Sulfation, structural analysis, and anticoagulant bioactivity of ginger polysaccharides.

In this study, ginger polysaccharide (GP), ginger polysaccharide 1 (GP1), and ginger polysaccharide 2 (GP2) from ginger were firstly modified by sulfation. Fourier transform infrared, and nuclear magnetic resonance spectra investigation of sulfated ginger polysaccharide (SGP), sulfated ginger polysaccharide 1 (SGP1), and sulfated ginger polysaccharide 2 (SGP2) revealed that the sulfation successfully occurred with the characteristic absorption peak of polysaccharide. Congo red experiment showed that triple helical structure existed in SGP and SGP1, but random coils existed in SGP2. SGP, SGP1, and SGP2 all showed a rough and rugged surface with plenty of small pores. The blood clotting time of SGP2 or SGP at 2 mg/mL in activated partial thromboplastin time (APTT) assay was 41.42 or 38.01 s, respectively, which were approximately 1.33- and 1.22-fold longer than that of the physiological saline. Compared to the saline control group, prothrombin time (PT) was increased by 1.22-fold with the addition of GP at 2 mg/mL. However, no clotting inhibition phenomenon was observed in thrombin time test even at the concentrations that APTT and PT were obviously prolonged. It indicated that GP2, SGP2, and SGP inhibited the intrinsic pathway of coagulation, but GP inhibited both the intrinsic and extrinsic pathways of coagulation. Hence, ginger polysaccharides might be used as anticoagulants and therapeutic reagents for thrombosis.

Oxaliplatin Regulates Chemotherapy Induced Peripheral Neuropathic Pain in the Dorsal Horn and Dorsal Root Ganglion via the Calcineurin/NFAT Pathway.

OBJECTIVE: The aim of this study was to investigate the mechanism of oxaliplatin in the induction of neuropathic pain as a symptom of Chemotherapy-Induced Peripheral Neuropathy (CIPN). METHODS: The CIPN rat model was induced with a one-time injection of oxaliplatin, and the paw withdrawal response was determined using von Frey filaments. The Paw Withdrawal Threshold (PWT) value was recorded and the Dorsal Horn (DH) and Dorsal Root Ganglion (DRG) tissues were collected. The mRNA and protein levels of Calcineurin (CaN), Nuclear Factor of Activated T cells (NFAT), and other relevant cytokines were determined. CaN and NFAT inhibition reagents, FK506 and 11R-VIVIT, were applied in order to investigate the functions of the CaN/NFAT pathway in the neuropathic pain processes. The levels of the downstream inflammatory cytokines, TNF-α and IL-1ß, were assessed by ELISA. RESULTS: The application of oxaliplatin reduced the value of PWT by 4 times on days 7（4±1.33）and 14（5.13±3.07）compared with the control group(14±0.91; 13.67±0.76). After treatment, the CaN mRNA level decreased and that of NFAT increased in DH and DRG tissues (P<0.05). However, treatment with FK506 and 11R-VIVIT decreased the value of PWT that had increased after oxaliplatin treatment. The expression of downstream cytokines related to the CaN/NFAT pathway increased, including CCR2, COX2, p-ERK, and p-P38 (all p<0.05). In addition, when the CaN/NFAT pathway was activated, the concentration of TNFα increased to 40pg/mg in DH tissues and 60pg/mg in DRG tissues compared with the control group, while the concentration of IL-1ß increased to over 60pg/mg in DH and DRG tissues. CONCLUSION: It was the first time to prove that oxaliplatin-induced neuropathic pain was correlated to the activation of the CaN/NFAT pathway in our rat model. This finding can provide a new direction to explore the mechanism of oxaliplatin-induced neuropathic pain.

Old age at diagnosis increases risk of tumor progression in nasopharyngeal cancer.

