Publications by authors named "Bo Lian"

44 Publications

Preparation of docetaxel-loaded, glycyrrhetinic acid-modified nanoparticles and their liver-targeting and antitumor activity.

Exp Ther Med 2021 Oct 9;22(4):1144. Epub 2021 Aug 9.

Shandong Key Laboratory of Medical and Health Sciences, Key Laboratory of Biotechnological Medicine in Universities of Shandong, School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong 261053, P.R. China.

Liver cancer is one of the most common malignancies worldwide and poses a serious threat to human health. The most important treatment method, liver cancer chemotherapy, is limited due to its high toxicity and poor specificity. Targeted drug delivery systems have emerged as novel therapeutic strategies that deliver precise, substantial drug doses to target sites via targeting vectors and enhance the therapeutic efficacy. In the present study, glycyrrhetinic acid-modified hyaluronic acid (GA-HA) was used as a carrier for the model drug docetaxel (DTX) to prepare DTX-loaded GA-HA nanoparticles (DTX/GA-HA-NPs). The results indicated that the DTX/GA-HA-NPs exhibited high monodispersity (particle dispersity index, 0.209±0.116) and desirable particle size (208.73±5.0 nm) and zeta potential (-27.83±3.14 mV). The drug loading capacity and encapsulation efficiency of the NPs were 12.59±0.68 and 85.38±4.62%, respectively. Furthermore, it was determined that FITC-GA-HA was taken up by cells and distributed in the cytoplasm. DTX and DTX/GA-HA (just the DTX delivered by the nanoparticle) aggregated and altered the structure of cellular microtubules. Compared with DTX alone, DTX/GA-HA-NPs had a stronger inhibitory effect on HepG2 cell proliferation and promoted apoptosis of HepG2 cells. All experimental results indicated that DTX/GA-HA-NPs were successfully prepared and had liver-targeting and antitumor activities , which provided a foundation for future studies of the antitumor effects of DTX/GA-HA-NPs.
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http://dx.doi.org/10.3892/etm.2021.10578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404033PMC
October 2021

Combined anti-hepatocellular carcinoma therapy inhibit drug-resistance and metastasis via targeting "substance P-hepatic stellate cells-hepatocellular carcinoma" axis.

Biomaterials 2021 09 9;276:121003. Epub 2021 Jul 9.

School of Bioscience and Technology, Weifang Medical University, PR China. Electronic address:

Peripheral nerves have emerged as the important components in tumor microenvironment (TME), which could activate hepatic stellate cells (HSCs) by secreting substance P (SP), leading to hepatocellular carcinoma (HCC) invasion and metastasis. Herein, we proposed a novel anti-HCC concept of blocking "SP-HSCs-HCC" axis for omnidirectional inhibition of HCC development. To pursue this aim, the novel CAP/GA-sHA-DOX NPs were developed for targeted co-delivery of capsaicin (CAP) and doxorubicin (DOX) using glycyrrhetinic acid (GA) modified sulfated-HA (sHA) as nanocarriers. Among that, CAP could inhibit the activation of HSCs as an inhibitor of SP. Notably, to real mimic "SP-HSCs-HCC" axis for in vitro and in vivo evaluation, both "SP + LX-2+BEL-7402" co-cultured cell model and "SP + m-HSC + H22" co-implantation mice model were attempted for the first time. Furthermore, in vivo anti-HCC effects were performed in three different tumor-bearing models: subcutaneous implantation of H22 or "SP + m-HSC + H22", intravenous injection of H22 for lung metastasis, and orthotopic implantation of H22 for primary HCC. Our results showed that CAP/GA-sHA-DOX NPs could be efficiently taken up by tumor cells and activated HSCs (aHSCs) simultaneously, and effectively inhibit tumor drug-resistance and migration by blocking SP-induced HSCs activation. In addition, CAP/GA-sHA-DOX NPs exhibited low ECM deposition, less tumor angiogenesis, and superior in vivo anti-HCC effects. The anti-HCC mechanisms revealed that CAP/GA-sHA-DOX NPs could down-regulate the expression level of Vimentin and P-gp, reverse epithelial-mesenchymal transition (EMT) of tumor cells. In brief, the nano-sized combination therapy based on GA-sHA-DOX polymers could effectively inhibit drug-resistance and metastasis of HCC by blocking "SP-HSCs-HCC" axis, which provides a promising approach for cancer therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121003DOI Listing
September 2021

Laparoscopic gastrectomy for elderly gastric-cancer patients: comparisons with laparoscopic gastrectomy in non-elderly patients and open gastrectomy in the elderly.

Gastroenterol Rep (Oxf) 2021 Apr 10;9(2):146-153. Epub 2020 Sep 10.

Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shanxi, P. R. China.

Background: The benefits of laparoscopic gastrectomy (LG) in elderly gastric-cancer patients still remain unclear. The purpose of this study was to evaluate the feasibility and safety of LG in elderly gastric-cancer patients.

Methods: We retrospectively evaluated patients who underwent LG or open gastrectomy (OG) between June 2009 and July 2015 in a single high-volume center. We compared surgical, short-term, and long-term survival outcomes among an elderly (≥70 years old) LG (ELG) group (=114), a non-elderly (<70 years old) LG (NLG) group (=740), and an elderly OG (EOG) group (=383).

Results: Except for extended time to first flatus, the surgical and short-term outcomes of the ELG group were similar to those of the NLG group. The ELG group revealed comparable disease-specific survival (DSS) rates to the NLG group (64.9% vs 66.2%, =0.476), although the overall survival (OS) rate was lower (57.0% vs 65.5%, <0.001) in the ELG group than in the NLG group. The ELG group showed longer operation time than the EOG group (236.4 ± 77.3 vs 179 ± 52.2 min, <0.001). The ELG group had less estimated blood loss (174.0 ± 88.4 vs 209.3 ± 133.8, =0.008) and shorter post-operative hospital stay (8.3 ± 2.5 vs 9.2 ± 4.5, =0.048) than the EOG group. The severity of complications was similar between the ELG and NLG groups. Multivariate analysis confirmed that LG was not a risk factor for post-operative complications.

Conclusions: LG is a feasible and safe procedure for elderly patients with acceptable short- and long-term survival outcomes.
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http://dx.doi.org/10.1093/gastro/goaa041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128003PMC
April 2021

Applications of Machine Learning in Solid Oral Dosage Form Development.

J Pharm Sci 2021 Sep 2;110(9):3150-3165. Epub 2021 May 2.

Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, United States; Biopharmaceutical Innovation and Optimization Center, University of Kansas, Lawrence, KS 66047, United States.

