MiR-139-5p inhibits the proliferation of gastric cancer cells by targeting Regulation of Nuclear Pre-mRNA Domain Containing 1B.

Regulation of Nuclear Pre-mRNA Domain Containing 1B (RPRD1B) has been of great interest in the field of oncology in recent years. The relationship between miRNAs and RPRD1B in gastric cancer (GC) has not been adequately reported. This study was designed to screen RPRD1B-targeted miRNAs and investigate its regulatory mechanism in GC cells. Quantitative RT-PCR and in situ hybridization were used to detect miRNA expression in GC tissues. Colony formation, EdU cell proliferation assay, and flow cytometry were used to analyze the cell cycle. Database-assisted gene expression analysis revealed that RPRD1B was targeted and regulated by miRNA-139-5p in GC. miRNA-139-5p expression was higher in GC tissue than in normal tissues and significantly correlated with tumor size, pathological stage, and disease-free survival of GC (p < 0.05). MiRNA-139-5p regulates GC cell proliferation and affects the transition from G1 to S phase. It binds explicitly to the 2013-2019 sites of the 3'UTR of RPRD1B and negatively regulates RPRD1B expression. We demonstrated that the ability of miR-139-5p to regulate GC cell proliferation depends on RPRD1B. This process is accompanied by changes in Cyclin D1 protein expression. We established a miR-139-5p/RPRD1B/tumor proliferation axis in GC, which may serve as novel biomarkers and drug targets for GC.

Tumor deposit serves as a prognostic marker in gastric cancer: A propensity score-matched analysis comparing survival outcomes.

BACKGROUND: Gastric cancer (GC) treatment is determined by accurate tumor staging. The value of tumor deposit (TD) in prognostic prediction staging system is not yet determined. METHODS: We retrospectively analyzed clinical information on GC patients who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital from July 2014 to June 2016. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. RESULTS: Of the 1034 GC patients, 240 (23.21%) presented with TD, which was associated with younger age and larger tumor size (all P < .05). TD-positive patients had a worse survival than TD-negative patients before (P < .001) and after (P = .017) matching. Multivariable analysis showed that mortality risk of patients with TD increased by 58%, 62%, 37%, and 40% in the crude (HR = 1.58, 95% CI 1.32-1.89, P < .001), adjusted I (HR = 1.62, 95% CI 1.35-1.94, P < .001), adjusted II (HR = 1.37, 95% CI 1.13-1.66, P = .001), and adjusted III (HR = 1.40, 95% CI 1.16-1.68, P < .001) models before matching. Similarly, in the PSM cohort patients with TD had worse prognosis in the crude (HR = 1.32, 95% CI 1.07-1.63, P = .011), adjusted I (HR = 1.35, 95% CI 1.09-1.67, P = .005), adjusted II (HR = 1.26, 95% CI 1.00-1.58, P = .049), and adjusted III (HR = 1.33, 95% CI 1.07-1.65, P = .010) models. TD had a similar value range between N1 and N2 stages among different models. CONCLUSIONS: Among GC patients, TD is associated with survival and may have a role in the staging of patients.

Clinicopathologic features and prognostic analysis of 240 patients with gastric neuroendocrine neoplasms / 中华胃肠外科杂志

