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Filgrastim, a recombinant type of granulocyte-colony stimulating factor (G-CSF), has a high potential to manage chemotherapy-induced leukopenia. It can increase stromal cell-derived factor 1 (SDF-1) which may stimulate C-X-C chemokine receptor type 4 (CXCR4) to migrate bone marrow-derived stem/progenitor cells to the bloodstream. Here, we aimed to investigate in vitro and in vivo effects of filgrastim on cell migration, invasion, and metastasis. A lentivirus vector of the anti-CXCR4 receptor was first used for the CXCR4 knockout. Effects of filgrastim on cell proliferation and migration were then investigated on 4T1 cells by Transwell migration and wound healing assay. At last, the effects of filgrastim on cell metastasis and the possible involved mechanisms have been investigated in a metastatic murine breast tumor. The knockout of the CXCR4 receptor could lead to a decrease in cell proliferation, migration, and invasion of the 4T1 cells. Filgrastim could directly target SDF-1 and upregulate the expression of the CXCR4 receptor. The knockout of the CXCR4 receptor reduced cell metastasis in an animal model of breast cancer. CXCR4 receptor stimulation by the filgrastim-affected pathways is a conserved evolutionary response that could increase cancer cell proliferation and consequent cell metastasis. Our results suggest that the activation of the CXCR4 receptor is a conserved evolutionary response that can increase cell proliferation, migration, and consequent metastasis. It seems that filgrastim may increase the chance of cancer cell metastasis in people continuously receiving it to increase the number of neutrophils. Filgrastim induces the SDF-1/CXCR4 axis on tumor cell growth. SDF-1 and its receptor CXCR4 are vital targets for filgrastim. The CXCR4 can stimulate the PI3K/AKT, NF-κB, and JAK/STAT signaling pathways. The SDF-1/CXCR4 pathway promotes cell chemotaxis and proliferation via MAPKs signaling. It also enhances cell survival, proliferation, and angiogenesis, increasing tumor cell metastasis. The STAT3-mediated inflammation is essential for tumorigenesis processes, and Akt, Wnt, STAT3, and CXCR4 signaling pathways are all correlated. CXCR4 = C-X-C chemokine receptor type 4, SDF-1 = stromal-derived-factor-1, MAPK = mitogen activated protein kinase; NF-κB = nuclear factor-κB, PI3K = phosphoinositide 3-kinase, JAK = Janus kinase, STAT = signal transducer and activator of transcription, PLC = phospholipase C, PKC = Protein kinase C, GRK = G protein-coupled receptor kinase [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis compares the efficacy of three combination therapies, including transarterial chemoembolization (TACE) with radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CRA) for the treatment of patients with hepatocellular carcinoma (HCC). Methods: Online databases, including Scopus, Web of Science, PubMed, Embase, CNKI, Google Scholar, and Cochrane Library were searched. Results: Forty-two studies with 5468 pooled patients (TACE + RFA: 21 studies with 3398 patients, TACE + MWA:14 studies with 1477 patients, and TACE + CRA: 7 studies with 593 patients) reported combination therapy versus TACE alone. The TACE + MWA subcohort had the best odds of long-term overall survival (OR 4.81, 95% CI 1.44, 16.08, P = 0.011) and objective response rate (OR 3.93, 95% CI 2.34, 6.61, P < 0.001) compared with the other two combination subcohorts. The TACE + RFA and TACE + MWA subcohorts had approximately similar odds of 1-year recurrence-free survival (OR 5.21, 95% CI 2.13, 12.75, P < 0.001 and OR 4.61, 95% CI 1.70, 12.51, P = 0.003, respectively). The disease control rate was similar between the TACE + MWA and TACE + CRA subcohorts (OR 4.01, 95% CI 2.66, 6.04, P < 0.001 and OR 4.05, 95% CI 1.68, 9.74, P = 0.002) but greater than the TACE + RFA subcohort (OR 3.23, 95% CI 2.14, 4.86, P < 0.001). Conclusion: Overall, the TACE + MWA subcohort had the best efficacy and outcomes, especially for younger patients (less than 60-year-old) with tumor size of ≤ 3 cm, compared with the TACE + RFA or TACE + CRA subcohorts. