The risk of hepatitis C virus recurrence in hepatitis C virus-infected patients treated with direct-acting antivirals after achieving a sustained virological response: A comprehensive analysis.

BACKGROUND & AIMS: The risk for hepatitis C virus (HCV) recurrence persists after HCV eradication with direct-acting antivirals (DAAs), particularly in patients with ongoing high-risk behaviours. Our aim was to assess the risk of HCV recurrence (late relapse and/or reinfection) post-sustained virological response (SVR). METHODS: We searched the literature for studies reporting HCV recurrence rates post-SVR in PubMed, Web of Science and the Cochrane Library. Identified publications were divided into groups based on patient risk for HCV reinfection: low-risk HCV mono-infection, high-risk HCV mono-infection and a human immunodeficiency virus (HIV)/HCV coinfection. The HCV recurrence rate for each study was calculated by using events divided by the person-years of follow-up (PYFU). HCV recurrence was defined as confirmed, detectable HCV RNA post-SVR. RESULTS: In the 16 studies of low-risk patients, the pooled recurrence rate was 0.89/1000 PYFU (95% confidence interval [CI], 0.16-2.03). For the 19 studies of high-risk patients, the pooled recurrence rate was 29.37/1000 PYFU (95% CI, 15.54-46.91). For the eight studies of HIV/HCV-coinfected patients, the pooled recurrence rate was 23.25/1000 PYFU (95% CI, 4.24-53.39). The higher pooled estimates of recurrence in the high-risk and HIV/HCV-coinfected populations were predominantly driven by an increase in reinfection rather than late relapse. CONCLUSIONS: The HCV recurrence risk after achieving SVR with all-oral DAAs therapy is low, and the risk of HCV recurrence in high-risk and HIV/HCV-coinfected populations was driven by an increase in reinfection rather than late relapse.

Incidence and risk factors of chronic pain following hysterectomy among Southern Jiangsu Chinese Women.

BACKGROUND: Chronic post-surgical pain (CPSP) after hysterectomy has been recognized as a major clinical problem in the Western World. Reports on post-hysterectomy pain are relatively scarce in China. The aim of the current study was to prospectively investigate the incidence and the potential risk factors of CPSP at 3 months following hysterectomy in Chinese population. METHODS: We assessed and collected data on preoperative socio-demographic characteristics, preexisting pain, anxiety and depression, sexual satisfaction, intra-operative variables, and acute postoperative pain intensity in a cohort of 870 women undergoing hysterectomy. The participants were interviewed to determine their suitability to diagnostic criteria of CPSP 3 months later. Logistic regression analyses were subsequently performed to identify predictors for CPSP. RESULTS: The incidence of CPSP at 3 months after hysterectomy was 27.7%. Most of the women with CPSP suffered from mild pain and had a slight impact on daily life with sleep and emotion functional limitation. Risk factors for CPSP after hysterectomy were preoperative anxiety, depression, pelvic pain, preexisting pain, very-moderate sexual dissatisfaction, and acute postoperative pain at movement. Intra-operative dexmedetomidine infusion with 0.5 µg/kg/h was associated with a decreased incidence rate of chronic post-hysterectomy pain. CONCLUSION: Twenty-eight percent of patients after hysterectomy in southern Jiangsu china had CPSP with 92% of those women describing it as mild with sleep and emotion functional limitation. Patients with preoperative anxiety and depression, poor sexual satisfaction, preexisting pain, and acute postoperative pain on movement have been identified to be at risk to develop CPSP.

Sevoflurane preconditioning attenuates the fall in adenosine triphosphate levels, but does not alter the changes in sodium and potassium levels during hypoxia in rat hippocampal slices.

