Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Chromatin architecture of two different strains of Artemisia annua reveals the alterations in interaction and gene expression.

MAIN CONCLUSION: The hierarchical architecture of chromatins affects the gene expression level of glandular secreting trichomes and the artemisinin biosynthetic pathway-related genes, consequently bringing on huge differences in the content of artemisinin and its derivatives of A. annua. The plant of traditional Chinese medicine "Qinghao" is called Artemisia annua L. in Chinese Pharmacopoeia. High content and the total amount of artemisinin is the main goal of A. annua breeding, nevertheless, the change of chromatin organization during the artemisinin synthesis process has not been discovered yet. This study intended to find the roles of chromatin structure in the production of artemisinin through bioinformatics and experimental validation. Chromosome conformation capture analysis was used to scrutinize the interactions among chromosomes and categorize various scales of chromatin during artemisinin synthesis in A. annua. To confirm the effect of the changes in chromatin structure, Hi-C and RNA-sequencing were performed on two different strains to find the correlation between chromatin structure and gene expression levels on artemisinin synthesis progress and regulation. Our results revealed that the frequency of intra-chromosomal interactions was higher in the inter-chromosomal interactions between the root and leaves on a high artemisinin production strain (HAP) compared to a low artemisinin production strain (LAP). We found that compartmental transition was connected with interactions among different chromatins. Interestingly, glandular secreting trichomes (GSTs) and the artemisinin biosynthetic pathway (ABP) related genes were enriched in the areas which have the compartmental transition, reflecting the regulation of artemisinin synthesis. Topologically associated domain boundaries were associated with various distributions of genes and expression levels. Genes associated with ABP and GST in the adjacent loop were highly expressed, suggesting that epigenetic regulation plays an important role during artemisinin synthesis and glandular secreting trichomes production process. Chromatin structure could show an important status in the mechanisms of artemisinin synthesis process in A. annua.

Integrated transcriptome and proteome analysis provides new insights into camptothecin biosynthesis and regulation in Camptotheca acuminata.

Camptotheca acuminata Decne., the main source of camptothecin (CPT), has received increasing attention for its remarkable antitumor activity. Many CPT derivatives are clinically used as effective anticancer agents worldwide. However, their biosynthesis mechanism remains unclear, and uncovering this pathway would greatly facilitate development of alternative CPT production methods to replace current inefficient plant-derived ones. The expression of >30,000 genes was accurately quantified using unique molecular identifier RNA sequencing in 10 C. acuminata tissues, and 7854 proteins from five tissues were quantified with label-free quantitative proteomics. Fifteen full-length transcriptomes were sequenced with long-read Oxford Nanopore Technologies, and 5692 alternative splicing events were discovered among 4746 genes. Integrated transcriptome and proteome analysis provided novel insights into CPT biosynthesis and its hierarchical regulation. Five cytochrome P450s and three O-methyltransferases were considered as candidates involved in the biosynthesis of CPT and its derivatives, while 15 transcription factors potentially regulating CPT biosynthesis were screened. These findings provide important clues for elucidating the biosynthetic mechanisms of CPT and its derivatives and substantially contribute to the future production of these anticancer agents with synthetic biology. The generated large-scale multiomics data also provide valuable resources for investigating the functional genomics of the most important CPT-producing plant species-C. acuminata.

Effect of a carbohydrate-rich beverage on rate of cesarean delivery in primigravidae with epidural labor analgesia: a multicenter randomized trial.

