[Long-term outcome of patients with rectal cancer who achieve complete or near complete clinical responses after neoadjuvant therapy: a multicenter registry study of data from the Chinese Watch and Wait Database].

Objective: To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT). Methods: This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups. Results: Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion: Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

[A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics].

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

[Short-term outcome of programmed cell death protein1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors].

Objective: Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer. This study aims to investigate the safety and feasibility of programmed cell death protein 1 (PD-1) antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors. Methods: A descriptive cohort study was conducted. Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed. Inclusion criteria: (1) rectal adenocarcinoma confirmed by pathology; patient age of ≥ 18 years and ≤ 80 years; (2) the distance from low margin of tumor to anal verge ≤ 10 cm under sigmoidoscopy; (3) ECOG performance status score 0-1; (4) clinical stage T3c, T3d, T4a or T4b, or extramural venous invasion (EMVI) (+) or mrN2 (+) or mesorectal fasciae (MRF) (+) based on MRI; (5) no evidence of distant metastases; (6) no prior pelvic radiation therapy, no prior chemotherapy or surgery for rectal cancer; (7) no systemic infection requiring antibiotic treatment and no immune system disease. Exclusion criteria: (1) anticipated unresectable tumor after neoadjuvant treatment; (2) patients with a history of a prior malignancy within the past 5 years, or with a history of any arterial thrombotic event within the past 6 months; (3) patients received other types of antitumor or experimental therapy; (4) women who were pregnant or breast-feeding; (5) patients with any other concurrent medical or psychiatric condition or disease; (6) patients received immunotherapy (PD-1 antibody). The neoadjuvant therapy consisted of three stages: PD-1 antibody (sintilimab 200 mg, IV, Q3W) combined with CapeOx regimen for three cycles; long-course intensity modulated radiation therapy (IMRT) with gross tumor volume (GTV) 50.6 Gy/CTV 41.8 Gy/22f; CapeOx regimen for two cycles after radiotherapy. After oncological evaluation following the end of the third stage of treatment, surgery or watch and wait would be carried out. Surgical safety, histopathological changes and short-term oncological outcome were analyzed. Results: There were 15 males and 9 females with a median age of 65 (47-78) years. Median distance from the lower margin of the tumor to the anal verge was 4 (3-7) cm. The median maximal diameter of the tumor was 5.1 (2.1-7.5) cm. Twenty patients were cT3, 4 were cT4, 8 were cN1, 5 were cN2a, 11 were cN2b. Ten cases were MRF (+) and 10 were EMVI (+). All the patients were mismatch repair proficient (pMMR). During the neoadjuvant treatment period, 6 patients (25.0%) developed grade 1-2 treatment-related adverse events, including 3 immune-related adverse events. As of April 30, 2021, 20 patients (83.3%, 20/24) had received surgical resection, including 19 R0 resections and 16 sphincter-preservation operations. Morbidity of postoperative complication was 25.0% (5/20), including 2 cases of Clavien-Dindo grade II (1 of anastomotic bleeding and 1 of pseudomembranous enteritis), 3 cases of grade I anastomotic stenosis. Pathological complete response (pCR) rate was 30.0% (6/20) and major pathological response rate was 20.0% (4/20). None of Ras/Raf mutants had pCR or cCR (0/5), while 6 of 17 Ras/Raf wild-type patients had pCR and 3 had cCR, which was significantly higher than that of Ras/Raf mutants (P<0.01). Nine of 16 patients with Ras/Raf wild-type and differentiated adenocarcinoma had pCR or cCR. Among other 4 patients without surgery, 3 patients preferred watch and wait strategy because their tumors were assessed as clinical complete response (cCR), while another one patient refused surgery as the tumor remained stable. After a median follow-up of 11 (6-24) months, only 1 patient with signet ring cell carcinoma had recurrence. Conclusions: PD-1 antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer has quite good safety and histopathological regression results. Combination of histology and genetic testing is helpful to screen potential beneficiaries.

