on suspicious LLNM without compromising the survival. Internal iliac artery and obturator lymph nodes can be regarded as regional lymph nodes with a satisfactory prognosis after LLND. For suspected external iliac or common iliac lymph node metastasis, the significance of LLND remains to be further evaluated.

Clinical analysis of 554 patients with colorectal diverticulosis / 中华胃肠外科杂志

Objective: Most patients with asymptomatic colorectal diverticulosis are easily overlooked. However, some of diverticulosis become diverticulitis, bleeding and even perforation, which cause extensive harm to patients. The purpose of this study is to analyze the incidence, clinical features, diagnosis and treatment of colorectal diverticulosis in order to improve the clinical understanding of diverticulosis and its related complications. Methods: A descriptive cohort study was carried out. Clinical data of 554 patients with colorectal diverticulosis confirmed by CT, colonoscopy, digestive tract radiography or operation in Peking University First Hospital from January 2009 to June 2019 were retrospectively analyzed. Patients with malignant tumors, autoimmune diseases, long term use of immunosuppressive drugs, chronic liver diseases and renal diseases, and mental disorders were excluded. The analysis parameters included gender, onset age, clinical symptoms, location of diverticulitis, treatment and prognosis. According to the criteria established by the World Society of Emergency Surgery (WSES), acute diverticulitis was divided into 5 stages based on the extension of the infectious process. Stage 0 was simple diverticulitis and stage 1-4 was complicated diverticulitis. Results: Among the 554 patients with colorectal diverticulosis, 358 (64.6%) were males, the median onset age was 63 years; 191 patients (34.5%) had various digestive symptoms, of whom 113 (20.4%) had chronic constipation and abdominal distension, 78 (14.1%) had chronic diarrhea and abdominal pain; the other 363 patients had no obvious abdominal symptoms. Four hundred and six patients were found by colonoscopy and 465 patients were found by CT. Twenty-five patients were diagnosed by lower gastrointestinal tract radiography and 3 were confirmed during operation. There were 339 patients with multiple diverticula (61.2%) and 215 patients with single diverticulum (38.8%). 76.5% (424/554) of diverticula were located in colon, 37.0% (205/554) in ascending colon, 21.3% (118/554) in multiple sites, and 2.2% (12/554) in rectum. The median diameter of diverticulum was 7 mm, and 78 cases (14.1%) was ≥30 mm. Forty-nine patients (8.8%) developed acute diverticulitis, including 13 patients with simple diverticulitis and 36 patients with complicated diverticulitis. Among 36 patients with complicated diverticulitis, 29 (80.6%) were males, 27 (75.0%) had recurrent abdominal pain and fever before onset; diverticula of 25 cases were located in sigmoid colon; 11 cases in ascending colon. Nine cases developed sigmoid colon perforation and 8 cases developed vesicocolonic fistula, and these 17 patients underwent surgical treatment. The other 19 cases with complicated diverticulitis developed gastrointestinal bleeding, of whom 18 cases were male, 11 cases were located in ascending colon; 13 cases were healed after conservative treatment, 4 cases received endoscopic hemostatic intervention, and 2 cases underwent surgery. Conclusions: Colorectal diverticulosis is more common in male patients, and CT and colonoscopy are main diagnostic methods. The symptoms of complicated colonic diverticulitis are related to the location of diverticulum. In addition to symptomatic treatment, surgical procedures are the most important treatments.