BACKGROUND: Labor represents a period of significant physical activity. Inefficient energy supply may delay labor process and even lead to cesarean delivery. Herein we investigated whether ingestion of a carbohydrate-rich beverage could reduce cesarean delivery in laboring women with epidural analgesia. METHODS: This multicenter randomized trial was conducted in obstetrician-led maternity units of nine tertiary hospitals in China. Primigravidae with single term cephalic pregnancy who were preparing for vaginal birth under epidural analgesia were randomized to intake a carbohydrate-rich beverage or commercially available low-carbohydrate beverages during labor. The primary outcome was the rate of cesarean delivery. Secondary outcomes included maternal feeling of hunger, assessed with an 11-point scale where 0 indicated no hunger and 10 the most severe hunger, and maternal and neonatal blood glucose after childbirth. RESULTS: Between 17 January 2018 and 20 July 2018, 2008 women were enrolled and randomized, 1953 were included in the intention-to-treat analysis. The rate of cesarean delivery did not differ between the two groups (11.3% [111/982] with carbohydrate-rich beverage vs. 10.9% [106/971] with low-carbohydrate beverages; relative risk 1.04, 95% CI 0.81 to 1.33; p = 0.79). Women in the carbohydrate-rich beverage group had lower subjective hunger score (median 3 [interquartile range 2 to 5] vs. 4 [2 to 6]; median difference - 1; 95% CI - 1 to 0; p < 0.01); their neonates had less hypoglycemia (1.0% [10/968] vs. 2.3% [22/956]; relative risk 0.45; 95% CI 0.21 to 0.94; p = 0.03) when compared with those in the low-carbohydrate beverage group. They also had higher rates of maternal hyperglycemia (6.9% [67/965] vs. 1.9% [18/953]; p < 0.01) and neonatal hyperglycemia (9.2% [89/968] vs. 5.8% [55/956]; p < 0.01), but none required special treatment. CONCLUSIONS: For laboring primigravidae with epidural analgesia, ingestion of a carbohydrate-rich beverage compared with low-carbohydrate beverages did not reduce cesarean delivery, but relieved maternal hunger and reduced neonatal hypoglycemia at the expense of increased hyperglycemia of both mothers and neonates. Optimal rate of carbohydrate supplementation remains to be determined. TRIAL REGISTRATION: www.chictr.org.cn ; identifier: ChiCTR-IOR-17011994 ; registered on 14 July 2017.

A New Method for Moving-Target HRRP via Double Step Frequency Verified by Simulation.

The stepped-frequency (SF) waveform is highly sensitive to the target motion, which induces range shift and echo spread in a high-range-resolution profile (HRRP). This paper proposes a method based on a cross-transmitted double-stepped frequency (DSF) waveform and the phase-cancellation technique. The proposed method obtains the stationary HRRP of the moving targets according to the inverse discrete Fourier transform (IDFT) and complex multiplication. The results also show that the proposed method eliminates the generated false peaks from the existing methods. As a result, the obtained signal-to-noise ratio (SNR) of the HRRP using the proposed method is improved. Due to the cross-transmitted DSF waveform application, the proposed method adapts to higher speed targets. The analysis and simulation results validate the effectiveness of the proposed approach.

Effect of calcinated pyrite on simultaneous ammonia, nitrate and phosphorus removal in the BAF system and the Fe2+ regulatory mechanisms: Electron transfer and biofilm properties.

To efficiently remove nitrogen and phosphorus from secondary effluent with low values of COD/TN, a novel biological aerated filter (BAF) utilizing calcined pyrite with a large specific surface area (SSA) and pore diameter (PD) was designed to address this challenge. From the perspective of nutrients removal performance, and the corresponding effluent total nitrogen (TN) and PO43--P in the calcined pyrite autotrophic denitrification (CPAD) process decreased from 40.21 to 1.07 mg/L to 1.22 and 0.14 mg/L, respectively. Furthermore, the nutrients removal kinetics analysis showed that the CPAD and pyrite autotrophic denitrification (PAD) processes could be fitted with Half-order and Zero-order reactions via kinetics analysis, respectively, indicating that the TN removal performance of CPAD processes was better than that of the PAD process. Moreover, CPAD combined with sulfur autotrophic denitrification (SAD) processes was fitted by First-order reaction, and the TN removal performance was further enhanced over the CPAD process. From the perspective of microregulation, Fe2+ production in the PAD and CPAD processes could accelerate the electron transfer rate by increasing electron transport system activity (ETSA) and reducing electrochemical impedance spectroscopy (EIS). Moreover, Fe2+ stimulated microbes to produce more proteins (PN) and C10-HSL, which improved biofilm stability and interspecific communication processes. Notably, nitrifiers and autotrophic denitrifiers were simultaneously enriched via detection of high-throughput sequencing of 16 S rRNA genes, which verified the feasibility of simultaneous nitrification and autotrophic denitrification. Therefore, BAF with calcined pyrite and sulfur as composite fillers have a considerable advantage in nutrients removal.

