Predictors of Lymph Node Metastasis and Differences Between Pure and Mixed Histologic Types of Early Gastric Signet-ring Cell Carcinomas.

The aim of this study was to investigate predictors of lymph node metastasis (LNM) in early gastric signet-ring cell carcinoma (SRCC) and determine clinicopathologic and prognostic differences of different histologic subtypes. We retrospectively analyzed 13,661 gastric cancer patients; 231 were eligible for inclusion. Data for clinical, endoscopic, and histopathologic characteristics and prognoses were collected. Patients were followed up regarding postresection survival; overall and disease-specific survival rates were estimated by the Kaplan-Meier method with a log-rank test, and prognostic factors were evaluated by Cox regression. LNM incidence in early SRCC was 16.0% (37/231) overall: 6.9% (8/116) and 25.2% (29/115) in patients with pure and mixed SRCC, respectively. Univariate and multivariate analyses revealed SM2 invasion (odds ratio [OR]=5.070, P=0.003), lymphovascular invasion (LVI) (OR=14.876, P<0.001), pathologic pattern of mixed SRCC (OR=3.226, P=0.026), ulcer presence (OR=3.340, P=0.019) and lesion size over 20 mm (OR=2.823, P=0.015) as independent risk factors for LNM. Compared with pure SRCC, the mixed subtype was associated with older age, larger lesion size, higher LVI frequency, more frequent perineural invasion, and most importantly, higher LNM incidence. Patients with pure SRCC showed significantly longer overall survival (P=0.004) and disease-specific survival (P=0.002) than mixed SRCC patients. Pathologic subtype (hazard ratio [HR]=3.682; P=0.047), age (HR=5.246; P=0.001), SM1 invasion (HR=6.192; P=0.023), SM2 invasion (HR=7.529; P=0.021) and LNM (HR=5.352; P<0.001) were independent prognostic factors. Independent risk factors for LNM in early gastric SRCC were SM2 invasion, LVI, pathologic pattern, ulcer presence and lesion size over 20 mm. Early SRCC should be further classified by the purity of the SRC component.

Feasibility of endoscopic treatment and predictors of lymph node metastasis in early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been routinely performed in applicable early gastric cancer (EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial. AIM: To determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. METHODS: We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients' clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. RESULTS: LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren's types. Multivariate analysis demonstrated SM1 invasion (odds ration [OR] = 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors. CONCLUSION: The absolute indications for ESD are reasonable, and the feasibility of expanding the indications for ESD requires further investigation. The predictors of LNM include invasion depth, LVI, mucinous adenocarcinoma, and lesion size.

An Experimental Study on Repeated Brief Ischemia in Promoting Sciatic Nerve Repair and Regeneration in Rats.

BACKGROUND: Research has shown that ischemic preconditioning reduced the severity of ischemia-reperfusion injury in brain in rats, we have a hypothesis that repeated brief ischemia has positive effects on peripheral nerve damage. This study was conducted to investigate the potential protective effects of repeated brief ischemia on peripheral nerve regeneration using a rat model of experimental sciatic nerve transection injury. METHODS: Treatment groups (groups A-D) received repeated, brief ischemia every 1 day/2 days/3 days/7 days. After surgery for 4, 8, 12 weeks, we evaluated sciatic functional index test, gastrocnemius muscle wet mass, axon and nerve fiber diameter, density, G-ratio, immunohistochemistry of S-100, vascular endothelial growth factor (VEGF), and the ultrastructure of the nerves. RESULTS: Sciatic functional index test and muscle wet mass were improved on the repeated brief ischemia groups. Ischemia treatment resulted in a significant increase in axon and nerve fiber density as well as S-100 and VEGF-positive cell, which indicated that repeated brief ischemia promotes Schwann cell proliferation and reconstruction. CONCLUSIONS: This study exhibits the positive effects of repeated brief ischemia in sciatic nerve transection injury, possibly in part because it can improve VEGF and the physiologic state of Schwann cells in the ischemic environment and then accelerate the ability of neurite outgrow.

Synthesis and biological characterization of novel rose bengal derivatives with improved amphiphilicity for sono-photodynamic therapy.

Sono-Photodynamic therapy (SPDT) utilizing ultrasound and light has been demonstrated that this novel approach can lower dosage resulting in reduction of the potential side effects caused by sensitizers. Recently, a new formulation of rose bengal (RB) as an intralesional injection has completed clinical trials phase II for PDT treatment of melanoma cancer. However, the inherent unfavorable pharmacological properties of RB hindered its extensive clinical development. With the aim to identify new RB derivatives (RBDs) with enhanced photodynamic and sonodynamic anticancer efficiency, a series of amphiphilic RBDs have been designed, synthesized and biological characterized. Among them, RBD4 significantly improved cellular uptake and enhanced intracellular ROS generation efficiency upon light and ultrasound irradiation, resulting in dramatically improved anticancer potency. Notably, RBD4 has a relative potency similar to sinoporphyrin sodium (DVDMS), indicating its further potential application for SPDT.