Objective@#To investigate clinicopathological features and prognostic factors of gastric neuroendocrine tumors (G-NEN).@*Methods@#Clinical and pathological data of patients with G-NEN diagnosed by pathological examination in Chinese PLA General Hospital from January 2000 to June 2018 were retrospectively analyzed in this case-control study. Patients with complicated visceral lesions, other visceral primary tumors, mental disorders and incomplete clinicopathological data were excluded. Finally, 240 hospitalized patients who met the inclusion criteria were enrolled. Physical examination information, tumor characteristics and pathological characteristics of patients were summarized. The Cox regression models were used to analyze the risk factors affecting G-NEN and the survival conditions were described by Kaplan-Meier survival curves and log-rank test.@*Results@#In 240 patients with G-NEN, the mean age was (60.3±10.1) years; 181 were male (75.4%) and 59 females (24.6%); mean tumor diameter was (4.2±2.8) cm; 51 cases (21.2%) were neuroendocrine tumor (NET), 139 cases (57.9%) neuroendocrine carcinoma (NEC), 50 cases (20.8%) mixed neuroendocrine carcinoma (MANEC); 28 cases (11.7%) were G1 low grades, 34 cases (14.2%) G2 medium grades, and 178 cases (74.2%) G3 high grades; tumor infiltration depth T1 to T4 were 44 cases (18.3%), 27 cases (11.2%), 60 cases (25.0%) and 109 cases (45.4%) respectively; 163 cases (67.9%) developed lymphatic metastasis and 46 patients (19.2%) distant metastasis; tumor stage from stage I to stage IV were 55 cases (22.9%), 42 cases (17.5%), 94 cases (39.2%) and 53 cases (22.1%) respectively. Of the 240 G-NEN patients, 223 cases (92.9%) were followed up. The median survival time of the patients was 39.2 (95% CI: 29.1 to 47.5) months. Univariate survival analysis showed that age ≥ 60 years, tumor diameter ≥ 4.2 cm, tumor grade G3, lymphatic metastasis, distant metastasis, and tumor stage III-IV were risk factors for G-NEN patients. Multivariate survival analysis revealed that lymphatic metastasis (HR=1.783, 95%CI: 1.007-3.155, P=0.047) and distant metastasis (HR=2.288, 95% CI: 1.307-4.008, P=0.004) were independent risk factors of the prognosis. Further analysis of the G3 subgroup of G-NEN showed that the 5-year survival rate of NET-G3 was 76.19%, which was significantly higher than that of NEC-G3 and MANEC-G3 (15.60% and 24.73%, P=0.012).@*Conclusions@#Most G-NEN patients are in advanced stage at diagnosis. Lymphatic metastasis and distant metastasis indicate poor prognosis. The prognosis of high proliferation NET-G3 patients is better as compared to those of NEC-G3 and MANEC-G3. This classification is worth further attention.

Comparison of the short-term and long-term outcome between robotic gastrectomy and laparoscopic gastrectomy: a propensity score matching analysis / 中华外科杂志

Objective@#To compare the short-term and long-term outcome between robotic gastrectomy and laparoscopic gastrectomy.@*Methods@#The clinical data of 517 patients who had received robotic gastectomy and laparoscopic gastrectomy between December 2011 and December 2013 at Department of General Surgery, Chinese People′s Liberation Army General Hospital was collected. After propensity score matching, 70 patients in robotic gastectomy and 70 patients in laparoscopic gastectomy were identified. Perioperative outcome and overall survival were compared between the two groups using t test, χ2 test, Kaplan-Meier curve and Log-rank test, respectively. Prognosis factors were analyzed by Cox′s proportional hazards regression.@*Results@#There were comparable baseline characteristics between patients in robotic group (RG) and those in laparoscopic group (LG). The conversion rate for RG and LG were 5.7% and 4.3% respectively (P=1.000). Compared with LG, RG had similar lymph node retrieval (25.5±7.2 vs. 24.5±8.3, t=0.770, P=0.443) and less blood loss ((147.0±96.8) ml vs. (188.0±111.2) ml, t=-2.326, P=0.021). There were also similar complications (χ2=0.233, P=0.629) and severity of complications (W=70.500, P=0.053). Although there tended to be early mobility, early flatus and less hospital stay for patients in RG group, the difference between RG and LG was not statistically significant. The 3-year survival rate was 72.9% and 60.0% for patients in RG and patients in LG (P=0.578). Multivariable analysis revealed gender (HR=2.529, 95% CI: 1.042 to 6.140, P=0.040), neoadjuvant chemotherapy (HR=0.272, 95% CI: 0.104 to 0.710, P=0.008) and vascular invasion (HR=2.135, 95% CI: 1.027 to 4.438, P=0.042) were independent prognostic factors.@*Conclusion@#Compared with laparoscopic gastrectomy, robotic gastectomy could achieve similar short-term and long-term outcomes.

