Fire Needling Therapy versus Manual Acupuncture in Post-Stroke Complex Regional Pain Syndrome of the Upper Limb: Study Protocol for a Pilot Randomised Controlled Trial.

Introduction: Post-stroke complex regional pain syndrome (CRPS) is a devastating disease that causes severe physical and emotional consequences. Conventional therapies are limited due to the insufficient benefits and side effects, and fire needling therapy is considered an alternative for post-stroke CRPS of the upper limb. Methods and Analysis: This is a study protocol for a pilot randomised, two-arm, single-centre, clinical trial at Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University. The trial started in March 2023 and is expected to end in December 2024. A total of 60 patients (aged 40-75 years, male or female) with post-stroke CRPS of the upper limb will be randomly assigned to treatment group (fire needling therapy, 5 sessions per week for 2 weeks) or control group (manual acupuncture, 5 sessions per week for 2 weeks) in a 1:1 ratio using block randomisation and opaque envelopes. Fire needling therapy or manual acupuncture will be performed in ten acupoints. Participants will complete the trial by visiting the research centre at Week 14 for a follow-up assessment. The primary outcome is the response rate. Secondary outcomes include FMA, Barthel Scale/Index (BI), pain threshold (PPT), and muscle elasticity modulus (using shear wave elastography [SWE]). A chi-squared test will be used for response rate. A mixed-effects linear model and a mixed-effects model will be used for FMA, BI, PPT, and SWE, respectively. Discussion: This is the first standardised protocol to compare the effectiveness of fire needling therapy and manual acupuncture. We will use a rigorous methodology to minimise bias and set up supervising committees to ensure the quality of our study, thus providing trustworthy evidence for better understanding of fire needling therapy in treating post-stroke CRPS of the upper limb.

Fire Needling Therapy of Different Frequencies versus External Diclofenac Diethylamine Emulgel for Knee Osteoarthritis: Study Protocol for a Pilot Randomized Controlled Trial.

Purpose: Knee osteoarthritis (KOA) is regarded as one of the leading musculoskeletal diseases. Although the efficacy is under exploration, fire needling therapy is considered an effective alternative for KOA. This trial aims to investigate the effectiveness of different frequencies of fire needling therapy in attenuating pain and promoting function in KOA patients. Methods: This is a study protocol for a pilot, three-arm, single-center, randomized controlled trial. A total of 90 participants with KOA will be recruited and randomly assigned to the high-frequency fire needling group (3 sessions per week, for 6 weeks), the low-frequency fire needling group (1 session per week, for 6 weeks) or the positive control group (Diclofenac Diethylamine Emulgel, 3 times per day, for 6 weeks) in a 1:1:1 ratio. Participants will accomplish the trial at Week 14 after a follow-up evaluation. The response rate will be set as the primary outcome that the proportion of participants obtaining a minimal clinically important difference, which is identified as ≥2 units on the numerical rating scale (NRS) and ≥6 units on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score at Week 6 compared with Week 0. Secondary outcomes are NRS, WOMAC, Brief Pain Inventory, Short-Form Health Survey-12, Timed Up and Go Test, and pain threshold. Discussion: This is the first standardized protocol comparing fire needling therapy and positive control drugs. This trial may provide reliable evidence for the effectiveness of fire needling therapy and dose-effect property of it in KOA. Trial registration: The trial has been registered on Chinese Clinical Trial Registry (Registered number: ChiCTR2100043041), registered on 4 February 2021.

Fire Needling Acupuncture Suppresses Cartilage Damage by Mediating Macrophage Polarization in Mice with Knee Osteoarthritis.

