Crosstalk between exosomes and autophagy in spinal cord injury: fresh positive target for therapeutic application.

Spinal cord injury (SCI) is a very serious clinical traumatic illness with a very high disability rate. It not only causes serious functional disorders below the injured segment, but also causes unimaginable economic burden to social development. Exosomes are nano-sized cellular communication carriers that exist stably in almost all organisms and cell types. Because of their capacity to transport proteins, lipids, and nucleic acids, they affect various physiological and pathological functions of recipient cells and parental cells. Autophagy is a process that relies on the lysosomal pathway to degrade cytoplasmic proteins and organelles and involves a variety of pathophysiological processes. Exosomes and autophagy play critical roles in cellular homeostasis following spinal cord injury. Presently, the coordination mechanism of exosomes and autophagy has attracted much attention in the early efficacy of spinal cord injury. In this review, we discussed the interaction of autophagy and exosomes from the perspective of molecular mechanisms, which might provide novel insights for the early therapeutic application of spinal cord injury.

Transient receptor potential vanilloid 4 is a critical mediator in LPS mediated inflammation by mediating calcineurin/NFATc3 signaling.

Transient Receptor Potential Vanilloid 4 (TRPV4) ion channel is thought to be an essential component of inflammatory response. However, its role and mechanism in regulating acute lung injury (ALI) and macrophages activation are not well characterized. In our study, we observe that blockade of TRPV4 using GSK2193874 or HC-067047 greatly improve the pneumonedema, the lung pathologic changes, the up-regulation of proinflammatory cytokines and the neutrophil infiltration in LPS-induced lung injury. In vitro, knockdown of TRPV4 in macrophages reduces the levels of pro-inflammatory cytokines, ROS production, Ca2+ concentration in cytoplasma and the activation of calcineurin/NFATc3 signaling. Importantly, change of extracellular Ca2+ in culture medium prevents LPS-induced NFATc3 nuclear translocation, up-regulation of proinflammatory cytokines and ROS production in macrophages. Inhibition of calcineurin with cyclosporine A, FK506 down-regulates the levels of NFATc3 nuclear translocation and proinflammatory cytokines expression. Our results demonstrate that TRPV4-dependent Ca2+ influx contributes to LPS-induced macrophage activation by calcineurin-NFATc3 pathway.

Involvement of Spinal CCR5/PKCγ Signaling Pathway in the Maintenance of Cancer-Induced Bone Pain.

Cancer-induced bone pain (CIBP) is a challenging medical problem that considerably influences cancer patients' quality of life. Currently, few treatments have been developed to conquer CIBP because of a poor understanding of the potential mechanisms. Our previous work has proved that spinal RANTES (a major ligand for CCR5) was involved in the maintenance of CIBP. In this study, we attempted to investigate whether spinal CCR5 and its downstream PKCγ pathway is involved in the maintenance of CIBP. Inoculation of Walker 256 cells into the tibia could induce a marked mechanical allodynia with concomitant upregulation of spinal CCR5 and p-PKCγ expression from day 6 to day 15 after inoculation. Spinal CCR5 was prominently expressed in microglia, and mechanical allodynia was attenuated by intrathecal injection of DAPTA (a specific antagonist of CCR5) with downregulation of spinal CCR5 and p-PKCγ expression levels at day 15 in inoculated rats. Pre-intrathecal injection of RANTES could reverse the anti-allodynia effects of DAPTA. Intrathecal administration of GF109203X (an inhibitor of PKC) could alleviate mechanical allodynia as well as decrease of spinal p-PKCγ expression level, but no influence on spinal CCR5 level. Our findings suggest that CCR5/PKCγ signaling pathway in microglia may contribute to the maintenance of CIBP in rats.

Connexin 43 Mediates CXCL12 Production from Spinal Dorsal Horn to Maintain Bone Cancer Pain in Rats.

