Value of number of negative lymph nodes in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model / 中华消化外科杂志

Objective:To investigate the value of number of negative lymph nodes (NLNs) in predicting the prognosis of patients with esophageal cancer after neoadjuvant therapy and the construction of nomogram prodiction model.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 924 patients with esophageal cancer after neoadjuvant therapy uploaded to the Surveillance, Epidemiology, and End Results Database of the National Cancer Institute from 2004 to 2015 were collected. There were 1 624 males and 300 females, aged 63 (range, 23?85)years. All 1 924 patients were randomly divided into the training dataset of 1 348 cases and the validation dataset of 576 cases with a ratio of 7:3 based on random number method in the R software (3.6.2 version). The training dataset was used to constructed the nomogram predic-tion model, and the validation dataset was used to validate the performance of the nomogrram prediction model. The optimal cutoff values of number of NLNs and number of examined lymph nodes (ELNs) were 8, 14 and 10, 14, respectively, determined by the X-tile software (3.6.1 version), and then data of NLNs and ELNs were converted into classification variables. Observation indicators: (1) clinicopathological characteristics of patients in the training dataset and the validation dataset; (2) survival of patients in the training dataset and the validation dataset; (3) prognostic factors analysis of patients in the training dataset; (4) survival of patients in subgroup of the training dataset; (5) prognostic factors analysis in subgroup of the training dataset; (6) construction of nomogram prediction model and calibration curve. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analyses. Based on the results of multivariate analysis, the nomogram prediction model was constructed. The prediction efficacy of nomogram prediction model was evaluated using the area under curve (AUC) of the receiver operating characteristic curve and the Harrell′s c index. Errors of the nomogram prediction model in predicting survival of patients for the training dataset and the validation dataset were evaluated using the calibration curve. Results:(1) Clinicopathological characteristics of patients in the training dataset and the validation dataset. There was no significant difference in clinicopatholo-gical characteristics between the 1 348 patients of the training dataset and the 576 patients of the validation dataset ( P>0.05). (2) Survival of patients in the training dataset and the validation dataset. All 1 924 patients were followed up for 50(range, 3?140)months, with 3-year and 5-year cumulative survival rate as 59.4% and 49.5%, respectively. The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the training dataset was 46.7%, 62.0% and 66.0%, respectively, and the 5-year cumulative survival rate was 38.1%, 52.1% and 59.7%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=33.70, P<0.05). The 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 in the validation dataset was 51.1%, 54.9% and 71.2%, respectively, and the 5-year cumulative survival rate was 39.3%, 42.5% and 55.7%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=14.49, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the training dataset was 53.9%, 60.0% and 62.7%, respectively, and the 5-year cumulative survival rate was 44.7%, 49.1% and 56.9%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=9.88, P<0.05). The 3-year cumulative survival rate of patients with number of ELNs as <10, 10?14 and >14 in the validation dataset was 56.2%, 47.9% and 69.3%, respectively, and the 5-year cumula-tive survival rate was 44.9%, 38.4% and 51.9%, respectively. There was a significant difference in the survival of these patients in the validation dataset ( χ2=9.30, P<0.05). (3) Prognostic factors analysis of patients in the training dataset. Results of multivariate analysis showed that gender, neoadjuvant pathological (yp) T staging, ypN staging (stage N1, stage N2, stage N3) and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=0.65, 1.44, 1.96, 2.41, 4.12, 0.69, 0.56, 95% confidence interval as 0.49?0.87, 1.17?1.78, 1.59?2.42, 1.84?3.14, 2.89?5.88, 0.56?0.86, 0.45?0.70, P<0.05). (4) Survival of patients in subgroup of the training dataset. Of the patients with NLNs in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 61.1%, 71.6% and 76.8%, respectively, and the 5-year cumulative survival rate was 50.7%, 59.9% and 70.1%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=12.66, P<0.05). Of the patients with positive lymph nodes in the training dataset, the 3-year cumulative survival rate of patients with number of NLNs as <8, 8?14 and >14 was 26.1%, 42.9% and 44.7%, respectively, and the 5-year cumulative survival rate was 20.0%, 36.5% and 39.3%, respectively. There was a significant difference in the survival of these patients in the training dataset ( χ2=20.39, P<0.05). (5) Prognostic factors analysis in subgroup of the training dataset. Results of multivariate analysis in patients with NLNs in the training dataset showed that gender, ypT staging and number of NLNs (>14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadju-vant therapy ( hazard ratio=0.67, 1.44, 0.56, 95% confidence interval as 0.47?0.96, 1.09?1.90, 0.41?0.77, P<0.05). Results of multi-variate analysis in patients with positive lymph nodes in the training dataset showed that race as others, histological grade as G2, ypN staging as stage N3 and number of NLNs (8?14, >14) were independent influencing factors for the prognosis of patients with esophageal cancer after neoadjuvant therapy ( hazard ratio=2.73, 0.70, 2.08, 0.63, 0.59, 95% confidence interval as 1.43?5.21, 0.54?0.91, 1.44?3.02, 0.46?0.87, 0.44?0.78, P<0.05). (6) Construction of nomogram prediction model and calibration curve. Based on the multivariate analysis of prognosis in patients of the training dataset ,the nomogram prediction model for the prognosis of patients with esophageal cancer after neoadju-vant treatment was constructed based on the indicators of gender, ypT staging, ypN staging and number of NLNs. The AUC of nomogram prediction model in predicting the 3-, 5-year cumulative survival rate of patients in the training dataset and the validation dataset was 0.70, 0. 70 and 0.71, 0.71, respectively. The Harrell′s c index of nomogram prediction model of patients in the training dataset and the validation dataset was 0.66 and 0.63, respectively. Results of calibration curve showed that the predicted value of the nomogram prediction model of patients in the training dataset and the validation dataset was in good agreement with the actual observed value. Conclusion:The number of NLNs is an independent influencing factor for the prognosis of esophageal cancer patients after neoadjuvant therapy, and the nomogram prediction model based on number of NLNs can predict the prognosis of esophageal cancer patients after neoadjuvant therapy.