MiR-7684-5p leads to surgery-induced cognitive decline in mice probably through the downregulation of SorLA.

BACKGROUND: Postoperative cognitive dysfunction is a postoperative severe complication caused by many factors. However, its specific pathogenesis remains unclear. MicroRNAs (miRNAs), which are involved in the pathogenesis of neurodegenerative diseases, may also affect POCD. METHODS: In this research, microarray technology was used to screen 26 miRNAs that had a differential expression in the hippocampus of mouse between the surgery group and control group. The qRT-PCR verification on the hippocampuses of 10 pairs of mouse testifies the high expression of miR-7684-5p in the surgery group (identical with the result of chip). RESULTS: Surgical trauma was found to induce the expression of miR-7684-5p with the accumulation of Aß in the hippocampus. Furthermore, miR-7684-5p knockdown effectively reduced the levels of Aß triggered by surgery, and attenuated hippocampal-dependent memory impairment. Moreover, we testify that sorLA is a target gene of miR-7684-5p through bioinformatics prediction and dual-luciferase report gene experiment. CONCLUSIONS: Our data indicate that decreased postoperative cognitive function may be caused by the increased generation of Aß by reducing sorLA expression. Our work implicates miR-7684-5p as a potential biomarker and a novel therapeutic target.

Potential sonodynamic anticancer activities of artemether and liposome-encapsulated artemether.

The potential application of artemether as a novel sonosensitizer for sonodynamic therapy (SDT) was explored and illustrated for the first time. In addition, liposome-encapsulated artemether exhibited significantly enhanced sonodynamic anticancer activity. Our findings indicated that artemisinin derivatives may serve as a new kind of sonosensitizer for SDT.

In vitro and in vivo evaluation of the developed PLGA/HAp/Zein scaffolds for bone-cartilage interface regeneration.

OBJECTIVE: To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on the repair of cartilage defects. METHODS: The PLGA/HAp/Zein composite scaffolds were fabricated by electrospinning method. The physiochemical properties and biocompatibility of the scaffolds were separately characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), and fourier transform infrared spectroscopy (FTIR), human umbilical cord mesenchymal stem cells (hUC-MSCs) culture and animal experiments. RESULTS: The prepared PLGA/HAp/Zein scaffolds showed fibrous structure with homogenous distribution. hUC-MSCs could attach to and grow well on PLGA/HAp/Zein scaffolds, and there was no significant difference between cell proliferation on scaffolds and that without scaffolds (P>0.05). The PLGA/HAp/Zein scaffolds possessed excellent ability to promote in vivo cartilage formation. Moreover, there was a large amount of immature chondrocytes and matrix with cartilage lacuna on PLGA/HAp/Zein scaffolds. CONCLUSION: The data suggest that the PLGA/HAp/Zein scaffolds possess good biocompatibility, which are anticipated to be potentially applied in cartilage tissue engineering and reconstruction.

[Association between vitamin D receptor gene Tru9I polymorphism and myasthenia gravis].

OBJECTIVE: To explore the associations between vitamin D receptor (VDR) gene Tru9I polymorphism and myasthenia gravis (MG). METHODS: A total of 302 MG patients, diagnosed and treated at Affiliated Hospital of Medical College, Qingdao University and Beijing Friendship Hospital from December 2006 to July 2010, were recruited. And 283 normal subjects were selected as the controls. Tru9I polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of genotypes and alleles were compared among different MG subgroups and control group. The relationship between the genotype and susceptibility or severity of MG and immediate efficacies of glucocorticoid were explored. The SPSS17.0 was applied to statistical analysis. RESULTS: In the MG patients whose age of onset was above 15 years, the frequency of TT and tt genotypes in females was lower than that of the control group. However the frequency of Tt genotype was higher than that of the control group. And there were significant differences (χ(2) = 8.847, P = 0.012). The frequency of Tt + tt genotype in females (58/139, 41.7%) was higher than that of the control group (56/189, 29.6%). And there were also significant differences (OR = 1.70, 95% CI 1.07 - 3.41, χ(2) = 5.169, P = 0.023). Although the frequency of t alleles in females (61/278, 21.9%) was higher than that of the control group (65/378, 17.2%), no significant differences existed (P > 0.05). There were no differences in frequencies of genotypes and alleles between the patients with varying severity and different immediate efficacies of glucocorticoid (P > 0.05). CONCLUSION: VDR gene Tru9I polymorphism may be related to the risk of MG in females aged above 15 years.

[Diagnostic value of combined modified Alvarado scores and computed tomography imaging in the pathological types of acute appendicitis in adults].