This review comprehensively summarizes the application of machine learning in solid oral dosage form development over the past three decades. In both academia and industry, machine learning is increasingly applied for multiple preformulation/formulation and process development studies. Further, this review provides the authors' perspectives on how pharmaceutical scientists can use machine learning for right projects and in right ways; some key ingredients include (1) the determination of inputs, outputs, and objectives; (2) the generation of a database containing high-quality data; (3) the development of machine learning models based on dataset training and model optimization; (4) the application of trained models in making predictions for new samples. It is expected by the authors and others that machine learning will promisingly play a more important role in tomorrow's projects for solid oral dosage form development.
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http://dx.doi.org/10.1016/j.xphs.2021.04.013DOI Listing
September 2021

The effectiveness of electro-acupuncture combined with dyclonine hydrochloride in relieving the side effects of gastroscopy: a controlled trial.

Ann Palliat Med 2021 Mar 1;10(3):2958-2970. Epub 2021 Mar 1.

Department of Intensive Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

Background: The present study aimed to explore the effectiveness of electro-acupuncture (EA) in combination with a local anesthetic used in Western medicine in preventing the side effects of gastroscopy.

Methods: A sample group of 150 patients were divided into three groups based on treatment methods: an EA group, a dyclonine hydrochloride mucilage group, and a combined treatment group. In the EA group, EA stimulation was given at the Hegu, Neiguan, and Zusanli acupoints; in the dyclonine hydrochloride mucilage group, patients took 10 mL of dyclonine hydrochloride mucilage orally; in the combined treatment group, prevention of side effects was attempted by administration of both acupuncture and oral local anesthetic. The incidences of nausea, emesis, salivation, cough, restlessness, and breath holding during gastroscopy were observed and recorded for the three groups. Mean arterial pressure, heart rate, and oxygen saturation were recorded before the examination, and changes in these measures were recorded as the gastroscope passed through the pylorus and after the examination. The visual analogue scale (VAS) values of nausea and emesis, the rate of successful first-pass intubation, and the time of gastroscopy were also recorded. Statistical analysis was performed using R-3.5.3 software.

Results: Incidences of side effects (e.g., nausea, emesis, salivation, restlessness, and breath holding) during the examination were lower in the combined treatment group than in the EA group and the dyclonine hydrochloride mucilage group (P<0.05 and P<0.01, respectively). Furthermore, the changes in heart rate and oxygen saturation when the gastroscope passed through the pylorus and after the examination were better in the combined treatment group than in the EA group and dyclonine hydrochloride mucilage group (P<0.01). The VAS values of nausea and emesis, the first-pass success rate, and examination duration were also better for the combined treatment group than for the other two groups (P<0.05 and P<0.01).

Conclusions: EA combined with local anesthesia with dyclonine hydrochloride mucilage can alleviate side effects during gastroscopy, reduce patient pain, and improve the efficiency of the procedure.
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http://dx.doi.org/10.21037/apm-20-831DOI Listing
March 2021

Protective effects of resveratrol liposomes on mitochondria in substantia nigra cells of parkinsonized rats.

Ann Palliat Med 2021 Mar 7;10(3):2458-2468. Epub 2021 Feb 7.

Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

Background: Parkinson's disease (PD) is a central nervous system degenerative disease. The progressive death of dopaminergic neurons is closely correlated to mitochondrial dysfunction. Resveratrol contains three hydroxyl groups, and has a strong neuroprotective effect. This study aimed to investigate the protective effect of resveratrol liposome on mitochondria of substantia nigra cells in Parkinsonized rats through experiment.

Methods: The investigators used 6-hydroxydopamine to establish the Parkinsonized rat model, and used resveratrol liposome from Polygonum cuspidatum (20 mg·kg-1) for gavage, up to a total volume of 1 mL, once-daily, for two weeks. After treatment, the levels of mitochondrial membrane potential, mitochondrial complexes I-IV, mitochondrial cytochrome C, apoptosis-inducing factor (AIF), PTEN-induced putative kinase 1 (PINK1), tumor necrosis factor-receptor-associated protein 1 (TRAP1) and phosphorylated TRAP1 in rat mesencephalic cells were detected according to the operation instructions of the kits.

Results: After two weeks of treatment, resveratrol liposomes could significantly enhance the activity of mitochondrial electron transfer chain complex I in the substantia nigra cells of Parkinsonized model rats, promote the expression of complex I subcomponent MT-ND1-37kD, improve mitochondrial membrane potential, inhibit the release of mitochondrial cytochrome C and apoptotic inducible factor, enhance the expression of mitochondrial functional protein PINK1, increase the phosphorylated TRAP1 level, and elevate the phosphorylated TRAP1/TRAP1 ratio.

Conclusions: Resveratrol liposome has positive effects on mitochondria in substantia nigra cells of Parkinsonized rats, and may be one of its pharmacological mechanisms.
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http://dx.doi.org/10.21037/apm-19-426DOI Listing
March 2021

Galactose Modified Liposomes for Effective Co-Delivery of Doxorubicin and Combretastatin A4.

Int J Nanomedicine 2021 15;16:457-467. Epub 2021 Jan 15.

School of Bioscience and Technology, Weifang Medical University, Weifang 261053, People's Republic of China.

Background: Tumor angiogenesis plays a crucial role in tumor development, and recent efforts have been focused on combining proapoptotic and antiangiogenic activities to enhance antitumor therapy.

Methods: In this study, galactose-modified liposomes (Gal-LPs) were prepared for co-delivery of doxorubicin (DOX) and combretastatin A4 phosphate (CA4P). The co-cultured system composed of BEL-7402 and human umbilical vein endothelial cells (HUVEC) cells was established to effectively evaluate in vitro anti-tumor activity through cell viability and cell migration assay. Furthermore, both in vivo bio-distribution and anti-hepatoma effect of DOX&CA4P/Gal-LPs were investigated on H22 tumor cell-bearing mice.

Results: The results showed that DOX&CA4P/Gal-LPs were spherical with a mean particle size of 143 nm, and could readily be taken up by BEL-7402 cells. Compared with a mixture of free DOX and CA4P, the DOX&CA4P/Gal-LPs were more effective in inhibiting cell migration and exhibited stronger cytotoxicity against BEL-7402 cells alone or a co-cultured system. The in vitro studies showed that the co-cultured system was a more effective model to evaluate the anti-tumor activity of combination therapy. Moreover, DOX&CA4P/Gal-LPs exhibited a greater anti-hepatoma effect than other drug formulations, indicating that Gal-LPs could promote drug accumulation in the tumor region and improve the anti-tumor activity.

Conclusion: Gal-LPs co-loaded with chemotherapeutic and antiangiogenic drugs are a promising strategy for anti-hepatoma therapy.
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http://dx.doi.org/10.2147/IJN.S283793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816220PMC
January 2021

Risk Factors and Clavien-Dindo Classification of Postoperative Complications After Laparoscopic and Open Gastrectomies for Gastric Cancer: A Single-Center, Large Sample, Retrospective Cohort Study.

Cancer Manag Res 2020 23;12:12029-12039. Epub 2020 Nov 23.

Department of Digestive Surgery, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, People's Republic of China.