Clinicopathological analysis and surgical strategy of primary appendiceal neoplasms / 中华胃肠外科杂志

Objective: To investigate the clinicopathological features, surgical methods and prognosis of primary appendiceal neoplasms. Methods: A descriptive case series study was performed. Clinical data of patients diagnosed with primary appendiceal neoplasms in Peking University First Hospital from 2006 to 2017 were retrospectively analyzed. Patients who underwent surgery and were confirmed as appendiceal neoplasms by postoperative pathology were included. Cases of cecal tumor invading the appendix and other organ tumors implanting in the appendix and cases of recurrent appendix tumors were excluded Pathological classification was based on the 4th edition of the WHO classification of digestive tract tumors (2010 edition), and the efficacy of operation methods of low grade appendiceal mucinous neoplasm (LAMN) were analyzed. Results: A total of 115 patients were enrolled, including 52 males and 63 females with a median age of 59 (51, 71) years. Clinical symptoms usually manifested as dormant pain in the right lower quadrant, migrating right lower abdominal pain, fever and bloating. Twenty-four cases were accidentally discovered during surgery, and 21 cases were found by physical examination. The preoperative diagnosis rate of CT and ultrasound was 40.2% (43/107) and 25.5% (24/94) respectively. The postoperative pathological types contained 83 cases of LAMN, 12 cases of mucinous adenocarcinoma, 9 cases of appendiceal neuroendocrine neoplasms (aNEN), 2 cases of mucinous adenocarcinoma with signet ring cells, 3 cases of serrated adenoma, 2 cases of goblet cell carcinoid, 2 cases of lymphoma, 1 case of leiomyoma and 1 case of schwannomas. All the patients underwent surgical resection, including 41 cases of appendectomy, 21 cases of partial cecectomy, 48 cases of right hemicolectomy, and 5 cases of combined organ resection due to appendiceal tumor infiltration or dissemination. Eighteen cases were diagnosed with pseudomyxoma peritonei (PMP) during operation. A total of 98 patients were enrolled for follow-up. The median follow-up time was 58 (5-172) months. The 5-year disease-free survival (DFS) rate was 84.5% and 5-year overall survival (OS) was 88.2%. Multivariate analysis revealed that high-grade malignancy tumors (HR=25.881, 95% CI: 2.827-236.935, P=0.004) and PMP formation (HR=42.166, 95% CI: 3.470-512.439,P=0.003) were independent risk factors for prognosis. Patients undergoing right hemicolectomy presented longer operation time, more blood loss and higher morbidity of complication as compared to those undergoing appendectomy and partial cecectomy (all P<0.05), while no significant differences in 5-year DFS (P=0.627) and 5-year OS (P=0.718) were found. Conclusions: Primary appendiceal neoplasms usually have no typical features, accompanied with low preoperative diagnosis rate. The common pathological types are LAMN, mucinous adenocarcinoma and aNEN. Appendectomy or partial cecectomy for LAMN may achieve satisfactory prognosis. High-grade malignancy tumors and PMP formation are independent risk factors for prognosis.

Protective Effect of Cimetidine on 0.3 Gy Accumulatively Irradiated Rats / 中国药学杂志

OBJECTIVE: To investigate the protective effect of cimetidine (CMTD) on rats irradiated with 60Co γ-rays at low dose rate.METHODS: Sixty male SD rats were randomly divided into normal group, model group, positive drug group, CMTD groups.The mice were irradiated with 60Co γ rays and an absorbed dose was 0.3 Gy, and the dose rate was 3.228 mGy•h-1. Twenty-four hours after irradiation, white blood cells, bone marrow DNA content, bone marrow polynuclear erythrocyte micronucleus rate (fMNPCE), sperm motility and sex hormones were detected. RESULTS When the cumulative absorbed dose was 0.3 Gy, the peripheral blood cells and bone marrow DNA content decreased significantly, fMNPCE increased significantly, and the sperm motility, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels reduced while the level of estradiol increased. Cimetidine not only could effectively increase the number of white blood cells, bone marrow DNA content, the level of FSH and LH but also reduce fMNPCE and the level of estradiol. CONCLUSION: CMTD could reduce the DNA damage which caused by 0.3 Gy cumulative irradiation, regulate sex hormone disturbance, and effectively improve hematopoietic function and reproductive function of irradiated rats.All RESULTS: shows that CMTD might be a good radioprotector.