Purpose: Macrophage polarization contributes to the mechanisms of treating knee osteoarthritis (KOA). In previous studies, fire needling acupuncture has been shown to affect KOA favorably. However, the mechanism of fire needling acupuncture on macrophage polarization is not well-defined. Thus, this study was conducted to determine that fire needling acupuncture exerts a therapeutic role in KOA by modulating macrophage polarization. Methods: Thirty mice were allocated at random into three groups of ten. The groups were labeled as "control", "model", and "fire needling acupuncture". Each group consisted of ten mice. From the second day of intra-articular injection MIA, the right "xiyan" (EX-LE5), "dubi" (ST35), "liangqiu" (ST34), and "xuehai" (SP10) acupoints were manipulated once every other day for two weeks in the fire needling acupuncture group. Mechanical withdrawal threshold and weight distribution were evaluated for behavioral testing in each group. The synovial morphology was monitored by HE staining. Pathological morphology was observed by HE staining, Saf-O staining, and toluidine blue staining. The polarization of macrophages in synovial tissue was detected using immunofluorescence (F4/80, CD86, and CD206). Results: Fire needling acupuncture increased the percentage weight-bearing difference and the mechanical withdrawal threshold, and improved synovial inflammation and cartilage damage in MIA-induced KOA mice. F4/80 and CD86 expression were downregulated by fire needling acupuncture, but CD206 was increased. Conclusion: Fire needling acupuncture decreases pain behaviors in KOA mice and improves synovial membrane injury and pathological cartilage damage. The macrophage polarization is involved in the mechanism of fire needling acupuncture's amelioration of articular cartilage damage.

Determining 5HT7R's Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine.

Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT7 receptor (5-HT7R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT7R could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase1 / 2 (ERK1 / 2)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT7R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK1 / 2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT7R antagonist (SB269970) or 5-HT7R agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HT7R and 5-HT7R-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT7R mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HT7R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK1 / 2. Injecting 5-HT7R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK1 / 2. Our findings indicate that 5-HT7R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK1 / 2 in TG and TNC.

Mechanism of Traditional Chinese Medicine in Treating Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a degenerative disease, making a unique contribution to chronic pain, edema, and limited mobility of knee joint. Traditional Chinese Medicine (TCM) is a common complementary therapy for KOA and has been found effective. The aim of this review is to consolidate the current knowledge about the mechanism of four interventions of TCM: acupuncture, moxibustion, herbs, and massage in treating KOA, and how they alleviate symptoms such as pain, swelling, and dysfunction. Furthermore, this review highlights that four therapies have different mechanisms but all of them can manage KOA through inhibiting inflammation, which indicates that alternative therapies should be considered as a viable complementary treatment for pain management in clinical practice.

Partial Purine Nucleoside Phosphorylase Deficiency Helps Determine Minimal Activity Required for Immune and Neurological Development.

Introduction: Complete or near complete absence of the purine nucleoside phosphorylase (PNP) enzyme causes a profound T cell immunodeficiency and neurological abnormalities that are often lethal in infancy and early childhood. We hypothesized that patients with partial PNP deficiency, characterized by a late and mild phenotype due to residual PNP enzyme, would provide important information about the minimal PNP activity needed for normal development. Methods: Three siblings with a homozygous PNP gene mutation (c.769C>G, p.His257Asp) resulting in partial PNP deficiency were investigated. PNP activity was semi-quantitively assayed by the conversion of [14C]inosine in hemolysates, mononuclear cells, and lymphoblastoid B cells. PNP protein expression was determined by Western Blotting in lymphoblastoid B cells. DNA repair was quantified by measuring viability of lymphoblastoid B cells following ionizing irradiation. Results: A 21-year-old female was referred for recurrent sino-pulmonary infections while her older male siblings, aged 25- and 28- years, did not suffer from significant infections. Two of the siblings had moderately reduced numbers of T, B, and NK cells, while the other had near normal lymphocyte subset numbers. T cell proliferations were normal in the two siblings tested. Hypogammaglobulinemia was noted in two siblings, including one that required immunoglobulin replacement. All siblings had typical (normal) neurological development. PNP activity in various cells from two patients were 8-11% of the normal level. All siblings had normal blood uric acid and increased PNP substrates in the urine. PNP protein expression in cells from the two patients examined was similar to that observed in cells from healthy controls. The survival of lymphoblastoid B cells from 2 partial PNP-deficient patients after irradiation was similar to that of PNP-proficient cells and markedly higher than the survival of cells from a patient with absent PNP activity or a patient with ataxia telangiectasia. Conclusions: Patients with partial PNP deficiency can present in the third decade of life with mild-moderate immune abnormalities and typical development. Near-normal immunity might be achieved with relatively low PNP activity.