Tumor metastasis to bone can subsequently lead to bone cancer pain (BCP). Currently, BCP is difficult to conquer due to a poor understanding of the potential mechanisms. Several studies have indicated that astrocyte-specific connexin 43 (Cx43) was involved in the neuropathic pain, and Cx43 induced the release of chemokine CXCL12 in bone marrow stromal cells. However, whether spinal Cx43 mediates the production of CXCL12 to participate in the maintenance of BCP is still unknown. Here we showed that Walker 256 tumor cells inoculation into the tibia induced a significant mechanical allodynia, which was accompanied by upregulation of spinal p-Cx43 and CXCL12 expression levels from day 6 to day 18 after inoculation. Spinal Cx43 was mainly expressed in astrocytes, and intrathecal (43)Gap26 (a selective Cx43 blocker) markedly attenuated mechanical allodynia as well as reduced p-Cx43 and CXCL12 expression at day 18 after inoculation. Pre-intrathecal administration of CXCL12 almost abolished the attenuated mechanical allodynia by (43)Gap26. Furthermore, intrathecal injection of anti-CXCL12 neutralizing antibody could ameliorate mechanical allodynia with concomitant inhibition of upregulation of CXCL12 expression, but not influence on p-Cx43 expression. Our results indicate that Cx43 mediates CXCL12 production from spinal dorsal horn in astrocytes to maintain bone cancer pain in rats. These findings may improve our understanding of the underlying mechanisms of BCP and provide a novel target for the treatment of BCP.

MicroRNA-204-5p Ameliorates Neurological Injury via the EphA4/PI3K/AKT Signaling Pathway in Ischemic Stroke.

Ischemic stroke has extremely high mortality and disability rates worldwide. miR-204-5p has been reported to be associated with neurological diseases. However, the relationship linking miR-204-5p to ischemic stroke and its molecular mechanism remain unclear. Herein, we found that expression of miR-204-5p was significantly decreased while EphA4 increased in vivo and vitro, which reached the peak at 24 h after cerebral ischemia/reperfusion. Then, we altered miR-204-5p expression in rats by cerebroventricular injection. Our study showed that miR-204-5p overexpression obviously reduced the brain infarction area and neurological score. We successfully cultured neurons to investigate the downstream mechanism. Upregulation of miR-204-5p increased cell viability and suppressed the release of LDH. Moreover, the proportion of apoptotic cells tested by TUNEL and flow cytometry and protein expression of Cleaved Caspase3 and Bax were inhibited. The relative expression of IL-6, TNF-α, and IL-1ß was repressed. In contrary, knockdown of miR-204-5p showed the opposite results. Bioinformatics and a dual luciferase assay illustrated that EphA4 was a target gene. Further research studies demonstrated that the neuroprotective effects of miR-204-5p could be partially mitigated by upregulating EphA4. Next, we proved that the miR-204-5p/EphA4 axis furtherly activated the PI3K/AKT pathway. We thoroughly illustrated the role of neuroinflammation and apoptosis. However, whether there are other mechanisms associated with the EphA4/PI3K/AKT pathway needs further investigation. Altogether, the miR-204-5p axis ameliorates neurological injury via the EphA4/PI3K/AKT pathway, which is expected to serve as an effective treatment for ischemic stroke.

Activation of spinal TDAG8 and its downstream PKA signaling pathway contribute to bone cancer pain in rats.

Bone cancer pain is difficult to treat and has a strong impact on the quality of life of patients. Few therapies have emerged because the molecular mechanisms underlying bone cancer pain are poorly understood. Recently, T-cell death-associated gene 8 (TDAG8) has been shown to participate in complete Freund's adjuvant-induced chronic inflammatory pain. In this study, we aimed to examine whether TDAG8 and its downstream protein kinase A (PKA) pathway are involved in bone cancer pain. A bone cancer pain model was made by inoculation of Walker 256 cells into the intramedullary space of rat tibia. Spinal TDAG8 expression was increased after inoculation with tumor cells. Intrathecal TDAG8 siRNA attenuated bone cancer pain behaviors during the initiation and maintenance phases; there were also concomitant decreases in TDAG8 mRNA and protein levels in spinal cord. Moreover, we found spinal PKA and phosphorylated cAMP response element-binding (pCREB) protein levels were up-regulated in the rat model of bone cancer pain. Knockdown of TDAG8 resulted in reduced bone cancer pain-induced spinal PKA and pCREB protein expression in two procedures. Furthermore, intrathecal H-89 (a PKA inhibitor) significantly attenuated bone cancer pain behaviors in rats. Our results suggest a causal relationship between TDAG8 expression and the initiation and maintenance of bone cancer pain. Activation of spinal TDAG8 contributes to bone cancer pain through the PKA signaling pathway in rats. These findings may lead to novel strategies for the treatment of bone cancer pain.