BACKGROUND: Sevoflurane preconditioning improves recovery after hypoxia. Sevoflurane administered before and during hypoxia improved recovery and attenuated the changes in intracellular sodium, potassium, and adenosine triphosphate (ATP) levels during hypoxia. In this study, the authors examine the effects of sevoflurane applied only before hypoxia on sodium, potassium, and ATP. METHODS: Hippocampal slices from adult male Sprague-Dawley rats were pretreated with 4% sevoflurane, washed, and then subjected to hypoxia (n≥8 animals/group). The cornus ammonis 1 regions of the hippocampal slices were micro-dissected and sodium, potassium, and ATP concentrations measured. RESULTS: Pretreatment with sevoflurane for 15 or 60 min did not attenuate the increase in intracellular sodium or the decrease in intracellular potassium during hypoxia. After 60 min of preconditioning and 5 min of hypoxia, sodium increased 57% (vs. nonpreconditioned hypoxia 54% increase) and potassium decreased 31% (vs. 26%). These changes were not statistically significant versus untreated hypoxia. The 60-min sevoflurane preconditioning group had statistically significant higher ATP levels at 5 min of hypoxia (3.8 nmol/mg dry wt.) when compared to untreated hypoxic tissue (2.1 nmol/mg). There was no significant difference in ATP levels between the sevoflurane preconditioned and the untreated tissue before hypoxia (8.9 vs. 8.5 nmoles/mg, respectively). CONCLUSION: Preconditioning with sevoflurane for 60 min before hypoxia does not alter changes in intracellular sodium and potassium during hypoxia but does attenuate the fall in intracellular ATP levels during hypoxia. Thus, there are differences between anesthetic preconditioning and when anesthetics are present before and during hypoxia.

High expression of ADAM8 correlates with poor prognosis in hepatocellular carcinoma.

OBJECTIVES: To evaluate the association between ADAM8 tissue expression and patient prognosis in hepatocellular carcinoma (HCC). METHODS: ADAM8 expression was analyzed using immunohistochemical staining methods on tissue samples from a consecutive series of 105 HCC patients who underwent resections between 2000 and 2006. The correlation of ADAM8 expression and patients' clinicopathological parameters was evaluated. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. RESULTS: ADAM8 was highly expressed in 54.3% of the HCC patients. The ADAM8 expression level was closely associated with serum AFP elevation, tumor size, histological differentiation, tumor recurrence, tumor metastasis, and tumor stage. Kaplan-Meier survival analysis showed that a high expression level of ADAM8 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that ADAM8 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. CONCLUSIONS: These findings provide evidence that a high expression level of ADAM8 serves as a biomarker for poor prognosis for HCC. Thus, we speculate that ADAM8 may be a potential target of antiangiogenic therapy for HCC.

High RIN1 expression is associated with poor prognosis in patients with gastric adenocarcinoma.

The aim of this study was to investigate the expression and prognostic significance of RIN1 in gastric adenocarcinoma. RIN1 expression was analyzed using quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemical staining on tissue samples from a consecutive series of 315 gastric adenocarcinoma patients who underwent tumor resections between 2003 and 2006. The relationship between RIN1 expression, clinicopathological factors, and patient survival was investigated. qRT-PCR results showed that the RIN1 mRNA expression was higher in tumor tissue samples than in the adjacent normal tissues, and a corresponding increase in protein expression was confirmed by Western blotting. Immunohistochemical staining indicated that RIN1 is highly expressed in 54.3 % of gastric adenocarcinomas. RIN1 expression levels were closely associated with tumor size, histological differentiation, tumor stage, and lymph node involvement. Kaplan-Meier survival analysis showed that high RIN1 expression exhibited a significant correlation with poor prognosis for gastric adenocarcinoma patients. Multivariate analysis revealed that RIN1 expression is an independent prognostic parameter for the overall survival rate of gastric adenocarcinoma patients. Our data suggest that RIN1 plays an important role in gastric adenocarcinoma progression and that a high RIN1 expression predicts an unfavorable prognosis in gastric adenocarcinoma patients.

PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma.