Background: Laparoscopy has been increasingly used for the surgery of gastric cancer. However, the postoperative complications are still under-investigated and the short-term results of laparoscopic gastrectomy remain controversial. This study aimed to explore the differences of postoperative complications between laparoscopic and open radical gastrectomies in patients with gastric cancer through the large sample size, retrospective cohort study, and evaluate the safety of laparoscopy in patients who underwent radical gastrectomy.

Patients And Methods: A total of 2,966 patients with gastric cancer (TNM I~III) who underwent laparoscopy or open gastrectomy from February 2009 to March 2016 were enrolled in this study. Complications were categorized according to the Clavien-Dindo classification. The incidence and severity of complications between laparoscopic and open gastrectomy were compared using one-to-three propensity score matching (PSM) analysis. Logistic regression analyses were performed to identify risk factors related to postoperative complications.

Results: A total of 2,966 patients were included in the study, including 687 (23.2%) in the LG (Laparoscopy gastrectomies) group and 2,279 (76.8%) in the OG (open gastrectomies) group. After PSM, a well-balanced cohort of 2,373 patients (676 cases in the LG group and 1,697 cases in the OG group) was further analyzed. The results showed that the incidence of overall complications in the LG group was significantly less than the OG group (15.4% vs 20.8%, =0.003). However, the severe complications of the LG group showed no difference towards the OG group (5.8% vs 5.8%, =0.952). Multivariate analysis revealed that laparoscopic surgery is a protective factor for the reduction of postoperative complications. Age ≥60 years, ASA classification IIIc and estimated blood loss ≥200 mL were confirmed as independent risk factors of overall complications.

Conclusion: Compared with traditional open gastrectomy, LG is safe and feasible with less trauma and fewer complications for patients with gastric cancer.
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http://dx.doi.org/10.2147/CMAR.S275621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700075PMC
November 2020

Maternal Separation-Induced Histone Acetylation Correlates with BDNF-Programmed Synaptic Changes in an Animal Model of PTSD with Sex Differences.

Mol Neurobiol 2021 Apr 27;58(4):1738-1754. Epub 2020 Nov 27.

School of Psychology, Weifang Medical University, 7166# Baotong West Street, Weifang, 261053, Shandong, People's Republic of China.

Maternal separation (MS) causes long-lasting epigenetic changes in the brain and increases vulnerability to traumatic events in adulthood. Of interest, there may be sex-specific differences in these epigenetic changes. In this study, the extent of histone acetylation in the hippocampus (HIP) and the expression of BDNF were measured to determine whether BDNF influences risk of PTSD following MS in early life. Rat offspring were separated from their dams (3 h/day or 6 h/day from PND2~PND14). Then, pups were treated with a single prolonged stress (SPS) procedure when they reached adulthood (PND80). In animals stressed with the SPS procedure in adulthood, those that had increased MS intensity in childhood demonstrated more significant changes in performance on tests of anxiety, depression, and contextual fear memory. Reduced levels of total BDNF mRNA and protein were observed after SPS treatment and further declined in groups with greater MS time in childhood. Interestingly, these changes were correlated with decreased H3K9ac levels and increased HDAC2 levels. Additional MS also led to more severe ultrastructural synaptic damage in rats that experienced the SPS procedure, particularly in the CA1 and CA3 region of the HIP, reflecting impaired synaptic plasticity in these regions. Interestingly, male rats in the MS3h-PTSD group showed decreased anxiety, but no similar changes were found in female rats, suggesting a degree of gender specificity in coping with stress after mild MS. In summary, this study suggests that the epigenetic signatures of the BDNF genes can be linked to HIP responses to stress, providing insights that may be relevant for people at risk of stress-related psychopathologies.
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http://dx.doi.org/10.1007/s12035-020-02224-6DOI Listing
April 2021

Beware Pathological Findings of the Stomach in Patients Undergoing Bariatric Surgery: a Systematic Review and Meta-analysis.

Obes Surg 2021 01 12;31(1):337-342. Epub 2020 Oct 12.

Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Changlexi St. 127#, Xi'An City, Shaanxi Province, China.

Abnormal anatomic findings are a major concern before performing bariatric surgery, while pathological changes are considered less often. The present study aimed to investigate the incidences of gastric lesions warranting follow-up in patients undergoing bariatric surgery. Meta-analyses were conducted to calculate the pooled incidences of gastric lesions in patients undergoing bariatric surgery. Fifty-nine studies including 32,789 patients were included: 26 on endoscopic biopsy, 26 on pathological findings of the excised specimen, five on the intraoperative exploration results, and two on both preoperative endoscopy and postoperative specimen. Generally, atrophic gastritis (3.05% (95% CI (confidence interval) 1.53-6.09)), intestinal metaplasia (2.44% (95% CI 1.76-3.25)), and GIST (gastrointestinal stromal tumor) (0.45% (95% CI 0.31-0.60)) were not rarely found. Routine preoperative endoscopy was applied in 16 studies, and the pooled incidences of atrophic gastritis and intestinal metaplasia were 2.64% (95% CI 0.78-8.9) and 2.70% (95% CI 0.9-5.42), respectively. Hp. (Helicobacter pylori) screening and eradication were routinely performed in 10 studies, and that was related to a reduced incidence of atrophic gastritis (0.94% (95% CI 0.03-2.92)) vs. 4.31% (95% CI 2.01-9.23). GIST was more likely to be found by intraoperative exploration than by preoperative endoscopy (0.68% (95% CI 0.50-0.93) vs. 0.23% (95% CI 0.11-0.52)). Patients undergoing bariatric surgery demonstrated non-negligible incidences of gastric pathologies warranting follow-up. Preoperative endoscopy and careful intraoperative exploration should be routinely performed, and Hp. screening and eradication are suggested before endoscopy. In condition that such findings are detected, sleeve gastrectomy may be preferred over Roux-en-Y gastric bypass.
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http://dx.doi.org/10.1007/s11695-020-05029-7DOI Listing
January 2021

Enhanced targeted delivery of adenine to hepatocellular carcinoma using glycyrrhetinic acid-functionalized nanoparticles in vivo and in vitro.

Biomed Pharmacother 2020 Nov 15;131:110682. Epub 2020 Sep 15.

School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China. Electronic address:

Hepatocellular carcinoma (HCC), a common malignancy in China and globally, is primarily treated through surgical resection and liver transplantation, with chemotherapy as a significant synergistic option. Adenine (Ade), a nucleobase, exhibits antitumor effects by blocking human hepatic carcinoma cells in S phase and inhibiting tumor cell proliferation. However, its use is limited owing to its low solubility, poor targeting ability, and nephrotoxicity. Therefore, liver-targeting drug delivery systems have attracted considerable attention for the treatment of HCC. In this study, we explored the liver-targeting efficacy and antitumor effect of adenine-loaded glycyrrhetinic acid-modified hyaluronic acid (Ade/GA-HA) nanoparticles in vitro and in vivo. The GA-HA nanoparticles possessed obvious targeting specificity toward liver cancer cells, which was mainly achieved by the specific binding of the GA ligand to the GA receptor that was highly expressed on the liver cell membrane. In vitro and in vivo results showed that Ade/GA-HA nanoparticles could inhibit liver cancer cell proliferation and migration, promote apoptosis, and significantly inhibit the growth of tumor tissues. Altogether, this study is the first to successfully demonstrate that the targeting activity and antitumor effect of Ade against HCC are enhanced by using GA-HA nanoparticles in vitro and in vivo.
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http://dx.doi.org/10.1016/j.biopha.2020.110682DOI Listing
November 2020

Improved efficacy of doxorubicin delivery by a novel dual-ligand-modified liposome in hepatocellular carcinoma.