Pharmacokinetic study of eight bioactive components following oral administration of Zhiqiao Gancao decoction and observation of its clinical efficacy.

Zhiqiao Gancao (ZQGC) decoction is widely used in China due to its therapeutic effect on lumbar disc herniation (LDH). In this study, we compared the clinical therapeutic effects among oral ZQGC decoction treatment, bed rest, and oral anti-inflammatory drug celecoxib treatment using visual analog scale, Oswestry Disability Index, and MacNab scores. The results showed that ZQGC decoction can significantly improve the symptoms of patients with LDH. A selective, sensitive, and rapid ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of eight bioactive components in rat plasma. The plasma samples were extracted by simple protein precipitation with methanol. The protonated analytes were quantitated simultaneously in positive and negative ion modes by multiple reaction monitoring with a mass spectrometer. The calibration curve of eight components in plasma showed good linearity (r > .996) and the extraction recovery was 81.19% ± 2.15% - 100.39 ± 3.36 (relative standard deviation: 1.21%-10.70%). The accuracy of all the lower limit of quantitation values was quantified within 80%-120%, and the precision was less than 15%. This validated method was successfully applied to the pharmacokinetics study in rat plasma after ZQGC decoction oral treatment. Our research can provide experimental basis for the rational clinical application of ZQGC decoction in the treatment of LDH.

The etiological contribution of GABAergic plasticity to the pathogenesis of neuropathic pain.

Neuropathic pain developing after peripheral or central nerve injury is the result of pathological changes generated through complex mechanisms. Disruption in the homeostasis of excitatory and inhibitory neurons within the central nervous system is a crucial factor in the formation of hyperalgesia or allodynia occurring with neuropathic pain. The central GABAergic pathway has received attention for its extensive distribution and function in neural circuits, including the generation and development of neuropathic pain. GABAergic inhibitory changes that occur in the interneurons along descending modulatory and nociceptive pathways in the central nervous system are believed to generate neuronal plasticity, such as synaptic plasticity or functional plasticity of the related genes or proteins, that is the foundation of persistent neuropathic pain. The primary GABAergic plasticity observed in neuropathic pain includes GABAergic synapse homo- and heterosynaptic plasticity, decreased synthesis of GABA, down-expression of glutamic acid decarboxylase and GABA transporter, abnormal expression of NKCC1 or KCC2, and disturbed function of GABA receptors. In this review, we describe possible mechanisms associated with GABAergic plasticity, such as central sensitization and GABAergic interneuron apoptosis, and the epigenetic etiologies of GABAergic plasticity in neuropathic pain. Moreover, we summarize potential therapeutic targets of GABAergic plasticity that may allow for successful relief of hyperalgesia from nerve injury. Finally, we compare the effects of the GABAergic system in neuropathic pain to other types of chronic pain to understand the contribution of GABAergic plasticity to neuropathic pain.

Programmed intermittent epidural bolus decreases the incidence of intra-partum fever for labor analgesia in primiparous women: a randomized controlled study.