OBJECTIVE: To explore the diagnostic value of combined modified Alvarado scores (MAS) and computed tomography imaging in the pathological types of acute appendicitis in adults. METHODS: Clinical data of a total of 396 adult patients with acute appendicitis confirmed by surgery and pathology were analyzed retrospectively from June 2007 to July 2010. Case-control study was used to investigate the MAS. CT signs were studied in 115 patients who underwent preoperative CT scan. Univariable analysis was performed using each indicator among different pathological types. Discriminant classification was formed by applying significant variables identified from univariable analysis and a Fisher discriminant function was created. RESULTS: Twenty three variables were statistically significant among different pathological types after univariable analysis(P<0.05) and were selected for discriminant analysis. Six variables including temperature(X1), leucocyte count(X2), the proportion of neutrophil(X3), MAS points(X4), periappendiceal fat stranding(X5), and extraluminal air(X6) were enrolled. The discriminant function equation was Y1=0.012X1+0.041X2+0.069X3-0.039X4+2.653X5+1.418X6, Y2=0.327X1+0.041X2-0.034X3-0.140X4-1.114X5+2.982X6. The accuracy was 76.5%(88/115) in retrospective assessment and 77.8%(21/27) in prospective assessment. CONCLUSION: The combined use of MAS and CT imaging signs is useful in identifying the pathological types of acute appendicitis in adults, so it is helpful in choosing reasonable therapeutic option for surgeons.

[Prevalence of allergic rhinitis and survey analysis of health service needs and utilization in Qingdao area].

OBJECTIVE: To investigate the need and utilization for health services in patients with allergic rhinitis in Qingdao area. METHODS: An investigation was conducted by the method of combining multi-stage sampling and cluster sampling. SPSS 13.0 software was used to analyse the data. RESULTS: Among Two thousand and four hundred questionnaires, two thousand and fifty-two questionnaires were available. The effective rate was 85.5%. The total two-week prevalence in male was 6.5%, while that in female was 6.2%. There was no significant difference between male and female (χ(2) = 0.103, P > 0.05). The total ratio of those who visited doctors was 1.7%. The ratio of those who visited doctors in the first two weeks was 26.7% (35/131). 49.0% of non-users of health service thought it was unnecessary to consult a doctor because of mild symptoms. In the investigation about the allergic rhinitis, 60.2% patients (1235/2052) confessed that they heard of allergic rhinitis, 30.0% patients (616/2052) thought of allergic rhinitis was common cold. CONCLUSIONS: The number of patients treated for allergic rhinitis was less than its prevalence. The primary reason for low attendance was that the majority of patients with mild symptoms thought it was no need to see a doctor. In order to improve the residents' health services utilization, medical education for allergic rhinitis is necessary.

An improved risk of malignancy index in diagnosis of adnexal mass.

BACKGROUND: With the advent of color Doppler flow imaging (CDFI) and technological development of detection of serum tumor markers, new opportunities are presented to the improved risk of malignancy index (RMI) based on Jacobs' research for predicting ovarian malignancy in patients with adnexal masses. METHODS: One hundred and eighty women with an adnexal mass admitted for primary laparotomy were studied. Tumor specific growth factor (TSGF) adjusted ultrasound scores and the results of Doppler blood flow analysis were obtained before the operation. Based on the parameters which had been studied in Jacobs' research, TSGF levels and the findings of color Doppler flow imaging, the risk of malignancy model was redesigned using a binary Logistic regression model. The diagnostic efficacy of the improved risk of malignancy index (improved RMI) was compared with the Jacobs' model RMI by receiver operator characteristic (ROC) curve. RESULTS: The ROC curve showed a higher sensitivity (Mcnamer's test, P < 0.05) in the discrimination between benign and malignant adnexal masses for the improved RMI than the RMI. Compared with the RMI, the improved RMI had an advantage in prediction of ovarian germ cell tumors and granular cell tumor (28.57% vs.71.43%, P < 0.05) and the early stage tumors and borderline tumors (33.33% vs. 66.67%, P < 0.05). CONCLUSION: The predictability of the improved RMI is better than the classic Jacobs' model, especially in diagnosis of the ovarian germ cell tumors and granular cell tumor and other early stage adnexal tumors.

Si-Ni-San, a traditional Chinese prescription, and its active ingredient glycyrrhizin ameliorate experimental colitis through regulating cytokine balance.

