Jinbo Gao

Sericin/Dextran Injectable Hydrogel as an Optically Trackable Drug Delivery System for Malignant Melanoma Treatment

Severe side effects of cancer chemotherapy prompt developing better drug delivery systems. Injectable hydrogels are an effective site-target system. For most of injectable hydrogels, once delivered in vivo, some properties including drug release and degradation, which are critical to chemotherapeutic effects and safety, are challenging to monitor. Developing a drug delivery system for effective cancer therapy with in vivo real-time noninvasive trackability is highly desired. Although fluorescence dyes are used for imaging hydrogels, the cytotoxicity limits their applications. By using sericin, a natural photoluminescent protein from silk, we successfully synthesized a hydrazone cross-linked sericin/dextran injectable hydrogel. This hydrogel is biodegradable and biocompatible. It achieves efficient drug loading and controlled release of both macromolecular and small molecular drugs. Notably, sericins photoluminescence from this hydrogel is directly and stably correlated with its degradation, enabling long-term in vivo imaging and real-time monitoring of the remaining drug. The hydrogel loaded with Doxorubicin significantly suppresses tumor growth. Together, the work demonstrates the efficacy of this drug delivery system, and the in vivo effectiveness of this sericin-based optical monitoring strategy, providing a potential approach for improving hydrogel design toward optimal efficiency and safety of chemotherapies, which may be widely applicable to other drug delivery systems.

The comprehensive summary of surgical versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomized controlled trials

Background Bariatric surgery has emerged as a competitive strategy for obese patients. However, its comparative efficacy against non-surgical treatments remains ill-defined, especially among nonseverely obese crowds. Therefore, we implemented a systematic review and meta-analysis in order for an academic addition to current literatures. Methods Literatures were retrieved from databases of PubMed, Web of Science, EMBASE and Cochrane Library. Randomized trials comparing surgical with non-surgical therapies for obesity were included. A Revised Jadads Scale and Risk of Bias Summary were employed for methodological assessment. Subgroups analysis, sensitivity analysis and publication bias assessment were respectively performed in order to find out the source of heterogeneity, detect the outcome stability and potential publication bias. Results 25 randomized trials were eligibly included, totally comprising of 1194 participants. Both groups displayed well comparability concerning baseline parameters (P > 0.05). The pooled results of primary endpoints (weight loss and diabetic remission) revealed a significant advantage among surgical patients rather than those receiving non-surgical treatments (P < 0.05). Furthermore, except for certain cardiovascular indicators, bariatric surgery was superior to conventional arms in terms of metabolic secondary parameters (P < 0.05). Additionally, the pooled outcomes were confirmed to be stable by sensitivity analysis. Although Eggers test (P < 0.01) and Beggs test (P<0.05) had reported the presence of publication bias among included studies, “Trim-and-Fill” method verified that the pooled outcomes remained stable. Conclusion Bariatric surgery is a better therapeutic option for weight loss, irrespective of follow-up duration, surgical techniques and obesity levels.

miR-219-5p plays a tumor suppressive role in colon cancer by targeting oncogene Sall4

Sall4 is a novel oncogene found upregulated in several malignancies including colon cancer. However, its upstream regulatory miRNA is still undefined. miR-219-5p is regarded as a tumor-related miRNA in cancer research. Nevertheless, its actual role of whether inhibiting or promoting tumorigenesis is unclear in colon cancer. Potential interaction between Sall4 and miR-219-5p is predicted by TargetScan. CCK-8 test was used for evaluation of cell proliferation and cell survival rates. Western blot analysis and real-time PCR were applied for detection of target molecules. Luciferase assay was a direct confirmation of mutual interaction. Wound healing assay and transwell assay were conducted for cell migration and invasion tests. Flow cytometry was used for cell apoptosis analysis. Tissue specimens and cell lines were explored for miR-219-5p inhibition on colon cancer proliferation, migration, invasion, apoptosis and drug resistance by targeting Sall4. The results show that miR-219-5p inhibited carcinogenesis of colon cancer by targeting oncogene Sall4.

Two-dimensional versus three-dimensional laparoscopy in surgical efficacy: a systematic review and meta-analysis