[Research of inflammatory factors and signaling pathways in knee osteoarthritis].

Knee osteoarthritis is the most common type of arthritis, which is manifested by the deformation and degeneration of articular cartilage and the discomfort of patients with joint pain, which affects the quality of life of patients and aggravates the medical burden of society. The pathogenesis of knee osteoarthritis is very complex. This paper reviews the inflammatory factors and signal pathways involved in knee osteoarthritis. It is found that most of the inflammatory factors involved are interleukin, such as IL-1 ß, IL-6, IL-15, IL-17, IL-18, and tumor necrosis factors, such as TNF-α. These inflammatory factors aggravate knee osteoarthritisby activating corresponding pathways and promoting the release of inflammatory mediators. The inflammatory signaling pathways involved in knee osteoarthritis are complex. Notch pathway, Wnt pathway, SDF-1 / CXCR4 pathway, TLRs pathway, MAPKs pathway, hippo Yap pathway, OPG-RANK-RANKL pathway and TGF-ß pathway are all involved in the regulation of knee osteoarthritis, and the pathways related to inflammatory mechanism are mainly MAPKs pathway and TLRs pathway. Different signaling pathways can cause the destruction of articular cartilage, promote the apoptosis of chondrocytes, and finally lead to the further imbalance of homeostasis in the knee joint. At the same time, the activation of signal pathway can promote the release of inflammatory factors, so under the cascade reaction of inflammatory factors and signal pathway, knee osteoarthritis is aggravating.

Prophylactic Electroacupuncture on the Upper Cervical Segments Decreases Neuronal Discharges of the Trigeminocervical Complex in Migraine-Affected Rats: An in vivo Extracellular Electrophysiological Experiment.

PURPOSE: This rat experiment aims to demonstrate the efficacy of electrical acupuncture in preventing migraine attacks by stimulating the acupoint GB20. INTRODUCTION: Migraine, which takes 2ed at level four causes of GBD's disease hierarchy, becomes a public health issue. It is important for physicians to supplement their knowledge of its treatment and consider alternative methods of therapy, such as acupuncture. However, the neurobiological and pathophysiological mechanisms of this prophylactic effect were unclear. The trigeminocervical complex is thought to be an important relay station in migraine pathophysiology as the key nuclei of the trigeminovascular system and the brainstem descending pain modulation system. METHODS: There were six groups involved in this study: control, model, electroacupuncture, non-acupoint electroacupuncture, saline+electroacupuncture and saline+non-acupoint electroacupuncture. We injected saline or inflammatory soup into dura mater to induce control or migraine in the rats. The mechanical pain threshold and the single-cell extraneural neurophysiology of the C1 spinal dorsal horn neurons in the trigeminocervical complex were detected. RESULTS: Pre-electroacupuncture could significantly increase the mechanical pain threshold of the periorbital region receptive field of the trigeminal nerve and decrease the discharges of neurons in the trigeminocervical complex. Acupuncture also reversed the abnormal skin pain response of the periorbital region receptive field of the trigeminal nerve caused by low-intensity stimulation. DISCUSSION: We believe that our study makes a significant contribution to the literature because it is the first of its kind to use GB20 to provide relief from migraine attacks and mechanical cephalic cutaneous hypersensitivity by regulating the neuronal discharge from trigeminocervical complex.

Electroacupuncture Inhibits Hyperalgesia by Alleviating Inflammatory Factors in a Rat Model of Migraine.