Effect and mechanism of transcutaneous electrical acustimulation on the improving gastrointestinal motility and inflammation in patients with acute pancreatitis / 中华消化杂志

Objective:To explore the regulation effect and possible mechanism of transcutaneous electrical acustimulation (TEA) on the improvement of gastrointestinal motility and inflammation in patients with acute pancreatitis (AP).Methods:A randomized, single-blinded, sham-controlled study was performed. A total of 62 AP patients were randomly divided into the TEA group ( n=31) and sham-TEA group ( n=31), on the basis of regular treatment, who received TEA treatment at Neiguan (PC6) and Zusanli (ST36) or sham-TEA treatment at corresponding pseudo stimulation acupoints for 2 days. Abdominal distension score, time to first defecation, gastric slow wave, heart rate variability (low frequency and high frequency, reflecting sympathetic and vagal activity, respectively), serum level of tumor tecrosis factor (TNF)-α, plasma levels of motilin, ghrelin and vasoactive intestinal peptide(VIP) tested by enzyme linked immunosorbent assay were compared before and after the treatment. Wilcoxon rank test, Mann-Whitney U test, t-test and two factor repeated measurement analysis of variance were used for statistical analysis. Results:After the treatment, abdominal distension score of TEA group was lower than that of sham-TEA group(1 (0 to 2) vs.5(3 to 6)) and time to first defecation was earlier than that of sham-TEA group((55.00±24.27) h vs.(67.95±23.84) h), the percentage of normal gastric slow wave was higher than that of sham-TEA group((57.42±11.16)% vs. (40.92±8.52)%), and the differences were statistically significant ( Z=-4.95、 t=-2.12、 F=61.53, all P<0.05). After the treatment, the serum level of TNF-α of TEA group was significantly lower than that of sham-TEA group((4.27±1.28) ng/L vs.(6.19±2.03) ng/L), and the difference was statistically significant ( F=28.65, P<0.05). The ratio of post/pre-treatment of low frequency heart rate variability of the TEA group was significantly lower than that of sham-TEA group, however, the result of high frequency was opposite (0.87±0.18 vs.1.14±0.16, 1.19±0.18 vs.0.96±0.13), and the differences were statistically significant ( t=-6.22 and 5.74, both P<0.05). After the treatment, the plasma level of ghrelin of TEA group was higher than that of sham-TEA group ((2.02±0.62) μg/L vs. (0.93±0.49) μg/L), the VIP level was lower than of sham-TEA group ((30.58±12.20) μg/L vs.(44.35±29.52) μg/L), and the differences were statistically significant ( F=59.22 and 5.50, both P<0.05). However, there was no significant difference in motilin levels between two groups ((24.57±9.58) ng/L vs. (22.75±9.58) ng/L, P>0.05). Conclusion:TEA treatment can improve gastrointestinal motility and inhibit the inflammation in early AP, which may be related with the regulation of autonomic function, gastrointestinal hormone ghrelin and VIP.

