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Pyroptosis is a type of programmed cell death, displaying caspase-1-dependent and pro-inflammatory features. Purinergic 2X4 (P2X4 ) receptor activation in response to high-adenosine triphosphate release can induce inflammation. Envelope glycoprotein 120 (gp120) of human immunodeficiency virus type 1 is considered one of the primary pathogens leading to neuronal injury. In this study, we investigated the possible role of P2X4 receptor activation in gp120-triggered pyroptosis in cultured satellite glial cells (SGCs) of rat dorsal root ganglia (DRG). MTS assay, TdT-mediated dUTP Nick-end labeling assay, real-time RT-PCR, and western blotting et al. methods were used. The results indicated that the expression of P2X4 receptor in SGCs of DRG was up-regulated upon cultured with gp120 for 24 h. The highest decrease in viability of SGCs due to gp120 treatment was accompanied by marked increases of positive pyroptosis cells and cellular lactate dehydrogenase release, elevated levels of interleukin-1β, interleukin-18, active caspase-1 and NOD-like receptor family, pyrin domain containing 1, and enhanced phosphorylation of p38MAPK. These abnormal changes because of gp120 were significantly inhibited and cell viability was markedly improved when SGCs of DRG were treated with short hairpin RNAs targeting P2X4 receptor. Our data suggest that silencing of P2X4 receptor may act effectively against gp120-induced pyroptosis mediated by the activation of NOD-like receptor family, pyrin domain containing 1 inflammasome and caspase-1 signaling in SGCs of DRG.

Diabetes mellitus (DM) is considered the primary cause of neuropathic pain. Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin) is a component extracted from Cnidium monnieri (L.) cusson plant seeds and has anti-inflammatory and anti-oxidative properties. The aim of the present study was to investigate the effects of osthole on diabetic neuropathic pain (DNP) involving the P2X4 receptor on satellite glial cells (SGCs) in the dorsal root ganglia (DRG) of type 2 diabetic rats. These data showed that the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in DM rats were lower than those in control rats. MWT and TWL in DM rats treated with osthole were higher compared with those in untreated DM rats. The expression levels of P2X4 mRNA and protein in the DRG of DM rats were higher compared with those in the control rats, while those in DM rats treated with osthole were significantly lower compared with those in the untreated DM rats. Osthole treatment decreased the co-expression levels of P2X4 and glial fibrillary acidic protein (GFAP) and reduced the up-regulated expression of interleukin-1 beta (IL-1β), tumour necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and phosphorylated-p38MAPK and enhanced the down-regulation of IL-10 in DM rats. Thus, osthole treatment may act on the P2X4 receptor to alleviate the mechanical and thermal hyperalgesia in DM rats.

The upregulation of nociceptive ion channels expressed in dorsal root ganglia (DRG) contributes to the development and retaining of diabetic pain symptoms. The flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) is a component extracted from various fruits and vegetables and exerts anti-inflammatory, analgesic, anticarcinogenic, antiulcer, and antihypertensive effects. However, the exact mechanism underlying quercetin's analgesic action remains poorly understood. The aim of this study was to investigate the effects of quercetin on diabetic neuropathic pain related to the P2X4 receptor in the DRG of type 2 diabetic rat model. Our data showed that both mechanical withdrawal threshold and thermal withdrawal latency in diabetic rats treated with quercetin were higher compared with those in untreated diabetic rats. The expression levels of P2X4 messenger RNA and protein in the DRG of diabetic rats were increased compared with the control rats, while quercetin treatment significantly inhibited such enhanced P2X4 expression in diabetic rats. The satellite glial cells (SGCs) enwrap the neuronal soma in the DRG. Quercetin treatment also lowered the elevated coexpression of P2X4 and glial fibrillary acidic protein (a marker of SGCs) and decreased the upregulation of phosphorylated p38 mitogen-activated protein kinase (p38MAPK) in the DRG of diabetic rats. Quercetin significantly reduced the P2X4 agonist adenosine triphosphate-activated currents in HEK293 cells transfected with P2X4 receptors. Thus, our data demonstrate that quercetin may decrease the upregulation of the P2X4 receptor in DRG SGCs, and consequently inhibit P2X4 receptor-mediated p38MAPK activation to relieve the mechanical and thermal hyperalgesia in diabetic rats.