Glycyrrhetinic acid extracted from Glycyrrhiza uralensis Fisch. induces the expression of Toll-like receptor 4 in Ana-1 murine macrophages.

Glycyrrhetinic acid (GA) is an active component of licorice root that has long been used as a herbal medicine for the treatment of peptic ulcer, hepatitis, and pulmonary and skin diseases in Asia and Europe. In this study, we analyzed the effect of GA extracted from Glycyrrhiza uralensis Fisch. on the expression of Toll-like receptors (TLRs) that play key roles in regulating the innate immune response against invading pathogens. Stimulation of Ana-1 murine macrophages with GA induced a significant dose-dependent expression of TLR-4, and its mRNA expression that increased from 3-h post-treatment was approximately fivefold over the level in the mock-treated cells. No endotoxin contamination contributed to the GA-induced TLR-4 expression, because polymyxin B treatment did not alter the upregulated expression of TLR-4 in GA-treated cells. Several molecules, such as myeloid differentiation factor 88, interferon-ß, and interleukin-6, which are involved in the TLR-4 downstream signaling pathway, were upregulated significantly in response to GA stimulation. Our findings demonstrate that GA is able to induce the expression of TLR-4 and activate its downstream signaling pathway.

Dexmedetomidine aggravates hypotension following mesenteric traction during total gastrectomy: a randomized controlled trial.

BACKGROUND: Mesenteric traction syndrome (MTS), which is characterized by arterial hypotension and tachycardia following mesenteric traction (MT), frequently occurs during abdominal surgery. Dexmedetomidine, commonly used in general anesthesia during major surgery, has a sympatholytic effect and attenuates the compensatory response to hypotension. OBJECTIVE: Assess the effect of dexmedetomidine on hypotension following mesenteric traction. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Department of Anesthesiology, Zhenjiang First People's Hospital in China. PATIENTS AND METHODS: Patients were randomly divided into three groups. Dexmedetomidine, 0.5 or 1.0 µg/kg, was intravenously administered over 15 minutes before skin incision followed by a maintenance rate of 0.5 µg/kg/h in groups D1 and D2, respectively; saline was administered in group C. MAIN OUTCOME MEASURE(S): The duration of hypotension, heart rate and plasma norepinephrine level in patients with MTS were recorded within 60 minutes following MT. SAMPLE SIZE: 75 patients. RESULTS: The duration of hypotension in the MTS patients in group D1 and D2 was significantly longer than that in groups C (D1 vs. C, P<.05; D2 vs. C, P<.01). Significantly more phenylephrine was required to treat hypotension in group D1 and D2 than was required for patients in group C (P<.05). The increase in heart rate during the first 15 minutes of MT in group D2 was significantly attenuated compared to that in group C (P<.0083). The increases in norepinephrine levels during the first 15 minutes of MT in group C were significantly higher than those in groups D1 and D2 (P<.0167). CONCLUSION: Adjunctive dexmedetomidine in general anesthesia aggravates hypotension during MTS in open total gastrectomy. LIMITATIONS: Postoperative complications were not evaluated. CONFLICT OF INTEREST: None.

Inhibition of calcineurin/NFATc4 signaling attenuates ventilator­induced lung injury.