PURPOSE: To evaluate whether programmed intermittent epidural bolus (PIEB) reduces the incidence of maternal intra-partum fever compared with continuous epidural infusion (CEI) during labor. METHODS: Parturients were randomized to receive CEI (CEI group) or PIEB (PIEB group) with 10 ml per hour for epidural labor analgesia with 1500 subjects in each group. The maintaining dose of two groups is 0.08% ropivacaine with 0.4 µg/ml sufentanil, with patient-controlled epidural analgesia (PCEA) dose of 5 ml and lockout interval of 30 min. The incidence of maternal fever, pain score, epidural sensory levels, the number and proportion of PCEA demand, anesthetics consumption, satisfaction score, neonatal Apgar scale, and maternal and neonatal side effects were recorded. RESULTS: It was significantly lower of the incidence of maternal fever beginning at 4 h post-analgesia and continuing until delivery in the PIEB group than the CEI group (4 h: 2.6% vs. 4.2%; 5 h: 7.3% vs. 10.2%; delivery: 5.6% vs. 7.9%; 1 h post-delivery: 3.9% vs. 6.2%; 2 h post-delivery: 2.1 vs. 3.5%; total: 5.8% vs. 8.4% in PIEB and CEI, respectively). Compared with CEI group, pain scores at 3, 4, 5 h post-analgesia and delivery (3 h: 2 [1, 2] vs. 2 [1-3]; 4 h: 2 [2, 3] vs. 3 [2-4]; 5 h: 2 [2, 3] vs. 3 [2-4]; delivery: 3 [2-4] vs. 4 [3, 4] in PIEB and CEI, respectively), the number and proportion of PCEA demand (number: 0.7 ± 0.9 vs. 2.2 ± 1.9; proportion: 42.0% vs. 80.3% in PIEB and CEI, respectively), and anesthetics consumption significantly decreased in the PIEB group (Ropivacaine: 60 ± 13 mg vs. 76 ± 17 mg; Sufentanil: 26 ± 4 mg vs. 32 ± 6 mg in PIEB and CEI, respectively), without severe maternal and neonatal side effects and any difference in neonatal Apgar scale. The epidural sensory levels 2 h post-analgesia (2 h: 8[8, 9] vs. 9[8, 9] in PIEB and CEI) and satisfaction score (9 [9, 10] vs. 7 [6, 7] in PIEB and CEI) were significantly higher in the PIEB group compared with those in the CEI group. CONCLUSIONS: PIEB with 10 ml of 0.08% ropivacaine and 0.4 µg/ml sufentanil hourly provided a lower incidence of intra-partum fever with a better analgesic effect compared with CEI, without any severe maternal and neonatal adverse reactions.

The etiological changes of acetylation in peripheral nerve injury-induced neuropathic hypersensitivity.

Neuropathic pain is a common chronic pain condition with mechanisms far clearly been elucidated. Mounting preclinical and clinical studies have shown neuropathic pain is highly associated with histone acetylation modification, which follows expression regulation of various pain-related molecules such as mGluR1/5, glutamate aspartate transporter, glutamate transporter-1, GAD65, Nav1.8, Kv4.3, µ-opioid receptor, brain-derived neurotrophic factor, and certain chemokines. As two types of pivotal enzymes involved in histone acetylation, histone deacetylases induce histone deacetylation to silence gene expression; in contrast, histone acetyl transferases facilitate histone acetylation to potentiate gene transcription. Accordingly, upregulation or blockade of acetylation may be a promising intervention direction for neuropathic pain treatment. In fact, numerous animal studies have suggested various histone deacetylase inhibitors, Sirt (class III histone deacetylases) activators, and histone acetyl transferases inhibitors are effective in neuropathic pain treatment via targeting specific epigenetic sites. In this review, we summarize the characteristics of the molecules and mechanisms of neuropathy-related acetylation, as well as the acetylation upregulation and blockade for neuropathic pain therapy. Finally, we will discuss the current drug advances focusing on neuropathy-related acetylation along with the underlying treatment mechanisms.

Complete Chloroplast Genome Sequence and Phylogenetic Analysis of Paeonia ostii.

Paeonia ostii, a common oil-tree peony, is important ornamentally and medicinally. However, there are few studies on the chloroplast genome of Paeonia ostii. We sequenced and analyzed the complete chloroplast genome of P. ostii. The size of the P. ostii chloroplast genome is 152,153 bp, including a large single-copy region (85,373 bp), a small single-copy region (17,054 bp), and a pair of inverted repeats regions (24,863 bp). The P. ostii chloroplast genome encodes 111 genes, including 77 protein-coding genes, four ribosomal RNA genes, and 30 transfer RNA genes. The genome contains forward repeats (22), palindromic repeats (28), and tandem repeats (24). The presence of rich simple-sequence repeat loci in the genome provides opportunities for future population genetics work for breeding new varieties. A phylogenetic analysis showed that P. ostii is more closely related to Paeonia delavayi and Paeonialudlowii than to Paeoniaobovata and Paeoniaveitchii. The results of this study provide an assembly of the whole chloroplast genome of P. ostii, which may be useful for future breeding and further biological discoveries. It will provide a theoretical basis for the improvement of peony yield and the determination of phylogenetic status.