Cancer Lett 2020 10 25;489:163-173. Epub 2020 Jun 25.

School of Bioscience and Technology, Shandong Key Lab of Medical and Health Sciences, Key Lab of Biotechnological Medicine in Universities of Shandong, Weifang Medical University, Weifang, 261053, China. Electronic address:

Liposomes have been widely used as drug carriers in both biomedical research and for clinical applications, allowing the stabilisation of therapeutic compounds and overcoming obstacles to cellular and tissue uptake. However, liposomes still have low targeting efficiency, resulting in insufficient killing of tumour cells and unnecessary damage to normal cells. In this study, glycyrrhetinic acid (GA) and peanut agglutinin (PNA) were used as ligands to prepare dual-ligand-modified doxorubicin-loaded liposomes (DOX-GA/PNA-Lips) to enhance the targeting accuracy and efficacy of drug delivery against malignant liver cancer. PNA and GA modification enhanced the binding ability of liposomes to liver cancer cells, leading to excellent tissue and cell targeting of DOX-GA/PNA-Lips. DOX-GA/PNA-Lips showed an effective anti-tumour effect in vivo and in vitro, with its targeted delivery facilitating attenuation of the toxic side effects of DOX. These results demonstrated that dual-ligand-modified liposomes may provide an effective strategy for the treatment of hepatocellular carcinoma.
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http://dx.doi.org/10.1016/j.canlet.2020.06.017DOI Listing
October 2020

[Thoughts and suggestions on arrangement, analysis and summary of medical data during COVID-19 epidemic].

Zhongguo Zhong Yao Za Zhi 2020 Apr;45(7):1526-1530

the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine Guangzhou 510405, China.

The analysis and utilization of clinical scientific research data is an effective means to promote the progress of diagnosis and treatment, and a key step in the development of medical sciences. During the epidemic of coronavirus disease 2019(COVID-19), how to transform the limited diagnostic data into clinical research resources has attracted much attention. Based on the low efficiency of data collection and extraction, the inconsistency of data analysis, the irregularity of data report and the high timeliness of data update during the epidemic, this paper briefly analyzed the background and reasons of data application under the current situation, and then discusses the problems and feasible solutions of clinical data applications under the epidemic situation and, more importantly, for future medical clinical research methods. We put forward several methodological suggestions: ① gradually improve the medical big data model and establish the national medical health data center; ② improve the scientific research literacy of medical staff and popularize the basic skills and knowledge of GCP; ③ promote a scientific, networked and shared data collection and management mode; ④ use the mixed research method and collective analysis to improve the efficiency of clinical data analysis; ⑤ pay attention to narration of the medical feelings and emphasize the humanistic data of clinical medicine. It is expected to promote the standardized and reasonable use of clinical scientific research data, the rigorous integration of expert opinions, and ultimately the development of big data for national health care.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200302.504DOI Listing
April 2020

Plasma Amine Oxidase-Induced Nanoparticle-to-Nanofiber Geometric Transformation of an Amphiphilic Peptide for Drug Encapsulation and Enhanced Bactericidal Activity.

ACS Appl Mater Interfaces 2020 Jan 14;12(4):4323-4332. Epub 2020 Jan 14.

School of Bioscience and Technology , Weifang Medical University , Weifang 261042 , P. R. China.

Patients with cancer have reduced immune function and are susceptible to bacterial infection after surgery, chemotherapy, or radiotherapy. Spherical nanoparticles formed by the self-assembled peptide VK can be used as carriers for poorly soluble antitumor drugs to effectively deliver drugs into tumor cells. VK was designed to achieve nanoparticle-to-nanofiber geometric transformation under induction by plasma amine oxidase (PAO). PAO is commercially available and functionally similar to lysyl oxidase (LO), which is widely present in serum. After the addition of fetal bovine serum (FBS) or PAO, the secondary structure of the peptide changed, while the spherical nanoparticles stretched and transformed into nanofibers. The conversion of the self-assembled morphology reveals the susceptibility of this amphiphilic peptide to subtle chemical modifications and may lead to promising strategies to control self-assembled architecture via enzyme induction. Enzymatically self-assembled VK had bactericidal properties after PAO addition that were surprisingly superior to those before PAO addition, enabling this peptide to be used to prevent infection. The amphiphilic peptide VK displayed antitumor properties and low toxicity in mammalian cells, demonstrating good biocompatibility, as well as bactericidal properties, to prevent bacterial contamination. These advantages indicate that enzymatically self-assembled VK has great biomedical application potential in cancer therapy.
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http://dx.doi.org/10.1021/acsami.9b21296DOI Listing
January 2020

Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy.

Int J Nanomedicine 2019 2;14:9437-9452. Epub 2019 Dec 2.

School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, People's Republic of China.

Background: The tumor-targeting ability and pH-sensitive properties of intelligent drug delivery systems are crucial for effective drug delivery and anti-tumor therapy.

Methods: In this study, sHA-DOX/HA-GA mixed micelles were designed with the following properties: sulfated hyaluronic acid (sHA) was synthesized to block cell migration by inhibiting HAase; sHA-DOX conjugates were synthesized via pH-sensitive hydrazone bond to realize DOX-sensitive release. The introduction of HA-GA conjugate could improve active-targeting ability and cellular uptake.

Results: The results showed that the mixed micelles possessed a nearly spherical shape, nanoscale particle size (217.70±0.89 nm), narrow size distribution (PDI=0.07±0.04), negative zeta potential (-31.87±0.61 mV) and pH-dependent DOX release. In addition, the sHA-DOX/HA-GA micelles exhibited concentration-dependent cytotoxicities against liver carcinoma cells (HepG2) and HeLa cells, and were shown to be effectively taken up by HepG2 cells by confocal microscopy analysis. Furthermore, the in vivo anti-tumor study showed that mixed micelles had a superior anti-tumor effect compared to that of free DOX. Further evidence obtained from the hematoxylin-eosin staining and immunohistochemistry analysis also demonstrated that sHA-DOX/HA-GA exhibited stronger tumor inhibition and lower systemic toxicity than free DOX.

Conclusion: The sHA-DOX/HA-GA mixed micelles could be a potential drug delivery system for anti-hepatoma therapy.
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http://dx.doi.org/10.2147/IJN.S214528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896933PMC
February 2020

An adenosine derivative (IFC-305) reduced the risk of radiation-induced intestinal toxicity in the treatment of colon cancer by suppressing the methylation of PPAR-r promoter.