Ventilator­induced lung injury (VILI) is a life­threatening condition caused by the inappropriate use of mechanical ventilation (MV). However, the precise molecular mechanism inducing the development of VILI remains to be elucidated. In the present study, it was revealed that the calcineurin/NFATc4 signaling pathway mediates the expression of adhesion molecules and proinflammatory cytokines essential for the development of VILI. The present results revealed that a high tidal volume ventilation (HV) caused lung inflammation and edema in the alveolar walls and the infiltration of inflammatory cells. The calcineurin activity and protein expression in the lungs were increased in animals with VILI, and NFATc4 translocated into the nucleus following calcineurin activation. Furthermore, the translocation of NFATc4 and lung injury were prevented by a calcineurin inhibitor (CsA). Thus, the present results highlighted the critical role of the calcineurin/NFATc4 signaling pathway in VILI and suggest that this pathway coincides with the release of ICAM­1, VCAM­1, TNF­α and IL­1ß.

The tcdA-negative and tcdB-positive Clostridium difficile ST81 clone exhibits a high level of resistance to fluoroquinolones: a multi-centre study in Beijing, China.

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea worldwide. In order to gain a better understanding about the molecular epidemiology of C. difficile in Beijing, China, molecular typing, antimicrobial susceptibility testing and drug resistance gene sequencing were performed on 174 strains of C. difficile collected from four large tertiary hospitals in Beijing. In total, 31 sequence types (STs) were identified among the 174 strains. ST81 was found to be the most prevalent (26.4%, 46/174), followed by ST2 (16.7%, 29/174) and ST54 (9.8%, 17/174). All isolates were susceptible to metronidazole and vancomycin. The test strains displayed resistance rates of 97.1%, 44.3% and 44.3% for ciprofloxacin, levofloxacin and moxifloxacin, respectively. ST81 isolates displayed a drug resistance rate of 97.8% for levofloxacin and moxifloxacin, which was significantly higher than ST2 (0%), ST54 (17.6%) and ST42 (0%) isolates (P<0.05). An amino acid mutation (T82I) was identified in GyrA, and the total mutation rate of the C. difficile strains was 40.8% (71/174). The mutation rate of ST81 isolates was 95.7% (44/46). Three amino acid mutations (D426N, S366A and D426V) were identified in GyrB, and the total mutation rate of GyrB was 39.1%. A double-site mutation in GyrB (S366A+D426V) was identified in all ST81 (n=46) isolates. In conclusion, the C. difficile ST81 clone showed a high level of resistance to fluoroquinolones in Beijing, highlighting the need for nationwide surveillance of CDI.

[Immune protection of tegument protein rSj29 against Schistosoma japonicum in mice].

OBJECTIVE: To clone, express and characterize a tegument protein gene of Schistosoma japonicum (Sj29) , and investigate the immune protection of the recombinant protein against S. japonicum in mice. METHODS: The gene coding for Sj29 protein was amplified by PCR, and the sequence was analyzed by bioinformatics tools. Partial fragment of Sj29 gene was subcloned into the prokaryotic expression vector pET28c(+). The recombinant plasmid was transformed into E. coli BL21 (DE3) and induced the recombinant with IPTG. The recombinant protein (rSj29) was purified by His-binding-resin affinity chromatography and characterized by Western blotting. Three groups each with 10 BALB/c mice were immunized subcutaneously three times (two weeks interval) respectively with 100 microl recombinant rSj29 (0.1 mg/ml) , adjuvant or PBS. At the 15th day after the final inoculation, each mouse was challenged by 40 +/- 2 cercariae of S. japonicum. At the 53rd day after infection, the mice were sacrificed to obtain the number of adult worms, number of eggs in liver and feces. Serum samples were collected at pre-immunization and certain time after immunization, and were analyzed for IgG by ELISA. The localization of rSj29 in worms of different developmental stages was demonstrated by immunofluorescent technique. mRNA expression level of Sj29 gene in worms of different developmental stages and three groups after infection was detected by quantitative real-time PCR. RESULTS: A 576 bp Sj29 gene fragment was obtained. The recombinant protein rSj29 with Mr 22,900 was expressed in the form of inclusion body. The recombinant rSj29 can be recognized by sera of mice immunized with rSj29 and sera of infected mice. The number of adult worms (15.4 +/- 5.9), number of hepatic eggs (40,143.3 +/- 2,995.9) and number of fecal eggs (3,803.9 +/- 110.9) in recombinant protein group were significantly higher than those of PBS control group (20 +/- 3.4, 49,318.1 +/- 6,648.3, 5,238.1 +/- 303.5, respectively) (P < 0.05) . There was a high level of specific IgG against rSj29 (maximum dilution 1:32000) in recombinant protein group. Immunohistochemical analysis showed the Sj29 protein expressed on the surface of different stages of S. japonicum. mRNA level of Sj29 was the highest at the 32nd day post-infection. CONCLUSION: The recombinant protein rSj29 induces certain degree of protective immunity in mice.