Diabetic neuropathic pain is a common complication of type 2 diabetes mellitus (DM). Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in neuropathic pain through the release of proinflammatory cytokines. The P2Y12 receptor is expressed in SGCs of the DRG. In this study, our aim was to investigate the role of the P2Y12 receptor on the pathological changes in diabetic neuropathic pain. The present study showed that diabetic neuropathic pain increased mechanical and thermal hyperalgesia in type 2 DM model rats. The results showed that the expression levels of P2Y12 messenger RNA (mRNA) and protein in DRG SGCs were increased in DM model rats compared with control rats. Glial fibrillary acidic protein (GFAP) and interleukin-1β (IL-1β) expression levels in the DRG were increased in DM rats. Upregulation of GFAP is a marker of SGC activation. Targeting the P2Y12 receptor by short hairpin RNA (shRNA) decreased the upregulated expression of P2Y12 mRNA and protein, coexpression of P2Y12 and GFAP, the expression of GFAP, IL-1β, and tumor necrosis factor-receptor 1 in the DRG of DM rats, and relieved mechanical and thermal hyperalgesia in DM rats. After treatment with the P2Y12 receptor shRNA, the enhancing integrated OPTICAL density (IOD) ratios of p-P38 MAPK to P38 mitogen activated protein kinase (MAPK) in the DM rats treated with P2Y12 shRNA were significantly lower than that in the untreated DM rats. Therefore, P2Y12 shRNA treatment decreased SGC activation to relieve mechanical and thermal hyperalgesia in DM rats.

Human immunodeficiency virus (HIV) envelope glycoprotein (glycoprotein 120, gp120) can induce chronic neuropathic pain by directly stimulating primary sensory afferent neurons. Activation of satellite glial cells (SGCs) in dorsal root ganglia (DRG) plays an important role in the transmission of neuropathic pain. The P2Y12 receptor is expressed in SGCs of DRG. In this study, we investigated the role of the P2Y12 receptor in HIV gp120-induced neuropathic pain. The results showed that peripheral nerve exposure to HIV gp120 increased mechanical and thermal hyperalgesia in gp120-treated model rats. The gp120 treatment increased the expression of P2Y12 mRNA and protein in DRG SGCs. Treatment with P2Y12 short hairpin RNA (shRNA) in DRG SGCs decreased the upregulated expression of P2Y12 mRNA and protein in DRG SGCs as well as relieved mechanical and thermal hyperalgesia in gp120-treated rats. Reduction of P2Y12 receptor decreased co-expression of P2Y12 and glial fibrillary acidic protein (GFAP), expression of GFAP, interleukin (IL)-1β, tumor necrosis factor (TNF)-receptor 1 (TNF-R1), and phosphorylation of Akt (p-Akt) proteins in DRG of gp120-treated rats. Upregulation of GFAP is a marker of SGC activation. Therefore, P2Y12 shRNA treatment decreased HIV gp120-induced mechanical and thermal hyperalgesia in gp120-treated rats.

The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2′,3′-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIV-gp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca2+]i activated by the P2Y12 receptor agonist 2-(Methylthio) adenosine 5′-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y12 receptor shRNA treatment inhibited 2-MeSADP-induced [Ca2+]i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y12 receptor in DRG SGCs reduced the release of pro-inflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