Value of tumor deposits in staging and prognostic evaluation in gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze relationships between the tumor deposits (TD) and clinicopathologic features of gastric cancer and investigate the value of TD in staging and prognosis in gastric cancer patients.</p><p><b>METHODS</b>Retrospective cohort study was conducted to evaluate the clinicopathologic data of 388 gastric cancer patients who underwent surgical procedures in Chinese PLA General Hospital between November 2011 and December 2012. Relationships between TD and clinicopathologic features were analyzed by χor Fisher exact tests. Survival curves were also generated by Kaplan-Meier method. The univariate and multivariate analysis were performed with Log-rank and COX proportional hazard model to examine the association between prognosis and TD.</p><p><b>RESULTS</b>TD were observed in 67 (17.3%) of 388 gastric cancer patients, including 48 male patients (48/289, 16.6%) and 19 female patients (19/99, 19.2%). There were 40 patients (40/198, 20.2%) whose age was above 64 years old. TNM staging of positive TD patients was as follows: for pathology, there were 5 patients (5/64, 7.8%) in stage II(b, 6 patients (6/58, 10.3%) in stage III(a, 14 patients (14/75, 18.7%) in stage III(b, 30 patients (30/135, 22.2%) in stage III(c, 12 patients (12/39, 30.8%) in stage IIII( and no one in stage I(b or II(a; for T-staging, there were 2 patients (2/18, 11.1%) in stage T2, 2 patients (2/27, 7.4%) in stage T3, 36 patients (36/259, 13.9%) in stage T4a and 27 patients (27/84, 32.1%) in stage T4b; for N-stage, there were 5 patients (5/72, 6.9%) in stage N0, 6 patients (6/72, 8.3%) in stage N1, 19 patients (19/82, 23.2%) in stage N2, 27 patients (27/100, 27.0%) in stage N3a and 10 patients(10/62, 16.1%) in stage N3b; for M-stage, there were 12 patients (12/40, 30.0%) in distal metastases; for vascular invasion, there were 29 patients (29/129, 22.5%). Among positive TD patients, the number of TD >3 was found in 38 of 67 cases(56.7%). TD was associated with pTNM-stage (χ=16.898, P=0.010), T-stage (χ=17.382, P=0.001), N-stage (χ=18.080, P=0.001), M-stage (χ=5.060, P=0.036) and vascular invasion(χ=3.675, P=0.039). The median survival time of positive TD patients was significantly shorter as compared to negative TD patients (22 months vs. 32 months, χ=23.391, P=0.012). Among positive TD patients, the median survival time of patients with TD number >3 was significantly shorter as compared to those with TD number <3 (17 months vs. 25 months, χ=5.157, P=0.023). Multivariate survival analysis showed that TD number >3 was the independent risk factor of prognosis (RR=2.350, 95%CI:1.345 to 4.106, P=0.003).</p><p><b>CONCLUSIONS</b>TD state is closely associated with the staging of gastric cancer and TD number >3 indicates a poor prognosis.</p>

Clinicopathologic features and prognostic analysis of 104 patients with gastric neuroendocrine neoplasms / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features and prognostic factors of gastric neuroendocrine neoplasms(gNENs).</p><p><b>METHODS</b>Clinicopathologic data of 104 patients with gastric neuroendocrine neoplasms admitted in Chinese PLA General Hospital between January 2000 and December 2014 were analyzed retrospectively. Tumor proliferation activity classification (G1, G2 and G3) and TNM staging were observed. The clinicopathologic features of the whole group were collected and the univariate and multivariate analysis were determined by Log-rank and Cox proportional hazard model to detect the prognosis-determining features.</p><p><b>RESULTS</b>Of all the patients, 66 cases(63.5%) were neuroendocrine carcinoma, 25 cases(24.0%) were mixed adenoendocrine carcinoma and 12 cases (11.5%) were neuroendocrine tumor. For G grades, 92 cases (88.5%) were G3 grade, 8 cases(7.7%) were G2 grade and 4 cases (3.8%) were G1 grade. TNM staging results showed that stageI( was found in 6 cases (5.8%), stageII(A in 6 cases (5.8%), stageII(B in 9 cases (8.7%), stage III(A in 8 cases (7.7%), stage III(B in 55 cases (52.9%) and stageIIII( in 20 cases (19.2%). For T stage, 7 cases (6.7%) were T1, 12 cases (11.5%) were T2, 24 cases (23.1%) were T3, and 61 cases (58.7%) were T4. Lymph node metastasis occurred in 73 cases (70.2%) and distant metastasis occurred in 20 cases(19.2%). Eighty-six patients were followed up for 6 to 186 months. The median survival was 33.0 months(95% CI: 28.3 to 36.6), and 1-, 3-, and 5-year survival rates were 80%, 49% and 31%. Clinicopathologic features which were considered statistically significant on univariate analysis were selected to Cox proportional hazard model. Univariate analysis showed that risk factors of reducing survival rate included tumor size, pathological type, proliferation activity grades, and depth of invasion (all P<0.05), as well as chromogranin A expression, tumor staging, lymph node metastasis and distant metastasis(all P<0.01). The multivariate analysis showed that the stage of gNEN was the independent risk factor of the prognosis (RR=14.213, 95% CI: 1.316 to 153.524, P=0.029).</p><p><b>CONCLUSION</b>Late staging is the main clinical feature and a prognostic factor for gNENs.</p>