Association of Common Variants in HNF1A Gene with Serum AFP Level in Healthy Chinese Individuals and HCC Patients.

Although alpha-fetoprotein (AFP) is a widely used tumor marker in hepatocellular carcinoma (HCC), 40% of newly diagnosed patients do not have an elevated AFP level. Research has revealed that mutations in the HNF1A binding site of the AFP gene promoter cause significantly elevated serum AFP levels in patients with hereditary persistence of AFP. This study investigated the relationship between HNF1A genetic variants and serum AFP levels. We examined the association between the HNF1A-rs1169288 (A/C), rs2464196 (G/A), and rs1169310 (C/T) polymorphisms and AFP levels in a healthy Chinese population (n = 1010) and HCC patients (n = 185). Single nucleotide polymorphisms were genotyped by the amplification refractory mutation system combined with TaqMan probe in real-time PCR. The serum AFP concentrations were measured using the Architect i2000 immunochemistry analyzer. In healthy individuals, serum AFP levels were significantly lower with the rs2464196-AA and rs1169310-TT genotypes. Similar significant differences were observed in HCC patients. Moreover, in HCC patients, the distribution frequencies of rs2464196-AA+AG and rs1169310-TT+TC among those with AFP ≤ 20 ng/ml or ≤400 ng/ml were significantly lower than those in patients with AFP > 20 ng/ml or >400 ng/ml. Among all subjects, those carrying the HNF1A-rs2464196-A or rs1169310-T allele tended to have low levels of AFP. However, the HNF1A-rs1169288 polymorphism showed no significant association with the serum AFP level. These findings provide new insight into the genetic determinants of serum AFP level and can aid the differential diagnosis of HCC patients with low serum AFP.

[Prediction for helper T cell epitopes and its application in vaccine development against parasite infection].

Cellular immunity plays an important role in defense against diseases, such as pathogenic infection, autoimmunity and tumor. With the progress of molecular immunology, mechanisms of T cellular immunity, and the T cell epitopes and functional genomics, studies on the prediction based on data-derived for T cell epitopes has been highlighted, and could be one of the useful tools for application in vaccine development. This review summarizes theory and methodology of prediction for helper T cell epitopes, and their application in vaccine development against parasites, and new research directions are also discussed.

Effect of dexmedetomidine on blood coagulation in patients undergoing radical gastrectomy under general anesthesia: A prospective, randomized controlled clinical trial.

BACKGROUND: Dexmedetomidine can inhibit the perioperative stress response, which plays an important role in postoperative hypercoagulability. This study aimed to investigate whether dexmedetomidine could attenuate the activation of postoperative coagulation. METHODS: Patients undergoing open radical gastrectomy under total intravenous anesthesia were randomly allocated to the control group (group Con) and the dexmedetomidine group (group Dex). Dexmedetomidine was intravenously infused at 0.5 µg/kg over 10 minutes before anesthesia induction and then infused at a rate of 0.5 µg/kg/h until peritoneal closure in group Dex, whereas saline was administered in group Con. Blood samples were collected for thrombelastograph (TEG) analysis [reaction time (R time), clot formation time (K time), and clot formation rate (α angle)] and laboratory coagulation testing before dexmedetomidine administration and at the end of surgery. RESULTS: Coagulation was activated after radical gastrectomy, as indicated by TEG analysis and the increased concentrations of plasma fibrin (fibrinogen) degradation product (FDP) and thrombin-antithrombin complex (TAT). The R and K times were significantly prolonged and α angle was significantly decreased in group Dex compared with that in group Con at the end of surgery (P < .05). The concentrations of plasma TAT and FDP in group Dex were significantly lower than those in group Con at the end of surgery (P < .05 or .01). CONCLUSION: Adjunctive dexmedetomidine with general anesthesia attenuates the activation of coagulation following radical gastrectomy.