BACKGROUND: Prenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC). METHODS: The expression of PRAF3 mRNA and protein in primary ESCC and the matched normal tissues (57cases) was determined by quantitative RT-PCR and Western blot. Immunohistochemical analysis of PRAF3 expression was carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The role of PRAF3 in apoptosis, migration and invasion was studied in ESCC cell lines of Eca109 and TE-1 through the adenovirus mediated PRAF3 gene transfer. The effect of PRAF3 on apoptosis was analyzed by annexin V-FITC assay. The regulation of PRAF3 on migration was determined by transwell and wounding healing assay, while the cellular invasion was analyzed by matrigel-coated transwell assay. RESULTS: We found that the expression of PRAF3 was significantly down-regulated in ESCC tissue compared with the matched normal tissue and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, overexpression of PRAF3 induced cell apoptosis through both caspase-8 and caspase-9 dependent pathways, and inhibited cell migration and invasion by suppressing the activity of both MMP-2 and MMP-9 in human ESCC cell lines. CONCLUSIONS: Our data suggest that PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC.

Downregulation of JWA expression in human esophageal squamous cell carcinoma and its clinical significance.

JWA is involved in the regulation of many cellular processes. Recent studies have indicated a potential role for altered JWA expression and function in tumor development and progression. The purpose of this study was to investigate the expression and prognostic significance of JWA in human esophageal squamous cell carcinoma (ESCC). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot assays were performed to detect the expression of JWA mRNA or protein in paired sample tissues from 20 ESCC patients. Expression levels of JWA protein in archival 292 formalin-fixed, paraffin-embedded specimens were also analyzed by immunohistochemistry. Finally, the correlation between JWA expression, clinicopathological factors, and patient survival was evaluated. RT-qPCR results showed that the levels of JWA mRNA were significantly lower in tumor tissue specimens than in the matched nontumor tissues. This finding was supported by Western blot analysis. Immunohistochemical staining data indicated that JWA protein level was correlated closely with the tumor cell differentiation, tumor invasion, lymph node metastasis, and distant metastasis. Kaplan-Meier survival analysis showed that low expression level of JWA resulted in a significantly poor prognosis of ESCC patients. Cox regression analysis revealed that the JWA expression level was an independent prognostic parameter for the overall survival rate of ESCC patients. In conclusion, our data suggest that JWA plays an important role in the occurrence and progress of human ESCC and that high expression level of JWA may predict a favorable prognosis in ESCC patients.

Intranasal sufentanil combined with intranasal dexmedetomidine: A promising method for non-anesthesiologist sedation during endoscopic ultrasonography.

Intranasal sufentanil combined with intranasal dexmedetomidine exhibited an estimated sedation success probability as high as 94.9%, higher satisfaction scores, and only minor adverse events during endoscopic ultrasonography (EUS). This is a promising method for EUS sedation that does not require the presence of an anesthesiologist.

Genetic Variants in KIR/HLA-C Genes Are Associated With the Susceptibility to HCV Infection in a High-Risk Chinese Population.

Background: KIR/HLA-C signaling pathway influences the innate immune response which is the first defense to hepatitis C virus (HCV) infection. The aim of this study was to determine the association between the genetic polymorphisms of KIR/HLA-C genes and the outcomes of HCV infection in a high-risk Chinese population. Methods: In this case-control study, four single nucleotide polymorphisms (SNPs) of KIR/HLA-C genes (KIR2DS4/KIR2DS1/KIR2DL1 rs35440472, HLA-C rs2308557, HLA-C rs1130838, and HLA-C rs2524094) were genotyped by TaqMan assay among drug users and hemodialysis (HD) patients including 1,378 uninfected control cases, 307 subjects with spontaneous viral clearance, and 217 patients with persistent HCV infection. Bioinformatics analysis was used to functionally annotate the SNPs. Results: After logistic regression analysis, the rs35440472-A and rs1130838-A alleles were found to be associated with a significantly elevated risk of HCV infection (OR = 1.562, 95% CI: 1.229-1.987, P < 0.001; OR = 2.134, 95% CI: 1.180-3.858, P = 0.012, respectively), which remained significant after Bonferroni correction (0.05/4). The combined effect of their risk alleles and risk genotypes (rs35440472-AA and rs1130838-AA) were linked to the increased risk of HCV infection in a locus-dosage manner (all Ptrend < 0.001). Based on the SNPinfo web server, rs35440472 was predicted to be a transcription factor binding site (TFBS) while rs1130838 was predicted to have a splicing (ESE or ESS) function. Conclusion: KIR2DS4/KIR2DS1/KIR2DL1 rs35440472-A and HLA-C rs1130838-A variants are associated with increased susceptibility to HCV infection in a high-risk Chinese population.