Superior cervical ganglia (SCG) innervate the myocardium and participate in sympathoexcitatory transmission. P2Y12 receptor is expressed in satellite glial cells (SGCs). This study seeks to clarify whether the P2Y12 receptor is involved in the sympathoexcitation reflex after myocardial ischemia (MI). MI model was induced by occlusion of the left coronary artery. P2Y12 were assayed by real time PCR and Western blotting. Our results showed that expression levels of P2Y12 mRNA and protein were significantly higher in the MI group than in the sham group. Administration of P2Y12 short hairpin RNA (shRNA) caused downregulation of the P2Y12 receptor in the SCG. In MI rats plus P2Y12 shRNA treatment group, the abnormal changes in diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR), electrocardiograms (ECGs), and cardiac tissue structures were alleviated. When the treatment of P2Y12 shRNA in MI rats, upregulated co-expression values of P2Y12 and glial fibrillary acidic protein (GFAP), the upregulation of tumor necrosis factor α (TNF-α) and phosphorylated P38 mitogen activated protein kinase (p-P38 MAPK) in the SCG were decreased. Downregulation of the P2Y12 receptor in the SCG after MI may improve cardiac function by alleviating the sympathoexcitatory reflex.

HIV-1 envelope glycoprotein (Glycoprotein 120, gp120) can directly stimulate primary sensory afferent neurons and cause chronic neuropathic pain. The P2X3 receptor in the dorsal root ganglia (DRG) is associated with the transmission of neuropathic pain. Curcumin isolated from the herb Curcuma rhizome has anti-inflammatory and anti-tumor effects. The water solubility, targeting and bioavailability of curcumin can be improved by nanoparticle encapsulation. In this study, we sought to explore the effects of nanoparticle-encapsulated curcumin (nano curcumin) on HIV-gp120-induced neuropathic pain mediated by the P2X3 receptor in DRG neurons. The results showed that mechanical and thermal hyperalgesia in rats treated with gp120 were increased compared to those in the control group. The expression levels of P2X3 mRNA and protein in rats treated with gp120 were higher than those in the control group. Nano curcumin treatment decreased mechanical hyperalgesia and thermal hyperalgesia and upregulated the expression levels of P2X3 mRNA and protein in rats treated with gp120. Nano curcumin treatment also reduced the ERK1/2 phosphorylation levels in gp120-treated rat DRG. In addition, P2X3 agonist α,β-methylene ATP (α,β-meATP)-induced currents in DRG neurons cultured with gp120 significantly decreased after co-treatment with nano curcumin. Therefore, nano curcumin treatment may inhibit P2X3 activation, decrease the sensitizing DRG primary afferents and relieve mechanical hyperalgesia and thermal hyperalgesia in gp120-treated rats.

The P2X7 receptor mediates afferent nerve activation and is related to chronic neuropathic pain. Resveratrol (RES) has also been reported to exhibit anti-inflammatory effects. In this study, we investigated the neuroprotective effect of RES on the transmission of neuropathic pain mediated by the P2X7 receptor. The P2X7 mRNA and protein expression levels in L4-L5 dorsal root ganglia (DRG)s of the chronic constriction injury (CCI) group were significantly higher than those observed in the Ctrl + NS, Sham + RES and Sham groups. RES increased the threshold of thermal and mechanical hypersensitivity in rats with chronic neuropathic pain. The P2X7 mRNA and protein expression levels in the CCI + RES group were decreased compared with those in the CCI group. Our results showed that RES inhibited the upregulated co-expression of P2X7 and glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in satellite glial cells of DRG in the CCI group. The results demonstrated that the expression of GFAP was increased in the CCI group and that RES inhibited the upregulated expression of GFAP in the rats in the CCI group. In addition, the phosphorylation levels of p38 and extracellular regulated protein kinases (ERK)1/2 in the CCI group were markedly higher than those observed in the Ctrl + NS, Sham + RES and Sham groups, whereas the phosphorylation levels of p38 and ERK1/2 in CCI + RES group were markedly lower than those observed in the CCI group. RES inhibited BzATP-activated currents in DRG non-neurons in the CCI rats. Our data provide evidence that RES may suppress the transmission of neuropathic pain mediated by the P2X7 receptor in the satellite glial cells of dorsal root ganglia.

