Hind-limb ischemia (HLI) is one of the major complication of diabetic patients. Angiogenesis potential in diabetic patients is severely disrupted, and the mechanism underlying it has not been fully elucidated, making it an obstacle for developing an efficient therapeutic angiogenesis strategy. Skeletal muscle cells, through their paracrine function, had been known to be critical for neoangiogenesis. Here we found that hyperglycemia upregulates the expression of skeletal muscle cells prolyl hydroxylase domain 3 (PHD3), which resulted in the decrease of the secretion of angiogenic factors, especially VEGF-A and PDGF-BB. We showed that treatment with salidroside, a small molecule drug, significantly suppresses PHD3 expression and increases VEGF-A and PDGF-BB secretion from skeletal muscle cells, which in turn enhances the proliferation and migration potentials of endothelial and smooth muscle cells. Finally, we demonstrated that intramuscular injection of salidroside into the ischemic hind limbs of diabetic HLI model mice could efficiently induce neoangiogenesis and blood perfusion recovery. Thus, our novel findings not only reveal the effects of hyperglycemia on the angiogenesis potential of skeletal muscle cells and the mechanism underlying it, but also provides a novel finding suggesting that salidroside might be a potential small molecule drug for diabetic HLI.

The aim of this study was to evaluate the prognostic role of neutrophil lymphocyte ratio (NLR) in patients with spontaneous intracerebral hemorrhage (ICH). PubMed, EMBASE, Web of Knowledge, Cochrane Library and China National Knowledge Infrastructure were searched for potentially relevant literature. The study and patient characteristics were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic role of NLR in patients with ICH. Poor functional outcome was defined as modified Rankin Scale≥3. Four studies with 1,720 patients were included. The pooled OR of higher NLR for poor functional outcome at 3 months was 2.74 (95% CI, 1.33-5.65). The pooled OR of higher NLR for death at 3 months was 1.58 (95% CI, 0.44-5.68). Subgroup analysis and sensitivity analysis were also performed. Publication bias was not present. In conclusion, for patients with ICH, higher NLR was associated with poorer functional outcome at 3 months, while higher NLR was not associated with higher risk of death at 3 months.

The purpose of this study was to evaluate the prognostic role of neutrophil lymphocyte ratio (NLR) in patients with glioma. PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure were searched for relevant literature. The study and patient characteristics were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic role of NLR in patients with glioma. Subgroup analysis and sensitivity analysis were also performed. Six studies with 1,021 patients were included. The pooled HR of elevated NLR for OS in patients with glioma was 1.48 (95% CI, 1.25-1.76). Among the included studies, five studies used 4 as the cut-off value of NLR. The pooled HR for OS of the five studies was 1.67 (95% CI, 1.37-2.03). No significant heterogeneity was observed (I2 = 42.4%, P=0. 122). Publication bias was not present. Elevated NLR was associated with poorer overall survival in patients with glioma.

The aim of this study was to evaluate the predictive role of preoperative retinal nerve fiber layer (RNFL) thickness for postoperative visual recovery in patients with chiasmal compression through performing a meta-analysis. PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure were searched for relevant studies. The study and patient characteristics were extracted. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the predictive value of RNFL thickness. Subgroup analyses were also performed. Four studies with 202 patients and 395 eyes were included. The pooled results showed that patients with normal RNFL thickness could achieve better visual recovery compared with those with thin RNFL with the OR of 15.61 (95% CI, 4.09-59.61). Significant heterogeneity was observed (I2 = 54.5%, P=0.086). Publication bias was not present. Normal preoperative RNFL thickness could predict better postoperative visual recovery than thin RNFL in patients with chiasmal compression.

The aim of this study was to systematically evaluate the association between D-dimer level and the risk of stroke through performing a meta-analysis. PubMed, Web of Science, EMBASE and Cochrane Library were searched for potentially eligible literature. Prospective observational studies or case-control studies were included. The study characteristics and relevant data were extracted. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the association between D-dimer level and the risk of stroke. Seven prospective studies with 22,207 patients and three case-control studies with 2,248 patients were included. For the prospective studies, the pooled HRs of higher D-dimer level for all types of stroke, ischemic stroke and hemorrhagic stroke were 1.55 (95% CI, 1.28- 1.87), 1.62 (95% CI, 1.18-2.22) and 1.30 (95% CI, 0.63-2.68), respectively. The pooled HRs per SD increase in log D-dimer for all types of stroke, ischemic stroke and hemorrhagic stroke were 1.16 (95% CI, 1.06-1.26), 1.11 (95% CI, 1.03-1.21) and 1.11 (95% CI, 0.95-1.30), respectively. For the case-control studies, the pooled OR of higher D-dimer level for acute ischemic stroke was 2.06 (95% CI, 1.08-3.96). No significant publication bias was found in the meta-analysis. In conclusion, our results suggested that higher D-dimer level was associated with higher risk of stroke, especially ischemic stroke.