High SVR12 With 8-Week Course of Direct-Acting Antivirals in Adolescents and Children With Chronic Hepatitis C: A Comprehensive Analysis.

Direct-acting antiviral (DAA) treatment for 8 weeks has a sustained virological response rate in adults with chronic hepatitis C. We have conducted a systematic review and meta-analysis to compare the efficacy and safety of the 8-week vs. 12/24-week DAA treatment in adolescents and children with CHC. The PubMed, Web of Science, and Cochrane databases were searched for the relevant articles from January 1, 2017 to August 28, 2020 and further screened for literature reviews on April 1, 2021. Pool proportions with 95% CIs for SVR12 were summarized with fixed/random effects models using Freeman-Tukey double arcsine transformation. Subgroup analysis was used to explore the source of heterogeneity. Thirty-six relevant publications were identified. For adolescents aged 12-17 years old, the pooled SVR12 and AE rate were 99.4% (95% CI: 98.7-99.9) and 34.7% (95% CI: 31.9-37.6). No one discontinued treatment due to drug intolerance. In addition, the SVR12 adolescents treated for 12 and 8/24 weeks were 99.3% (95% CI: 98.4-99.9) and 100%, respectively. The pooled SVR12 rate, AEs, and SAEs for children younger than 12 years were 98.9% (95% CI: 97.3-99.8), 51.6% (95% CI: 47.0-56.2), and 1.1% (95% CI: 0.4-2.5), respectively. The most common AE was fatigue (28.4%). The SVR12 was 98.8% (95% CI: 97.1-99.8) and 100% for the pediatric patients treated for 12 weeks and 8/24 weeks, respectively. Taken together, DAAs are generally effective against CHC and well-tolerated by the adolescents and children. A treatment duration of 8 weeks is equally effective and safe as 12/24 weeks in this demographic group.

Genetic Variants in TNFSF4 and TNFSF8 Are Associated With the Risk of HCV Infection Among Chinese High-Risk Population.

BACKGROUND: The tumor necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) play important roles in the immune responses to infections. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several TNFSF/TNFRSF genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population. METHODS: The TNFSF4-rs1234313, TNFSF4-rs7514229, TNFSF8-rs3181366, TNFSF8-rs2295800, TNFRSF8-rs2298209, and TNFRSF8-rs2230625 SNPs were genotyped in 2309 uninfected controls, 597 subjects with spontaneous HCV clearance and 784 patients with persistent HCV infection using the TaqMan-MGB assay. The putative functions of the positive SNPs were determined using online bioinformatics tools. RESULTS: After adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), IL28B-rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection (all P FDR < 0.05). Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2-4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele (all P < 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles (P trend < 0.001). In silico analysis showed that rs7514229, rs3181366, and rs2295800 polymorphisms may affect the transcription of mRNA by regulating miRNA binding, TF binding, and promoter activation, respectively, which may have biological consequences. CONCLUSION: TNFSF4-rs7514229, TNFSF8-rs3181366, and TNFSF8-rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.

Thiourea-Grafted Graphite Felts as Positive Electrode for Vanadium Redox Flow Battery.