Type 2 diabetes mellitus (T2DM) accounts for more than 90% of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. Sinomenine is a natural bioactive component extracted from the Sinomenium acutum and has anti-inflammatory effects. The aim of our study was to investigate the effects of sinomenine on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with sinomenine were higher compared with those in T2DM rats. The expression levels of the P2X3 protein and mRNA in T2DM rat DRG were higher compared with those of the control, while those in T2DM rats treated with sinomenine were significantly lower compared with those of the T2DM rats. Sinomenine significantly inhibited P2X3 agonist ATP-activated currents in HEK293 cells transfected with the P2X3 receptor. Sinomenine decreased the phosphorylation and activation of P38MAPK in T2DM DRG. Therefore, sinomenine treatment may suppress the up-regulated expression and activation of the P2X3 receptor and relieve the hyperalgesia potentiated by the activation of P38MAPK in T2DM rats.

Diabetic cardiac autonomic neuropathy (DCAN) is a serious and common complication in diabetes mellitus (DM). Long noncoding RNAs (lncRNAs), an important class of regulatory molecules in diverse biological processes, have attracted considerable interest in DCAN. Our previous study has indicated a lncRNA, NONRATT021972 (NONCODE ID), was enhanced in sympathetic neuronal-like PC12 cells in the setting of high glucose (HG) and high FFAs (HF); its silence was found to significantly alleviate HGHF-induced tumor necrosis factor-α (TNF-α) release in PC12 cells. Here we further explore the effects of NONRATT021972 small interference RNA (siRNA) on heart rate variability (HRV) mediated by superior cervical ganglia (SCG) in diabetic rats and the possible mechanism underlying. We found an increment of NONRATT021972 in SCG of DM rats. Treatment of NONRATT021972 siRNA in DM rats decreased the elevated expression of TNF-α, blocked serine phosphorylation of insulin receptor substrate (IRS) 1 and increased the down-regulated expression of IRS1 in SCG. Meanwhile, NONRATT021972 siRNA rescued decreased HRV in DM rats. Therefore, inhibition of NONRATT021972 may serve as a novel therapeutic strategy for preventing the development of DCAN.

Pyroptosis is a type of programmed cell death, displaying caspase-1-dependent and pro-inflammatory features. Purinergic 2X

The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y

Diabetic autonomic neuropathy includes the sympathetic ganglionic dysfunction. P2X7 receptor in superior cervical ganglia (SCG) participated in the pathological changes of cardiac dysfunction. Abnormal expression of long noncoding RNAs (lncRNAs) was reported to be involved in nervous system diseases. Our preliminary results obtained from rat lncRNA array profiling revealed that the expression of the uc.48+ was significantly increased in the rat SCG in response to diabetic sympathetic pathology. In this study, we found that lncRNAuc.48+ and P2X7 receptor in the SCG were increased in type 2 diabetic rats and were associated with the cardiac dysfunction. The uc.48+ small interference RNA (siRNA) improved the cardiac autonomic dysfunction and decreased the up-regulation P2X7 and the ratio of phosphorylated extracellular regulated protein kinases1/2 (p-ERK1/2) to ERK1/2 in SCG of type 2 diabetic rats. In conclusion, lncRNA uc.48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats through regulating the expression of P2X7 and ERK signaling in SCG.

Insulin resistance and type 2 diabetes mellitus (T2DM) are highly prevalent around the world. Elevated concentrations of free fatty acids (FFAs) are closely related to insulin resistance and T2DM. P2X7 receptor is an ion channel gated by ATP, which is implicated in various scenarios including immune response, pain, and inflammation. In this study, we have explored whether P2X7 receptor is involved in pathological changes in human umbilical vein endothelial cells (HUVECs) induced by high FFA treatment, and the potential beneficial effects of evodiamine. Evodiamine could effectively suppress the enhanced expression of P2X7 receptor caused by high FFAs at both mRNA and protein levels. In addition, high FFA-induced cytotoxicity, the upregulated release of ATP, and production of reactive oxygen species (ROS) could be ameliorated by evodiamine in HUVECs. Evodiamine could also reverse the decreased NO formation and the increased adhesive events of immune cells at high FFAs. Moreover, evodiamine inhibited P2X7-dependent TNF-α expression and ERK 1/2 phosphorylation due to high FFAs. All these results indicated that evodiamine could correct the upregulated expression of P2X7 receptor induced under high FFA condition in HUVECs, and consequently suppressed oxidative stress and inflammatory responses.