Identification and validation of a hub gene prognostic index for hepatocellular carcinoma.

Aims: We aim to provide new insights into the mechanisms of hepatocellular carcinoma (HCC) and identify key genes as biomarkers for the prognosis of HCC. Materials & methods: Differentially expressed genes between HCC tissues and normal tissues were identified via the Gene Expression Omnibus tool. The top ten hub genes screened by the degree of the protein nodes in the protein-protein interaction network also showed significant associations with overall survival in HCC patients. Results: A prognostic model containing a five-gene signature was constructed to predict the prognosis of HCC via multivariate Cox regression analysis. Conclusion: This study identified a novel five-gene signature (CDK1, CCNB1, CCNB2, BUB1 and KIF11) as a significant independent prognostic factor.

Lay abstract Given the poor success of traditional treatments in improving the prognosis of hepatocellular carcinoma (HCC), we need new techniques to improve survival. The new techniques must be checked for accuracy and we must assess whether we can utilize it to achieve individualized treatment. The finding of this study, which examined genetic differences between tumor tissues and normal tissues, is that patients with a high-risk genetic 'signature' have worse results and a shorter survival time than those with a low-risk profile. We first screen hub genes related to the survival status of HCC patients. Then we construct a risk score model to predict the prognosis of HCC and confirm that the model is highly credible. It is reasonable to believe that our risk score model has a high predictive value for the prognosis of HCC.

[The effects and immunologic mechanisms of Helicobacter pylori infection on AOM/DSS induced colitis-associated cancer in mice].

Objective: To investigate the effects and potential mechanisms of Helicobacter pylori (H.pylori) infection on azoxymethane (AOM)/dextran sulfate sulphate (DSS) induced colitis-associated cancer (CAC) in mice. Methods: A total of 60 specific pathogen free C57BL/6J mice were randomly divided into four groups: normal control group (control group, n=9), H. pylori-infected group (Hp group, n=9), AOM/DSS-treated group (AOM/DSS group,n=21) and AOM/DSS-treated with H.pylori infection group (Hp+AOM/DSS group, n=21). Mice were sacrificed on day19, 45 or 85 after AOM/DSS challenge. Histopathological changes in colonic tissues were determined by hematoxylin and eosin staining. Flow cytometry analysis was performed to determine T helper cells 17 (Th17) and regulatory T cells (Treg) in colonic lamina propria. The expression levels of Th17-and Treg-associated cytokines and transcription factors [interleukin (IL)-10, IL-17A, retinoic acid receptor-related orphan receptor γt (RORγt) and forkhead box P3 (Foxp3)] were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: There were no histopathological changes in colonic tissues of mice in control group and Hp group. H.pylori colonization reduced the histopathological scores at the stages of colitis (day 19) and dysplasia (day 45), and also decreased tumor load (day 85) in mice treated with AOM/DSS (all P<0.05). Compared with AOM/DSS group, the percentages of CD3(+)CD4(+)IL-17A(+)Th17 and CD3(+)CD4(+)IL-17A(+)Foxp3(+)Treg cells (1.88±0.17 vs 2.07±0.89, 1.06±0.13 vs 1.89±0.23) and the expression levels of RORγt and IL-17A (1.08±0.59 vs 2.35±1.35, 2.96±0.92 vs 7.78±4.57) were decreased in colonic tissues of Hp+AOM/DSS group (all P<0.05). The percentages of CD3(+)CD4(+)CD25(+)Foxp3(+)Treg and CD3(+)CD4(+)IL-10(+)Foxp3(+)Treg cells (20.60±3.39 vs 15.63±2.71, 2.94±0.52 vs 2.14±0.47) and the expression levels of Foxp3 and IL-10 [17.59(13.77,24.87) vs 6.27(4.41,13.36), 3.52(1.59,5.99) vs 1.17(1.15,2.75)] in colonic tissues were higher (all P<0.05) in mice of Hp+AOM/DSS group compared with AOM/DSS group on day 85. Conclusion: H.pylori infection slows the progress from inflammation to tumor in a AOM/DSS induced CAC modal, accompanied with the downregulation of Th17 response and upregulation of Treg response.