Endoplasmic reticulum stressed promotes colorectal cancer cell proliferation and invasion through ATG5-mediated autophagy pathway / 中华内分泌外科杂志

Objective:To explore the effect of endoplasmic reticulum stressed (ER) on colorectal cancer (CRC) cell proliferation and invasion via ATG5-mediated autophagy pathway and the underlying mechanism.Methods:We performed bioinformatics analysis to identify the expression level of PERK, ATF6 and ATG5 in CRC tissues and adjacent tissues and the correlation between PERK and ATG5 expression in CRC tissues.The expression level of PERK in CRC cell lines was examined by qRT-PCR assay. Cell proliferation was quantified by CCK-8.The invasion of the cells was detected by Transwell.Western blot assay was performed to verify the levels of protein. The levels of autophagy were examined by electron microscopy.Results:PERK and ATF6 expression in CRC tissues was higher than that in the adjacent tissues and PERK expression was higher in CRC cells than intestinal mucosal cells. Expression level of PERK in CRC cell lines HCT116,SW480,HT29,LoVo and colonic mucosa cell lines FHC was 1.51±0.04,3.12±0.05,2.19±0.04,2.38±0.06 and 0.98±0.04 ( P<0.001) .The increased expression of PERK promoted CRC cell proliferation and invasion. PERK expression levels was positively associated with ATG5 expression levels ( r=0.52, P<0.001) and overexpression of PERK accelerated the protein expression of ATG5 (1.00±0.04,3.53±0.07, t=74.61, P<0.001) . ATG5 was highly expressed in CRC tissues. Overexpression of ATG5 could promote proliferation,invasion and accelerate autophagy of CRC cells (the number of autophagosomes in the blank control group,the negative control group and ATG5-Overexpression group was 4.33±1.53, 4.00±1.00, 9.67±2.52, and t=3.14,3.62, P=0.035,0.022, respectively) .ATG5 promoted colorectal cancer cell proliferation and invasion through autophagy pathway. Conclusion:ER stressed-CRC cells could promote CRC cell proliferation and invasion through ATG5-mediated autophagy pathway.

Progress of comprehensive surgical treatment for esophageal cancer / 中华消化外科杂志

Esophageal cancer is one of the common malignant tumors in the worldwide and has regional characteristics in China. At present, the treatment of esophageal cancer is still a comprehensive diagnosis and treatment mode based on surgery. With the application of minimally invasive technique in surgery of esophageal cancer, the concept of surgical diagnosis and treatment for esophageal cancer is constantly updating. The application of robotic surgical system in esophageal surgery promotes the surgical quality of lymph node dissection and improves the technique of intraluminal anastomosis under total endoscopy. For locally advanced esophageal cancer, a diagnosis and treatment mode based on neoadjuvant therapy has been gradually accepted by most of doctors around China. Combined with the latest researches at home and abroad, the authors investigate the development of surgical techniques, the renewal of surgical concept and the changes on diagnosis and treatment, summarize the new advances in comprehensive surgical treatment for esophageal cancer, in order to provide the theoretical guidance for the standardized treatment of esophageal cancer.

Moderation effect of antecedent rainfall conditions on incidence of bacillary dysentery following heavy rainfall in Anhui Province / 环境与职业医学

Background Climate change leads to frequent heavy rainfall events, and higher incidences of bacillary dysentery after heavy rainfall have been observed. The impacts of heavy rainfall and its antecedent rainfall conditions on the disease are worth paying attention to. Objective To quantitatively analyze how the relationship between heavy rainfall events and bacillary dysentery occurrence is modified by antecedent rainfall conditions in Anhui Province and explore the different moderation effects in urban and rural contexts. Methods CN05.1 meteorological data of Anhui Province and cases of bacillary dysentery of the same area were collected from January 1, 2006 to August 31, 2017. An exposure-response Poisson regression model of heavy rainfall events and the number of daily cases was constructed to explore the moderation effect of antecedent rainfall conditions on the incidence of bacillary dysentery, and further stratified by urban and rural areas. Results This study included 129 459 cases of bacillary dysentery, with a daily average of 30.39. Compared with dry antecedent conditions without heavy rainfall, dry antecedent conditions with heavy rainfall had no obvious different effect on the incidence of bacillary dysentery for the whole province (P>0.05). But wet antecedent conditions significantly increased the risk of bacillary dysentery for the whole province after heavy rainfall (wet antecedent conditions without heavy rainfall: RR=1.281, 95%CI: 1.264-1.298; wet antecedent conditions with heavy rainfall: RR=1.267, 95%CI: 1.167-1.376). After urban and rural stratification, antecedent rainfall conditions also showed a significant moderation effect on the incidence of bacillary dysentery following heavy rainfall events. Compared with dry antecedent conditions without heavy rainfall, dry antecedent conditions with heavy rainfall had no obvious effect on the incidence of bacillary dysentery for the urban and the rural populations (P > 0.05). However, wet antecedent conditions without heavy rainfall (urban: RR=1.391, 95%CI: 1.362-1.421; rural: RR=1.222, 95%CI: 1.201-1.243) and wet antecedent conditions with heavy rainfall (urban: RR=1.364, 95%CI: 1.193-1.559; rural: RR=1.218, 95%CI: 1.098-1.352) significantly increased the risk of bacillary dysentery in both rural and urban areas. Conclusion In the influence of heavy rainfall on the incidence of bacillary dysentery in Anhui Province, antecedent rainfall conditions have a certain moderation effect in the whole province and in both urban and rural areas, and the risk of bacillary dysentery is increased under wet antecedent conditions.