Diabetes mellitus (DM) is considered the primary cause of neuropathic pain. Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin) is a component extracted from Cnidium monnieri (L.) cusson plant seeds and has anti-inflammatory and anti-oxidative properties. The aim of the present study was to investigate the effects of osthole on diabetic neuropathic pain (DNP) involving the P2X

The upregulation of nociceptive ion channels expressed in dorsal root ganglia (DRG) contributes to the development and retaining of diabetic pain symptoms. The flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) is a component extracted from various fruits and vegetables and exerts anti-inflammatory, analgesic, anticarcinogenic, antiulcer, and antihypertensive effects. However, the exact mechanism underlying quercetin's analgesic action remains poorly understood. The aim of this study was to investigate the effects of quercetin on diabetic neuropathic pain related to the P2X

Superior cervical ganglia (SCG) innervate the myocardium and participate in sympathoexcitatory transmission. P2Y

Human immunodeficiency virus (HIV) envelope glycoprotein (glycoprotein 120, gp120) can induce chronic neuropathic pain by directly stimulating primary sensory afferent neurons. Activation of satellite glial cells (SGCs) in dorsal root ganglia (DRG) plays an important role in the transmission of neuropathic pain. The P2Y

Background Chronic pain is a common symptom in human immunodeficiency virus (HIV)-1 infection/acquired immunodeficiency syndrome patients. The literature shows that the HIV envelope glycoprotein 120 (gp120) can directly cause hyperalgesia by stimulating primary sensory afferent nerves. The P2X7 receptor in the dorsal root ganglia (DRG) is closely related to neuropathic and inflammatory pain. In this study, we aimed to explore the effect of resveratrol (RES) on gp120-induced neuropathic pain that is mediated by the P2X7 receptor in the rat DRG. Results Mechanical hyperalgesia in rats treated with gp120 was increased compared with that in the sham group. The P2X7 expression levels in rats treated with gp120 were higher than those in the sham group. Co-localization of the P2X7 receptor and glial fibrillary acidic protein (GFAP, a marker of satellite glial cells [SGCs]) in the DRG SGCs of the gp120 group exhibited more intense staining than that of the sham group. RES decreased the mechanical hyperalgesia and P2X7 expression levels in gp120 treatment rats. Co-localization of the P2X7 receptor and GFAP in the gp120+ RES group was significantly decreased compared to the gp120 group. RES decreased the IL-1β and TNF-α receptor (R) expression levels and ERK1/2 phosphorylation levels as well as increased IL-10 expression in the DRG of gp120-treated rats. Whole cell clamping demonstrated that RES significantly inhibited adenosine triphosphate-activated currents in HEK293 cells that were transfected with the P2X7 plasmid. Conclusions RES relieved mechanical hyperalgesia in gp120-treated rats by inhibiting the P2X7 receptor.

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). More than 90% of all cases of DM belong to type 2 diabetes mellitus (T2DM). Emodin is the main active component of Radix et rhizoma rhei and has anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects. Nanoparticle encapsulation of drugs is beneficial for drug targeting and bioavailability as well as for lowering drug toxicity side effects. The aim of this study was to investigate the effects of nanoparticle-encapsulated emodin (nano emodin) on diabetic neuropathic pain (DNP) mediated by the Purin 2X3 (P2X3) receptor in the dorsal root ganglia (DRG). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with nano emodin were higher compared with those in T2DM rats. Expression levels of P2X3 protein and messenger RNA (mRNA) in the DRG of T2DM rats were higher than those of controls, while levels in T2DM rats treated with nano emodin were significantly lower than those of the T2DM rats. Phosphorylation and activation of ERK1/2 in the T2DM DRG were decreased by nano emodin treatment. Nano emodin significantly inhibited currents activated by the P2X3 agonist α,β-meATP in HEK293 cells transfected with the P2X3 receptor. Therefore, nano emodin treatment may relieve DNP by decreasing excitatory transmission mediated by the DRG P2X3 receptor in T2DM rats.