OBJECTIVE: Acupuncture has a therapeutic effect similar to that of prophylactic drugs and can be considered a treatment option for migraineurs. However, the mechanism of acupuncture treatment's effect on migraine is uncertain. An approach based on anti-inflammatory effects is an important treatment strategy for migraine because non-steroidal anti-inflammatory drugs (NSAIDs) are usually used during migraine attacks. Meningeal inflammation is thought to be responsible for the activation of the trigeminovascular system. Our previous study found that electroacupuncture (EA) decreased neurogenic inflammation mediator expression in the trigeminal ganglion (TG) and alleviated hyperalgesia. The present study examined whether EA would inhibit hyperalgesia by alleviating neurogenic inflammatory factors. METHODS: A rat model of migraine was established using dural electrical stimulation (DES). Five groups were analyzed in this study. The Model group received DES three times to mimic migraine attacks, a Control group had sham DES, and three groups received electroacupuncture after DES: a Non-Acu group at a non-acupuncture point, a GB20 group at GB20, and a GB20/34 group at GB20 and GB34 acupuncture points. We evaluated mechanical hyperalgesia using an electronic von Frey esthesiometer in the awake state. After sacrifice, the dura mater was analyzed using immunofluorescence. Serum calcitonin gene-related peptide, cyclooxygenase-2, brain-derived neurotrophic factor, IL-1ß, IL-6, and TNF levels were determined using enzyme-linked immunosorbent assays to evaluate the anti-inflammatory effect of acupuncture. RESULTS: After repeated DES, we observed facial and hind paw mechanical hyperalgesia, which was inhibited by electroacupuncture. Electrical stimulation increased the number of mast cells and macrophages and serum levels of inflammatory factors. GB20 and GB20/34 electroacupuncture significantly decreased the number of mast cells and macrophages and serum levels of inflammatory factors. Moreover, electroacupuncture at GB20/34 was superior to that at GB20 alone in inhibiting hyperalgesia and alleviating inflammatory factors. CONCLUSION: Electroacupuncture inhibits DES-induced hyperalgesia by alleviating inflammatory factors. Inhibition of dural mast cells, macrophages, and serum inflammatory factors may be one of the mechanisms involved in acupuncture treatment's effect on migraine.

Electro-acupuncture inhibits C-fiber-evoked WDR neuronal activity of the trigeminocervical complex: Neurophysiological hypothesis of a complementary therapy for acute migraine modeled rats.

INTRODUCTION: Acupuncture has become a relevant complementary and alternative treatment for acute migraine; however, the neurophysiological mechanism (C-fibers) underlying this effect remains unclear. C-fibers play a crucial role for diffuse noxious inhibitory controls (DNIC) at wide dynamic range (WDR) neurons in the trigeminocervical complex (TCC) in migraine attacks, and we supposed that this may be the mechanism of acupuncture analgesia. This study aimed to examine the neurophysiology of acupuncture intervention in an acute migraine rat model. METHODS: Inflammatory soup (IS) or saline was injected into the dura mater to establish a migraine and control model in rats. To explore the neurobiological mechanism of acupuncture for migraine, we implemented electro-acupuncture (EA), non-electric-stimulation acupuncture, and no-acupuncture in IS and saline injected rats, and recorded the single-cell extraneural neurophysiology of the atlas (C1) spinal dorsal horn neurons in the TCC. RESULTS: Our research shows that electro-acupuncture at GB8 (Shuaigu), located in the periorbital region receptive field of the trigeminal nerve, may rapidly reduce the C-fiber evoked WDR neuronal discharges of the TCC within 60 s. DISCUSSION: This study provides pioneering evidence of a potential neurobiological mechanism for the analgesic effect on migraine attacks achieved by electro-acupuncture intervention via DNIC. The data indicates that EA may become a crucial supplementary and alternative therapy for migraineurs that failed to respond to acute medications, e.g., fremanezumab, which achieves its analgesic effect via modulating Aσ-fibers, not C-fibers.

Erratum to "Effect of Electroacupuncture on Hyperalgesia and Vasoactive Neurotransmitters in a Rat Model of Conscious Recurrent Migraine".

[This corrects the article DOI: 10.1155/2019/9512875.].

A clinical study to assess the influence of acupuncture at "Wang's Jiaji" acupoints on limb spasticity in patients in convalescent stage of ischemic stroke: study protocol for a randomized controlled trial.