[Analysis of trends on smoking prevalence and its risk factors in Shaanxi province 2007-2015].

Objective: To analyze the trend of smoking prevalence and its risk factors among adults in Shaanxi province from 2007 to 2015. Methods: We used data from China Chronic Disease and Risk Factor Surveillance in 2007, 2010, 2013 and 2015. The current smoking prevalence and trends of the four surveys were calculated. Its risk factors were analyzed by multivariate logistic regression from each survey and then from all pooled data of the three surveys. Results: The number of participants in 2007, 2010, 2013 and 2015 was 1 542, 3 000, 10 166 and 6 330, respectively. The current smoking prevalence dropped from 34.34% in 2007 to 26.22% in 2013, but increased to 28.33% in 2015 (trend χ(2) test: Z=2.53, P=0.01). The results from four pooled data showed that the current smoking prevalence of men was higher than that of women (OR=75.03, 95%CI: 63.57-88.55). The current smoking prevalence of people aged 45-59 was higher than that of people aged 18-44 (OR=1.28, 95%CI: 1.15-1.41). In addition, the current smoking prevalence of those who were educated for 7-9 years and more than 9 years were higher than those who were educated for less than 6 years (people with education for 7-9 years OR=1.44, 95%CI: 1.29-1.61; people with education >9 years OR=1.43, 95%CI: 1.26-1.63). The current smoking prevalence of the single was lower than those of married/cohabitants (OR=0.54, 95%CI: 0.37-0.77). The current smoking prevalence of retirees were lower than those of employees (OR=0.46, 95%CI: 0.38-0.57) and smoking prevalence of alcohol drinkers were higher than those of non-drinkers (OR=2.92, 95%CI: 2.67-3.19). Conclusion: From 2007 to 2015, the current smoking prevalence of Shaanxi population was high and the trends remained stable. It is necessary to strengthen smoking control and health education for men, people over 45 years old, people with education level 7 years and above, and working personnel in Shaanxi province.

[Total neoadjuvant therapy followed by watch and wait approach or organ preservation for MRI stratified low-risk rectal cancer: early result from a prospective, single arm trial].

Objective: To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer. Methods: A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR). Results: Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE. Conclusion: Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.

Prognostic and predictive values of CXCL10 in colorectal cancer.

BACKGROUND: The role of CXCL10 in progression and prognosis of colorectal cancer (CRC) has been studied for years, yet results remain controversial. AIM: This study aims to explore the relationship between CXCL10 and CRC progression and prognosis. METHODS: We evaluated plasma CXCL10 in CRC patients using ELISA. We also performed a meta-analysis of the associations between CXCL10 and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), relapse-free survival (RFS), and clinicopathological features. Finally, correlations between CXCL10 and methylation or immune infiltration were performed using TCGA data. RESULTS: ELISA analysis showed that CXCL10 was associated with age, red blood cells, blood platelets, and blood urea nitrogen. A separate analysis of 3,763 patients from 24 studies revealed that there were significant associations between low CXCL10 expression and OS (HR 1.25, 95% CI 1.01-1.53), DFS (HR 1.65, 95% CI 1.17-2.34), and RFS (HR 1.43, 95% CI 1.20-1.71) in CRC. Additionally, downregulated CXCL10 expression was significantly correlated with age [odds ratio (OR) 1.31, 95% CI 1.13-1.52], metastasis (OR 1.34, 95% CI 1.11-1.63), recurrence (OR 1.46, 95% CI 1.16-1.83), tumor location (OR 1.88, 95% CI 1.58-2.24), differentiation (OR 0.57, 95% CI 0.35-0.93), microsatellite instability (OR 0.23, 95% CI 0.15-0.35), BRAF mutation (OR 1.62, 95% CI 1.25-2.08), p53 mutation (OR 0.28, 95% CI 0.16-0.47), and CIMP (OR 0.27, 95% CI 0.17-0.43). Furthermore, significant associations were observed between CXCL10 and methylation and immune infiltration. CONCLUSIONS: The study suggests that CXCL10 might be a potential target for the treatment of CRC. TRIAL REGISTRATION: NCT03189992. Registered 4 June 2017, https://www.clinicaltrials.gov/ct2/show/study/NCT03189992?term=NCT03189992&rank=1 .