Age at diagnosis has been found to be a prognostic factor of outcomes in various cancers. However, the effect of age at diagnosis on nasopharyngeal cancer (NPC) progression has not been explored. We retrospectively evaluated the relationship between age and disease progression in 3,153 NPC patients who underwent radiotherapy, chemotherapy, or chemoradiotherapy between 2007 and 2009. Patients were randomly assigned to either a testing cohort or a validation cohort by computer-generated random assignment. X-tile plots determined the optimal cut-point of age based on survival status to be ≤61 vs. >61 years. Further correlation analysis showed that age >61 years was significantly correlated with the tumor progression and therapeutic regimen in both testing and validation cohorts (P <0.05). In the present study, we observed that older age (>61 years) was a strong and independent predictor of poor disease-free survival (DFS) and cancer-specific survival (CSS), in both univariate and multivariate analyses. Age was also found to be a significant prognostic predictor as well (P <0.05) when evaluating patients with the same disease stage. ROC analysis confirmed the predictive value of age on NPC-specific survival in both cohorts (P <0.001) and suggested that age may improve the ability to discriminate outcomes in NPCs, especially regarding tumor progression. In conclusion, our study suggests that older age at NPC diagnosis is associated with a higher incidence of tumor progression and cancer-specific mortality. Age is a strong and independent predictor of poor outcomes and may allow for more tailored therapeutic decision-making and individualized patient counseling.

[Analgesic effect and safety of intercostal nerve cryoanalgesia after the video-assisted thoracoscopic surgery].

OBJECTIVE: To investigate the analgesic efficacy and safety of intercostal nerve cryoanalgesia after video-assisted thoracoscopic surgery (VATS). METHODS: This was a prospective randomized controlled study. From May 2014 to April 2015, 80 patients who would undergoing selective surgery performed by the same surgeon team were chosen, and were randomly divided into cryoanalgesia group and intravenous analgesia group by a random number table. Visual analogue scale (VAS) at resting and movement were measured on postoperative 4 h, 1 d, 2 d, 3 d, and the amount of supplemental morphine use and adverse reactions were recorded; plasma concentration of cortisol, blood glucose, C-reactive protein (CRP) and interleukin-6 (IL-6) were detected on preoperative and postoperative 4 h,1 d,2 d. RESULTS: Seventy-one patients with complete test process were included in the statistical analysis, including cryoanalgesia group (35 cases) and intravenous group (36 cases). No statistical differences were found in terms of age, gender, body mass index (BMI) between the two groups. VAS scores of cryoanalgesia group at movement on postoperative 4 h, 1 d, 2 d, 3 d were 5(5,7), 4(3,6), 3(3,4), 3(0,3), and in intravenous group were 5(5,6), 5(3,5), 3(3,4), 2(0,3), respectively, but there was no statistically different between two groups (P>0.05). Resting VAS scores of cryoanalgesia group on postoperative 4 h, 1 d, 2 d, 3 d were 3(2,4), 0(0,3), 0(0,0), 0(0,0), and in intravenous group were 3(0.5,4), 2(0,3), 0(0,1.5), 0(0,0) respectively, but there was no statistically different between two groups (P>0.05). Resting analgesic effectiveness (VAS≤5) of cryoanalgesia group were 91.4%, and in intravenous group were 97.2%, respectively. Median of morphine dosage was equal between two groups on postoperative 4 h, 1 d, 2 d, cumulative amount of morphine of cryoanalgesia group was higher than intravenous group, but the difference between the two groups was not statistically significant. Incidence of nausea and vomiting for intravenous group was 36.1%, significantly higher than cryoanalgesia group (17.1%, χ(2)=4.148, P<0.05). The change of plasma concentration of cortisol, C-response protein (CRP), interleuken-6(IL-6) was noticeable, but there was no statistical significance in each time point. CONCLUSION: The analgesic effect of both Intercostal nerve cryoanalgesia and intravenous analgesia after VATS is almost the same.Compare with intravenous analgesia, incidence of the adverse reactions of cryoanalgesia is lower, and there is no increasing in the stress response.