BACKGROUND: Stroke is characterized by high morbidity, high mortality, and high disability. Spasticity, one of the most common complications after stroke, may reduce the potential success of rehabilitation and has a detrimental effect on stroke patients' daily function and quality of life. Moreover, the long-term management of spasticity is a financial burden to patients and increases societal costs. The current treatments, mainly including physical therapy, oral drugs, drug injection therapy, and surgical interventions, have been used to reduce spasticity. However, every conventional approach has its limitations. Acupuncture at the "Wang's Jiaji" acupoints, based on the experience of the famous old doctor of traditional Chinese medicine (TCM) Le Ting Wang in treating post-stroke limb spasm, has been widely practiced in our department. This intervention has effectively avoided the controversy around acupuncture at local acupoints on the limbs, and is easy to apply without side effects. Our previous studies had found that acupuncture at the "Wang's Jiaji-points" can reduce the occurrence and severity of spasticity occurring after stroke in the early stage (the first 21 days). In this study, we chose patients in the convalescent stage, 1-6 months after stroke, so as to study the efficacy and the specific intervention time of "Wang's jiaji" in the convalescent stage after stroke. METHODS: This is a randomized, controlled, and single-blind study. Patients in the convalescent stage within 1-6 months of ischemic stroke will be selected as subjects. A total of 100 subjects will be randomly assigned to two groups. The acupuncture group will be given acupuncture treatment five times a week; the medicine group will be given 10mg baclofen three times a day. These two groups will continue to receive current usual care for the prevention and treatment of cerebrovascular diseases, but drugs that affect muscle tone will not be allowed. The treatment will last for 2 weeks. The primary outcome measurement is the simplified Fugl-Meyer Assessment. The secondary outcome measurements are the Modified Ashworth Scale, Modified Barthel Scale, and the H-reflex, F response, and H/M ratios of electromyography. All outcome measurements are assessed at baseline, 2 weeks, 4 weeks, and 12 weeks after first treatment except the electromyography, which is assessed at baseline and 2 weeks after first acupuncture. DISCUSSION: This trial aims to evaluate the effects and the specific intervention time of "Wang's Jiaji" acupoints on spasticity after stroke. TRIAL REGISTRATION: ISRCTN registry, ISRCTN31511176 . Registered on 29 August 2017. Version number of protocol 2016-2-1161 Version date of protocol: 2016-1.

Effect of Electroacupuncture on Hyperalgesia and Vasoactive Neurotransmitters in a Rat Model of Conscious Recurrent Migraine.

Migraine onset is associated with the abnormal release of vasoactive neurotransmitters from perivascular nerves, and these neurotransmitters are involved in the pathophysiology of migraine. Hyperalgesia is a key feature of migraine, and accumulating evidence indicates that electroacupuncture (EA) at the single acupuncture point (Fengchi [GB20]) is effective in ameliorating hyperalgesia. In clinical practice, multiple acupuncture points are widely used, especially GB20 and Yanglingquan (GB34). However, the role played by vasoactive neurotransmitters in acupuncture antihyperalgesic effect at the single or multiple acupuncture points remains unknown. We aimed to determine whether EA would exert its antihyperalgesic effects by modulating vasoactive neurotransmitter release from the perivascular nerves. Furthermore, we examined whether targeting multiple acupuncture points would be more effective than targeting a single point in reducing hyperalgesia. The mechanical and thermal hyperalgesia were evaluated by measuring the facial and hind-paw mechanical withdrawal thresholds, tail-flick and hot-plate latencies. Plasma concentrations of vasoactive neurotransmitters were determined using rat-specific ELISA kits from jugular vein, including calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), pituitary adenylate cyclase-activating polypeptide (PACAP), nitric oxide (NO), and endothelin-1 (ET-1). The result suggested that EA significantly ameliorated the mechanical and thermal hyperalgesia, reduced c-Fos levels in the trigeminal ganglion, and attenuated plasma and dural levels of vasoactive neurotransmitters, especially in the multiple acupuncture points group (GB20+GB34). In conclusion, EA exerts antihyperalgesic effect in a rat model of conscious recurrent migraine, possibly via modulation of the vasoactive neurotransmitters. Furthermore, targeting multiple acupuncture points is more effective than targeting a single point in reducing hyperalgesia.