Immune checkpoint inhibitors in the treatment of colorectal cancer: a review of clinical trials / 中华胃肠外科杂志

Colorectal cancer is the third most common cancer in the world. The treatments include surgery, chemotherapy, radiotherapy and targeted therapy. The guidelines of many tumor types have been rewritten with the advent of immune checkpoint inhibitors. There are significant differences in the efficacy of immune checkpoint inhibitors in colorectal cancer according to microsatellite status. Microsatellite instability-high (MSI-H) colorectal cancer has made a breakthrough in immunotherapy, whether in the late-line, first-line, adjuvant or neoadjuvant therapy. The success of KEYNOTE-177 study has changed the guidelines with pembrolizumab becoming a standard treatment in the first-line treatment of MSI-H advanced colorectal cancer. The NICHE study, which used immunotherapy as neoadjuvant treatment of colorectal cancer, has made exciting achievements in MSI-H colorectal cancer. For microsatellite stability (MSS) colorectal cancer, many studies are ongoing, and immunotherapy is still unable to challenge the status of traditional treatment. In this paper, we review the clinical trials related to immune checkpoint inhibitors of colorectal cancer, expecting to provide references for the development of colorectal cancer immunotherapy.

Circular RNA circ0025847 supresses colorectal cancer proliferation by promoting of RNA-binding protein QK1 expression / 中华内分泌外科杂志

Objective:To uncover the effect of circ0025847 on the proliferation of colorectal cancer cells and its molecular mechanisms.Methods:qRT-PCR was utilized to analyze the expression of circ0025847 and QK1 in human colorectal cancer cells (HCT116, SW480) and normal mucosa cells (NCM460) .CCK-8 was used to analyze the effect of circ0025847 and QK1 on proliferation in colorectal cancer cells. Bioinformatics method was used to screen RBP which could bind to circ0025847. RNA pulldown and RIP was utilized to confirm whether QK1 binds to circ0025847.Effects of circ0025847 over-expression on QK1 expression was analyzed by Western blot.NC group, circ0025847 overexpression group and circ0025847 overexpression+ QK1 inhibitor group were established and the proliferation effect was determined by CCK8.Results:circ0025847 (the expression levels in NCM460, HCT116 and SW480 cells were 1.01±0.05, 0.49±0.08, 0.45±0.10) and QK1 (the expression levels in NCM460, HCT116 and SW480 cells were 0.98±0.07, 0.50±0.07, 0.47±0.09) expression was significantly downregulated in colorectal cancer cells. Overpression of circ0025847 and QK1 suppressed colorectal cancer cells growth.RNA pull-down and RIP clarified that circ0025847 bind to QK1 and circ0025847 positively regulate QK1 expression (7 199.20±12.44 VS 3 889.80±11.03) . circ0025847 inhibiting the proliferation of colorectal cancer cells by promoting the expression of QK1 was confirmed by rescue experiment.Conclusion:circ0025847 inhibits colorectal cancer cells proliferation via positively regulating QK1 expression, indicating that circ0025847 may be potential therapeutic target of colorectal cancer.

Mechanism of Wenshen Yangxue Prescription Improving Endometrial Receptivity of Aged Female Mice by Regulating PI3K/Akt/FoxO3A Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the effective components， targets， and possible mechanisms of Wenshen Yangxue prescription in improving endometrial receptivity of aged female mice based on network pharmacology and experimental verification. Method:Based on Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine， the components and targets of Wenshen Yangxue prescription were retrieved， and the targets of ovulatory dysfunctional infertility were collected from the Online Mendelian Inheritance in Man （OMIM） and GeneCards with "anovulatory sterility" and "anovulatory infertility" as keywords. The protein-protein interaction （PPI） network was constructed based on STRING and the core targets of Wenshen Yangxue prescription against ovulatory dysfunctional infertility were screened by Cytoscape， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the core targets in DAVID database. Then， the "medicinal-component-target-pathway" network was established and the core targets were verified by animal experiment. Result:A total of 253 components and 326 targets of Wenshen Yangxue prescription， 819 disease targets， and 74 common targets were screened out. The common targets were mainly involved in the biological processes such as positive regulation of nitric oxide biosynthetic process， positive regulation of cell proliferation， response to estradiol， aging， response to oxidative stress， and angiogenesis. The GO term of response to oxidative stress and five of the top 20 KEGG pathways were analyzed. According to the "medicinal-component-target-biological process/pathway" network， 41 chemical components in 20 medicinals participated in hypoxia inducible factor-1 （HIF-1） signaling pathway， tumor necrosis factor （TNF） signaling pathway， forkhead box O （FOXO） signaling pathway， Toll-like receptor （TLR） signal pathway， and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway by affecting 35 targets. The results of animal experiment showed that the prescription could increase the expression of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， forkhead box O3A （FoxO3A）， and phosphorylated FoxO3A （p-FoxO3A） in uterus of aged female ICR mice. Conclusion:Wenshen Yangxue prescription interferes with oxidative stress and PI3K/Akt/FoxO3A signaling pathway by influencing Akt1， dual oxidase 2 （DUOX2）， epidermal growth factor receptor （EGFR）， heme oxygenase-1 （HMOX1）， myeloperoxidase （MPO）， and other targets， thereby improving endometrial receptivity of aged female mice.

