Resolvin D1 Alleviates Mechanical Allodynia via ALX/FPR2 Receptor Targeted Nod-like Receptor Protein 3/Extracellular Signal-Related Kinase Signaling in a Neuropathic Pain Model.

The current study aimed to investigate the role and underlying mechanism of Resolvin D1 (RvD1) alleviating spinal nerve ligation (SNL)-induced neuropathic pain (NP) and its interplay with regulatory cascades of Nod-like Receptor Protein 3 (NLRP3) inflammasome. Sprague-Dawley male rat models of SNL-stimulated NP were established, which were pre-treated with different doses of RvD1, WRW4 (ALX/FPR2 inhibitor) or U0126 (ERK inhibitor) for three successive days following the operation. Pain behavior was assessed by measuring changes in the mechanical sensitivity of the hind paws during an observation period of seven consecutive days. The spinal cord (SC) and dorsal root ganglions (DRGs) tissues were collected on postoperative day 7. Immunohistochemistry (IHC) and Western blot were performed to determine the expression levels of NLRP3 inflammasome complex, ALX/FPR2 receptor and extracellular signal-related kinase (ERK). The pro-inflammatory mediators (IL-1ß and IL-18) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that RvD1 could alleviate mechanical allodynia significantly in the SNL-induced NP rat models. Also, RvD1 inhibited the expression of p-ERK, the NLRP3 inflammasomes complex and its corresponding downstream pro-inflammatory mediators which were significantly enhanced in the SC and DRGs of the rat SNL models. While these changes were partially reversed by pre-administration of WRW4 and further strengthened by co-treated with U0126. Our results suggest that RvD1 dependent on ALX/FPR2 may have an analgesic and anti-inflammatory influence on SNL-induced NP driven by inhibiting NLRP3 inflammasome via ERK signaling pathway. These data also provide strong support for the recent modulation of neuro-inflammatory priming and highlight the potential for specialized pro-resolving mediators (SPMs) as novel therapeutic avenues for NP.

Comparison between thermophilic and mesophilic anaerobic digestion of waste activated sludge by combined NaOH-microwave pretreatment.

The purpose of this study was to investigate the performance of the thermophilic and mesophilic anaerobic digestion process (TADP, MADP) fed with NaOH-microwave pretreated waste activated sludge. The experiment was conducted in anaerobic CSTR reactors. During this experiment, the reactors were stable in operation and were not inhibited by ammonia. The methane production and reduction of organic matters from MADP were less than those from TADP. The dewatering performance of mesophilic sludge was better than that of the thermophilic sludge. The experimental results showed that the continuous TADP and MADP were effective, when the reactors were fed with the waste activated sludge pretreated by NaOH-microwave. MADP was more suitable to combine the NaOH-MW pretreatment process than TADP.

The Role of NF-κB/NLRP3 Inflammasome Signaling Pathway in Attenuating Pyroptosis by Melatonin Upon Spinal Nerve Ligation Models.

Accumulated evidence has demonstrated causative links between neuropathic pain (NP) and immune-mediated inflammatory disorders. However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. A rat model of spinal nerve ligation (SNL) was established to explore the potential association between melatonin and pyroptosis. Behavioral experiments revealed that SNL provoked severe allodynia which was suppressed by the administration of melatonin, a caspase-1 inhibitor (VX-765), or an NF-κB inhibitor (BAY 11-7085). SNL significantly up-regulated the inflammatory cytokines associated with the excessive activation of NLRP3 components and NF-κB signaling, as well as a marked pyroptosis activation. These effects were partially inhibited by melatonin, VX-765 or BAY 11-7085, and when melatonin and inhibitors were added together, the effect was enhanced. In conclusion, melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway.

Intrathecal delivery of hydromorphone vs morphine for refractory cancer pain: a multicenter, randomized, single-blind, controlled noninferiority trial.

Hydromorphone is an alternative to morphine for intrathecal drug delivery system to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (ITHM) and intrathecal morphine (ITMO) groups, respectively. The primary outcome was the clinical success rate, which was defined as ratio of patients achieving ≥50% pain relief. The noninferiority margin was defined as -0.15. Other outcomes included daily visual analogue scale score, breakthrough pain (BTP) incidence, intrathecal dose change, and patient-controlled analgesia bolus count change, GAD-7/PHQ-9. Clinical success was achieved in 85 and 79 of the 121 ITHM patients (70.2%) and 112 ITMO patients (70.5%), respectively. Compared to the corresponding baseline findings, significantly decreased visual analogue scale scores and BTP incidence were noted in both groups. The dose change rate decreased and increased with time in the ITHM and ITMO groups, respectively (ITHM -3.33% vs ITMO 35.4%, P < 0.01, t test) from the third week. The patient-controlled analgesia bolus change rate was lower in the ITHM group than in the ITMO group (ITHM -19.88% vs ITMO 7.79%, P < 0.01, t test) from first week. Our result shows that ITHM is noninferior to ITMO on pain relief to treat refractory cancer pain, however, at different doses and that the doses of morphine tended to increase, whereas those of hydromorphone decreased over time. Hydromorphone offers advantage over morphine in controlling BTP.