Complete Chloroplast Genome Sequence and Phylogenetic Analysis of Aster tataricus.

We sequenced and analyzed the complete chloroplast genome of Aster tataricus (family Asteraceae), a Chinese herb used medicinally to relieve coughs and reduce sputum. The A. tataricus chloroplast genome was 152,992 bp in size, and harbored a pair of inverted repeat regions (IRa and IRb, each 24,850 bp) divided into a large single-copy (LSC, 84,698 bp) and a small single-copy (SSC, 18,250 bp) region. Our annotation revealed that the A. tataricus chloroplast genome contained 115 genes, including 81 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. In addition, 70 simple sequence repeats (SSRs) were detected in the A. tataricus chloroplast genome, including mononucleotides (36), dinucleotides (1), trinucleotides (23), tetranucleotides (1), pentanucleotides (8), and hexanucleotides (1). Comparative chloroplast genome analysis of three Aster species indicated that a higher similarity was preserved in the IR regions than in the LSC and SSC regions, and that the differences in the degree of preservation were slighter between A. tataricus and A. altaicus than between A. tataricus and A. spathulifolius. Phylogenetic analysis revealed that A. tataricus was more closely related to A. altaicus than to A. spathulifolius. Our findings offer valuable information for future research on Aster species identification and selective breeding.

[Statues and research strategy of molecular breeding in Artemisia annua].

Malaria is one of the three most deadly diseases in the world. Artemisinin is the first line and effective drug for treating malaria, and only can be extracted from Artemisia annua. Therefore, it is of great significance to cultivate new varieties of A. annua with high artemisinin content. Based on the germplasm bank and the whole genome, transcriptome and genetic map, the authors can explore high-quality genes, stress-resistant genes and genetic markers which have been used for rapid breeding of superior varieties of A. annua. So these methods of molecular breeding will become the main breeding direction of A. annua in the future. The breeding times of new varieties of A. annua can be shortened with molecular breeding technology. Based on the genetic background and the current situation of molecular breeding of A. annua, the strategy and technical route of molecular breeding were discussed and worked out in this paper, which provided a guidance and scientific reference for molecular breeding of A. annua in the future.

Threshold Effect of G9a/Glp on Peripheral Nerve Injury Induced Hypersensitivity.

Background: Previous studies disclosed the pivotal role of methyltransferase complex G9a/Glp in the pathogenesis of neuropathic hypersensitivity induced by peripheral nerve injury. We observed that higher dose of G9a inhibitor improved nociceptive behavior, but the lower dose worsened pain. The aim of this study is to extensively observe the differential effect of various dosages of G9a/Glp inhibitors on nerve injury-induced allodynia. Materials and methods: After approval by the institutional ethical committee on pain research in conscious animals, C57BL/6 mice were used for measuring nociceptive behavior evoked with von Frey filaments after spared nerve injury. G9a/Glp inhibitor BIX01294 or UNC0638 was injected through the pre-buried intrathecal catheter. The dose­response curves of behavioral changes were depicted when inhibitors were administered once in bolus at the 14th day post spared nerve injury. Withdrawal behaviors were compared during the 49 days' observation window after spared nerve injury with various dosages of inhibitors injected intrathecally for 14 days. Results: Dose­behavior curves of a single bolus of both BIX01294 and UNC0638 displayed a "V"-shaped responses of allodynia withdrawal from lower through higher dose when measured at the 14th day post spared nerve injury. A threshold dose of 10.0 µg for BIX01294 and 80.0 µg for UNC0638 significantly worsened allodynia. However, daily bolus intrathecal injection for 14 days of both inhibitors lower or higher than these threshold doses prominently improved nociceptive behavior, producing contrasting results. On the same animal, threshold dose followed by a lower or higher dose with a 14 days' interval also showed contrast effect on nociceptive behavior, and a lower or higher dose to threshold dose sequence of inhibitor administration was vice versa. Conclusions: Methyltransferase complex G9a/Glp has a threshold role in mediating peripheral nerve injury-induced hypersensitivity at its low level versus high level through inhibiting and facilitating the nociceptive behavior, respectively.