Protective effects of cimetidine on rats with low-dose rate 60Co γ-ray cumulative irradiation / 解放军医学杂志

Objective To investigate the protective effects of cimetidine on rats with low dose rate (LDR) 60Co γ-ray cumulative irradiation. Methods Sixty male SD rats (6-8 weeks old) were randomized into 6 groups (10 each): normal control group, model group, positive control group (89.0 mg/kg lentinan), low-dose cimetidine group (23.3 mg/kg cimetidine), medium-dose cimetidine group (70.0 mg/kg cimetidine), and high-dose cimetidine group (210.0 mg/kg cimetidine). Except for rats in normal control group, the rest rats were irradiated with 60Coγ-ray to a cumulative dose of 0.5 Gy with a dose rate of 3.228 mGy/ h. Twenty-four hours after the last irradiation, peripheral blood cells, bone marrow DNA content, frequencies of micronucleated polychromatic erythrocytes (fMNPCE), bone marrow nucleated cells, sperm count, testis HE, sex hormones, superoxide dismutase (SOD), glutathione (GPx), catalase (CAT) activity, and malondialdehyde (MDA) content were measured. Results Compared with normal control group, in model group, WBC, lymphocyte and granulocyte content, bone marrow DNA content and the number of nucleated cells significantly decreased (P<0.05), but fMNPCE increased significantly (P<0.01). In addition, sperm count, testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels significantly reduced (P<0.05 or P<0.01), estradiol (E2) levels significantly increased (P<0.05), SOD, GPx and CAT activities significantly decreased (P<0.05 or P<0.01), and MDA levels significantly increased (P<0.01). Rat models were established successfully. Compared with model group, in positive control group, the bone marrow DNA content and T content significantly increased (P<0.05), antioxidant enzyme activity of SOD, GPx and CAT significantly increased (P<0.05 or P<0.01), while the contents of fMNPCE, MDA and E2 significantly reduced (P<0.05 or P<0.01). In the cimetidine-treated groups, the blood lymphocyte number and bone marrow DNA content significantly increased (P<0.01), the activity of antioxidant enzymes SOD, CAT, GPx, T, FSH and LH increased, and the content of fMNPCE, E2 and MDA decreased, the damage of testicular tissue structure decreased (P<0.05), and the number of sperm increased, but there has no statistic significance. Conclusion Cimetidine, as a potential radiation protection drugs, could effectively improve the rat injury with low-dose-rate 60Coγ-ray cumulative irradiation.

The antenatal diagnosis of placentaaccreta by ultrasound / 医学研究生学报

As one of the pregnancy complications， Placenta accreta is becoming increasingly common. Ultrasound is the primary technique for prenatal diagnosis of placenta accreta, whereas the features of the image are complex and the diagnostic criteria are not still uncover. This article reviewed the ultrasonographic features of placenta accrete on two-dimensional, color doppler and power doppler ultrasonography.

New preclinical mouse model: Patient-derived xenografts / 肿瘤

The mouse models of nude mice bearing subcutaneous xenografts derived from tumor cell lines provide a preclinical testing system for exploring novel anticancer therapies. However, due to the lack of heterogeneity and an ability of spontaneous distant metastasis, these traditional models are difficult to accurately simulate the clinical condition of the patient. Recently, some researchers have developed better preclinical models by using patient-derived xenografts (PDXs) in mice. It has been shown that transplanting a variety of patient-derived tumor tissues into an appropriate anatomical site of immunocompromised or transgenic mice can authentically mimic the primary tumor in patients, especially with distant metastatic ability. PDXs can not only faithfully preserve the molecular phenotypes and genomic alterations of the primary tumors in patients, but also reproduce the heterogeneity of primary tumors; therefore, PDXs have been used in investigation of mechanism of drug resistance. This review summarizes the methodology of establishing PDXs, verification of similarity in original tumor and the corresponding xenograft, and the value and limitations of PDXs used in the development of new drugs. Copyright © 2014 by TUMOR.