In this paper, thiourea was successfully grafted onto the surface of acid preprocessed graphite felts [sulfuric acid-treated graphite felt (SA-GFs)] by thiol-carboxylic acid esterification. The thiourea-grafted graphite felts (TG-GFs) were investigated as the positive electrode for vanadium redox flow battery (VRFB). X-ray photoelectron spectroscopy results suggested that thiourea was grafted into the surface of graphite felts. The cyclic voltammetry showed that the peak potential separation decreased by 0.2 V, and peak currents were greatly enhanced on TG-GF electrode compared with SA-GF electrode, implying improved electro-catalytic activity and reversibility of TG-GF electrode toward VO2+/ VO 2 + redox reaction. The initial capacity of TG-GF-based cell reached 55.6 mA h at 100 mA cm-2, 22.6 mA h larger than that of SA-GF-based cell. The voltage and energy efficiency for TG-GF-based cell increased by 4.9% and 4.4% compared with those of SA-GF-based cell at 100 mA cm-2, respectively.

Quantum Dots-Based Point-of-Care Measurement of Procalcitonin in Finger-Prick Blood and Venous Whole Blood Specimens.

OBJECTIVE: To determine whether the performance of a new quantum dots-based point-of-care test (POCT) devices is qualified for procalcitonin testing. METHODS: Finger-prick and venous blood specimens from 153 patients were measured with a quantum dots-based POCT device; the results were compared with those from the reference method. RESULTS: The quantum dots-based POCT device correlated well with the reference method in measuring plasma, venous whole blood, and finger-prick blood. No significant bias was observed (-0.08 ng/mL). At 0.5 ng per mL cutoff value, the concordances were 96.6%, 94.6%, and 90.5% for plasma, venous whole blood, and finger-prick blood, respectively. And at 2 ng per mL cutoff value, the concordances were 98.0%, 96.6%, and 95.3%, respectively. CONCLUSIONS: The quantum dots-based POCT device measured procalcitonin with multiple specimen types, high sensitivity, wide detection range, and short turnaround time. It would allow a more widespread use of procalcitonin and help lessen the burden of overcrowding in healthcare facilities in China.

Efficacy and Safety of Glecaprevir/Pibrentasvir in HCV Patients With Previous Direct-Acting Antiviral Therapy Failures: A Meta-Analysis.

Background: Since a greater number of hepatitis C virus (HCV) patients have access to direct-acting antiviral (DAA) based therapies, the number of patients not properly responding to prior DAA regimens is increasing. The objective of this comprehensive analysis was to assess the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in HCV patients who experienced previous DAA therapy failures. Methods: Bibliographic databases were systematically searched for relevant articles published by November 2020. The main endpoints were sustained viral response after 12 weeks (SVR12), adverse events (AEs; any grade) and severe adverse events (SAEs). Publication bias assessment was performed using funnel plots and the Egger's test. Results: Fourteen studies consisting of a total of 1,294 subjects were included in this study and the pooled estimate of SVR12, AEs and SAEs rates were 96.8% (95%CI: 95.1-98.2), 47.1% (95%CI: 26.0-69.3), and 1.8% (95%CI: 0.7-3.4), respectively. Subgroup analysis showed that pooled SVR12 rates were 97.9% (95%CI: 96.7-98.9) for Japan and 91.1% (95%CI: 87.3-94.3) for the United States; 95.8% (95%CI: 93.9-97.4) for genotype (GT)1 and 100.0% (95%CI: 99.6-100.0) for GT2; 95.3% (95%CI: 92.4-97.2) for cirrhosis and 96.3% (95%CI: 94.2-97.7) for non-cirrhosis cases. There was no publication bias included this study. Conclusion: This comprehensive analysis revealed that GLE/PIB is an effective and secure retreatment option for patients who did not optimally respond to DAA treatment, especially the Asian population with GT1-2.

Effect of ultrasound-guided proximal and distal approach for obturator nerve block in transurethral resection of bladder cancer under spinal anesthesia.