Complete Chloroplast Genome Sequence and Phylogenetic Analysis of the Medicinal Plant Artemisia annua.

The complete chloroplast genome of Artemisia annua (Asteraceae), the primary source of artemisinin, was sequenced and analyzed. The A. annua cp genome is 150,995 bp, and harbors a pair of inverted repeat regions (IRa and IRb), of 24,850 bp each that separate large (LSC, 82,988 bp) and small (SSC, 18,267 bp) single-copy regions. Our annotation revealed that the A. annua cp genome contains 113 genes and 18 duplicated genes. The gene order in the SSC region of A. annua is inverted; this fact is consistent with the sequences of chloroplast genomes from three other Artemisia species. Fifteen (15) forward and seventeen (17) inverted repeats were detected in the genome. The existence of rich SSR loci in the genome suggests opportunities for future population genetics work on this anti-malarial medicinal plant. In A. annua cpDNA, the rps19 gene was found in the LSC region rather than the IR region, and the rps19 pseudogene was absent in the IR region. Sequence divergence analysis of five Asteraceae species indicated that the most highly divergent regions were found in the intergenic spacers, and that the differences between A. annua and A. fukudo were very slight. A phylogenetic analysis revealed a sister relationship between A. annua and A. fukudo. This study identified the unique characteristics of the A. annua cp genome. These results offer valuable information for future research on Artemisia species identification and for the selective breeding of A. annua with high pharmaceutical efficacy.

Comparing pain reduction following kyphoplasty and vertebroplasty : A meta-analysis of randomized and non-randomized controlled trials.

PURPOSE: The aim of the study was to compare the extent of pain reduction with kyphoplasty (KP) and vertebroplasty (VP) in the treatment of osteoporotic vertebral compression fractures (OVCF) using a visual analog scale (VAS). METHODS: A computerized database search was performed to compare pain relief from VP and KP in OVCF. The available literature was analysed to quantify the amount of pain reduction using VAS as the primary outcome. RESULTS: A total of 10 studies encompassing 902 patients met the inclusion criteria. Subgroup meta-analyses were performed according to the study design. VAS for the KP group was not significant compared with the VP group at 1 week, 1 month, and 6 months. Pain relief in the KP group was greater than that in the VP group at 12 months and 2 years. CONCLUSION: KP is superior to VP in patients requiring pain relief. More large-scale, double-blinded controlled trials are necessary in order to quantify the pain relief afforded by VP more precisely.

Recombinant human platelet-derived growth factor-BB versus autologous bone graft in foot and ankle fusion: A systematic review and meta-analysis.

Today, autogenous bone graft (ABG) is still considered as the gold standard for joint fusion. Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) which is of chemotactic and mitogenic to mesenchymal stem cells and possesses outstanding osteogenetic potentials has been used for ankle and foot fusion in recent years. The goal of this article is to evaluate the safety and efficacy of rhPDGF-BB versus ABG in foot and ankle fusion. The PubMed MEDLINE, EMBASE, Web of Science, and Cochrane Library were systematic searched. Finally, three randomized controlled trials (RCTs) with 634 patients were enrolled in this study. Results of radiologic effectiveness which included CT and radiographic union rates revealed that there was no significant difference between rhPDGF-BB approach and ABG approach. Analysis of clinical results held the same outcomes expect that ABG group was superior in long-term Short Form-12 physical component scores. The pooled results also demonstrated that rhPDGF-BB was as safe as ABG in foot and ankle surgery. However, autograft harvesting procedure has some drawbacks such as donor-site pain and morbidity, additional operation time, blood loss, and scarring, which can be overcome by rhPDGF-BB. Thus, rhPDGF-BB is a viable alternative to autograft in foot and ankle fusion surgery. Yet, more high-quality RCTs with long-term follow-up are still required to make the final conclusion.

Potential immunotoxic effects of trichloroethylene-induced IV allergic reaction in renal impairment.