[Trends of smoking and passive smoking in residents in Shaanxi province: an analysis on results of four cross-sectional surveys, 2007-2015].

Objective: To understand the trends of smoking and passive smoking exposure in adults in Shaanxi province from 2007 to 2015. Methods: Data was from China Chronic Disease and Risk Factor Surveillance in 2007, 2010, 2013 and 2015 to calculate the rates of smoking, smoking cessation and passive smoking exposure, as well as the amount of smoking of smokers indicated by each surveillance. Cochran-Armitage test was used to assess the trends across survey periods. The weighting rate was calculated by using sampling weight and data from the 6(th) national census in 2010. Sensitivity analysis was done to test the trends as well. Results: The results of the surveillance indicated that the smoking rate in 2007 was 38.26%, highest in the results of four surveys, it decreased to 30.95% in 2013 and then increased to 34.11% in 2015 (Cochran-Armitage test: Z=2.46, P=0.014). The amount of smoking increased from 16.90 cigarettes per day in 2007 to 17.76 cigarettes per day in 2015. The overall rate of smoking cessation was 11.02% in 2007 and 16.95% in 2015 (Cochran- Armitage test: Z=-4.18, P<0.01). We observed the passive smoking exposure rate was 48.10% in 2010 and 63.88% in 2015 (Cochran-Armitage test: Z=-10.60, P<0.01). We found no difference in trends by sensitivity analysis. Conclusions: The smoking rate and amount of cigarettes smoked in adults in Shaanxi remained stable and at a high level. The rate of smoking cessation increased gradually, while the passive smoking exposure rate increased rapidly.

[The research of sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer patients].

With the extensive use of sentinel lymph node biopsy (SLNB), some breast cancer patients could avoid axillary lymph node dissection (ALND) and its complications. Neoadjuvant chemotherapy plays an important role in the multimodality therapies of breast cancer. After neoadjuvant chemotherapy, some patients with breast cancer were down-staged from positive axillary lymph node (cN+ ) to clinically negative (cN0). For these patients, the feasibility and safety of sentinel lymph node biopsy remains controversial. However, with the application of new technologies, SLNB is expected to become the main treatment for breast cancer patients with stage cN0 after neoadjuvant chemotherapy.

[The 8th edition of the American Joint Committee on Cancer staging system provide improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients].

Objective: To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods: a total of 1 823 female patients with T1-2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log-rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic (ROC) analyses and the concordance index (C-index). Results: 5-year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5-year distant metastasis (DM) rate was 11.5%, 5-year disease-free survival (DFS) was 85.0%, and 5-year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS (P<0.05). Compared with stage by 7th edition, 1 278(70.1%) were assigned to a different prognostic stage group: 1 088 (85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stage ⅠA, ⅠB, ⅡA, ⅡB and ⅢA according to 8th edition of the AJCC staging system(P<0.001). Prognostic stage had significantly higher C-indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system (P<0.001). Conclusion: The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1-2N1M0 breast cancer, and has better clinical therapeutic guidance value.

[Protective effects of sucralfate on gastric mucosal injury induced by Helicobacter pylori and its effects on gastrointestinal flora in mice].