Background: Ultrasound-guided proximal or distal approach for obturator nerve block is preformed to prevent adductor muscle spasm during transurethral resection of bladder tumors. The aim of the study was to compare the effectiveness of two different techniques in blocking the obturator nerve during transurethral resection of a bladder tumor. Methods: Fifty obturator nerve blocks were performed for transurethral bladder tumor resection and divided into two groups. One group received ultrasound-guided proximal obturator nerve block approach (proximal group), and the other group received ultrasound-guided distal obturator nerve block approach (distal group). Grade of adductor muscle spasm, the rate of clinical effectiveness, duration of block procedure, and complications were recorded. Patients with grade two adductor spasms were transferred to general anesthesia. Results: Two patients in the distal group and one in the proximal group were transferred to general anesthesia for severe adductor muscle spasms. No difference was found in clinical effectiveness rate of obturator nerve block between the two groups. differed insignificantly. The number of patients who had no adductor muscle spasms in the proximal group was significantly higher than that of the distal group. Vascular puncture was detected in two patients in the proximal group and one patient in the distil group. No other complications were observed. Conclusion: No difference was found for clinical effectiveness between the two groups. However, vascular puncture should receive more attention.

GdPO4-Based Nanoprobe for Bioimaging and Selective Recognition of Dipicolinic Acid and Cysteine by a Sensing Ensemble Approach.

Multiple functions incorporated in one single-component nanoplatform pave the way for important biomedicine applications. Herein, a multifunctional terbium-doped gadolinium orthophosphate (GdPO4:Tb-EDTA) nanoplatform was prepared through a simple, ecofriendly, one-step hydrothermal method. Results showed that dipicolinic acid (DPA), the biomarker of bacterial spores, significantly increased the fluorescence intensity of this nanoplatform and conferred it with rapid response and excellent selectivity. Subsequently, the fluorescence of the ensemble GdPO4:Tb-EDTA-DPA can be remarkably quenched by Cu2+, which led to a rewritable nanosensor used in the detection of cysteine (Cys) with excellent sensitivity. In addition, GdPO4:Tb-EDTA can also be a potential T1-weighted magnetic resonance imaging (MRI) contrast agent, which indicated a satisfactory in vitro MRI with r1 relaxivity values of 13.9 mM-1 s-1 and in vivo MRI through intravenous administration on a rat model. Overall, the proposed assay may have great theoretical and practical significance for designing multifunctional biomaterials.

Long non-coding RNA DANCR promotes the progression of non-small-cell lung cancer by inhibiting p21 expression.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in human cancers. However, the functional roles of lncRNAs in non-small-cell lung cancer (NSCLC) and the underlying mechanisms are not well understood. METHODS: We examined the expression of lncRNA DANCR in NSCLC by qRT-PCR and explored its biological roles in NSCLC progression by cell and molecular biology studies. RESULTS: DANCR expression level was increased in human NSCLC. The knockdown of DANCR inhibited NSCLC cell proliferation by inducing cell apoptosis and cell cycle arrest. In addition, DANCR knockdown suppressed NSCLC cell migration and invasion via inhibition of epithelial-mesenchymal transition (EMT). On the contrary, DANCR overexpression had the opposite effects. DANCR knockdown inhibited EZH-2-mediated epigenetic silencing of p21 promoter and increased p21 expression. Moreover, DANCR knockdown inhibited NSCLC cell proliferation, migration, and invasion in a p21-dependent manner. CONCLUSION: DANCR plays oncogenic roles in NSCLC and may provide a novel biomarker for NSCLC diagnosis and prognosis.

Evidence that inhibition of spinal nitric oxide production contributes to the antinociceptive effects of emulsified isoflurane on formalin-induced pain in rats.

