PRMT3 methylates HIF-1α to enhance the vascular calcification induced by chronic kidney disease.

BACKGROUND: Medial vascular calcification is commonly identified in chronic kidney disease (CKD) patients and seriously affects the health and life quality of patients. This study aimed to investigate the effects of protein arginine methyltransferase 3 (PRMT3) on vascular calcification induced by CKD. METHODS: A mice model of CKD was established with a two-step diet containing high levels of calcium and phosphorus. Vascular smooth muscle cells (VSMCs) were subjected to ß-glycerophosphate (ß-GP) treatment to induce the osteogenic differentiation as an in vitro CKD model. RESULTS: PRMT3 was upregulated in VSMCs of medial artery of CKD mice and ß-GP-induced VSMCs. The inhibitor of PRMT3 (SGC707) alleviated the vascular calcification and inhibited the glycolysis of CKD mice. Knockdown of PRMT3 alleviated the ß-GP-induced osteogenic transfomation of VSMCs by the repression of glycolysis. Next, PRMT3 interacted with hypoxia-induced factor 1α (HIF-1α), and the knockdown of PRMT3 downregulated the protein expression of HIF-1α by weakening its methylation. Gain of HIF-1α reversed the PRMT3 depletion-induced suppression of osteogenic differentiation and glycolysis of VSMCs. CONCLUSION: The inhibitory role of PRMT3 depletion was at least mediated by the regulation of glycolysis upon repressing the methylation of HIF-1α.

mTOR inhibition suppresses Myc-driven polyposis by inducing immunogenic cell death.

Myc is a key driver of colorectal cancer initiation and progression, but remains a difficult drug target. In this study, we show that mTOR inhibition potently suppresses intestinal polyp formation, regresses established polyps, and prolongs lifespan of APCMin/+ mice. Everolimus in diet strongly reduces p-4EBP1, p-S6, and Myc levels, and induces apoptosis of cells with activated ß-catenin (p-S552) in the polyps on day 3. The cell death is accompanied by ER stress, activation of the extrinsic apoptotic pathway, innate immune cell recruitment, and followed by T-cell infiltration on day 14 persisting for months thereafter. These effects are absent in normal intestinal crypts with physiologic levels of Myc and a high rate of proliferation. Using normal human colonic epithelial cells, EIF4E S209A knockin and BID knockout mice, we found that local inflammation and antitumor efficacy of Everolimus requires Myc-dependent induction of ER stress and apoptosis. These findings demonstrate mTOR and deregulated Myc as a selective vulnerability of mutant APC-driven intestinal tumorigenesis, whose inhibition disrupts metabolic and immune adaptation and reactivates immune surveillance necessary for long-term tumor control.

Mitotic CDK1 and 4E-BP1 I: Loss of 4E-BP1 serine 82 phosphorylation promotes proliferative polycystic disease and lymphoma in aged or sublethally irradiated mice.

4E-BP1 is a tumor suppressor regulating cap-dependent translation that is in turn controlled by mechanistic target of rapamycin (mTOR) or cyclin-dependent kinase 1 (CDK1) phosphorylation. 4E-BP1 serine 82 (S82) is phosphorylated by CDK1, but not mTOR, and the consequences of this mitosis-specific phosphorylation are unknown. Knock-in mice were generated with a single 4E-BP1 S82 alanine (S82A) substitution leaving other phosphorylation sites intact. S82A mice were fertile and exhibited no gross developmental or behavioral abnormalities, but the homozygotes developed diffuse and severe polycystic liver and kidney disease with aging, and lymphoid malignancies after irradiation. Sublethal irradiation caused immature T-cell lymphoma only in S82A mice while S82A homozygous mice have normal T-cell hematopoiesis before irradiation. Whole genome sequencing identified PTEN mutations in S82A lymphoma and impaired PTEN expression was verified in S82A lymphomas derived cell lines. Our study suggests that the absence of 4E-BP1S82 phosphorylation, a subtle change in 4E-BP1 phosphorylation, might predispose to polycystic proliferative disease and lymphoma under certain stressful circumstances, such as aging and irradiation.