Objective: To investigate the effects of sucralfate suspension gel (SC) on Helicobacter pylori (H.pylori) colonization, H.pylori-induced gastric mucosal injury and gastrointestinal microecology in mice. Methods: C57BL/6J mice were randomly divided into 3 groups, including normal control (NC) group, H.pylori model (HP) group, and SC prevention (HP+SC) group. H.pylori infection mouse model was established by gavage with H.pylori Sydney strain (SS1). And HP+SC group was also administered with SC for 14 days. After mice were sacrificed, the gastric mucosa was taken for HE staining, immunohistochemical (IHC) staining [H.pylori, zonula occludens-1 (ZO-1), Occludin, interleukin (IL)-8, IL-10 and tumor necrosis factor-α (TNF-α)], qPCR (IL-8, IL-10, TNF-α) . And cell ultrastructure was observed by electron microscopy. Microbiota communities in the gastric mucosa or fecal were investigated using 16S ribosomal RNA (rRNA) gene sequencing. The detection of H.pylori in IHC staining or Giemsa staining was defined as H.pylori infection. Results: The H.pylori positive rate of HP group was 91.67%, and that of HP+SC group was 50.00%. The EDS of HP group were significantly higher than those of the NC group [(3.42±0.19) vs (1.17±0.17), P<0.05], while EDS of HP+SC group (2.42±0.29) were significantly lower than that of HP group (P<0.05). The mRNA levels and immunostaining scores of IL-8, IL-10 and TNF-α in HP group was higher than NC group (all P<0.05). Compared with HP group, mRNA levels and IHC scores of IL-8 significantly decreased (all P<0.05) in HP+SC group, while those of IL-10 and TNF-α was similar between two groups (all P>0.05). The IHC scores of ZO-1 and Occludin in HP group was significantly lower than NC group (all P<0.05), and that of ZO-1 and Occludin in the HP+SC group increased compared with HP group [(2.00±0.26) vs (1.17±0.48), P>0.05; (3.50±0.43) vs (2.33±0.21), P<0.05]. Compared with NC group, the diversity of gastric microbiota in HP group was significantly lower, and diversity of gut microbiota decreased insignificantly. There was no significant difference between HP+SC group and HP group in gastric or gut microbiota. Conclusion: SC reduces H.pylori colonization, protects H.pylori-induced gastric mucosal injury, decreases H.pylori-induced IL-8 expression, enhances Occludin. However, its effects on H.pylori-induced gastrointestinal microbiota disorders are limited.

Effect of lncRNA H19 on the apoptosis of vascular endothelial cells in arteriosclerosis obliterans via the NF-κB pathway.

OBJECTIVE: To explore the effect of long non-coding ribonucleic acid (lncRNA) H19 on the apoptosis of vascular endothelial cells in arteriosclerosis obliterans (ASO) via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. PATIENTS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured, and lncRNA H19 was inhibited by Si-H9 and overexpressed by H19-OE. Then, the apoptosis rate was detected by flow cytometry, the target of lncRNA H19 was detected by dual luciferase reporter gene assay, and changes in the protein level were determined via Western blotting (WB). RESULTS: LncRNA H19 exhibited high expression in serum of patients with ASO, and compared with that in congeneric normal mice, the expression of lncRNA H19 in ASO mice rose. Besides, the proliferation ability of cells transfected with H19-OE was markedly strengthened, and H19-OE treatment could down-regulate the expression level of the apoptin, active cysteinyl aspartate-specific proteinase-3 (Caspase-3). In addition, lncRNA H19 bound to micro ribonucleic acid (miR)-19a in a targeted way. After lncRNA H19 was overexpressed, the expression of the NF-κB pathway key factors, p38 and p65, were notably increased, and the nuclear translocation of p65 was significantly enhanced after transfection with miR-19a. CONCLUSIONS: LncRNA H19 promotes the proliferation of vascular endothelial cells in ASO and inhibits the apoptosis of them via the NF-κB pathway.

[Retrospective cohort study on subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy in the treatment of senile slow transit constipation].