Biomed Pharmacother 2019 Oct 19;118:109202. Epub 2019 Aug 19.

Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, Liaoning Province, People's Republic of China.

Background: IFC-305, an adenosine derivative, has been proved to exert a therapeutic effect on radiation-induced intestinal toxicity in colon cancer (CC). The aim of the present study was to investigate the underlying molecular mechanism of protective role of IFC-305 in CC by modifying the methylation of peroxisome proliferator-activated receptor (PPAR)-r promoter.

Method: Peripheral blood and cancerous tissues samples were collected from the CC patients. Irradiation (IR) mice models were established in comparison with control mice accordingly. Bisulfite sequencing, real-time PCR, Western-blot analysis, immunohistochemistry (IHC) and hematoxylin eosin (HE) staining were performed upon both human and animal samples.

Result: The results upon the human CC samples demonstrated that the level of methylation of PPAR-r promoter in methylated patients was increased, while the risk of radiation-induced intestinal toxicity in methylated patients was also increased compared with unmethylated patients. Also, the PPAR-r mRNA/protein expression was lower in methylated patients compared with unmethylated patients, thus indicating the presence of PPAR-r promoter methylation repressed PPAR-r expression in vivo. Moreover, in the mice models, IFC-305 treatment partially alleviated radiation-induced toxicity in the columnar epithelia and tubular glands of IR mice, and villus height and the number/circumference of crypts were also increased while the relative number of inflammatory cells was decreased in IR + IFC-305 mice group compared with the control mice. Compared with the control group, the levels of PPAR-r mRNA/protein expression were significantly decreased in IR mice, while the presence of IFC-305 exerted therapeutic effect upon IR rats via elevating the PPAR-r mRNA/protein expression to a certain extent.

Conclusion: In this study, we demonstrated the relationship between PPAR-r promoter methylation and the risk of radiation-induced intestinal toxicity via studying the clinical samples collected from CC patients. And the study upon mice models suggested that the administration of IFC-305 could alleviate radiation-induced intestinal toxicity through decreasing the methylation of PPAR-r promoter and enhancing the expression of PPAR-r in IR mice.
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http://dx.doi.org/10.1016/j.biopha.2019.109202DOI Listing
October 2019

Systematic review and meta-analysis of splenectomy in gastrectomy for gastric carcinoma.

Int J Surg 2019 Aug 2;68:104-113. Epub 2019 Jul 2.

Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China. Electronic address:

Background: The role of splenectomy for patients with gastric cancer still remains controversial. We performed this meta-analysis to evaluate the safety and long-term oncological outcomes of splenectomy for patients with gastric cancer.

Methods: A systematic literature search was performed using PubMed, EMBASE, Cochrane Library, and Web of Science from January 1997 to October 2018. The results were analyzed according to predefined criteria. All statistical analyses were performed using RevMan 5.3 software.

Results: In total, 16 studies with 4457 patients, including 3 randomized controlled trials (RCTs) and 13 non-randomized controlled trials (nRCTs), were analyzed. The meta-analysis showed the splenectomy group was associated with higher rates of overall postoperative complication, anastomosis leakage, abdominal abscess, and pancreatic fistula. Regarding long-term oncological outcomes, the splenectomy group showed lower 5-year overall survival (OS) and higher recurrence rates on subgroup analysis for the nRCTs. No significant difference was observed in the 5-year OS and recurrence rates between the two groups on subgroup analysis for the RCTs.

Conclusions: Splenectomy increases postoperative complications without clearly improving long-term prognosis.
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http://dx.doi.org/10.1016/j.ijsu.2019.06.018DOI Listing
August 2019

Liver-Targeted Combination Therapy Basing on Glycyrrhizic Acid-Modified DSPE-PEG-PEI Nanoparticles for Co-delivery of Doxorubicin and Bcl-2 siRNA.

Front Pharmacol 2019 22;10. Epub 2019 Jan 22.

School of Bioscience and Technology, Weifang Medical University, Weifang, China.

Combination therapy based on nano-sized drug delivery system has been developed as a promising strategy by combining two or more anti-tumor mechanisms. Here, we prepared liver-targeted nanoparticles (GH-DPP) composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-polyetherimide (DSPE-PEG-PEI) with Glycyrrhetinic acid-modified hyaluronic acid (GA-HA) for co-delivery of doxorubicin (DOX) and Bcl-2 siRNA. Particles size, zeta potential and morphology were determined for the drug-loaded GH-DPP nanoparticles (siRNA/DOX/GH-DPP). Cellular uptake and cytotoxicity were analyzed against HepG2 cells. bio-distribution and anti-tumor therapeutic effects of siRNA/DOX/GH-DPP were evaluated in H22-bearing mice. The results showed that siRNA/DOX/GH-DPP nanoparticles were nearly spherical and showed dose-dependent cytotoxicity against HepG2 cells. Compared to Glycyrrhetinic acid-free co-delivery system (siRNA/DOX/DPP) and GH-DPP nanoparticles for delivery of DOX or Bcl-2 siRNA alone, siRNA/DOX/GH-DPP nanoparticles could induce more cellular apoptosis, and showed higher anti-tumor effect. Herein GH-DPP nanoparticles could simultaneously deliver both chemotherapy drugs and siRNA into the tumor region, exhibiting great potential in anti-tumor therapy.
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http://dx.doi.org/10.3389/fphar.2019.00004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349772PMC
January 2019

Long-term oncological outcomes in laparoscopic versus open gastrectomy for advanced gastric cancer: A meta-analysis of high-quality nonrandomized studies.

Am J Surg 2019 09 26;218(3):631-638. Epub 2019 Jan 26.

Department of Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 127 Changle West Road, Xi'an, 710032, China. Electronic address:

Background: Multicenter randomized controlled trials (RCTs) and several meta-analyses have confirmed that laparoscopic gastrectomy (LG) is a safe and feasible procedure for patients with locally advanced gastric cancer (AGC) in terms of short-term outcomes. However, the long-term oncological outcomes of LG for AGC are still needed for further evaluation. This study aimed to compare the long-term oncological outcomes of LG with open gastrectomy (OG) for patients with AGC.

Methods: We performed a systematic literature search in various databases from January 1997 to August 2018. Studies comparing the long-term oncological outcomes between LG with OG were evaluated and data were extracted accordingly. We performed the meta-analysis using RevMan 5.3 software.

Results: Fifteen studies with 4494 patients (2273 in LG group and 2221 in OG group) were included. The 5-year overall survival (OS) rate (HR 0.95, 95% CI 0.86 to 1.05, P = 0.28), disease-free survival (DFS) rate (HR 0.93, 95% CI 0.81 to 1.06, P = 0.27), and recurrence rate (OR 0.87, 95% CI 0.72 to 1.04, P = 0.13) were comparable in LG and OG. Subgroup analysis showed the publication year, study region, sample size, extent of resection, extent of lymphadenectomy, retrieved lymph nodes, proportion of stage III, and patients with serosa-positive (pT4a) did not influence the estimates.