Polylactide-caprolactone composite mesh for ventral hernia repair: a prospective, randomized, single-blind controlled trial.

BACKGROUND: Although composite surgical meshes are widely used in laparoscopic repair of ventral hernia, the risk of postoperative complications associated with these type of mesh is relatively high. In this report, we demonstrated the safety as well as the effectiveness of a new composite polypropylene mesh coated with poly L-lactide-co-ε-caprolactone (EasyProsthes™) for the repair of ventral hernia. METHODS: This study was a randomized, controlled trial designed to compare EasyProsthes composite mesh (EPM) with Parietex™ Composite (PCO) in patients undergoing laparoscopic ventral hernia repair. Hernia recurrence, chronic pain, seroma formation, intestinal fistula or obstruction, wound or abdominal infection, and viscera adhesion were evaluated. 80 patients who needed repair surgery for primary or secondary ventral hernias were enrolled in this study. Patients were divided into two groups: the EPM group (N.=40) and the PCO group (N.=40). Patients completed 12 months of follow-up. RESULTS: Our results revealed that one patient in the EPM group (2.5%) and two patients in the PCO group (5%) developed mesh-viscera adhesions after surgery (P=1.000). We had no case of intestinal fistulas or obstruction. Seventeen patients in EPM group (42.5%) and 21 in PCO group (52.2%) developed post-surgical seromas in the surgery area (P=0.370). One patient from each group developed postoperative wound infection. There was no case of abdominal infection, chronic pain or hernia recurrence. The incidence of postoperative complications in the EPM group was similar to that observed in the PCO group. CONCLUSIONS: EPM is a safe and effective method to be used in ventral hernia repair surgeries.

Description of three new species of Ooencyrtus (Hymenoptera: Encyrtidae) from China.

Hymenoptera parasitoids of Megaloptera, particularly the family Corydalidae, are rarely found. Ooencyrtus Ashmead is a genus that attacks eggs of many orders of Insecta, including Megaloptera. Here, three species, O. longicauda sp. n., O. noyesi sp. n. and O. protohermeasis sp. n. are described. Two of them, O. longicauda and O. protohermesis were reared from eggs of corydalids (Megaloptera: Corydalidae). The three new species and O. yoshidai Noyes & Hirose are included in the newly established protohermesis species-group of Ooencyrtus because of shared similar morphological characters and what is apparently a shared host family (unknown for O. noyesi).

[Stellar spectral outliers detection based on Isomap].

How to find the spectra misclassified by traditional methods is the key problem that has been widely studied by the experts of astronomical data processing. We found that Isomap algorithm performs well for this problem. By comparing the performance of Isomap with that of principal component analysis (PCA), we found that (1) Isomap can project the spectra with similar features together and project the spectra with different features far away, while PCA may project the spectra with different features into nearby regions; (2) the outliers given by Isomap can be easily determined, and most of the outliers are binary stars with high scientific values; while the outliers given by PCA are difficult to determine and most of outliers are not binary stars. Thus, Isomap is more efficient than PCA in finding the outliers. Since the spectral data used in experiment are the spectra from the ninth data release of Sloan Digital Sky Survey (SDSS DR9), Isomap can find the spectra misclassified by SDSS pipeline efficiently and improve the classification accuracy obviously. Furthermore, since most of the spectra misclassified by SDSS pipeline are binary stars, Isomap can improve the efficiency of finding the binary stars with high scientific values. Though the experiment results show that Isomap is more sensitive to the noise than PCA, this disadvantage will not affect the application of Isomap in spectral classification since most of the spectra with low signal-to-noise ratios are the spectra whose spectral type can't be determined manually.

Effects of DNMT1 silencing on malignant phenotype and methylated gene expression in cervical cancer cells.

BACKGROUND: DNA methylation has been widely used in classification, early diagnosis, therapy and prediction of metastasis as well as recurrence of cervical cancer. DNMT methyltransferase 1 (DNMT1), which plays a significant role in maintaining DNA methylation status and regulating the expression of tumor suppressor genes. The aim of this research was to investigate the relationship between DNMT1 and abnormal methylation of tumor suppressor genes and malignant phenotype in cervical cancer. METHODS: Levels of DNMT1 mRNA and protein were detected using qPCR and Western blot, respectively. Cell proliferation was analyzed by MTT and apoptosis was performed by Annexin V-FITC/PI double staining flow cytometry, respectively. MeDIP-qPCR and qPCR were performed to measure demethylation status and mRNA re-expression level of 7 tumor-suppressor genes (CCNA1, CHFR, FHIT, PAX1, PTEN, SFRP4, TSLC1) in Hela and Siha cells after silencing DNMT1. RESULTS: The average expression levels of DNMT1 mRNA and protein in Hela and Siha cells were decreased significantly compared with control group. The flow cytometry and MTT results showed that Hela and Siha cells apoptosis rates and cell viabilities were 19.4 ± 2.90%, 25.7 ± 3.92% as well as 86.7 ± 3.12%, 84.16 ± 2.67% respectively 48 h after transfection (P < 0.01). Furthermore, the promoter methylation of five tumor suppressor genes was decreased with the increased mRNA expression after silencing DNMT1, whereas there were no significant changes in PTEN and FHIT genes in Hela cells, and CHFR and FHIT genes in Siha cells. CONCLUSIONS: Our experimental results demonstrate that methylation status of DNMT1 can influence several important tumor suppressor genes activity in cervical tumorigenesis and may have the potential to become an effective target for treatment of cervical cancer.