Trichloroethylene (TCE) is known to induce allergic contact dermatitis and subsequent occupational medicamentosa-like dermatitis (OMLD) with multi-system injuries, including liver, kidney, and skin injuries. However, the mechanisms underlying immune system dysfunction that result in organ injury have not yet been clearly elucidated. In the present study, we measured the levels of secreted cytokines by effect or T cells in TCE-treated guinea pigs to better understand the contribution of allergic disorders in renal injuries. We immunized guinea pigs with trichloroethylene using the Guinea Pig Maximization Test (GPMT) and scored the inflammation on the guinea pigs' skin. The kidney function and ultra-structural changes in the kidneys were detected using biochemical methods and electron microscopy. The deposition of cytokines was determined using immunohistochemistry. The sensitization rate was 63.16% in the TCE-sensitized groups. The electron microscopy results showed tubular epithelial cell mitochondrial swelling, vacuolar degeneration, and atrophy of the microvillus in the sensitized groups. A high degree of cytokine deposition was observed in the renal tubular proximal epithelial cells in the TCE-sensitized groups. As observed in this study, the variation in the level of immune system activation not only indicates that TCE can largely magnify the immune reaction but also suggests a potential role of immune dysfunction in renal impairment.

Dopaminergic inhibition by G9a/Glp complex on tyrosine hydroxylase in nerve injury-induced hypersensitivity.

The neural balance between facilitation and inhibition determines the final tendency of central sensitization. Nerve injury-induced hypersensitivity was considered as the results from the enhanced ascending facilitation and the diminished descending inhibition. The role of dopaminergic transmission in the descending inhibition has been well documented, but its underlying molecular mechanisms are unclear. Previous studies demonstrated that the lysine dimethyltransferase G9a/G9a-like protein (Glp) complex plays a critical role in cocaine-induced central plasticity, and given cocaine's role in the nerve system is relied on its function on dopamine system, we herein proposed that the reduced inhibition of dopaminergic transmission was from the downregulation of tyrosine hydroxylase expression by G9a/Glp complex through methylating its gene Th After approval by the Animal Care and Use Committee, C57BL/6 mice were used for pain behavior using von Frey after spared nerve injury, and Th CpG islands methylation was measured using bisulfite sequencing at different nerve areas. The inhibitor of G9a/Glp, BIX 01294, was administered intraventricularly daily with bolus injection. The protein levels of G9a, Glp, and tyrosine hydroxylase were measured with immunoblotting. Dopamine levels were detected using high-performance liquid chromatography. The expression of G9a but not Glp was upregulated in ventral tegmental area at post-injury day 4 till day 49 (the last day of the behavioral test). Correspondingly, the Th CpG methylation is increased, but the tyrosine hydroxylase expression was downregulated and the dopamine level was decreased. After the intracerebroventriclar injection of BIX 01294 since the post-injury days 7 and 14 for consecutive three days, three weeks, and six weeks, the expression of tyrosine hydroxylase was upregulated with a significant decrease in Th methylation and increase in dopamine level. Moreover, the pain after G9a/Glp inhibitor was attenuated significantly. In sum, methytransferase G9a/Glp complex partially controls dopaminergic transmission by methylating Th in peripheral nerve injury-induced neuropathic pain.

[Correlation analysis between effectiveness of element in rhizonsphere soil and quality of Danshen (Salvia miltiorrhiza)].

In order to investigate the content and distribution of available element in the rhizonsphere soil of the growing areas of Salvia miltiorrhiza Bunge, the contents of available element (N,P,K,B,Cu,Zn,Fe,Mn) in 26 soil samples were tested and evaluated. The results showed that the contents of available P and Fe were very plentiful, available K, Cu and Zn were rich, available N and Mn were deficient, available B was extremely deficient in all growing areas of S. miltiorrhiza of eight provinces in China. The correlation analysis showed that the contents of eight kinds of available elements were varying degree correlation. The stepwise regression analysis between the contents of available elements of rhizonsphere soil and ten kinds of active ingredients of Danshen (Salviae Miltiorrhizae Radix et Rhizoma) were researched. The results showed that the rates of contribution of available N,B,Mn and Fe to quality of Danshen were relatively large and they were the significant factors, and the other factors did not show statistical significance. The recommended fertilizing strategies is that the usage of N,B and Mn fertilizers should be controlled according to different stages of growth of S. miltiorrhiza, and P fertilizer should be reduced in all growing areas of S. miltiorrhiza.