Epidermal growth factor receptor (EGFR) T790M mutation accounted for over half of drug resistance cases in EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) and led to different outcomes. This study aimed to assess the prognostic role of T790M in NSCLC patients treated with EGFR-TKIs that developed drug resistance. Eligible literatures were reviewed from various databases and a meta-analysis was performed to evaluate the prognostic role of T790M mutation in EGFR-TKIs treated patients that went progression. Three studies containing 192 patients were included in the meta-analysis. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were 0.66 (95% CI 0.49-0.89, P = 0.007) and 0.53 (95% CI 0.35-0.79, P = 0.002) respectively. Subgroups analyses were also performed on OS and PFS according to patients' districts, gender and histological type. In conclusion, T790M as a common mutation to cause drug-resistance in EGFR-TKIs treated NSCLC patients may be a favorable prognostic factor on OS and PFS both. Further studies are necessary to demonstrate the prognostic role of secondary T790M in NSCLC patients.

We conducted a meta-analysis to assess the efficacy and safety of dose-dense chemotherapy in the treatment of patients with urothelial carcinoma. A systematic search was conducted in PubMed, Medline, Embase, Web of Science and Cochrane Collaboration's Central register of controlled trials (CENTRAL) for relevant articles. Data was obtained from 10 trials with a total of 1093 patients. The pooled pathologic complete response (pCR) was 27.8% in the ten studies with a full cohort of 684 patients who received dose-dense methotrexate, vinblastine, adriamycin and cisplatin (dd-MVAC). In the controlled trials, although the difference was not significant, the pCR rate in the dd-MVAC group has a trend of increase (odds ratio (OR) 1.52; 95% confidence interval (CI) 0.78-2.98, P = 0.22) compared with classic MVAC group. A significant improvement of overall survival (OS) (hazard ratio (HR) 0.77, 95% CI 0.61-0.97, p = 0.03) was also observed. Hematologic toxicities were the most frequent grade ≥ 3 toxicities including neutropenia/febrile neutropenia (17.5%), anemia (9.4%) and thrombocytopenia (6.1%). Compared with the classic MVAC group, dd-MVAC was associated with significantly decreased risks of all-grade adverse events (AEs) such as anemia (OR 0.457, 95% CI 0.249-0.840, p = 0.012), febrile neutropenia (OR 0.398 95% CI 0.233-0.681, p = 0.001), and neutropenia (OR 0.373, 95% CI 0.201-0.691, p = 0.002). In conclusion, dose-dense chemotherapy was effective and tolerable in patients with urothelial carcinoma, which could be considered as a reasonable therapeutic option.

Colorectal carcinoma (CRC) remains one of the leading causes of death in cancer-related diseases. In this study, we aimed to investigate the anticancer effect of Jolkinolide B (JB), a bioactive diterpenoid component isolated from the dried roots of Euphorbia fischeriana Steud, on CRC cells and its underlying mechanisms. We found that JB suppressed the cell viability and colony formation of CRC cells, HT29 and SW620. Annexin V/PI assay revealed that JB induced apoptosis in CRC cells, which was further confirmed by the increased expression of cleaved-caspase3 and cleaved-PARP. iTRAQ-based quantitative proteomics was performed to identify JB-regulated proteins in CRC cells. Gene Ontology (GO) analysis revealed that these JB-regulated proteins were mainly involved in ER stress response, which was evidenced by the expression of ER stress marker proteins, HSP90, Bip and PDI. Moreover, we found that JB provoked the generation of reactive oxygen species (ROS), and that inhibition of the ROS generation with N-acetyl L-cysteine could reverse the JB-induced apoptosis. Confocal microscopy and flow cytometry showed that JB treatment enhanced intracellular and mitochondrial Ca2+ level and JC-1 assay revealed a loss of mitochondrial membrane potential in CRC after JB treatment. The mitochondrial Ca2+ uptake and depolarization can be blocked by Ruthenium Red (RuRed), an inhibitor of mitochondrial Ca2+ uniporter. Taken together, we demonstrated that JB exerts its anticancer effect by ER stress-Ca2+-mitochondria signaling, suggesting the promising chemotherapeutic potential of JB for the treatment of CRC.