简介：AbstractBackground:Pulsed radiofrequency (PRF), as a non-invasive treatment of neuropathic pain (NP), has been widely administered clinically. Previous studies have shown that PRF has the potential to improve hyperalgesia in animal models of NP. However, there have been few reports to clarify whether the mechanism of PRF treatment of NP involves intervention in the expression of substance P (SP). Therefore, this study administered PRF treatment to chronic constriction injury (CCI) model rats and observed the sciatic nerve mechanical pain threshold and SP expression in the spinal cord to explore the mechanism of PRF treatment.Methods:A total of 96 Sprague-Dawley rats were randomly divided into the sham-surgery-sham-treatment group (S-S group), the sham-surgery-PRF group (S-P group), the CCI-sham-treatment group (C-S group), and the CCI-PRF group (C-P group). The C-S group and the C-P group underwent sciatic nerve CCI, while the other groups received a sham operation. At 14 days after the operation, the C-P group and the S-P group were treated with PRF for 300 s. We recorded the hindpaw withdrawal threshold (HWT) and the thermal withdrawal latency (TWL) of rats in the various groups at baseline, before treatment (0 days), and at 1, 7, 14, and 28 days after treatment. L4 to L6 spinal cord tissues were taken before treatment (0 days) and 1, 7, 14, and 28 days after treatment. The transcription and translation of SP were measured by quantitative polymerase chain reaction and Western blotting, respectively.Results:The HWT and the TWL in the C-P group 28 days after PRF treatment were significantly higher than those in the C-S group (95% confidence interval [CI]: 5.84–19.50, P < 0.01; 95% CI: 2.58–8.69, P = 0.01). The expression of SP in the C-P group 28 days after PRF treatment was significantly lower than that in the C-S group (95% CI: 1.17–2.48, P < 0.01).Conclusions:PRF may alleviate CCI-induced NP by down-regulating the expression of SP in the spinal cord of CCI model rats.

简介：AbstractBackground:Dysuria is one of the main symptoms of genitourinary syndrome of menopause, which causes serious disruption to the normal life of peri-menopausal women. Studies have shown that it is related to decrease of detrusor contractile function, but the exact mechanism is still poorly understood. Previous results have suggested that the sphingosine-1-phosphate (S1P) pathway can regulate detrusor contraction, and this pathway is affected by estrogen in various tissues. However, how estrogen affects this pathway in the detrusor has not been investigated. In this study, we detected changes of the S1P/RhoA/Rho associated kinases (ROCK)/myosin light chain (MLC) pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.Methods:Thirty-six female Sprague-Dawley rats were randomly divided into SHAM (sham operation), OVX (ovariectomy), and E groups (ovariectomy + estrogen), with 12 rats in each group. We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting, respectively. We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay. Finally, we compared results between the groups with one-way analysis of variance.Results:The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased, as compared with SHAM group. The percent decreases of the components in the S1P pathway were as follows: sphingosine kinase 1 (mRNA: 39%, protein: 45%) (both P < 0.05), S1P (21.73 ± 1.09 nmol/g vs. 18.86 ± 0.69 nmol/g) (P < 0.05), and S1P receptor 2/3 (S1PR2/3) (mRNA: 25%, 27%, respectively) (P < 0.05). However, the protein expression levels of S1PR2/3 and the protein and mRNA levels of SphK2 and S1PR1 did not show significant differences between groups (P > 0.05). The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows: ROCK2 (protein: 41%, mRNA: 36%) (both P < 0.05), p-MYPT1 (protein: 54%) (P < 0.05), and p-MLC20 (protein: 47%) (P < 0.05), but there were no significant differences in the mRNA and protein levels of RhoA, ROCK1, MYPT1, and MLC20 (all P > 0.05). In addition, all of the above-mentioned decreases could be reversed after estrogen supplementation (E group vs. SHAM group) (all P > 0.05).Conclusion:In this study, we confirmed that ovariectomy is closely associated with the down-regulation of the S1P/RhoA/ROCK/MLC pathway in the rat detrusor, which may be one mechanism of dysuria caused by decreased contractile function of the female detrusor during peri-menopause.

简介：AbstractBackground:Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells.Methods:Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis.Results:MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P < 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs.Conclusion:MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.

简介：AbstractBackground:The programmed intermittent epidural bolus (PIEB) technique is widely used in labor analgesia, but the parameter settings of PIEB have not yet been standardized. We designed a study to identify the optimal interval duration for PIEB using 10 mL of ropivacaine 0.08% and sufentanyl 0.3 μg/mL, a regimen commonly used to control labor pain in China, to provide effective analgesia in 90% of women during the first stage of labor without breakthrough pain.Methods:We conducted a double-blind sequential allocation trial to obtain the effective interval 90% (EI90%) during the first stage of labor between April 2019 and May 2019. This study included the American Society of Anesthesiologists physical status II–III nulliparous parturients at term, who requested epidural analgesia. The bolus volume was fixed at 10 mL of ropivacaine 0.08% with sufentanyl 0.3 μg/mL. Participants were divided into four groups (groups 60, 50, 40, and 30) according to the PIEB intervals (60, 50, 40, and 30 min, respectively). The interval duration of the first parturient was set at 60 min and that of subsequent parturients varied according to a biased-coin design. The truncated Dixon and Mood method and the isotonic regression analysis method were used to estimate the EI90% and its 95% confidence intervals (CIs).Results:Forty-four women were enrolled in this study. The estimated optimal interval was 44.1 min (95% CI 41.7–46.5 min) and 39.5 min (95% CI 32.5–50.0 min), using the truncated Dixon and Mood method and isotonic regression analysis, respectively. The maximum sensory block level above T6 was in nearly 20% of parturients in group 30; however, 5.3%, 0%, and 0% of the parturients presented with sensory block level above T6 in groups 40, 50, and 60, respectively. There were no cases of hypotension and only one parturient complained of motor block.Conclusion:With a fixed 10 mL dose of ropivacaine 0.08% with sufentanyl 0.3 μg/mL, the optimal PIEB interval is about 42 min. Further studies are warranted to define the efficacy of this regimen throughout all stages of labor.Trial registration:Chinese Clinical Trial Registry, ChiCTR1900022199; http://www.chictr.org.cn/com/25/historyversionpuben. aspx?regno=ChiCTR1900022199.