HIV-1 envelope glycoprotein (Glycoprotein 120, gp120) can directly stimulate primary sensory afferent neurons and cause chronic neuropathic pain. The P2X

Hepatic glucokinase (GK) expression and activity are decreased in type 2 diabetes mellitus (T2DM), and glycogen synthase kinase-3 (GSK-3) inhibits the synthesis of GK. In hepatocytes, the activation of the protein kinase B (PKB/AKT) signaling pathway enhances GK expression and inhibits the phosphorylation of GSK-3β. The dysfunction of certain long noncoding RNAs (lncRNAs) has been associated with a variety of diseases.This study explored the effects of the lncRNA NONRATT021972 small interfering RNA (siRNA) on the dysfunction of hepatic GK through AKT signaling in T2DM rats.Livers from type 2 diabetic rats and hepatocytes cultured in high glucose and high fatty acid media were studied. The changes in expression of AKT, GK and GSK 3β were detected by western blotting or RT-PCR. The application of bioinformatics technology (CatRAPID) was used to identify the targets of NONRATT021972 RNA.We found that lncRNA NONRATT021972 levels in the liver were increased in type 2 diabetic rats, and the increase was associated with an increase in the blood glucose levels. The NONRATT021972 siRNA enhanced phospho-AKT (p-AKT) levels, GK expression and hepatic glycogen synthesis. This siRNA also reduced phospho-glycogen synthase kinase-3β (p-GSK-3β) levels and hyperglycemia in T2DM rats, as well as in hepatocytes cultured in high glucose media with fatty acids. CatRAPID predicted that there was the interaction between NONRATT021972 and p-AKT.LncRNA NONRATT021972 siRNA may have beneficial effects on T2DM.

Neuropathic pain is a type of chronic pain caused by nervous system damage and dysfunction. The pathogenesis of chronic pain is complicated, and there are no effective therapies for neuropathic pain. Studies show that the P2X

Glycoprotein 120 (gp120) is an HIV envelope glycoprotein. Gp120 can directly stimulate the primary sensory afferent neurons and cause hyperalgesia. The P2X

The P2X

A new analytical method was developed to simultaneously determine residues of 109 pesticides (including isomers) in the foods of animal origin. Acetonitrile was selected for accelerated solvent extraction (ASE) for effectively extracting the pesticides from the fatty samples. The cleanup was performed with an automated gel permeation chromatography (GPC) cleanup system. The prepared samples were analysed with GC–MS in the selected ion monitoring mode (SIM) using one target and two qualitative ions for each analyte. Chlorpyrifos-d10 was used as an internal standard. The lowest limit of detection was 0.3 μg kg−1 for some pesticides. The recoveries and relative standard deviations (RSDs) were checked by spiking untreated samples with pesticides at 0.05, 0.1 and 0.2 mg kg−1. The average recoveries of most pesticides were from 62.6% to 107.8%. The precision values expressed as RSD were all ⩽20.5% (n = 6). Good linearity (r ⩾ 0.99) was observed between 0.05 and 1.5 μg mL−1.