Interactions between genetic variants and environmental risk factors are associated with the severity of pelvic organ prolapse.

OBJECTIVE: Both environmental and genetic risk factors contribute to pelvic organ prolapse (POP). No genome-wide study has investigated the gene-environment (G × E) interactions. In this study, we aim to identify single nucleotide polymorphisms (SNPs) that may interact with the potential environmental factors, maximum birth weight, and age in Chinese women. METHODS: We recruited 576 women for phase 1 and 264 women for phase 2 with stages III and IV prolapse from six geographic regions of China. Genomic DNAs from blood samples were genotyped using Affymetrix Axiom Genome-Wide CHB1 Array of 640,674 SNPs for phase 1 and Illumina Infinium Asian Screening Array of 743,722 SNPs for phase 2. Meta-analysis was used to combine the two results. Interactions of genetic variants with maximum birth weight and age on POP severity were identified. RESULTS: In phase 1, 502,283 SNPs in 523 women passed quality control and 450 women had complete POP-quantification measurements. In phase 2, 463,351 SNPs in 257 women passed quality control with complete POP-quantification measurements. Three SNPs rs76662748 ( WDR59 , Pmeta = 2.146 × 10 -8 ), rs149541061 ( 3p26.1 , Pmeta = 9.273 × 10 -9 ), and rs34503674 ( DOCK9 , Pmeta = 1.778 × 10 -9 ) respectively interacted with maximum birth weight, and two SNPs rs74065743 ( LINC01343 , Pmeta = 4.386 × 10 -8 ) and rs322376 ( NEURL1B - DUSP1 , Pmeta = 2.263 × 10 -8 ), respectively, interacted with age. The magnitude of disease severity associated with maximum birth weight and age differed according to genetic variants. CONCLUSIONS: This study provided preliminary evidence that interactions between genetic variants and environmental risk factors are associated with POP severity, suggesting the potential use of combining epidemiologic exposure data with selected genotyping for risk assessment and patient stratification.

Precise preparation of biomass-based porous carbon with pore structure-dependent VOCs adsorption/desorption performance by bacterial pretreatment and its forming process.

Pore distribution characteristic is one of the most crucial factors for porous adsorption materials, and the variety of volatile organic compounds (VOCs) approaches about how to simply and accurately tailor practical porous carbons for VOCs adsorption has gradually attracted attention. Here, precursors with different lignocellulose mass ratios have been used to produce porous carbon for model experiments to investigate the influence of the precursor lignocellulose contents on the pore structure and distribution characteristics of porous carbon, and the applicability of these mechanisms to real biomass materials has been further verified through bacteria-targeted bagasse decomposition: the microvolumes of ultra-micropores have decreased with decrease in cellulose contents, while mesopores have followed the reverse trend. The dynamic toluene adsorption/desorption performances of the obtained samples have been tested. The BACs-36 exhibits high toluene adsorption performance in low concentration with 635 mg/g while the BACs-48 shows excellent reusability in 10 times cycles. Based on this the balance between the adsorptive and regenerative capacities has been observed which indicates that carbon materials with abundant micropores and narrow mesopores have much better adsorption performance than porous carbon with a hierarchical pore structure, while the latter show better regeneration abilities than the former, which resulting in less desorption as a counter-acting force at the pore wall. Furthermore, the porous carbon has been shaped by one-step co-pyrolysis method using phenolic resin, which can not only maintain the hardness but also can avoid pore plugging phenomenon.

The main effect and gene-environment interaction effect of the ADCYAP1R1 polymorphism rs2267735 on the course of posttraumatic stress disorder symptoms-A longitudinal analysis.