Objective: To investigate the clinical efficacy of laparoscopic subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy (SCBCAC) in the treatment of senile slow transit constipation. Methods: A retrospective cohort study was performed. Clinical data of 30 colonic slow transit constipation patients aged ≥70 years old undergoing laparoscopic SCBCAC from July 2012 to October 2016 (bypass plus colostomy group), and 28 patients undergoing laparoscopic subtotal colonic bypass with antiperistaltic cecoproctostomy (SCBAC) from February 2009 to June 2012 (bypass group) at our institute were collected. Efficacy was compared between the two procedures. Inclusion criteria: (1) meeting the Rome III diagnosis criteria for constipation; (2) confirmed diagnosis of slow transit constipation; (3) age ≥ 70 years old; (4) receiving non-surgical treatment for more than 5 years, and Wexner constipation score > 15; (5) follow-up for more than 2 years. Those with psychiatric symptoms or previous psychiatric history, obvious signs of outlet obstructive constipation, organic diseases of the colon and life-threatening cardiovascular diseases or cancer were excluded. In the bypass plus colostomy group, laparoscopy was performed via five trocars. The ileocecal junction and the ascending colon were mobilized and the ileocecal junction was pulled down to the pelvic inlet. The ascending colon was transected and the appendix was excised. The lateral peritoneum of the sigmoid colon and the rectal mesentery were dissected and the upper rectum was transected. The avil of a circular stapler was placed in the bottom of the cecum. The shaft of the stapler was placed in the rectum via the anal canal to complete end-to-side anastomosis (end rectum to lateral cecum). The end of the rectal-sigmoid colon was used for colostomy via an extraperitoneal approach to complete the operation. The following efficacy indexes were collected before surgery and 3, 6, 12, and 24 months after surgery: the number of daily bowel movements, the Wexner incontinence scale (WIS, 0-20, the lower the better), the Wexner constipation scale (WCS, 0-30, the lower the better), the gastrointestinal quality of life index (GIQLI, 0-144, the higher score, the better), abdominal pain intensity indicated by the numerical rating scale (NRS, 0-10, the lower score, the better), and the abdominal bloating score (ABS, 0-4, the lower score, the better). The complications defined as Clavien-Dindo class II or above were observed and recorded. Results: No significant differences in preoperative WCS, WIS, GIQLI, NRS, and ABS were observed between bypass plus colostomy group and bypass group (all P>0.05). All the patients successfully underwent laparoscopic surgery and no patient in either group experienced postoperative fecal incontinence. WCS and GIQLI were significantly improved (all P<0.001) at 3, 6, 12, and 24 months after surgery in both groups. At 12 months after surgery, the number of bowel movements was significantly less in bypass plus colostomy group than that in bypass group [(2.4±0.7) times vs. (3.4±1.2) times, t=4.048, P<0.001]. At 3, 6, 12 and 24 months after surgery, the improvement of GIQLI in bypass plus colostomy group was significantly better than that in bypass group (all P<0.001). At 24 months after surgery, GIQLI in bypass plus colostomy group and bypass group was 122.3±5.3 and 92.8±16.6, respectively, with a significant difference (t=9.276, P<0.001). At 12 and 24 months after surgery, NRS in bypass plus colostomy group was significantly better than that in bypass group (both P<0.001). At 24 months after surgery, NRS in bypass plus colostomy group was 0.9±0.7, while that in bypass group was 3.7±2.7. There was a significant difference between two groups (t=5.585, P<0.001). At 6, 12 and 24 months after surgery, the improvement of ABS in bypass plus colostomy group was also significantly better than that in bypass group. At 24 months after surgery, ABS in bypass plus colostomy group was 0.6±0.6, while that in bypass group was 2.5±1.0, with a significant difference between two groups (t=8.797, P<0.001). At 1 year after surgery, barium enema examination was performed in all the patients of both groups. The barium emptying time was (21.2±3.8) hours and (95.8±86.2) hours in bypass plus colostomy group and bypass group respectively. The former group was significantly better than the latter group (t=4.740, P<0.001). Conclusions: Laparoscopic SCBCAC is an effective and safe procedure for the treatment of senile slow transit constipation and can significantly improve prognosis. Its clinical efficacy is better than laparoscopic SCBAC.