Conclusions: For patients with AGC, LG is a feasible surgical procedure alternative to OG in terms of long-term oncological outcomes.
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http://dx.doi.org/10.1016/j.amjsurg.2019.01.020DOI Listing
September 2019

miR-135a Protects Dextran Sodium Sulfate-Induced Inflammation in Human Colorectal Cell Lines by Activating STAT3 Signal.

Cell Physiol Biochem 2018 26;51(3):1001-1012. Epub 2018 Nov 26.

Department of colorectal surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang,

Background/aims: miR-135a is reduced in several cancers and has been suggested to mediate immune and inflammatory responses. However, the effect of miR-135a on inflammatory bowel diseases was obscure. This study firstly attempted to investigate the hypothesis that miR-135a alleviates dextran sodium sulfate (DSS)-induced inflammation in colonic cells and potential mechanisms are also studied.

Methods: Caco-2 and HT-29 cells in this study were treated with DSS, miR-135a mimic, and S3I-201, and then CKK-8 assay was used to test cell viability. Expressions of miR-135a, cytokines, and signal transducers and activators of transcription factors (STATs) were determined by RT-PCR. Also, cytokine productions were further tested by using ELISA kits. Activation or inactivation of STAT3 signal was validated by western blotting analysis.

Results: The results showed that DSS markedly downregulated miR-135a expression (P< 0.05) and induced inflammatory response in Caco-2 and HT-29 cells evidenced by the up regulations and productions of interleukin-1β (IL-1β) and tumor necrosis factor-ɑ (TNF-ɑ) (P< 0.05). Transfection with miR-135a mimic significantly alleviated DSS-induced upregulation and productions of IL-1β and TNF-ɑ in Caco-2 and HT-29 cells (P< 0.05). STATs were analyzed and miR-135a mimic treatment reversed STAT3 downregulation in DSS-challenged Caco-2 and HT-29 cells compared with the mimic control (P< 0.05). Also, STAT3 phosphorylation was inhibited in DSS-challenged Caco-2 cells and miR-135a mimic activated STAT3 signal (P< 0.05). S3I-201, an inhibitor of STAT3 signal, further used to inactivate STAT3 signal and the results showed that S3I-201 blocked the anti-inflammatory effect of miR-135a mimic on Caco-2 and HT-29 cells evidenced by the lowered expressions and productions of proinflammatory cytokines ((IL-1β and TNF-ɑ) (P< 0.05).

Conclusion: Our results indicated that miR-135a alleviated DSS-induced inflammation and activated STAT3 signal in colonic cells. Inhibition of STAT3 reversed the anti-inflammatory function of miR-135a by regulating proinflammatory cytokines. Thus, STAT3 signal might serve, at least in part, as the potential mechanism of miR-135a-mediated anti-inflammatory effect in colonic cells.
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http://dx.doi.org/10.1159/000495481DOI Listing
January 2019

Is adjuvant chemotherapy necessary for locally advanced rectal cancer patients with pathological complete response after neoadjuvant chemoradiotherapy and radical surgery? A systematic review and meta-analysis.

Int J Colorectal Dis 2019 Jan 27;34(1):113-121. Epub 2018 Oct 27.

Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People's Republic of China.

Purpose: Current clinical guidelines recommended the routine use of adjuvant chemotherapy for locally advanced rectal cancer (LARC) patients. However, the effects of adjuvant chemotherapy in patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy and radical surgery showed discrepancies in different investigations.

Methods: A systematic review and meta-analysis were conducted using PubMed, Embase and Web of Science databases. All original comparative studies published in English that were related to adjuvant versus non-adjuvant chemotherapy for LARC patients with pCR were included.

Results: A total of 6 studies based on 18 centres or databases involving 2948 rectal cancer patients with pCR (adjuvant group = 1324, non-adjuvant group = 1624) were included in our overall analysis. Based on our meta-analysis, LARC patients with pCR who received adjuvant chemotherapy showed a significantly improved overall survival (OS) when compared to patients with observation (HR = 0.65, 95% CI = 0.46-0.90, P = 0.01). In addition, investigations focused on this issue based on the National Cancer Database (NCDB) were systematically reviewed in our current study. Evidence from all three analyses demonstrated that LARC patients with clinical nodal positive disease that achieved pCR might benefit the most from additional adjuvant chemotherapy.

Conclusion: Our meta-analysis indicated that adjuvant chemotherapy is associated with improved OS in LARC patients with pCR after neoadjuvant chemoradiotherapy and radical surgery.
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http://dx.doi.org/10.1007/s00384-018-3181-9DOI Listing
January 2019

miR-128 Targets the SIRT1/ROS/DR5 Pathway to Sensitize Colorectal Cancer to TRAIL-Induced Apoptosis.

Cell Physiol Biochem 2018 26;49(6):2151-2162. Epub 2018 Sep 26.

Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.

Background/aims: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an ideal anti-tumor drug because it exhibits selective cytotoxicity against cancer cells. However, certain cancer cells are resistant to TRAIL, and the potential mechanisms are still unclear. The aim of this study was to reduce the resistance of colorectal cancer (CRC) cells to TRAIL.

Methods: Quantitative real-time PCR analysis was performed to detect the expression of microRNA-128 (miR-128) in tissues from patients with CRC and CRC cell lines. MTT assays were used to evaluate the effect of miR-128 on TRAIL-induced cytotoxicity against CRC cell lines. The distribution of death receptor 5 (DR5) and the production of reactive oxygen species (ROS) were detected by flow cytometry analysis. Western blot, flow cytometry, and luciferase reporter assays were performed to evaluate the potential mechanism and pathway of miR-128-promoted apoptosis in TRAIL-treated CRC cells.

Results: MiR-128 expression was downregulated in tumor tissues from patients with CRC as well as in CRC cell lines in vitro. The enforced expression of miR-128 sensitized CRC cells to TRAIL-induced cytotoxicity by inducing apoptosis. Mechanistically, bioinformatics, western blot analysis, and luciferase reporter assays showed that miR-128 directly targeted sirtuin 1 (SIRT1) in CRC cells. miR-128 overexpression suppressed SIRT1 expression, which promoted the production of ROS in TRAIL-treated CRC cells. This increase of ROS subsequently induced DR5 expression, and thus increased TRAIL-induced apoptosis in CRC cells.

Conclusion: The combination of miR-128 with TRAIL may represent a novel approach for the treatment of CRC.
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http://dx.doi.org/10.1159/000493818DOI Listing
October 2018

Surgical and Long-Term Survival Outcomes After Laparoscopic and Open Total Gastrectomy for Locally Advanced Gastric Cancer: A Propensity Score-Matched Analysis.

World J Surg 2019 Feb;43(2):594-603

Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.