Background: Many studies have been performed to investigate the association between the ADCYAP1R1 polymorphism rs2267735 and posttraumatic stress disorder (PTSD), but the results have been inconsistent, and the way in which this gene affects the course of PTSD has not been widely investigated. Thus, a longitudinal study of the course (development trajectory) of PTSD is needed. Methods: In this study, we performed a longitudinal analysis of rs2267735 in 1017 young, trauma-exposed Chinese people (549 females and 468 males, ranging from 7 to 11 years old). At four time points after trauma exposure (2.5, 3.5, 4.5, and 5.5 years), we measured PTSD symptoms with the University of California, Los Angeles PTSD Reaction Index (PTSD-RI) for DSM-IV (Child Version). We employed a latent growth model (LGM) for the longitudinal data to test the association between rs2267735 (main and gene-environment interaction effects) and the course of PTSD symptoms. Results: The results of LGM showed that the gene-environment interaction (rs2267735 × trauma exposure) effects were associated with PTSD symptoms in girls at 2.5 years (ß = -0.291 and P = 0.013 for LGM intercept). The gene-environment interaction (rs2267735 × trauma exposure) effect was also correlated with PTSD symptoms in girls at 3.5 and 4.5 years (ß = -0.264 and P = 0.005; ß = -0.217 and P = 0.013). Conclusion: Our study revealed that the gene-environment interaction of the ADCYAP1R1 polymorphism rs2267735 is associated with PTSD symptoms in girls at 2.5 years and that the effects may be stable over time and not related to the PTSD symptom recovery rate. This is the first study to detect the how the ADCYAP1R1 gene affects the course of PTSD after trauma exposure in a longitudinal view.

Verification of combustion rate of recovery and counting efficiency in the analysis of organically bound tritium in biota samples.

The analysis procedure of five biota samples's organically bound tritium (OBT) based on oxidation combustion and liquid scintillation counter (LSC) measurement was established. The combustion experiment under one atmospheric pressure in the presence of Pt-Al2O3 catalyst were carried out. The experiment results shown that the combustion recovery of five samples ranged from 86.4 % to 91.1 %, the combustion recovery of glucose monohydrate is about 93.7 %, which indicate that combustion recovery of biota samples differed from one species to another. Meanwhile, The counting efficiency of quenching agents CH3NO2 and CCl4 decreases from 20.3 % to 0 and from 19.3 % to 0 respectively as the quench agent mass increases from 10 µL to 500 µL. The counting efficiency of quenching agent HNO3 decreases from 22.4 % to 14.6 % as the quench agent mass increases from 10 µL to 500 µL. The SQP (E) value of CH3NO2 and CCl4 decreases as the mass of quenching agents increases, while the SQP (E) value of HNO3 increases as the quench agent mass increases. The SQP(E) of three tested quench agents ranges from 401.8 to 738.4, which covers the SQP(E) range of all the monitored biota samples in recent years. Therefore, the mapped curves and fixed equations are applicable. In addition, comparison experiment of four biota samples between two laboratories shown a relative deviation from 1.2 % to 12.8 %.

In Silico Prediction and Validation of CB2 Allosteric Binding Sites to Aid the Design of Allosteric Modulators.

Although the 3D structures of active and inactive cannabinoid receptors type 2 (CB2) are available, neither the X-ray crystal nor the cryo-EM structure of CB2-orthosteric ligand-modulator has been resolved, prohibiting the drug discovery and development of CB2 allosteric modulators (AMs). In the present work, we mainly focused on investigating the potential allosteric binding site(s) of CB2. We applied different algorithms or tools to predict the potential allosteric binding sites of CB2 with the existing agonists. Seven potential allosteric sites can be observed for either CB2-CP55940 or CB2-WIN 55,212-2 complex, among which sites B, C, G and K are supported by the reported 3D structures of Class A GPCRs coupled with AMs. Applying our novel algorithm toolset-MCCS, we docked three known AMs of CB2 including Ec2la (C-2), trans-ß-caryophyllene (TBC) and cannabidiol (CBD) to each site for further comparisons and quantified the potential binding residues in each allosteric binding site. Sequentially, we selected the most promising binding pose of C-2 in five allosteric sites to conduct the molecular dynamics (MD) simulations. Based on the results of docking studies and MD simulations, we suggest that site H is the most promising allosteric binding site. We plan to conduct bio-assay validations in the future.

Interferon b drives intestinal regeneration after radiation.