Characterization of cytoplasmic viscosity of hundreds of single tumour cells based on micropipette aspiration.

Cytoplasmic viscosity (µ c) is a key biomechanical parameter for evaluating the status of cellular cytoskeletons. Previous studies focused on white blood cells, but the data of cytoplasmic viscosity for tumour cells were missing. Tumour cells (H1299, A549 and drug-treated H1299 with compromised cytoskeletons) were aspirated continuously through a micropipette at a pressure of -10 or -5 kPa where aspiration lengths as a function of time were obtained and translated to cytoplasmic viscosity based on a theoretical Newtonian fluid model. Quartile coefficients of dispersion were quantified to evaluate the distributions of cytoplasmic viscosity within the same cell type while neural network-based pattern recognitions were used to classify different cell types based on cytoplasmic viscosity. The single-cell cytoplasmic viscosity with three quartiles and the quartile coefficient of dispersion were quantified as 16.7 Pa s, 42.1 Pa s, 110.3 Pa s and 74% for H1299 cells at -10 kPa (n cell = 652); 144.8 Pa s, 489.8 Pa s, 1390.7 Pa s, and 81% for A549 cells at -10 kPa (n cell = 785); 7.1 Pa s, 13.7 Pa s, 31.5 Pa s, and 63% for CD-treated H1299 cells at -10 kPa (n cell = 651); and 16.9 Pa s, 48.2 Pa s, 150.2 Pa s, and 80% for H1299 cells at -5 kPa (n cell = 600), respectively. Neural network-based pattern recognition produced successful classification rates of 76.7% for H1299 versus A549, 67.0% for H1299 versus drug-treated H1299 and 50.3% for H1299 at -5 and -10 kPa. Variations of cytoplasmic viscosity were observed within the same cell type and among different cell types, suggesting the potential role of cytoplasmic viscosity in cell status evaluation and cell type classification.

[Clinical differences between primary nasopharyngeal NK/T-cell lymphoma and primary nasal cavity NK/T-cell lymphoma with nasopharynx extension].

Objective: To investigate the clinical and prognostic differences between primary nasopharyngeal natural killer (NK)/T-cell lymphoma (NP NKTCL) and extranodal NK/T-cell lymphoma of the nasal cavity with nasopharynx extension (N-NP NKTCL). Methods: A total of 89 patients with NP NKTCL and 113 patients with N-NP NKTCL from January 2000 to June 2015 were retrospectively analyzed. Clinical and pathological features, treatment responses and prognosis were compared between the two groups. Results: NP NKTCL patients showed similar clinicopathological features with those with N-NP NKTCL, except that the former had a relative low proportion of elevated lactate dehydrogenase (LDH) levels (28.1% vs. 41.6%; P=0.001). Both of two groups presented with high proportion of cervical lymph node involvement (55.1% and 42.5%; P=0.076). The 5-year overall survival (OS) rates in these two groups were 63.2% and 54.6%, respectively, whereas 5-year progress-free survival (PFS) rates were 50.7% and 45.6%, respectively. For the patients with stage Ⅰ and Ⅱ, the 5-year OS and PFS rates in these two groups were 68.8% and 55.7% as well as 55.6% and 47.2%, respectively. These were no statistically significant differences between two groups (all P>0.05). The complete response (CR) rate after initial chemotherapy in NP NKTCL group was 43.8%, which was significant higher than that of 19.6% in N-NP NKTCL group (P=0.006). Additionally, the CR rate after primary radiotherapy was 63.4% and 62.7%, respectively (P=0.629). The NP NKTCL patients with stage Ⅰ and Ⅱ who accepted radiotherapy with or without chemotherapy had similar survival times with chemotherapy alone, showing the 5-year OS rates of 70.5% and 33.3% (P=0.238), as well as the 5-year PFS rates of 56.7% and 33.3%, respectively (P=0.431). Similar results were found in N-NP NKTCL group, the 5-year OS rates for patients with radiotherapy with or without chemotherapy and chemotherapy alone were 57.4% and 33.3% (P=0.246), while the 5-year PFS rates were 49.3% and 16.7% (P=0.177), respectively. Besides, the relapse pattern of NP NKTCL and N-NP NKTCL groups was also similar, mainly involving the distant extra-nodal organs followed by lymph nodes. Conclusion: The patients with N-NP NKTCL and NP NKTCL showed similar clinical and prognostic features, however, the initial response to chemotherapy was different.