Background: To compare the surgical and long-term survival outcomes of laparoscopic and open total gastrectomy (OTG) for locally advanced gastric cancer (AGC).

Methods: We retrospectively evaluated 308 and 900 patients in pathological locally AGC who underwent laparoscopic total gastrectomy (LTG) or OTG between June 2008 and December 2014. We compared surgical and long-term outcomes between the two groups using propensity score matching method.

Results: The LTG group showed a longer operation time (261.42 vs. 171.00 min, P = 0.001), less blood loss (185.47 vs. 217.84 ml, P = 0.000), earlier time to first flatus (3.47 vs. 4.12 days, P = 0.000), earlier time to start liquid diet (3.76 vs. 4.27 days, P = 0.000), and shorter postoperative hospital stay (7.56 vs. 8.22 days, P = 0.007). The overall complication rate was 15.2% in the LTG group and 17.2% in the OTG (P = 0.503). No significant difference was observed in overall survival (OS) and disease-free survival (DFS) between LTG and OTG (60.5% vs. 57.1%, P = 0.337; 57.4% vs. 54.4%, P = 0.341).

Conclusions: Compared to OTG, LTG provides surgical benefits and comparable survival outcomes for patients with locally AGC.
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http://dx.doi.org/10.1007/s00268-018-4799-zDOI Listing
February 2019

Long-term outcomes of laparoscopic versus open D2 gastrectomy for advanced gastric cancer.

Surg Oncol 2018 Sep 26;27(3):441-448. Epub 2018 May 26.

Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xi'an 710032, China. Electronic address:

Background: Technical safety and short-term surgical outcomes of laparoscopy-assisted gastrectomy (LAG) for advanced gastric cancer (AGC) have been investigated in many clinical trials. However, studies with large sample size and sufficient follow-up comparing LAG and open gastrectomy (OG) for AGC have seldom been reported. The purpose of this study was to compare the long-term outcomes of LAG versus open OG for AGC using a propensity score matching analysis.

Methods: We retrospectively evaluated 459 and 856 patients who underwent LG or OG with D2 lymph node dissection, respectively, for AGC between June 2007 and June 2012. One-to-one propensity score matching was performed to compensate for heterogeneity between groups. We compared long-term outcomes between the two groups after propensity score matching.

Results: In the propensity score-matched cohort, no significant differences were observed in 5-year overall survival (OS) (52.0% vs. 53.4%; P = 0.805) and disease-free survival (DFS) (46.8% vs. 47.3%; P = 0.963) between the LAG group and OG group. Stratified analysis showed that the 5-year OS and DFS rates were comparable between the two groups in each tumor stage (P > 0.05). Multivariate analysis revealed that the operation method was not an independent prognostic factor for OS or DFS. Further analysis showed that the recurrence pattern was similar between the LAG group the OG group (P > 0.05).

Conclusion: LAG is a feasible surgical procedure for AGC in terms of long-term prognosis, although the results should be confirmed by the ongoing randomized controlled trials.
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http://dx.doi.org/10.1016/j.suronc.2018.05.022DOI Listing
September 2018

Synaptic Ultrastructure Might Be Involved in HCN-Related BDNF mRNA in Withdrawal-Anxiety After Ethanol Dependence.

Front Psychiatry 2018 29;9:215. Epub 2018 May 29.

Department of Clinical Medicine, Weifang Medical University, Weifang, China.

Withdrawal from ethanol dependence has been associated with heightened anxiety and reduced expression of Brain-derived neurotropic factor which promotes the synaptic transmission and plasticity of synapses. Hyperpolarization-activated cyclic nucleotide-gated channel 1 regulates expression; however, whether Hyperpolarization-activated cyclic nucleotide-gated channel 1-related Brain-derived neurotropic factor is involved in the synaptic ultrastructure that generates withdrawal-anxiety has been poorly perceived. Sprague-Dawley rats were treated with ethanol 3-9% (v/v) for a period of 21 days. Conditioned place preference and body weight were investigated during ethanol administration. Rats were subjected to behavioral testing and biochemical assessments after ethanol withdrawal, which was induced by abrupt discontinuation of the treatment. The results showed that the ethanol administration induced severe ethanol dependence behaviors, with higher body weight and more time in the ethanol-paired compartment. After withdrawal, rats had a higher total ethanol withdrawal score and explored less. Additionally, increased Hyperpolarization-activated cyclic nucleotide-gated channel 1 protein and gene expression and decreased Brain-derived neurotropic factor protein and gene expression were detected in the Ethanol group. Eventually, there was a negative correlation between the level of Brain-derived neurotropic factor mRNA and Hyperpolarization-activated cyclic nucleotide-gated channel 1 protein. Importantly, the synaptic ultrastructure changed in the Ethanol group, including increased synaptic cleft width and reduction in postsynaptic density thickness or synaptic curvature. The synthesis of the Brain-derived neurotropic factor mRNA could be down-regulated by higher Hyperpolarization-activated cyclic nucleotide-gated channel 1 protein expression. Changes in synaptic ultrastructure may be induced by lower Brain-derived neurotropic factor protein, which could be associated with the withdrawal-anxiety that is experiences after ethanol dependence.
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http://dx.doi.org/10.3389/fpsyt.2018.00215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986948PMC
May 2018

miR‑218 promotes apoptosis of SW1417 human colon cancer cells by targeting c‑FLIP.

Oncol Rep 2018 Aug 23;40(2):916-922. Epub 2018 May 23.

Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.

MicroRNAs (miRNAs) are suggested to act as either tumor oncogenes or tumor suppressors in different types of cancer. miRNA‑218 (miR‑218) is a type of short, non-coding RNA which is involved in gastric cancer development. In the present study, we evaluated the functions of miR‑218 in SW1417 human colon cancer cells and its potential mechanisms. Following overexpression of miR‑218 in human colon cancer cells, cell viability was determined by CKK‑8 assay, cell apoptosis was observed using a TUNEL Kit, the expression of caspase‑8, and its inhibitor cellular Fas‑associated death domain‑like interleukin‑1β‑converting enzyme inhibitory protein (c‑FLIP) was assessed by RT‑PCR, western blot analysis and immunohistochemistry. The results indicated that miR‑218 and caspase‑8 expression was decreased while c‑FLIP expression was elevated in human colon cancer tissues. In cultured SW1417 human colon cancer cells, miR‑218 overexpression potently inhibited cell viability and promoted cell apoptosis. Furthermore, downregulation of c‑FLIP expression and upregulation of caspase‑8 expression were detected in miR‑218‑stimulated SW1417 cells. In addition, following the knockdown of c‑FLIP using c‑FLIP siRNA, the apoptotic effects of miR‑218 on SW1417 cells were significantly reduced. Collectively, the present study demonstrated that miR‑218 induced the apoptosis of SW1417 cells by targeting c‑FLIP. Therefore, miR‑218 may represent a potential therapeutic method for screening and treating colon cancer.
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http://dx.doi.org/10.3892/or.2018.6460DOI Listing
August 2018

Severity of complications and long-term survival after laparoscopic total gastrectomy with D2 lymph node dissection for advanced gastric cancer: A propensity score-matched, case-control study.