The cGAS-STING cytosolic DNA sensing pathway is critical for host defense. Here, we report that cGAS-STING­dependent type 1 interferon (IFN) response drives intestinal regeneration and animal recovery from radiation injury. STING deficiency has no effect on radiation-induced DNA damage or crypt apoptosis but abrogates epithelial IFN-ß production, local inflammation, innate transcriptional response, and subsequent crypt regeneration. cGAS KO, IFNAR1 KO, or CCR2 KO also abrogates radiation-induced acute crypt inflammation and regeneration. Impaired intestinal regeneration and survival in STING-deficient mice are fully rescued by a single IFN-ß treatment given 48 hours after irradiation but not by wild-type (WT) bone marrow. IFN-ß treatment remarkably improves the survival of WT mice and Lgr5+ stem cell regeneration through elevated compensatory proliferation and more rapid DNA damage removal. Our findings support that inducible IFN-ß production in the niche couples ISC injury and regeneration and its potential use to treat acute radiation injury.

Dexmedetomidine Reduces the Lidocaine-Induced Neurotoxicity by Inhibiting Inflammasome Activation and Reducing Pyroptosis in Rats.

Local anesthetic toxicity is closely related to neuronal death and activation of the inflammatory response. Dexmedetomidine (Dex) is an adrenergic α2 receptor agonist that can reduce the neurotoxicity induced by lidocaine. It also has anti-inflammatory effects. However, the mechanism underlying the neuroprotective effects of Dex against lidocaine-induced toxicity remains to be defined. We hypothesized that Dex exerts its neural protective effect through inhibiting inflammasome activation and through anti-pyroptosis effects against local anesthetic-induced nerve injury. In a rat model of lidocaine-induced spinal cord injury, we studied the protective effect of Dex on lidocaine-induced changes in spinal cord function, inflammasome formation and pyroptosis, pro-inflammatory cytokine expression, and protein kinase C (PKC)-δ phosphorylation. Dex reduced lidocaine-induced neurotoxicity and inhibited PKC-δ phosphorylation in the spinal cord of rats. Furthermore, Dex inhibited pyroptosis and inflammasome formation (caspase-1, NLRP3, and apoptosis-associated speck-like protein (ASC)). Finally, Dex attenuated interleukin (IL)-1ß and IL-18 expression, as well as microglia response. In conclusion, Dex can reduce the severity of lidocaine-induced spinal cord injury in rats by inhibiting priming and inflammasome activation and reducing pyroptosis via PKC-δ phosphorylation.

The ADCYAP1R1 Gene Is Correlated With Posttraumatic Stress Disorder Symptoms Through Diverse Epistases in a Traumatized Chinese Population.

The adenylate cyclase activating polypeptide 1 (pituitary) receptor (ADCYAP1R1) gene is associated with the hypothalamic-pituitary-adrenal (HPA) axis, which controls stress responses. The single-nucleotide polymorphism of ADCYAP1R1, rs2267735, has been investigated in many studies to test its association with posttraumatic stress disorder (PTSD), but the results have not been consistent. It is worth systematically exploring the role of rs2267735 in PTSD development. In this study, we analyzed rs2267735 in 1,132 trauma-exposed Chinese individuals (772 females and 360 males). We utilized the PTSD checklist for DSM-5 (PCL-5) to measure the PTSD symptoms. Then, we analyzed the main, G × E (rs2267735 × trauma exposure), and G × G (with other HPA axis gene polymorphisms) effects of rs2267735 on PTSD severity (total symptoms). There were no significant main or G × E effects (P > 0.05). The G × G ADCYAP1R1-FKBP5 interaction (rs2267735 × rs1360780) was associated with PTSD severity (beta = -1.31 and P = 0.049) based on all subjects, and the G × G ADCYAP1R1-CRHR1 interaction (rs2267735 × rs242924) was correlated with PTSD severity in men (beta = -4.72 and P = 0.023). Our study indicated that the ADCYAP1R1 polymorphism rs2267735 may affect PTSD development through diverse gene-gene interactions.

Fibrin Glue-Kartogenin Complex Promotes the Regeneration of the Tendon-Bone Interface in Rotator Cuff Injury.