[Analysis on chronic diseases and risk factors of adult residents in Shaanxi province].

Objective: To explore the prevalence of chronic diseases and related risk factors in Shaanxi province. Methods: Multi-stage stratified cluster random sampling was used to collect the sample from permanent residents in 10 national surveillance points in Shaanxi province in 2015. Behavioral risk factors (smoking, drinking, diet and physical activity) were investigated by face-to-face interviews and biological risk factors (BMI, blood pressure, blood glucose and blood lipid) were collected by physical measurements and laboratory tests. Designed weight, no response weight and post hierarchical weight were taken into account in the data analysis. Binary logistic regression models were used to examine the pair-wise associations among 8 risk factors. Results: A total of 6 174 persons were included in the analysis. The following weighted prevalence were noticed in Shaanxi province in 2015, that including current smoking as 28.19%, harmful use of alcohol as 6.20%, inadequate intake of vegetables and fruits as 55.62%, physical inactivity as 19.56%, overweight and obesity as 46.82%, hypertension as 31.12%, raised fasting blood glucose as 4.27%, and raised total cholesterol as 20.96%. Eight risk factors were found to be associated with each other. The mean numbers of risk factors were 2.41 per male and 1.85 per female, 1.94 per urban resident and 2.28 per rural resident. Conclusions: Risk factors for chronic diseases among adults aged 18 or older were more than the national levels in Shaanxi province in 2015. Male and rural residents presented more risk factors than their counterparts. Correlations between risk factors implied that a combined package of interventions was needed to reduce these risk factors.

Incidence and risk factors of osteomyelitis in adult and pediatric systemic lupus erythematosus: a nationwide, population-based cohort study.

OBJECTIVE: The objective of this paper is to investigate the incidence rate, risk factors and outcome of osteomyelitis among patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We conducted a cohort study using data for patients enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. Patients with SLE and age- and sex-matched controls without SLE were enrolled. Primary endpoint was the first occurrence of osteomyelitis. Risks of osteomyelitis in SLE patients were analyzed with Cox proportional hazards regression models, including age, sex, comorbidities and medications. RESULTS: Among 24,705 SLE patients (88.4% women, mean age 35.8 years) with a median follow-up of 9.1 years, 386 patients had osteomyelitis. The incidence rate ratio (IRR) of osteomyelitis in the SLE group vs the control group was 8.52 (95% confidence interval (CI) 7.24-10.05). The SLE group had higher incidence rates of osteomyelitis than the control group, especially in pediatric subgroups (IRR 41.1 95% CI 18.57-107.35). Compared to controls, SLE patients experienced osteomyelitis at a younger age (42.3 vs 58.1 years) but did not have an increased risk of mortality (hazard ratio 0.7; 95% CI 0.21-2.38). Age >60 years, male gender, malignancy within five years, prior bone fracture and higher daily prednisolone dose (>7.5 mg) cumulatively for >180 days increased risk for osteomyelitis. CONCLUSIONS: SLE patients have a higher IRR of osteomyelitis than controls. Pediatric and elder SLE patients, patients with a history of bone fracture, malignancy within five years and higher-dose glucocorticoid use have a higher risk of osteomyelitis and should be carefully monitored.