Retrospective analysis on endoscopic treatment for non-ampullary duodenal mucosal lesions / 中华消化内镜杂志

To study the clinical effect of non-ampullary duodenal mucosal lesions treated by endoscopic resection. A retrospective analysis was performed on the data of 58 cases of duodenal non-ampullary mucosal lesions treated by endoscopic resection from January 2016 to June 2019 from 3 hospitals. Among 58 cases, 27 lesions (46.6%) were located in the duodenal bulb and 31 (53.4%) in the duodenal descending part (including the ball-drop boundary). Forty-six patients (79.3%) received endoscopic mucosal resection, 7 (12.1%) received endoscopic submucosal dissection and 5 (8.6%) received pre-cut endoscopic mucosal resection. Few postoperative complications were found except for 1 case of intraoperative bleeding, 1 case of delayed bleeding 2 days after surgery, 1 case of lesion residual and 2 cases of postoperative abdominal pain. No perforation occurred. Endoscopic treatment of non-ampullary duodenal mucosal lesions is safe and effective.

Effect of Vaccarin on atherosclerosis in mouse model and its mechanism / 中国药理学通报

Aim To investigate the effect of vaccarin on mouse atherosclerosis in vivo and the underlying mechanism. Methods AopE mice aged 6 to 8 weeks old were used to establish the atherosclerosis model. Oil red O staining was used to determine the lipid levels in aorta and aortic root. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory factors. Results Vaccarin could effectively reduce the levels of blood glucose and blood pressure in AopE

Analysis on transcriptionomic characteristics of Naoxintong Capsules in prevention of post-ischemic inflammation based on RNA-Seq technology / 中国中药杂志

In this research, high-throughput sequencing was used to investigate the mechanism of Naoxintong Capsules(NXTC) in prevention of post-ischemic inflammation. First, microglia BV-2 inflammatory model was induced by 1.0 μg·mL~(-1) LPS to investigate the effect of intestinal absorption solution of NXTC(NXTCIA) at different concentrations(62.5, 31.25, 15.63, 7.81 μg·mL~(-1)) on LPS-induced BV-2 inflammatory factors in microglia. Then, an RNA-Seq high-throughput sequencing method was performed to identify the differentially expressed mRNAs in microglia BV-2 after pre-treatment with NXTC. GO and KEGG enrichment analysis was used to screen the potential biological processes and related signaling pathways of NXTC in inhibiting inflammation. The results showed that four NXTCIA concentrations could significantly inhibit the release of LPS-induced inflammatory mediators in BV-2 in a dose-dependent manner. Furthermore, high-throughput sequencing results showed that 392 mRNA transcripts were reversed following pre-treatment with NXTC. GO enrichment analysis showed that the transcripts reversed by NXTC were mainly involved in Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway. Taken together, our findings showed that NXTC treatment could provide protective effects against inflammatory response and the mechanism might be related to the regulation of Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway.

Chromosomal aberrations detection in chronic lymphocytic leukemia by conventional cytogenetics using DSP30 and IL-2 / 中华血液学杂志

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion: DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

Analysis of the current situation of road traffic accidents in the 31 provinces/municipalities of China and the projection for achieving the SDGs target of halving the numbers of death and injury / 中华疾病控制杂志

Objective To analyze the data of road traffic accidents, deaths and injuries in 31 provinces and municipalities in China from 2010 to 2017, and to predict that the number of deaths and injuries caused by road accidents set in the sustainable development goals (SDGs) will be halved by 2020 compared with the target set in 2015. Methods Describing and analyzing the current situation of road traffic accidents in 31 provinces and municipalities in China, and using the trend extrapolation method to predict whether the SDGs target can be achieved by 2020. Results The numbers of traffic accidents, deaths and injuries in Guangdong, Jiangsu, Zhejiang and Shandong Provinces showed a downward trend from 2010 to 2017, but still ranked the front in China. In 2017, Beijing had the highest death rate followed by Guizhou as the second, and Guizhou had the highest injury rate followed by Tianjin as the second. The projected results showed that the numbers of deaths and injuries caused by road traffic accidents in China would be increased by 17% and 1.3% respectively in 2020 indicating that SDGs target could not be met. Among the 31 provinces/municipalities, it was predicted that the numbers of deaths and injuries in Hunan would be reduced to 50.7% and 65.3% in 2015, respectively by 2020, and the target could be achieved; the number of injuries in Shanghai was decreased by 83.3%, but the deaths was only decreased by 34.5%, and there was still a gap with the target; the rest 29 provinces/municipalities could not meet SDGs target. It was expected that the deaths in 11 provinces and municipalities would increase by 2020, with Beijing, Jilin, Jiangxi, Hubei and Guizhou Provinces showing the most significant growth. The number of injured people in 8 provinces and municipalities shows an increasing trend, with Jilin, Jiangxi, Hubei and Guizhou provinces showing significant growth. Conclusions Except for Hunan Province, it was difficult for the whole country and the rest provinces and municipalities to reach the SDGs target. According to the forecast results and the actual situation, a targeted scientific prevention and control strategy can be formulated. The measures taken by Hunan and Shanghai in traffic accident prevention and control were effective and worth learning.