OBJECTIVE: Rotator cuff injury healing is problematic because the tendon-bone junction often forms cicatricial tissues, rather than fibrocartilage, which leads to mechanical impairment and is prone to redamage. Kartogenin (KGN) is a newly discovered small molecule compound which can induce cartilage formation through chondrogenesis of endogenous mesenchymal stem cells. METHODS: In this study, we used KGN with fibrin glue (FG) to repair the rotator cuff injury by promoting the formation of fibrocartilage at the tendon to bone interface. Firstly, we assessed the release rate of KGN from the FG-KGN complex and then created a rabbit rotator cuff tendon graft-bone tunnel model. The rabbits received saline, FG-KGN, or FG injections onto the tendon to bone interface after injury. Shoulder tissues were harvested at 6 and 12 weeks, and the sections were stained with HE and Safranin O/Fast green. The samples were assessed by histologic evaluation and biomechanical testing. Synovial mesenchymal stem cells derived from the synovial tissue around the rotator cuff were harvested for western blotting and qRT-PCR analysis. RESULTS: KGN was released rapidly from the FG-KGN complex during first 4 hrs and followed by a slow release until 7 days. The tendon graft-bone interface in the control (saline) group and the FG group was filled with scar tissue, rather than cartilage-like tissue, and only a small number of chondrocytes were found at the adjacent bone surface. In the FG-KGN group, the tendon to bone interface was fully integrated and populated by chondrocytes with proteoglycan deposition, indicating the formation of fibrocartilage-like tissues. At 12 weeks, the maximum tensile strength of the FG-KGN group was significantly higher than that of the FG and control groups (P < 0.01). The RNA expression levels of tendinous genes such as Tenascin C and the chondrogenic gene Sox-9 were substantially elevated in SMSCs treated with the FG-KGN complex compared to the other two groups. CONCLUSION: These results indicated that fibrin glue is an effective carrier for KGN, allowing for the sustained release of KGN. The FG-KGN complex could effectively promote the regeneration and formation of fibrocartilage tissue of the tendon-bone interface in the rabbit rotator cuff tendon graft-bone tunnel model.

Extracellular HMGB-1 activates inflammatory signaling in tendon cells and tissues.

BACKGROUND: Increasing evidence indicates that secretion of high mobility group box 1 protein (HMGB-1) is functionally associated with tendinopathy development. However, the underlying effect and mechanism of extracellular HMGB-1 on tendon cells are unclear. METHODS: We tested the effect of exogenous HMGB-1 on cell growth, migration, and inflammatory signaling responses with isolated rat Achilles tendon cells. Also, we studied the role of extracellular HMGB-1, when administrated alone or in combination with mechanical overloading induced by intensive treadmill running (ITR), in stimulating inflammatory effects in tendon tissues. RESULTS: By using in vitro and in vivo models, we show for the first time that exogenous HMGB-1 dose-dependently induces inflammatory reactions in tendon cells and tendon tissue. Extracellular HMGB-1 promoted redistribution of HMGB-1 from the nucleus to the cytoplasm, and activated canonical nuclear factor kappa B (NF-κB) signaling and mitogen-activated protein kinase (MAPK) signaling. Short-term administration of HMGB-1 induced hyper-cellularity of rat Achilles tendon tissues, accompanied with enhanced immune cell infiltration. Additional ITR to HMGB-1 treatment worsens these responses, and application of HMGB-1 specific inhibitor glycyrrhizin (GL) completely abolishes such inflammatory effects in tendon tissues. CONCLUSION: Collectively, these results confirm that HMGB-1 plays key roles in the induction of tendinopathy. Our findings improve the understanding of the molecular and cellular mechanisms during tendinopathy development, and provide essential information for potential targeted treatments of tendinopathy.

300 kV/6 mA integrated Cockcroft-Walton high voltage power supply for a compact neutron generator.