Association of prognosis with insulin-like growth factor receptor type I expression in gastric cancer patients: a meta-analysis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To systemically evaluate the relationship between the expression of insulin-like growth factor receptor type I (IGF-1R) and prognosis in gastric cancer (GC) patients.</p><p><b>METHODS</b>A literature search was conducted from PubMed, EMBASE, Web of Science, CNKI, Wanfang and VIP databases to retrieve the clinical studies relevant to IGF-1R expression and its prognostic value in GC patients. Meta-analysis was performed using STATA 12.0 software. The methodology was assessed according to the European Lung Cancer Working Party Quality Scale for Biological Prognostic Factors for Lung Cancer. The quality of studies was assessed using the Newcastle-Ottawa scale.</p><p><b>RESULTS</b>Four eligible studies including 685 patients were enrolled for this meta-analysis. Analysis results suggested that up-regulation of IGF-1R in GC patients was significantly associated with TNM staging (OR=5.20, 95%CI:1.12 to 24.15, P=0.035), lymph node metastasis(OR=8.24, 95%CI:2.68 to 25.34, P=0.000) and distant metastasis(OR=17.34, 95%CI:6.52 to 46.15, P=0.000). Moreover, up-regulated IGF-1R expression was significantly associated with poor overall survival of gastric cancer patients(HR=2.63, 95% CI:1.29 to 5.40, Z=2.64, P=0.008).</p><p><b>CONCLUSION</b>High IGF-1R expression may be an adverse prognostic factor in gastric cancer patients.</p>

Development and in vitro evaluation of estradiol transdermal film-forming spray / 药学学报

To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.

Research progress of gene recombinant mesenchymal stem cells as tumor targeting delivery vehicles / 药学学报

The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.

Study on relationship of properties and drug release rate of hot melt pressure sensitive adhesive / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the relationship of properties and drug release rate of hot melt pressure sensitive adhesive (HMPSA), and to provide a recommendation of preparing and selecting of HMPSA for transdermal use.</p><p><b>METHOD</b>HMPSA with different properties were prepared using styrene-isoprene-styrene triblock copolymer as main material, and the tacks, adhesions and cohesions were determined. Drug-in-adhesive type patches were prepared using alpha-asarone as model drug, and the drug release rates were investigated on single chamber diffusion cells using 60% ethanol solution as release media.</p><p><b>RESULT</b>The prepared HMPSAs had different tacks, adhesions and cohesions. The drug release rates of HMPSA patches were related to the cohesions. The release rate decreased when the cohesion increased.</p><p><b>CONCLUSION</b>The HMPSA with appropriate cohesion should be selected when preparing patches to balance the drug release rate and patch property.</p>

Formulation study on cryptotanshinone gel for topical administration / 中国中药杂志

<p><b>OBJECTIVE</b>To screen the formulations of cryptotanshinone gel for treatment of topical diseases such as acne.</p><p><b>METHOD</b>Different cryptotanshinone gels incorporating various penetration enhancers at different concentrations were prepared using carbopol 934L as matrix. The steady transdermal fluxes and drug retention amounts in skin of the gels were investigated on single chamber diffusion cells using excised rat abdomen skin as model and 40% polyethylene glycol-400 saline as releasing media. The optimal formulation would be the gel which had the maximum drug retention amount/ transdermal drug flux ratio.</p><p><b>RESULT</b>The promotion effects of menthol at different concentrations were as follows: 5% > 3% > 1%, and the effects on drug retention amount in skin were followed as: 5% approximately equal 3% > 1%; The promotion effects of a zone at different concentrations were as follows: 5% approximately equal 3% > 1%, and the effects on drug retention amount in skin were as follows: 5% > 3% approximately equal 1%. Combination of enhancers showed no superior effects compared to single uses. 5% azone had the maximum retention amount/ transdermal flux ratio.</p><p><b>CONCLUSION</b>The optimal formulation was the cryptotanshinone gel containing 5% azone.</p>

PREDICTING SKIN PERMEABILITY OF DRUGS WITH THEORETICAL PARAMETERS / 药学学报

AIM　To predict skin permeability of drugs with theoretical parameters. METHODS　The semiempirical self-consistent field molecular calculation AM1 method is utilized to obtain the structural parameters of drug molecules. Stepwise multiple regression analysis or BP neural network is then utilized to establish the correlation between skin permeability of drugs and their structural parameters. RESULTS　The calculated human skin permeability coefficients (kp) of 22 model drugs in vitro or the R values (R=absorbed/unabsorbed) of 17 drugs in vivo are in good agreement with their observed values. CONCLUSION　Theoretical parameters can be used to predict skin permeability of drugs.