Int J Surg 2018 Jun 23;54(Pt A):62-69. Epub 2018 Apr 23.

Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xian 710032, China. Electronic address:

Background: Increasing numbers of studies have shown that postoperative complication is a negative predictor of long-term survival outcomes in various malignancies. However, the impact of severity of complications on long-term survival for patients with gastric cancer still remains unclear. This study aimed to explore the relationship between the severity of complications and long-term survival outcomes after laparoscopic total gastrectomy (LTG) for advanced gastric cancer (AGC).

Methods: The study analyzed 571 patients with AGC who underwent LTG in a single institution between April 2008 and June 2015. Patients were divided into two groups based on the occurrence or absence of postoperative complications which were recorded using the Clavien-Dindo (C-D) classification. Long-term survival outcomes were compared between groups in the propensity score-matched cohort.

Results: The groups were well balanced after the propensity score matched. The complication (C) group was associated with decreased 5-year cancer-specific survival (CSS) (65.1% vs. 76.2%, P=0.049). Subgroup analysis showed that the severe complication (C-D grade > II) group was associated with decreased 5-year overall survival (OS) (46.3% vs. 65.9%, P = 0.042) and cancer-specific survival (CSS) (53.7% vs. 74.4%, P = 0.030). However, a comparative analysis of 5-year OS and CCS showed no significant differences between the minor complication (C-D grade II) group and matched NC group (68.9% vs. 72.2%, P = 0.578; 75.6% vs. 77.8%, P = 0.649; respectively). Multivariate analysis confirmed severe complication was an independent risk factor for decreased OS. Further analysis showed that older age, lower body mass index (BMI), and combined resection were independent risk factor for the occurrence of severe complications.

Conclusions: Severe complications adversely affected long-term survival outcomes after LTG with D2 lymph node dissection for AGC. More attention should be paid to patients at high risk for severe complications in preoperative assessment and postoperative management.
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http://dx.doi.org/10.1016/j.ijsu.2018.04.034DOI Listing
June 2018

Robotic versus laparoscopic gastrectomy with D2 lymph node dissection for advanced gastric cancer: a propensity score-matched analysis.

Cancer Manag Res 2018 10;10:705-714. Epub 2018 Apr 10.

Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.

Background: Robotic gastrectomy (RG) is a new surgical method alternative for gastric cancer. However, few studies have evaluated the outcomes of RG for advanced gastric cancer (AGC). Thus, the aim of this study was to compare the short-and long-term outcomes of RG and laparoscopic gastrectomy (LG) with D2 lymph node dissection for AGC.

Patients And Methods: We retrospectively evaluated 454 patients with AGC who underwent RG or LG with D2 lymph node dissection for AGC between August 2013 and March 2017. The short-and long-term outcomes were compared between the propensity score-matched groups.

Results: The RG group was associated with longer operation time, less intraoperative blood loss, and higher hospital cost. Additionally, there was a tendency favoring RG in terms of number of harvested lymph nodes, time to first flatus, time to first start diet, and postoperative hospital stay, although the differences were not statistically significant. The overall postoperative complication rate was 13.4% and 11.6% in the RG and LG groups, respectively, with no significant difference (=0.686). The 3-year overall survival and recurrence rates of the RG and LG groups were also comparable (78.6% vs 74.1%, =0.483; 18.8% vs 21.4%, =0.617; respectively).

Conclusion: RG with D2 lymph node dissection is safe and feasible for AGC in terms of both short- and long-term outcomes. High-volume randomized controlled trials with sufficient follow-up are needed to confirm this rationale.
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http://dx.doi.org/10.2147/CMAR.S161007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901130PMC
April 2018

Anxiety-like behaviour assessments of adolescent rats after repeated maternal separation during early life.

Neuroreport 2018 05;29(8):643-649

Department of Psychology.

Maternal separation (MS) plays a central role in developing physiology and psychology during the individual ontogeny process. MS is used to research the neurobiological mechanisms of mental disorders and early life stress. In this study, we investigated the effects of repeated MS and early handling (EH) on locomotor activity in an open-field test, a light-dark box test and an elevated plus-maze test of adolescent rats. The results showed that MS reduced locomotor activities in the open-field test, and increased anxiety-like behaviours in the light-dark box test and the elevated plus-maze test in adolescent rats. These tests indicated that early life stress caused by MS might induce anxiety-like behaviours during adolescence. However, compared with the control group, both the MS and EH groups showed conflicting anxiety levels. The results also suggested that females were more prone to showing anxiety-like behaviour compared with males when suffering from high-intensity stimulation. However, because of the low anxiety level associated with EH, the sex difference in behaviour was not significant. The present study provides novel insights into the effects of MS and EH on behaviour, which shows unique anxiety levels different in adolescent male and female rats.
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http://dx.doi.org/10.1097/WNR.0000000000001010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959263PMC
May 2018

Laparoscopy-assisted distal gastrectomy versus laparoscopy-assisted total gastrectomy with D2 lymph node dissection for middle-third advanced gastric cancer.

Surg Endosc 2018 05 2;32(5):2255-2262. Epub 2017 Nov 2.

Department of Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, No. 127 Changle West Road, Xian, 710032, China.

Background: There still remains controversy for the choice of resection extent for gastric cancer involving the middle-third of the stomach. The aim of this study was to compare the technical feasibility and long-term outcomes of laparoscopy-assisted distal gastrectomy (LADG) versus laparoscopy-assisted total gastrectomy (LATG) for middle-third advanced gastric cancer (AGC) and to determine which is the optimal surgical procedure.

Methods: For this study, clinical data for 379 patients who underwent LADG or LATG with D2 lymph node dissection between April 2005 and June 2014 were analyzed retrospectively. The short- and long-term outcomes were compared between the propensity score-matched groups.

Results: The LADG group had a significantly shorter operating time (212.74 vs. 241.79 min, P < 0.001), less estimated blood loss (114.38 vs. 181.51 ml, P = 0.000), shorter first flatus and postoperative hospital stay. Additionally, the total cost of hospitalization was significantly higher in the LATG group than LADG group (71187.58 vs. 65783.25 RMB, P = 0.000). There were no significant differences in postoperative complications rate between the LADG group and the LATG group. The 5-year overall survival (OS) rates were 64.4% in the LADG group and 61.0% in the LATG group (P = 0.548). The resection extent was not an independent prognostic factor for the OS.

Conclusions: LADG with D2 nodal dissection is a feasible treatment strategy for middle-third AGC with better short-term outcomes and similar long-term survival rates compared with LATG. We recommended that DG should be the optimal surgical procedure for middle one-third AGC under the premise of negative proximal resection margin.
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http://dx.doi.org/10.1007/s00464-017-5919-9DOI Listing
May 2018
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