The aim of the present study was to investigate the contribution of spinal nitric oxide (NO) to the antinociceptive effects of emulsified isofluane in rats. The formalin test was used to assess nociceptive responses. Immunocytochemistry and histochemistry were performed to determine the effects of emulsified isoflurane on formalin-induced changes in Fos-like immunoreactive (Fos-LI)- and nicotinamide adenine dinucleotide phosphatediaphorase (NADPH-d)-positive neurons, respectively. The results showed that emulsified isofluane, administered intraperitoneally, significantly decreased the formalin-induced paw licking time and that this was attenuated by pretreatment with intrathecal injection of the NO precursor L-arginine. Furthermore, Fos-LI- and NADPH-d-positive neurons were mainly found in the ipsilateral dorsal horn after injection of formalin, some of which were Fos-LI/NADPH-d double-labelled neurons. Administration of emulsified isofluane significantly decreased Fos-LI- and NADPH-d-positive, as well as Fos-LI/NADPH-d double-labelled, neurons. Finally, emulsified isofluane produced a significant reduction of NOS activity and a decrease of NO production in the spinal cord of formalin-treated rats. In conclusion, the results suggest that inhibition of spinal NO production contributes to the antinociceptive effects of emulsified isofluane on formalin-induced pain in rats.

A novel visual ratiometric fluorescent sensing platform for highly-sensitive visual detection of tetracyclines by a lanthanide- functionalized palygorskite nanomaterial.

A palygorskite (Pal)-based ratiometric fluorescent nanoprobe is designed in order to establish a real time, on-site visual, and highly sensitive detection method for tetracyclines (TCs). The nanoprobe comprises the green emissive dye molecules embedded in the natural Pal, which serve as the internal reference signal. The potential red-emissive seed-europium (Eu3+) ions are covalently bound on the surface of modified Pal, and they can act as the specific recognition element. The emission intensity of Eu3+ ions significantly increases upon TC addition. The nanoprobe fluorescence changes from green to yellow, orange, or red, thereby accomplishing the visual ratiometric fluorescent detection. This nanoprobe exhibits a high sensitivity with a detection limit of 7.1nM and an excellent selectivity in monitoring the levels of TCs in milk samples. In addition, this nanoprobe is useful for quantitative determination of TCs, and it is not affected with intensity fluctuations due to instrumental or environmental factors. The nanoprobe-immobilized test paper realizes real-time TCs analysis by using a smartphone with an easy-to-access color-scanning APP as the detection platform. Moreover, the reported construction of visual ratiometric detection system follows the sustainable development idea, that is, from nature, for nature, and into the nature.

Involvement of local orphanin FQ in the development of analgesic tolerance induced by morphine microinjections into the dorsal raphe nucleus of rats.

It is well known that dorsal raphe nucleus (DRN) is one of the key structures for the development of opioid analgesia and tolerance. An increased activity of 'antiopioids' like orphanin-FQ (OFQ) has been proposed as a possible mechanism for opioid tolerance. The present study evaluates the role of DRN-located OFQ in the opioid analgesic tolerance induced by repeated microinjections of morphine (MOR) into DRN. Male rats were implanted with chronic guide cannulae aimed at the DRN. Microinjection of MOR (0.5 microg in 0.5 microl) into DRN caused antinociception as quantified with the tail flick and the hot plate tests. When MOR microinjection was repeated twice daily, the antinociceptive effect disappeared within 2 days (tolerance). However, if each MOR microinjection was preceded (within 15 min) by a microinjection of the OFQ receptor antagonist nocistatin (NST) (1 ng in 0.5 microl) into the same DRN site, the microinjections of MOR always produced antinociception and did not induce tolerance. If NST microinjections were suspended, subsequent MOR microinjections induced tolerance. In MOR-tolerant rats, a single NST microinjection into the same DRN site was enough to restore the antinociceptive effect of MOR. On the other hand, if OFQ (1 ng in 0.5 microl) was microinjected into DRN, then MOR microinjection administered 15 min later into the same DRN site did not elicit antinociception. Finally, opioid tolerance induced by repeated systemic MOR injections (5 mg/kg, i.p.) was reversed by a single microinjection of NST into DRN. This emphasizes the central importance of DRN-located OFQ in the MOR analgesic tolerance.