C-terminal 20 residues of ORF3 protein of duck circovirus genotype 2 regulates the nuclear localization and inhibits apoptotic activity of ORF3 protein.

Duck circovirus (DuCV) is divided into genotypes 1 and 2. The DuCV ORF3 protein is a newly identified viral protein with apoptotic activity. In this study, the differences in the gene sequences, subcellular localization, and apoptotic activities of the ORF3 proteins of DuCV genotypes 1 and 2 were analyzed. A T-to-A point mutation at nucleotide 236 (T236A) in the ORF3 gene sequence of DuCV genotype 1 was observed, which generates a premature stop codon (TAG) and resulted in a truncated ORF3 protein. The ORF3 protein of DuCV genotype 2 is 20 amino acids longer at its C-terminus than the truncated ORF3 protein of genotype 1. A variant monopartite-type nuclear localization signal (RRLRTCNCRACRTLK) was identified within the C-terminal region of the ORF3 protein of DuCV genotype 2, which is essential for the nuclear localization of the protein. The 20 C-terminal residues of the DuCV genotype 2 ORF3 protein also inhibits the apoptotic activity of the protein. Our findings provide insight into the biological and functional characteristics of the DuCV ORF3 protein.

Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry to identify MLST clade 4 Clostridium difficile isolates.

Clostridium difficile is the leading cause of health care-associated infections. Previous studies suggest that C. difficile MLST clade 4 strains with higher drug resistance rates constitute the major clone spreading in China. Thus development of a rapid and accurate typing method for these strains is needed to monitor the epidemiology of this clone and to guide clinical treatment. A total of 160 non-duplicate C. difficile isolates recovered from three large teaching hospitals in Beijing were studied. All the 41 clade 4 C. difficile isolates clustered together on the PCA dendrogram. Spectra peak statistics revealed that five markers (2691.43Da, 2704.91Da, 2711.93Da, 3247.27Da and 3290.76Da) can easily and reliably distinguish between clade 4 and non-clade 4 isolates, with area under the curve (AUC) values of 0.991, 0.997, 0.973, 1 and 1, respectively. In conclusion, MALDI-TOF MS is a very simple and accurate method for identifying C. difficile MLST clade 4 strains.

[Application of reverse vaccinology in Schistosoma vaccine development: advances and prospects].

OBJECTIVE: Current advances in reverse vaccinology based on the principle of "sequence-structure-function" and such integrated platform technologies as immunoinformatics, computer-aid design, and various high-throughput omics (including genomics, transcriptomics and proteomics) may pave a new way for the discovery of candidate vaccine molecules against schistosomiasis. Both theoretical prediction and experimental approaches conventionally used in the field of reverse vaccinology are briefly introduced in this review; and the applications of these approaches to screening and confirming candidate Schistosoma vaccine molecules are also summarized. Furthermore, potential research prospects of the application of reverse vaccinology to Schistosoma vaccine development are discussed by simulating immune effect mechanisms of immunization with radiation-attenuated cercaria vaccine in animal hosts and naturally acquired immunity in human population.

Intranasally Administered Adjunctive Dexmedetomidine Reduces Perioperative Anesthetic Requirements in General Anesthesia.