Investigation of Molecular Mechanism of Yangxue Antai Fang in Improving Prethrombolic State of Recurrent Spontaneous Abortion Based on Integrated Pharmacology Techniques / 中国实验方剂学杂志

Objective:To predict the potential molecular mechanism of Yangxue Antai Fang in treating prethrombolic state of recurrent spontaneous abortion （RSA-PTS）. Method:The chemical constituents and drug targets of Yangxue Antai Fang were collected by Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP V2.0）. RSA-PTS disease target information was collected by TCMIP V2.0 and improved by Online Mendelian Inheritance in Man （OMIM） database. The interaction of these targets was analyzed and key target network was constructed. Gene ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were further performed. Finally， Cytoscape 3.5.1 was used to build up a multidimensional network of TCM-ingredient-target-pathway. The levels of absorption， distribution， metabolism， excretion and toxicity （ADMET） of the main components in the network were analyzed. Result:A total of 310 chemical constituents and 975 targets were collected from 8 TCMs in Yangxue Antai Fang. A total of 143 targets of RSA-PTS were obtained. A total of 243 core targets were obtained by the interrelationship analysis of drug and disease targets. The analysis of the top 100 core targets showed that these targets might participate in treating RSA-PTS by affecting biological processes related to thrombosis， such as blood coagulation， platelet activation， positive regulation of angiogenesis and so on. Pathway analysis showed that these targets were mainly concentrated in complement and coagulation cascades， platelet activation， estrogen signaling pathway， thyroid hormone signaling pathway， etc. Multidimensional network analysis in combination with ADMET level showed that 14 components （leonurine， paeonol， vanillin， and so on） may play a therapeutic role in RSA-PTS by affecting coagulation factors Ⅱ （F2）， plasminogen （PLG） and estrogen receptor 1 （ESR1） proteins involved in complement and coagulation cascades， platelet activation， thyroid hormone signaling pathway and others. Conclusion:The main chemical constituents in Yangxue Antai Fang may improve RSA-PTS by regulating complement and coagulation cascades， blood coagulation， platelet activation and other biological processes.

Effects and mechanisms of CD5 + CD19 + B lymphocytes on CD8 + cells in chronic hepatitis B virus infection / 中华消化杂志

Objective:To explore whether CD5 + CD19 + B cells has the function of secreteing interleukin-10 (IL-10) in vitro, and to further investigate its possible effects and mechanisms on CD8 + cells in the process of hepatitis B virus (HBV) infection. Methods:From July 2017 to June 2018, at Wuxi Second People′s Hospital Affiliated to Nanjing Medical University, 23 patients with chronic hepatitis B (chronic hepatitis B group), 18 patients with liver cirrhosis (liver cirrhosis group) and 19 healthy individuals in the same period as healthy controls (healthy control group) were enrolled. Peripheral blood mononuclear cell (PBMC) were isolated and cultured. CD5 + CD19 + B cells were isolated. The cells were analyzed by flow cytometry. The ratio of high CD5 + CD19 + B cells content (>6 % of lymphocytes), the secretion of IL-10 by CD5 + CD19 + B and the ratio of high IL-10 + cells content (>4 % of lymphocytes) of three groups were compared. The effects and possible mechanisms of CD5 + CD19 + B cells on the secreting of interferon-γ (IFN-γ) by CD8 + cells were analyzed. Liver biopsy and immunohistochemistry examination were conducted in 18 patients (13 patients with chronic hepatitis B and 5 patients with liver cirrhosis) and the expression of CD5 + CD19 + B cells in human liver tissues was analyzed. Chi square test and Fisher exact probability test were used for statistical analysis. Results:The ratio of high CD5 + CD19 + B cells content of liver cirrhosis group was higher than that of healthy control group (8/18 vs. 2/19) and the difference was statistically significant (Fisher exact probability test, P=0.029). The precentage of CD5 + CD19 + B cells in healthy control group ( n=10), chronic hepatitis B group ( n=23) and liver cirrhosis group ( n=18) accounted for 81.6%, 82.3% and 70.1%of IL-10 + cells, respectively, and the number of patients with high IL-10 + cells precentage was 2, 7 and 2, respectively. There were no statistically significant differences among three groups (all P>0.05). After stimulated with lipopolysaccharide and cultured for 48 hours, the precentage of CD8 + IFN-γ + cells in lymphocytes of healthy control group ( n=10), chronic hepatitis B group ( n=10) and liver cirrhosis group ( n=10) were compared, and the differences were not statistically significant (all P>0.05). After CD5 + CD19 + B cells were eliminated, the precentage of CD8 + IFN-γ + cells in lymphocytes increased in 5, 4 and 4 patients of healthy control group ( n=10), chronic hepatitis B group ( n=10) and liver cirrhosis group ( n=10). After adding IL-10 receptor blocker, the precentage of CD8 + IFN-γ + cells in lymphocytes in PBMC increased compared with that before the addition of IL-10 receptor blocker (7.23% vs. 6.87%). The results of immunohistochemistry examination of liver biopsy indicated that CD4 + and CD8 + cells were strong expressed in portal area of liver tissue of patients, while CD5 + and CD19 + were less expressed. Conclusions:CD5 + CD19 + B cells do not show obvious quantitative and functional differences in the process of chronic HBV infection, however the ability of CD8 + cells to secrete IFN-γ, which may be achieved by secreting IL-10 rather than by direct contact between cells.