Background Laparoscopy is a revolutionary technique in modern surgery. However, the comparative efficacy between two-dimensional laparoscopy and three-dimensional laparoscopy remains in uncertainty. Therefore we performed this systematic review and meta-analysis in order to seek for answers. Methods Databases of PubMed, Web of Science, EMBASE and Cochrane Library were carefully screened. Clinical trials comparing two-dimensional versus three-dimensional laparoscopy were included for pooled analysis. Observational and randomized trials were methodologically appraised by Newcastle-Ottawa Scale and Revised Jadads Scale respectively. Subgroup analyses were additionally conducted to clarify the potential confounding elements. Outcome stability was examined by sensitivity analysis, and publication bias was analyzed by Beggs test and Eggers test. Results 21 trials were screened out from the preliminary 3126 records. All included studies were high-quality in methodology, except for Bilgen 2013 and Ruan 2015. Three-dimensional laparoscopy was superior to two-dimensional laparoscopy in terms of surgical time (P < 0.00001), blood loss (P = 0.01), perioperative complications (P = 0.04) and hospital stay (P = 0.03). Additionally, both techniques demonstrated comparable results of secondary endpoints, including drainage volume (P = 0.74), drainage time (P = 0.26), numbers of retrieved lymphnodes (P = 0.85), hospital expenses (P = 0.49), anastomosis time in prostatectomy (P=0.15) and 6-month continence rate (P = 0.61). The pooled outcomes of primary endopoints were verified to be stable by sensitivity analysis. Although Beggs test (P = 0.215) and Eggers test (P = 0.003) revealed that there was publication bias across included studies, Trim-and-Fill method confirmed that the results remained stable. Conclusion Three-dimensional laparoscopy is a preferably surgical option against two-dimensional laparoscopy due to its better surgical efficacy.

Prognostic role of Gli1 expression in solid malignancies: a meta-analysis

Gli1 is a downstream transcriptional factor of Sonic hedgehog pathway in mammalians, and has been recognized as a proliferative indicator of carcinogenesis. However, its actual role in prognosis among solid malignancies remains unclear. Therefore we performed this meta-analysis aiming to discover the correlation between Gli1 positivity and clinical prognosis in patients suffering from diverse carcinomas. A total of 39 studies containing 4496 cases were selected into our quantitative analysis via electronic database search. Original data of 3-year, 5-year, 10-year overall survival and disease-free survival were extracted and calculated using odds ratio and Mantel-Haenszel model. Subgroup analysis was also conducted to clarify the possible confounding factors. P < 0.05 was considered significant in statistics. Gli1 redundancy was associated with worse 3-year, 5-year, 10-year overall survival and disease-free survival in solid malignancies. Different source regions, sample-size, mean-age and detection approaches had no impact on the negative prognostic effect of Gli1 over-expression. Nevertheless, stratified by cancer type and subcellular localization, cytoplasmic Gli1 expression and Gli1 positivity in intracranial tumors was not correlated to poorer 3-year and 5-year prognosis. The over-expression of Gli1 is a credible indicator of poorer prognosis in most of solid malignancies, irrespective of intracranial tumors.

Oncogenic protein SALL4 and ZNF217 as prognostic indicators in solid cancers: a meta‑analysis of individual studies

Background SALL4 and ZNF217 have been widely acknowledged as pivotal effectors stimulating embryonic immortalization as well as oncogenicity. Nevertheless, their prognostic worthiness towards solid tumors remains obscure. Hence we performed this comprehensive meta-analysis aiming to unveil the survival significance of both aberrantly expressed proteins. Results Overall we included 22 eligible entries comprising of 3093 participants. Over-expression of SALL4 and ZNF217 were negatively correlated with clinical prognosis of 3-year, 5-year, 10-year and disease-free survival in solid malignancies, irrespective of cancer types, source regions, mean-age and sex predominance. Results of sensitivity analysis additionally verified the stability of the pooled outcomes. No publication bias was observed on the basis of Eggers test and Beggs test. Methods Studies were eventually included via database searching and rigorous eligibility appraisal. Data extraction and methodological assessment were implemented under a standard manner. Review Manager 5.3 and STATA 12.0 were utilized as statistical platforms following the recommendations by Cochrane Collaboration protocols. Conclusions Aberrant amplification of SALL4 and ZNF217 serve as unfavorable predictors of survival expectancy among cancer sufferers, revealing great potential as targeted spots in future therapeutics.

Clinicopathologic Features of Gastric Schwannoma: 8-Year Experience at a Single Institution in China.

AbstractTo explore the clinicopathologic characteristics, diagnosis, treatment, and prognosis of gastric schwannoma in the imatinib era.The clinicopathologic characteristics and postoperative outcomes of patients diagnosed with gastric schwannoma at our institution between January 2007 and February 2015 were retrospectively collected and analyzed.The main patient complaint was epigastric pain or discomfort. Tumor sizes ranged from 15 to 80 mm (mean, 57.1 mm). In 17 patients, the tumors were located in the body of the stomach. A total of 20 patients were preoperatively misdiagnosed with a gastrointestinal stromal tumor. The rate of correct preoperative diagnosis was only 3.3%. All patients underwent surgical resection and showed strong S-100 protein positivity. Laparoscopic surgery for gastric schwannoma was associated with less blood loss and a shorter postoperative hospital stay than open surgery (P < 0.01). Total 28 patients were disease free without recurrence or metastasis at a median follow-up time of 50 months.Gastric schwannoma is often preoperatively misdiagnosed as gastric gastrointestinal stromal tumor. Laparoscopic resection of gastric schwannoma is considered safe and effective, and it may be the preferred surgery for most small- and moderate-sized tumors. The long-term outcome is excellent, as this type of neoplasm is uniformly benign.