Purpose: Traumatic diaphragmatic rupture (TDR) needs early diagnosis and operation. However, the early diagnosis is usually difficult, especially in the patients without diaphragmatic hernia. The objective of this study was to explore the early diagnosis and treatment of TDR. Methods: Data of 256 patients with TDR treated in our department between 1994 and 2013 were analyzed retrospectively regarding to the diagnostic methods, percentage of preoperative judgment, incidence of diaphragmatic hernia, surgical procedures and outcome, etc. Two groups were set up according to the mechanism of injury (blunt or penetrating). Results: Of 256 patients with a mean age of 32.4 years (9e84), 218 were male. The average ISS was 26.9 (13e66); and shock rate was 62.9%. There were 104 blunt injuries and 152 penetrating injuries. Preoperatively diagnostic rate was 90.4% in blunt injuries and 80.3% in penetrating, respectively, P < 0.05. The incidence of diaphragmatic hernia was 94.2% in blunt and 15.1% in penetrating respectively, P < 0.005. Thoracotomy was performed in 62 cases, laparotomy in 153, thoracotomy plus laparotomy in 29, and combined thoraco-laparotomy in 12. Overall mortality rate was 12.5% with the average ISS of 41.8; and it was 21.2% in blunt injuries and 6.6% in penetrating, respectively, P < 0.005. The main causes of death were hemorrhage and sepsis. Conclusions: Diagnosis of blunt TDR can be easily obtained by radiograph or helical CT scan signs of diaphragmatic hernia. For penetrating TDR without hernia, “offside sign” is helpful as initial assessment. CT scan with coronal/sagittal reconstruction is an accurate technique for diagnosis. All TDR require operation. Penetrating injury has a relatively better prognosis.

Type 2 diabetes mellitus (T2DM) accounts for more than 90% of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. Sinomenine is a natural bioactive component extracted from the Sinomenium acutum and has anti-inflammatory effects. The aim of our study was to investigate the effects of sinomenine on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with sinomenine were higher compared with those in T2DM rats. The expression levels of the P2X3 protein and mRNA in T2DM rat DRG were higher compared with those of the control, while those in T2DM rats treated with sinomenine were significantly lower compared with those of the T2DM rats. Sinomenine significantly inhibited P2X3 agonist ATP-activated currents in HEK293 cells transfected with the P2X3 receptor. Sinomenine decreased the phosphorylation and activation of P38MAPK in T2DM DRG. Therefore, sinomenine treatment may suppress the up-regulated expression and activation of the P2X3 receptor and relieve the hyperalgesia potentiated by the activation of P38MAPK in T2DM rats.

BackgroundChronic pain is a common symptom in human immunodeficiency virus (HIV)-1 infection/acquired immunodeficiency syndrome patients. The literature shows that the HIV envelope glycoprotein 120...

A novel method has been developed for the rapid separation and determination of 7 nipagin ester preservatives in leather by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled with gel permeation chromatographic (GPC) clean-up. Nipagin ester preservatives in leather were extracted by ultrasonic extraction with methanol. The extract was dried by a rotavapor and purified by GPC, then redissolved in the solvent of methanol-water (1 : 1, v/v). The chromatographic analysis was performed on an Acquity UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 microm) with a gradient elution of methanol and water as the mobile phases. The analytes were detected by electrospray ionization (ESI) tandem mass spectrometry with multiple reaction monitoring (MRM) in negative ion mode. Good linearity (r0.99) was observed between 0.1 and 1.0 mg/L for all the analytes. The recoveries and relative standard deviations (RSDs) were checked by spiking samples with the 7 nipagin ester preservatives at the three levels of 0.5, 1.0 and 3.0 mg/kg. The average recoveries of the 7 nipagin ester preservatives were from (79.44 +/- 5.67)% to (98.07 +/- 9.50)%. The precision values expressed as RSD ranged from 4.24% to 14.00% (n = 6). The limits of detection were 4 -12 microg/kg and the limits of quantification were 13.2 - 39.6 microg/kg for the analytes. The method is simple, rapid, sensitive and accurate, and suitable for the quantitative determination and confirmation of 7 nipagin ester preservatives in leather.