A high voltage power supply system for a compact neutron generator is developed. A four-stage symmetrical Cockcroft-Walton voltage multiplier circuit is adopted to produce 300 kV direct current high voltage. A two-stage 360 kV isolation transformer system is used to drive the ion source power supply. The high voltage power supply and the isolation transformer system are integrated in an epoxy bucket with a size of ϕ360 × 700 containing No. 25 transformer oil. The maximum output voltage of the power supply can reach 300 kV. The variation in the high voltage power supply is less than 0.5% when the power supply works at 300 kV/6 mA with an input voltage variation of ±8%. Meanwhile, the isolation transformer system can withstand more than 360 kV, with its output power being about 2.5 kW. No overvoltage protection devices are used in the power supply, and the protection resistors are connected in series to two pairs of rectifiers at the highest and lowest potential terminals and to the output terminal of the voltage multiplier to prevent overcurrent.

Anesthesia management in neonatal congenital bronchobiliary fistula: case report and literature review.

BACKGROUND: There is very little published literature and none that discussed care in a neonate regarding anesthetic risk and management of neonate with congenital bronchobiliary fistula during thoracoscopy and thoracotomy. This article analyzes related risk factors and literature review from perioperative ventilation, circulation and other aspects of management. CASE PRESENTATION: A neonate diagnosed as congenital bronchobiliary fistula combined with severe chemical pneumonia, consolidation of the lungs, and infection was facing the risk of anaesthesia under thoracoscopy exploration surgery, who experiened more than 20 days diagnostic period before operation. Many risk factors have led to conversion from minimally invasive surgery to thoracotomy, including persistent hypoxemia, hypercapnia, difficult surgical exposure and extremly difficulty of intraoperative ventilation management. Anesthesia maintenance after conversion to open access remained problematic. Fortunately the patient showed no sign of any adverse CNS effects after 4 months of follow-up. CONCLUSIONS: The most prominent anesthesia challenges are hypoxemia, increased airway resistance, impaired ventilation, and the risk of metabolic acidosis. Close cooperation among the entire neonatal medical team is the key factors in successful management of this rare case.

A study of self-magnetic insulated ion beam diode with liquid anode.

An experimental study of the semi-cylindrical self-magnetic insulated diode with No. 25 transformer oil and methyl silicone oil filled into stainless steel metal foam as anode discharging materials is carried out for the first time. The results show that the lifetime of this type of ion beam diode is about 3000 discharges, significantly higher than that of the conventional solid-film ion beam diode, which is about 400 discharges. Meanwhile, the ion beam current density of transformer oil and methyl silicone oil is higher than the polyethylene film, and the maximum ion beam current density of No. 25 transformer oil and methyl silicone oil is 330 A/cm2 and 250 A/cm2, respectively. In addition, the ion beam current density of No. 25 transformer oil and methyl silicone oil is more stable than that of the polyethylene film.

Magnetically insulated transmission lines in the form of cone with ribs: Exploratory design and analysis.

This paper numerically confirms that in the ideal case, the form of cone with 16 ribs benefits the reduction in impedance and the promotion (about 20%-30%) on transmission efficiency of a magnetically insulated transmission line, in comparison with the traditional form of cone. Magnetically insulated transmission lines in the form of cone, cone with 4, 8, 12, and 16 ribs, are first designed by using CREO and then imported to COMSOL for obtainment of their circuit parameters. Two codes based on the wave process and wave process coupled with RLC circuits, respectively, simulating the propagation of external waves through non-uniform transmission lines are analyzed and presented in detail. The obtained parameters are then used in these codes for deriving the designed transmission lines' transmission efficiency of peak power. As a comparison, the obtained data are also employed in PSpice for derivation of the transmission efficiency. These derived results consistently verify that the form cone with ribs may effectively promote the transmission efficiency of magnetically insulated transmission lines.

Enhanced degradation of triclosan by cobalt manganese spinel-type oxide activated peroxymonosulfate oxidation process via sulfate radicals and singlet oxygen: Mechanisms and intermediates identification.