Si-Ni-San, a traditional Chinese medicinal formula, exerts an important function in the treatment of inflammatory bowel diseases based upon thousands of years of clinical practice, but the underlying mechanism is still unclear. In this study, we investigated the therapeutic potential of Si-Ni-San and its ingredient glycyrrhizin in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice, a well-characterized murine model for Crohn's disease. Si-Ni-San and glycyrrhizin significantly ameliorated TNBS-induced colitis with reduced mortality and recovery of body weights. In addition, Si-Ni-San and glycyrrhizin dose-dependently decreased macroscopic inflammation scores, microscopic histological scores, and myeloperoxidase activity. Furthermore, Si-Ni-San and glycyrrhizin caused a decrease in pro-inflammatory cytokines including IFN-gamma, IL-12, TNF-alpha and IL-17 and an increase in regulatory cytokine IL-10 in colon of the mice. It should be noticed the therapeutic effect of Si-Ni-San at 450 mg/kg was much better than that of its contained content of glycyrrhizin at 10 mg/kg. In conclusion, Si-Ni-San and glycyrrhizin significantly ameliorated TNBS-induced colitis in mice through regulating pro- and anti-inflammatory cytokine production.

Saikosaponin a inhibits the proliferation and activation of T cells through cell cycle arrest and induction of apoptosis.

In the present study, we aimed at examining the immunosuppressive activity of saikosaponin a, a triterpene saponin derived from Bupleurum falcatum L. (Umbelliferae), and the underlying mechanisms. Saikosaponin a significantly inhibited the proliferation and activation of T cells activated by concanavalin A (Con A) in a concentration-dependent manner. Additionally, it potently suppressed Con A-stimulated IL-2, IFN-gamma and TNF-alpha production in mouse T cells. Saikosaponin a also caused G0/G1 arrest of activated T cells through down-regulating the protein levels of CDK6 and Cyclin D3 and up-regulating the protein level of p27(kip). Furthermore, the compound dose-dependently induced apoptosis of Con A-activated T cells rather than those non-activated, as determined by Annexin V/PI staining. Besides, it induced a remarkable collapse of mitochondrial membrane potential and caused significant release of cytochrome c from mitochondria to cytosol. In summary, these results suggest that the G0/G1 arrest as well as the induction of apoptosis via mitochondrial pathway are involved in the immunosuppressive activity of saikosaponin a against activated T cells. This may herald a novel approach for further studies of saikosaponin a as a candidate for the treatment of inflammatory and autoimmune diseases.

[Multivariate logistic regression analysis of postoperative severe complications and discriminant model establishment in gastric cancer post gastrectomy].

OBJECTIVE: To investigate the main risk factors for postoperative severe complications, and establish Logistic regression model to predict severe complications in gastric cancer following gastrectomy. METHODS: The data of 1728 gastric cancer patients underwent gastrectomy between June 2001 and June 2007 were analyzed retrospectively. Logistic regression analysis was used to investigate the risk factors for postoperative severe complications in those patients. RESULTS: Postoperative severe complications were associated with extent of lymph node dissection (D(2)(+)-D(3)), chronic obstructive pulmonary disease (COPD), invasion to the adjacent organ, combined organ resection, extent of lymph node dissection (D(2)), diabetes mellitus (DM), TNM staging IV, heart diseases, malnutrition, surgeon's operative volume, operative time, blood loss and age. The Logistic regression model was P = 1/[1+e((14.806-2.523X1-1.792X2-1.558X3-1.551X4-1.270X5-1.150X6-1.101X7-0.981X8-0.817X9-0.657X10-0.578X11-0.542X12-0.309X13))]. A testing sample showed that the accuracy, sensitivity and specificity of the Logistic model were 72.5%, 70.0% and 75.0%, respectively. CONCLUSIONS: The extent of nodal dissection (D(2)(+)-D(3)), COPD, invasion to the adjacent organ, combined organ resection, extent of nodal dissection (D(2)), diabetes mellitus, TNM staging IV, heart diseases, malnutrition, surgeon's operative volume, operative time, blood loss and age are the independent risk factors associated with severe complications in gastric cancer post gastrectomy. The Logistic regression model based on these factors is reliable in predicting the severe complications.

[Statistical analysis of articles, citations and authors in Chinese Journal of Gastrointestinal Surgery from 2002 to 2004].

OBJECTIVE: To study the characteristics of of articles, citations and authors in Chinese Journal of Gastrointestinal Surgery(CJGS). METHODS: The data of articles,citations and authors of CJCS from 2002 to 2004 were collected and analyzed in terms of bibliometric parameters. RESULTS: There were 546 papers in CJCS during the past 3 years and project-funded papers accounted for 14.3%. The average number of articles per issue was 34; the average number of article per page was 0.44; the average publishing cycle of the articles was 7.52 months. The authors came from 28 provinces and Hong Kong SAR; the coauthor rate was 88.88%; the cooperation rate was 4.18. The papers with citation accounted for 92% and 93.78% of the citations were from journals. The Prices indicator was 60.1%. CONCLUSION: Chinese Journal Gastrointestinal Surgery is a high quality academic journal with strong influence, and promotes the development and construction of gastrointestinal surgery in China.