Effects of D-methionine on the hematopoietic system injury in irradiated mice / 中国实验血液学杂志

The aim of this study was to investigate the effects of D-methionine (D-met) on the hematopoietic system injury in irradiated mice. C57BL/6 mice were divided into control group, irradiated group, 300 mg/kg D-met plus irradiation group and 1000 mg/kg D-met plus irradiation group. The control mice received sham irradiation, and the mice in remainder groups were exposed to 7.5 Gy; 1,4,8 Gy and 1 Gy of (137)Cs γ-ray respectively, were used to detect the survival rate, survival rate of bone marrow cells, WBC and its differential counts as well the colony formation ability in irradiated mice, respectively. The D-met was intraperitoneally injected to mice at 30 min before irradiation. The results showed that 300 and 1000 mg/kd D-met did not obviously enhance the survival rate of mice exposed to 7.5 Gy; the 10(-2),10(-3),10(-4) mol/L D-met significantly increased the survival rate of bone marrow cells in mice exposed to 1,4,8 Gy; 300 and 1000 mg/kg D-met even so increased the WBC count of peripheral blood in mice exposed to 1 Gy, but there was no statistical difference as compared with irradiated alone mice, moreover 300 and 1000 mg/kg D-met could obviously promote the colony formation ability of bone marrow cells in irradiated mice, the CFU-GM count was higher than that in 1 Gy irradiated mice (P < 0.05). It is concluded that the D-met can effectively mitigate the marrow cell injury resulted from irradiation, enhance the survival rate of bone marrow cells in irradiated mice, promote the recovery of hematopoietic function from radiation injury in mice.

Relationship between Chinese medicine syndrome type and mRNA expressions of IL-10, IL-18 and Fas in peripheral blood mononuclear cells in patients with systemic lupus erythematosus / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mRNA expressions of IL-10, IL-18 and Fas in peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients of various Chinese medicine syndrome types in order to seek the objective indices for syndrome differentiation of SLE.</p><p><b>METHODS</b>SLE patients were sorted into various syndrome types by Chinese medicine syndrome differentiation. In them, patients with the 4 often encountered types were selected, i.e. the qi-xue excessive heat type (Group A, 12 patients), the Pi-Shen yang-deficiency type (Group B, 19 patients), the qi-yin deficiency with blood stasis type (Group C, 23 patients), and the qi stagnation and blood stasis with gan stagnation type (Group D, 28 patients). The mRNA expressions of IL-10, IL-18 and Fas in PBMCs were detected by SYBR Green I real time PCR.</p><p><b>RESULTS</b>The mRNA expressions of IL-10, IL-18 and Fas in PBMC of all SLE patients (0.40 +/- 0.53, 1.41 +/- 1.93 and 0.33 +/- 0.70) were significantly higher than those in the normal control group (0.07 +/- 0.11, 0.24 +/- 0.25, 0.08 +/- 0.21, P<0.01, P<0.05), their levels in different syndrome types decreased in order of type A-->B-->C-->D. The levels of the three indices in patients of type A and B were obviously higher than those in patients of type C and D (P<0.01), while no significant difference was found between type A and B (P>0.05), and between type C and D (P>0.05).</p><p><b>CONCLUSION</b>The mRNA expressions of IL-10, IL-18 and Fas in PBMCs could be taken as the objective indices for reference in syndrome differentiation of SLE.</p>

Relationship between Simple Obesity and Fibrinogen,B?448 G/A Gene Polymorphism in Children / 实用儿科临床杂志

0.05).The FMPV of the B?448 AA plus GA was higher than that of the GG type in obesity group(P0.05).Conclusions The simple obesity in children is associated with Fg and FMPV,which have become the high risk factors of the disease of heart and brain.The Fg B?448 G/A gene polymorphism may be an accumulative efficiency gene of children with simple obesity by influencing FMPV.