[Effect of Rapamycin and Cyclosporin A on the expression of TLR5 and Foxp3 in allorejection].

AIM: To study the effect of Rapamycin (RAPA) and Cyclosporin A (CsA) on the expression of TLR5 and Foxp3 in allotransplantation model in vivo. METHODS: The murine model of skin allotransplantation was established, and divided into three groups, injected with CsA 10 mg/(kg.d), RAPA 1.5 mg/(kg.d)) and normal saline respectively for 14 consecutive days. The grafts survival was observed daily. The expression of TLR5 and Foxp3 mRNA was detected by RT-PCR. RESULTS: The survival time was obviously longer in RAPA and CsA treated groups than control group. The expression of TLR5 mRNA in allotransplantation treated with RAPA was higher than that in control group(P<0.05) and remained at a higher level than the other two groups until day 21. TLR5 showed the highest expression on day 10 among three groups, which was the top point of allorejection. Compared with CsA group, RAPA treatment in vivo caused the higher expression of Foxp3 mRNA(P<0.05), which remained at a high level after treatment stopped. However, in CsA group, Foxp3 mRNA expression increased on day 7 and 10, and then decreased significantly on day 14. TLR5 and Foxp3 expression was positively correlated among three groups. RAPA and CsA promoted the expression of TLR5 in T cells when treated with flagellin for 6 hours in vitro and RAPA has stronger effect. CONCLUSION: RAPA and CsA can promote the expression of TLR5 and Foxp3 in allotransplantation model in vivo and flagellin enhanced this effect in vitro.

[Early treatment for the unstable fracture of the thoracolumbar].

OBJECTIVE: To research the efficacy and feasibility for unstable fracture of thoracolumbar with AF spine internal fixation device. METHODS: Thirty-two patients with unstable fractures of T11-L3 were treated with AF spine internal fixation device and autograft between vertebral lamina vertebral body transverse process from January 2002 to June 2006. There were 21 female and 11 male, aging from 58 to 72 years with a mean of 62 years. All these patients were examined with x-ray and CT preoperative and postoperative respectively. They were followed-up thirteen months averagely, observing the stability of spinal column, bone grafting fusion, the height of vertebra and recovery of anterior bone fragment herniation. RESULTS: All these AF spine internal fixation devices treated for the unstable fractures of thoracolumbar had not removed because of internal fixation failure or pain. Fracture healing and grafting fusion appeared after operation three months averagely. X-rays revealed post-protrusion angle were recovered from 22 degrees to 8.5 degrees, the heights of anterior were recovered from 50% to 86%, the angle of posterior were recovered from 94% to 98%. The postoperative CT scan showed that six cases with herniation to canal gained a completely recoveries. CONCLUSION: AF spine internal fixation device used in early stage for unstable fracture of thoracolumbar is a simple and effective method. It has advantages such as providing early substantial fixation, maintaining a well three column stability. Bone grafting is a key factor in this operative technique.

[Expression of heat shock protein 72 in leukocytes from patients with acute trauma and its relationship with survival].

OBJECTIVE: To determine the expression of heat shock protein 72 (HSP 72) in leukocytes of patients with acute trauma, and evaluate its relationship with survival. METHODS: Thirty acute trauma patients with acute physiology and chronic health evaluation III (APACHE III) > or = 18 were included as study subjects. Blood samples were serially obtained at three time points: days 0-1, days 2-6 and days 7-14 after the trauma. Expression of HSP72 was assessed with immunohistochemistry, and the expression of HSP72 mRNA was assessed with semi-quantified reverse transcription-polymerase chain reaction (RT-PCR), and the relationship between their levels and the survival rate (survival period > 2 months) was analyzed. RESULTS: The expression of HSP72 was significantly enhanced on post-trauma days 2-6. The levels of HSP72 in the survivor groups were higher than that in non-survivors. CONCLUSION: The study suggests that acute trauma can lead to a marked elevation of HSP72, and its peak level appears on days 2-6, which might be correlated with 2-month survival of the afflicted patients.