Clinicopathological and Prognostic Analysis of Primary Gastrointestinal Stromal Tumor Presenting with Gastrointestinal Bleeding: a 10-Year Retrospective Study

ObjectivesThe objectives of this paper were to investigate the clinicopathological characteristics and prognostic factors of GI-bleeding GIST patients and explore whether GI bleeding is a risk factor for GIST relapse.MethodsPrimary GIST patients with initial symptoms of GI bleeding or no GI bleeding were retrospectively studied.ResultsUp to 178 GI-bleeding GIST patients including 108 (60.7%) males and 70 (39.3%) females were evaluated for the clinicopathological characteristics. The stomach, small bowel, and colorectum were the tumor sites in 82 (46.1%), 85 (47.8%), and 11 (6.2%) patients. Of the 178 patients, 163 GI-bleeding patients had follow-up while another 363 patients from the total population presented without GI bleeding were followed up. Up to 526 patients who received postoperative follow-up were included in the survival analysis. Compared with the 363 non-GI-bleeding patients, GI-bleeding patients developed smaller tumors (P = 0.015) and had a longer relapse-free survival (RFS; P = 0.014). For the 163 GI-bleeding patients, a Cox regression analysis showed that the mitotic count and the platelet-lymphocyte ratio before surgery were independent prognostic predictors for poor outcome regarding RFS. For all 526 patients, a Cox regression analysis indicated that tumor location, mitotic index, platelet-lymphocyte ratio, and GI bleeding were independent prognosis predictors.ConclusionCompared to non-GI-bleeding GIST patients, patients with GI bleeding were more likely to be male and to have more small intestine GISTs, smaller tumors, and a longer RFS. For GI-bleeding patients, mitotic count and platelet-lymphocyte ratio were independent prognostic indicators. GI bleeding served as a surrogate for smaller GIST and was a protective factor for GIST recurrence.

Prognostic significance of AMPK in human malignancies: A meta-analysis

Background AMPK is a well-investigated kinase mediating cellular metabolism and stress responses. However, its indicative role in survival prognosis remains ill-defined. Therefore we performed this meta-analysis in order to clarify the prognostic impact of AMPK expression in human malignancies. Methods Literatures were retrieved via searching databases of PubMed, Web of Science, Embase and Cochrane Library. Studies comparing the prognostic significance between different AMPK levels among human malignancies were included into the pooled analysis. The statistical procedures were conducted by Review Manager 5.3 and the effect size was displayed by model of odds ratio. Subgroup analyses were additionally implemented to disclose the potential confounding elements. The outcome stability was examined by sensitivity analysis, and both Beggs test and Eggers test were utilized to detect the publication bias across the included studies. Results 21 retrospective cohorts were eventually obtained with a total sample-size of 9987 participants. Patients with higher AMPK expression had better outcomes of 3-year overall survival (P<0.0001), 5-year overall survival (P<0.0001), 10-year overall survival (P<0.0001), 3-year disease free survival (P<0.0001), 5-year disease free survival (P=0.002) and 10-year disease free survival (P=0.0004). Moreover, the majority of subgroup results also verified the favorably prognostic significance of AMPK over-expression. The outcome stability was confirmed by sensitivity analysis. Results of Beggs (P=0.76) and Eggers test (P=0.09) suggested that there was no publication bias within the included trials. Conclusions Higher expression of AMPK significantly indicates better prognosis in human malignancies.

The prognostic value of AGR2 expression in solid tumours: a systematic review and meta-analysis

The prognostic value of anterior gradient-2 (AGR2) in tumours remains inconclusive. Here, we systematically reviewed the literature evidence and assessed the association between AGR2 expression and prognosis in solid tumours. The primary outcomes were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS). All analyses were performed by STATA 12.0, with the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) as the effect size estimate. A total of 20 studies containing 3285 cases were included. Pooled analyses revealed that AGR2 overexpression had an unfavourable impact on OS (HR 1.93, 95% CI 1.32–2.81) and time to tumour progression (TTP) (DFS/RFS/PFS) (HR 1.60 95% CI 1.06–2.40) in solid tumour patients. Subgroup analyses indicated that AGR2 overexpression in breast cancer patients was significantly associated with poor OS (HR 3.02, 95% CI 1.03–8.81) and TTP (HR 1.93, 95% CI 1.17–3.20). Excluding breast cancer, AGR2 overexpression was also found to have a significant correlation with poor OS in the remaining solid tumour patients (HR 1.51, 95% CI 1.04–2.19). Overall, AGR2 might be a potential biomarker to predict prognosis in solid tumour patients.