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review and meta-analysis aimed to assess renal function and cardiometabolic biomarkers after treatment with beraprost sodium in patients with diabetes mellitus. Methods: We systemically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library up to August 2020. Statistical heterogeneities were computed using Cochrane's Q test and I2 test. A fixed- or random-effects model was used to calculate the weighted mean difference (WMD) and corresponding 95% confidence intervals (CI). Results: From 341citations, seven trials were included into our meta-analysis. Our findings demonstrated that beraprost sodium intake significantly decreased blood urea nitrogen (BUN) (WMD = −5.62, 95% CI [−8.49, −2.74], P < 0.001) and cystatin C (WMD = −0.57, 95% CI [−0.68, −0.46], P < 0.001). Beraprost sodium intake had no significant effect on fasting blood sugar (FBS), hemoglobin A1c (HbA1c), cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, systolic blood pressure (SBP), diastolic blood pressure (DBP), and creatinine (Cr) in patients with diabetes receiving beraprost sodium in comparison with the controls. Conclusion: Our meta-analysis revealed that beraprost sodium administration significantly decreased BUN and cystatin C levels in patients with diabetes. However, no significant effect was observed on the cardiometabolic profile. [ABSTRACT FROM AUTHOR]

Purpose: The main purpose of this systematic review was to reflect on recent literature on bariatric LGA embolization for obesity treatment and to compare this new procedure in human and animal studies. Methods: A systematic search of Scopus, MEDLINE, Web of Science, Embase, and Google Scholar was performed to identify human and animal studies employing bariatric LGA embolization to treat obesity. As well, Cochrane's Q test and the I2 statistic were utilized to determine heterogeneity. Results: Nine human and four animal studies recruiting a total of 118 cases (n = 78 patients and n = 40 animals) were included in analysis. All assessments on body mass index (BMI), weight, and ghrelin levels had been fulfilled based on before-after (human studies) and intervention-control designs (animal studies) using bariatric LGA embolization. The findings suggested that bariatric LGA embolization had significantly decreased BMI (mean difference (MD): − 2.66, 95% confidence interval [CI] − 3.74, − 1.58, P < 0.001) and weight (MD: − 8.69, 95% CI − 10.48, − 6.89, P < 0.001) in humans. Although overall pooled estimate showed no significant changes in ghrelin levels following this procedure (Hedges' g statistic: − 0.91, 95% CI − 1.83, 0.01, P = 0.05) in humans, a significant reduction was observed in animal studies (MD: − 756.56, 95% CI − 1098.79, − 414.33, P < 0.001) along with a significant drop in weight (MD: − 7.64, 95% CI − 13.73, − 1.54, P < 0.001). Conclusion: The present study concluded that ghrelin levels in humans had not been affected, although bariatric LGA embolization might significantly improve BMI and weight. [ABSTRACT FROM AUTHOR]

.: The high rate of medical errors, malpractice payments, legal issues, and complaints from physicians leads to waste of the physician's time and energy as well as high costs for related individuals and organizations. Patients and methods: We analyzed the outcomes of 275 medical malpractice cases reported in the Department of Forensic Medicine in Fars Province from January 2006 to December 2016. The study population included all the internists as defendants and the patients who had filed a complaint against them. Results: Based on the plaintiffs' gender in the investigated cases, the maximum age of patients with complaints by gender among males ranged between 30–39 and 50–59 years (22.4%) and among females it was 30–39 years (22.8%). The degrees of physicians who had been accused of medical commission were recognized as follows: 5 (1.8%) medical students, 36 (13.1%) GPs (general practitioners), 126 (45.8%) internists, 6 (2.2%) pulmonologists, 6 (2.2%) nephrologists, 4 (1.5%) hematologists, 2 (0.7%) rheumatologists, and 38 (13.9%) gastroenterologists. Conclusions: Annual malpractice from the beginning of 2006 to the end of 2016 varied from 0 to 5%, while the rate of annual complaints in the same period varied from 0 to 45%. Maximum malpractice payment belonged to gynecology which is about 50,358,000 Rials equivalent to US$11,990 involving malpractice and complaint concurrent with internists. Specially fields of general surgery(9.4%), gynecology (9.1%), subspecialty fields of thoracic cardiovascular surgery (6.9%), and family general practice (13.1%) were the fields of most complaints parallel with those of internists. [ABSTRACT FROM AUTHOR]