Early Enzyme Replacement Therapy Improves Hearing and Immune Defects in Adenosine Deaminase Deficient-Mice.

Background: Inherited defects in adenosine deaminase (ADA) cause severe immune deficiency, which can be corrected by ADA enzyme replacement therapy (ERT). Additionally, ADA-deficient patients suffer from hearing impairment. We hypothesized that ADA-deficient (-/-) mice also exhibit hearing abnormalities and that ERT from an early age will improve the hearing and immune defects in these mice. Methods: Auditory brainstem evoked responses, organ weights, thymocytes numbers, and subpopulations, lymphocytes in peripheral blood as well as T lymphocytes in spleen were analyzed in ADA-/- and ADA-proficient littermate post-partum (pp). The cochlea was visualized by scanning electron microscopy (SEM). The effects of polyethylene glycol conjugated ADA (PEG-ADA) ERT or 40% oxygen initiated at 7 days pp on the hearing and immune abnormalities were assessed. Results: Markedly abnormal hearing thresholds responses were found in ADA-/- mice at low and medium tone frequencies. SEM demonstrated extensive damage to the cochlear hair cells of ADA-/- mice, which were splayed, short or missing, correlating with the hearing deficits. The hearing defects were not reversed when hypoxia in ADA-/- mice was corrected. Progressive immune abnormalities were detected in ADA-/- mice from 4 days pp, initially affecting the thymus followed by peripheral lymphocytes and T cells in the spleen. ERT initiated at 7 days pp significantly improved the hearing of ADA-/- mice as well as the number of thymocytes and T lymphocytes, although not all normalized. Conclusions: ADA deficiency is associated with hearing deficits and damage to cochlear hair cells. Early initiation of ERT improves the hearing and immune abnormalities.

Intracellular Delivery of Human Purine Nucleoside Phosphorylase by Engineered Diphtheria Toxin Rescues Function in Target Cells.

Despite a wealth of potential applications inside target cells, protein-based therapeutics are largely limited to extracellular targets due to the inability of proteins to readily cross biological membranes and enter the cytosol. Bacterial toxins, which deliver a cytotoxic enzyme into cells as part of their intoxication mechanism, hold great potential as platforms for delivering therapeutic protein cargo into cells. Diphtheria toxin (DT) has been shown to be capable of delivering an array of model proteins of varying sizes, structures, and stabilities into mammalian cells as amino-terminal fusions. Here, seeking to expand the utility of DT as a delivery vector, we asked whether an active human enzyme, purine nucleoside phosphorylase (PNP), could be delivered by DT into cells to rescue PNP deficiency. Using a series of biochemical and cellular readouts, we demonstrate that PNP is efficiently delivered into target cells in a receptor- and translocation-dependent manner. In patient-derived PNP-deficient lymphocytes and pluripotent stem cell-differentiated neurons, we show that human PNP is efficiently translocated into target cells by DT, where it is able to restore intracellular hypoxanthine levels. Further, through replacement of the native receptor-binding moiety of DT with single-chain variable fragments that were selected to bind mouse HBEGF, we show that PNP can be retargeted into mouse splenocytes from PNP-deficient mice, resulting in restoration of the proliferative capacity of T-cells. These findings highlight the versatility of the DT delivery platform and provide an attractive approach for the delivery of PNP as well as other cytosolic enzymes implicated in disease.

Gene therapy for primary immune deficiencies: a Canadian perspective.

The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term studies have shown that adenosine deaminase (ADA) gene delivery into ADA-deficient hematopoietic stem cells that are then transplanted into the patients corrects the abnormal function of the ADA enzyme, which leads to immune reconstitution. In contrast, the outcome was disappointing for patients with X-linked SCID, Wiskott-Aldrich syndrome and chronic granulomatous disease who received GT followed by autologous gene corrected transplantations, as many developed hematological malignancies. The malignancies were attributed to the predilection of the viruses used for gene delivery to integrated at oncogenic areas. The availability of safer and more efficient self-inactivating lentiviruses for gene delivery has reignited the interest in GT for many PID that are now in various stages of pre-clinical studies and clinical trials. Moreover, advances in early diagnosis of PID and gene editing technology coupled with enhanced abilities to generate and manipulate stem cells ex vivo are expected to further contribute to the benefit of GT for PID. Here we review the past, the present and the future of GT for PID, with particular emphasis on the Canadian perspective.