PURPOSE: Intranasal dexmedetomidine is an effective sedative for premedication and is regularly used to reduce preoperative tension and anxiety in children. This study aimed to assess the effect of intranasally adjunctive dexmedetomidine on perioperative sedative and analgesic requirements in adults. MATERIALS AND METHODS: Patients were randomly divided into four groups to receive preoperative administration of saline, intranasal dexmedetomidine 1 µg/kg and 2 µg/kg, and intravenous dexmedetomidine 1 µg/kg, respectively. Propofol and remifentanil were target-controlled infused to maintain intraoperative bispectral index at 45-55 and blood pressure at baseline value±20%. Sufentanil was administered to maintain postoperative visual analogue scale ≤3. Perioperative anesthetics requirements were compared using nonparametric tests. RESULTS: Intranasal dexmedetomidine significantly attenuated propofol requirements for anesthesia induction and maintenance in a dose-dependent manner. Patients given intranasal dexmedetomidine 2 µg/kg required less remifentanil for anesthesia maintenance. The first postoperative request for sufentanil analgesia was delayed in patients given intranasal dexmedetomidine 2 µg/kg. The anesthetics-sparing effect of intranasal dexmedetomidine was significantly weaker than intravenous dexmedetomidine at the same dose of 1 µg/kg. The incidences of adverse events, including hemodynamic instability and delayed recovery, were comparable with and without intranasal dexmedetomidine. CONCLUSION: Intranasal administration of dexmedetomidine can reduce perioperative anesthetic requirements, and a dose of dexmedetomidine 2 µg/kg produces a better effect in adults. The anesthetics-sparing effect of intranasal dexmedetomidine 1 µg/kg is less than that with the same intravenous dose of dexmedetomidine.

Efficacy of traditional Chinese medicine on sepsis: a systematic review and Meta-Analysis.

BACKGROUND: Traditional Chinese medicine (TCM) has been used for treatment of sepsis in China, but results still remain equivocal. To evaluate the safety and efficacy of TCM for sepsis, we conducted this Meta-analysis. METHODS: Databases searched included randomized controlled trials (RCTs) published in PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) (up to December 2014). The studies included used routine therapy treating sepsis in the control group and TCM was added on that basis in the experimental group. Methodological quality was assessed by Cochrane criteria for risk of bias. RESULTS: Ten RCTs with 691 participants were identified and analyzed. In the meta-analysis, TCM plus routine therapy reduced the 28-day mortality compared to routine therapy alone, [RR = 0.67; 95% CI: 0.51~0.87; P = 0.002]; The decrease in length of ICU-stay [MD = -1.82; 95% CI: -2.60~-1.04; P<0.00001]; Acute physiology and chronic health evaluation system (APACHE II) score [MD = -2.95; 95% CI: -3.99~-1.91; P<0.00001]; Serum inflammatory factors concentration after treatment [SMD = -0.50; 95% CI:-0.68~-0.33; P<0.00001], including TNF-α [SMD = -0.61; 95% CI: -0.85~-0.38; P<0.00001] and IL-6 [SMD = -0.40; 95% CI: -0.75~-0.04; P = 0.03] in subgroup analysis all had statistical significance. CONCLUSION: Addition of TCM has better effects in participants with sepsis, while more high-quality studies are needed to draw firm conclusion.

Involvement of Spinal Bv8/Prokineticin 2 in a Rat Model of Cancer-Induced Bone Pain.

Cancer-induced bone pain (CIBP) is seriously disruptive to the quality of life in cancer patients, and present therapies are limited. The Bv8/prokineticin 2, a new family of chemokines, has been demonstrated to be involved in inflammatory and neuropathic pain. However, whether it is involved in CIBP remains unclear. This study was designed to examine whether spinal Bv8 was involved in the development of CIBP in rats. A rat CIBP model was constructed by injecting Walker 256 carcinoma cells into the medullary cavity of rat tibia. Tibia inoculation with Walker 256 tumour cells resulted in the development of mechanical hyperalgesia. Compared with sham rats, spinal Bv8 mRNA and protein levels were markedly and time-dependently increased in CIBP rats. Intrathecal administration of Bv8 neutralizing antibody (5 ng) could markedly attenuate pain behaviour as well as up-regulation of spinal TNF-α expression at day 18 after inoculation. Intrathecal pre-treatment with synthetic Bv8 (50 pg) almost completely abolished these effects. These data suggested that spinal Bv8/prokineticin 2 participated in the development of CIBP. Targeting of spinal Bv8 might be a promising strategy for the management of cancer-induced bone pain.