Indication analysis of therapeutic effects of pre-cut-endoscopic mucosal resection on colorectal lateral spreading tumors (with video) / 中华消化内镜杂志

Objective:To investigate the indication of pre-cut-endoscopic mucosal resection (pre-cut-EMR) on the treatment of colorectal laterally spreading tumors (LSTs).Methods:A retrospective study was performed on data of colorectal LSTs patients, who underwent pre-cut-EMR in Wuxi Second People’s Hospital and Zhongshan Hospital from January 2014 to June 2019. The relationships between the clinical characteristics of the lesions and the success rate and complications of pre-cut-EMR were analyzed.Results:Data of 132 colorectal LSTs cases were included in the study. Morphology of 29 (22.0%) LSTs were homogeneous granular type, 43 (32.6%) LSTs were mixed non-granular type, 58 (43.9%) LSTs were flat elevated type, and 2 (1.5%) LSTs were pseudo-depressed type. The diameter of lesions was 2.3±1.5 cm (ranged from 2.0 cm to 5.0 cm). Among the 132 LSTs, 36 (27.3%) tumors were located in rectum, 15 (11.4%) in sigmoid colon, 10 (7.6%) in descending colon, 17 (12.9%) in splenic flexure of colon, 21 (15.9%) in transverse colon, 24 (18.2%) in hepatic flexure of colon, 6 (4.5%) in ascending colon, and 3 (2.3%) in cecum. The histopathological diagnoses of the 132 LSTs included low grade intraepithelial neoplasia in 58 cases (43.9%), high grade intraepithelial neoplasia in 69 cases (52.3%), intramucosal carcinoma in 2 cases (1.5%), and canceration in 3 cases (2.3%). Pre-cut-EMR was achieved in all 132 patients, and the operation time was 25.3±13.6 min (ranged 20-65 min). The rate of en bloc resection and complete resection were 95.5% (126/132) and 100.0% (132/132), respectively. Two cases (1.5%) had intraoperative perforation, and were both located in the sigmoid colon with the diameter of 4.0 cm and 4.5 cm, respectively. Twelve cases (9.0%) had immediate bleeding during operation, and 2 cases (1.5%) had delayed bleeding after operation. Patients had been followed up for 6-24 months, the wound healed well after operation, and no local recurrence was found.Conclusion:Pre-cut-EMR is an effective and safe therapy for colorectal LSTs with diameter less than 4.0 cm.

Antineoplastic mechanism of antimicrobial peptides: Selective membrane destruction and non-membrane dissolution / 中国组织工程研究

BACKGROUND: Antimicrobial peptides, an extract from nature, are a basic component of host immunity that make toxic effect on highly proliferative cells. They have attracted extensive attention of scientists. The understanding of the antineoplastic mechanism of antimicrobial peptides can contribute to its application in clinical practice. OBJECTIVE: To summarize the research advances in antineoplastic mechanism of antimicrobial peptides. METHODS: The first author conducted a computer-based retrieval of PubMed, Springerlink, Web of Science, and ScienceDirect databases for relevant articles published from January 2015 to May 2019. The keywords were “antimicrobial, peptide, antitumor mechanisms, antitumor activity and anti-neoplastic”. The articles concerning antineoplastic mechanism of antimicrobial peptides and research progress were selected. RESULTS AND CONCLUSION: Cationic antimicrobial peptides synthesized by ribosomes and the host defense peptides can interact with the membrane of bacteria, which showed a broad-spectrum antimicrobial activity. Compared with normal cells, the proportion of phosphatidylserine on the surface of cancer cells, which is negatively charged, is increased dramatically. As a result, the cationic amphiphilic peptides are good candidate for the antineoplastic drugs, and possess a high selectivity. There are two major antitumor mechanism of antimicrobial peptides, which are selective membrane destruction and non-membrane dissolution (α-defensin-1 and lactoferrin B). The clinical application of antimicrobial peptides against tumors is mainly restricted by their stability and the ways to administration. By optimizing its structure and drug delivery systems, these antimicrobial peptides will play a critical role in the cancer treatment.