Liver trauma, the main cause of death in patients suffering abdominal injury, remains an unresolved problem, especially in its most severe forms. The objective of this study was to probe effective surgical procedures and improve the outcome for patients with severe hepatic injury. A retrospective study of 348 patients with hepatic trauma seen in our institution during the past 12 years was carried out. Of these 348 patients, 259 (74.4%) underwent surgery. To manage severe liver trauma (American Association for the Surgery of Trauma grade III to grade V), procedures such as packing of the laceration with omentum, hepatectomy or direct control of bleeding vessels within the liver substance by means of the Pringle maneuver, selective hepatic artery ligation, retrohepatic caval repair with total hepatic vascular occlusion, and perihepatic packing were selected and combined based on the specific injury. In the 259 patients treated operatively, the survival rate was 86.9% (225/259); and 15 of 40 with retrohepatic venous injury (RHVI) were cured with the maximum blood transfusion of 60 units. In 42 patients treated by perihepatic packing, the bleeding was stopped in 20 of 25 (80%) with RHVI and in 14 of 17 (82%) without such injury ( p > 0.75). The percentage of failure of nonoperative management was 17.2% (17/99); and it was 46.7% (14/30) in patients with grade III-V injury. Death occurred in 3 (50%) of 6 failures of grade IV-V injury. The overall mortality rate was 11.8% (41/348), and 51% of the deaths were due to exsanguination. The results suggest that severe hepatic injuries, especially grade IV-V injuries, usually require surgical intervention; reasonable surgical procedures based on classification of liver trauma and combined application of techniques can increase the survival rate; and perihepatic packing is effective in dealing with RHVI.

To probe into effective surgical procedures and improve the outcome of treatment for patients with severe hepatic injury.A retrospective study involving 113 patients with severe hepatic trauma (AAST grade IV and V) during the past 12 years was carried out. Ninety-eight patients underwent surgical treatment. Surgical interventions including hepatectomy or direct control of bleeding vessels by finger fracture technique with Pringle maneuver, selective ligation of hepatic artery, retrohepatic caval repair with total hepatic vascular occlusion, and perihepatic packing were mainly used.In the 98 patients treated operatively, the survival rate was 69.4% (68/98). Among 40 patients with juxtahepatic venous injury (JHVI), 15 were cured with the maximum blood transfusion of 12,000 ml. Eight cases of Grade IV injury treated nonoperatively were cured. The percentage of failure of nonoperative management was 42.9% (6/14). The overall mortality rate was 32.7% (37/113), and 57% of the deaths were due to exsanguination.Reasonable surgical procedures based on classification of hepatic injuries can increase the survival rate of severe liver trauma. Accurate perihepatic packing is effective in dealing with JHVI.

A novel method has been developed for the rapid extraction and determination of eight defoliants including thidiazuron, butiphos, methabenzthiazuron, abscisic acid, carfentra-zone-ethyl, diuron, paraquat, and pyrithiobac-sodium in cotton by accelerated solvent extraction (ASE) coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The defoliants in cotton were extracted by ASE and the extracts were dried by a rotavapor, then redissolved in the solvents of acetonitrile and water (1:9, v/v). The chromatographic analysis was performed on an Acquity UPLC HSS T3 column (50 mmx 2. 1 mm, 1. 8 microm) by a gradient elution employing of acetonitrile and 0.05% (v/v) formic acid as mobile phases. The analytes were detected by electrospray ionization (ESI) tandem mass spectrometry with multiple reaction monitoring (MRM) in positive ion mode. Good linearities (r >0.99) were observed between 0. 01 and 0. 3 mg/L for all the compounds. The recoveries and relative standard deviations (RSDs) were obtained by spiking untreated samples with the eight defoliants at 0. 1, 0. 5 and 1.0 mg/kg. The average recoveries of the eight defoliants were from (84. 18 +/- 8.04)% to (95.99 +/- 6.76)%. The precision values expressed as RSDs were from 7. 04% to 10. 60% (n = 6). The limits of detection were 0. 8 - 29 microg/kg and the limits of quantification were 2.5 - 96 1/4g/kg for the analytes. The results ahowed that the method is simple, rapid, sensitive and accurate, and is suitable for the quantitative determination and confirmation of the eight defoliants in cotton.