Spinel is a kind of desirable catalyst to activate peroxymonosulfate (PMS) for chemical oxidation of organic contaminants in wastewater treatment. However, apart from classic sulfate radical based AOPs (SR-AOPs), the generation and oxidative pathways of singlet oxygen (1O2) by Co/Mn spinels have been little explored in PMS catalysis. In this study, spinel-type oxide Co2Mn1O4 was successfully synthesized, and used as highly effective catalyst in PMS activation for heterogeneous degradation of TCS (up to 96.4% within 30 min) at initial pH of 6.8, which was also slightly impacted by coexisting ions. Based on radical scavengers and electron paramagnetic resonance (EPR) experiments, sulfate radicals and singlet oxygen (1O2) were unveiled to be the dominant reactive oxygen species (ROS) in Co2Mn1O4/PMS system. Co2Mn1O4 catalyst exhibited reversible redox properties based on the results of cyclic voltammetry (CV). More importantly, the generation of 1O2 might not only promote the TCS removal rate directly, but also facilitate the metal redox cycle in spinel structure in Co2Mn1O4/PMS system. Finally, degradation pathways of TCS in Co2Mn1O4/PMS system were proposed, which involved the breakage of ether bond and cycloaddition reaction.

HMGB1 mediates the development of tendinopathy due to mechanical overloading.

Mechanical overloading is a major cause of tendinopathy, but the underlying pathogenesis of tendinopathy is unclear. Here we report that high mobility group box1 (HMGB1) is released to the tendon extracellular matrix and initiates an inflammatory cascade in response to mechanical overloading in a mouse model. Moreover, administration of glycyrrhizin (GL), a naturally occurring triterpene and a specific inhibitor of HMGB1, inhibits the tendon's inflammatory reactions. Also, while prolonged mechanical overloading in the form of long-term intensive treadmill running induces Achilles tendinopathy in mice, administration of GL completely blocks the tendinopathy development. Additionally, mechanical overloading of tendon cells in vitro induces HMGB1 release to the extracellular milieu, thereby eliciting inflammatory and catabolic responses as marked by increased production of prostaglandin E2 (PGE2) and matrix metalloproteinase-3 (MMP-3) in tendon cells. Application of GL abolishes the cellular inflammatory/catabolic responses. Collectively, these findings point to HMGB1 as a key molecule that is responsible for the induction of tendinopathy due to mechanical overloading placed on the tendon.

Efficacy of CT Guided Pulsed Radiofrequency Treatment for Trigeminal Postherpetic Neuralgia.

OBJECTIVES: Trigeminal postherpetic neuralgia (TPHN) often presents with moderate to severe pain, hyperalgesia, and allodynia. Conventional analgesic treatments are poorly effective, which seriously affects the quality of life. This retrospective study aimed to evaluate the efficacy of pulsed radiofrequency (PRF) for the treatment of TPHN. METHODS: A total of 90 TPHN patients were selected between January 2014 and December 2016 in the Department of Pain Management, Shengjing Hospital, China Medical University. Patients were randomly divided into two groups according to the order of enrollment (n = 45 per group): group A, peripheral nerve (supraorbital nerve, infraorbital nerve and mental nerve) PRF; group B, gasserian ganglion PRF. Follow-up assessments of visual analogue scale (VAS) pain assessment, SF-36 health status questionnaire, total efficiency rate, and drug dosage of anticonvulsants and opioid analgesics were performed at time points of 1 week, 1 month, 3 months, 6 months, and 1 year after surgery. RESULTS: At each postsurgery time point, the VAS decreased, SF-36 (physical and mental components) increased, and drug dosage of anticonvulsants and opioids analgesics decreased in both treatment groups; values at each time point were significantly different from presurgery values (P < 0.05). Compared with group A, VAS decreased, SF-36 increased, and dosage of anticonvulsants and opioids analgesics decreased significantly in group B (P < 0.05). The total efficiency rates one year after surgery in group A and group B were 68.9 and 86.7%, respectively. The total efficiency rate of group B was statistically higher than that of group A (P < 0.05). CONCLUSION: PRF relieved TPHN, and gasserian ganglion PRF was more effective than peripheral nerve PRF. The method was effective and improved the quality of life of the patients. PRF is recommended as a treatment for TPHN.