Treatment of intrahepatic cholangiocarcinoma / 国际外科学杂志

Intrahepatic cholangiocarcinoma has low resectability rate, high recurrence and short survival. It is very important to formulate and optimize the strategy of surgical treatment. The only potentially effective treatment for intrahepatic cholangiocarcinoma is surgical resection. Liver transplantation also has some application prospects. Intrahepatic cholangiocarcinoma can be divided into four types: mass forming type, intraductal growth type, periductal infiltration type, mass forming + periductal infiltration(mixed)type. Clinically, the treatment strategy is mainly determined according to the general classification. The application of methods such as preoperative portal vein embolism, neoadjuvant therapy and lymph node dissection make it possible for more patients to undergo surgical resection and improve the surgical effect. Adjuvant treatment including chemotherapy and radiotherapy can significantly improve the prognosis of the patients. The rapid development of molecular targeted therapy and immunotherapy is gradually changing the clinical treatment of intrahepatic cholangiocarcinoma.

Pharmacokinetics of Sinapic Acid from Stir-fried Raphani Semen in Rats and Its PK-PD Correlation Analysis / 中国实验方剂学杂志

Objective::To study the pharmacokinetics of sinapic acid from stir-fried Raphani Semen in normal rats and the correlation between pharmacokinetics-pharmacodynamics (PK-PD) in asthma rats. Method::Normal rats received 4.5, 9, 18 g·kg-1 of stir-fried Raphani Semen by oral administration, respectively. Blood was taken from ophthalmic venous plexus at different time points according to the experimental design, the plasma concentration of sinapic acid was analyzed by UHPLC-MS/MS, and data analysis was performed using DAS 3.2.8 software to obtain the pharmacokinetic parameters. Rat asthma model was established by intraperitoneal injection of ovalbumin with aluminum hydroxide, and treated with ethanol extract of stir-fried Raphani Semen (low and high doses of 4.5, 9 g·kg-1). After treatment for 3 weeks, taking blood at different time points, plasma and serum were separated. UHPLC-MS/MS was established for the determination of plasma concentration of sinapic acid, contents of interleukin-5 (IL-5), immunoglobuin E (IgE), tumor necrosis factor-α (TNF-α) in serum at different time points were detected by enzyme-linked immunosorbent assay (ELISA), DAS 3.2.8 software was used for PK-PD model fitting and data analysis. Result::After normal rats were administrated with low, medium and high doses of stir-fried Raphani Semen, the peak concentration (Cmax) of sinapic acid in plasma were (29.35±10.32), (62.70±27.47), (137.33±40.95) μg·L-1, its area under the curve (AUC0-t) were (92.83±27.16), (240.74±75.09), (633.95±195.88) μg·L-1·h, its peak time (Tmax) were (2.58±0.80), (3.00±0), (5.50±1.23) h, respectively. Compared with the low dose group, AUC0-t and mean retention time (MRT0-t) were all increased in the medium and high dose groups, showing statistical differences (P<0.05, P<0.01). The linear relationship of AUC0-t in sinapic acid was good within the dose range of 4.5-18 g·kg-1. After treating with ethanol extract of stir-fried Raphani Semen for 0.083, 0.167 h, compared with the model group of asthmatic rats, serum levels of IL-5, IgE, TNF-α of the medication groups were decreased to different degrees (P<0.05, P<0.01). Cmax of sinapic acid in the low and high dose groups were (58.43±29.94), (61.16±18.79) μg·L-1, its AUC0-t were (188.75±37.07), (247.90±36.89) μg·L-1·h, respectively. AUC0-t, apparent volume of distribution (Vz/F) and clearance rate (CLz/F) all increased significantly with the increase of dose. The best pharmacokinetic model of sinapic acid was fitted as a one-compartment model for extravascular administration, PK-PD model may be applicable to indirect connection model. Conclusion::The plasma concentration of sinapic acid is correlated with contents of IL-5, IgE and TNF-α, dosage and functional state (pathological or physiological state) can affect the pharmacokinetic behavior of sinapic acid from stir-fried Raphani Semen in rats, and it has a certain correlation with the anti-asthmatic effect.

Clinical Significance of Common Gene Mutations in 53 Patients with Acute Myeloid Leukemia Harboring 11q23/MLL Rearrangements / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients.@*METHODS@#53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing.@*RESULTS@#21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy.@*CONCLUSION@#A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.