[Mechanism of neural plasticity of acupuncture on chronic migraine].

Chronic migraine is one of neurological disorders with high rate of disability, but sufficient attention has not been paid in this field. A large number of clinical studies have shown traditional Chinese acupuncture is a kind of effective treatment with less side effects. Through the analysis of literature regarding acupuncture and migraine published from 1981 to 2017 in CNKI and PubMed databases, the mechanism of neural plasticity of acupuncture on chronic migraine was explored. It was believed the progress of chronic migraine involved the changes of neural plasticity in neural structure and function, and the neural plasticity related with neural sensitization during the process of chronic migraine was discussed from three aspects of electrophysiology, molecular chemistry and radiography. Acupuncture could treat and prevent chronic migraine via the mechanism of neural plasticity, but there was no related literature, hindering the further spreading and development of acupuncture for chronic migraine.

Placental transfer of dechlorane plus in mother-infant pairs in an e-waste recycling area (Wenling, China).

It has been reported that breastfeeding can expose newborns to dechlorane plus (DP), but transplacental transfer of DP has not been documented. We measured DP and its dechlorinated analogs in matched maternal blood-placenta-cord blood samples from 72 residents of the e-waste recycling area of Wenling, China. DP was detected in cord sera, indicating the occurrence of prenatal DP exposure and the transfer of DP across the placenta. The concentration ratio in the cord serum and maternal serum was estimated to be 0.45 for syn-DP and 0.35 for anti-DP, indicating the placenta partially limited DP transfer with a greater extent for anti-DP. The DP concentrations in the maternal serum, placenta, and cord serum strongly correlated, indicating that DP could transfer between the tissues. The DP concentrations in the matched samples could be predicted from each other. The anti-DP/total DP concentration ratios in the placentas and cord sera were significantly different from those in the maternal sera, suggesting that DP stereoselectively bioaccumulates in human tissues. When the congener concentrations of polybrominated diphenyl ethers (PBDEs) were used as control variables, DP and total triiodothyronine concentrations were associated in the sera from mothers who had lived in Wenling for over 20 years.

Dechlorane Plus and its dechlorinated analogs from an e-waste recycling center in maternal serum and breast milk of women in Wenling, China.

We measured Dechlorane Plus (DP) and its dechlorinated analogs in the blood and milk from women living in e-waste recycling sites in Wenling of Taizhou region, China (n = 49). Both syn-DP and anti-DP were detected in all samples. Another compound, Cl(11)-DP, was detected in 45% and 84% of milk and serum samples, respectively. DP levels in blood and milk from residents living in the local environment >20 yrs (R(20) group) were significantly higher than those living in Taizhou <3 yrs (R(3) group) (p < 0.05). The milk/serum partition coefficient from the same women was approximately 0.43 and 0.47 for syn-DP and anti-DP, respectively. A similar value in milk compared with anti-DP/∑DPs (f(anti)) in serum suggested that stereoselective DP bio-accumulation did not occur during the DP transport from blood to milk. This result indicate that DP can bio-accumulate in blood and milk with the low milk/serum partition coefficient and similar blood and milk stereoselective bio-accumulation profiles.

Application of counter-current chromatography as a new pretreatment method for the determination of polycyclic aromatic hydrocarbons in environmental water.

Counter-current chromatography (CCC) was investigated as a new sample pretreatment method for the determination of trace polycyclic aromatic hydrocarbons (PAHs) in water environmental samples. The experiment was performed with a non-aqueous binary two-phase solvent system composed of n-heptane and acetonitrile. The CCC column was first filled with the upper stationary phase, and then a large volume of water sample was pumped into the column while the CCC column was rotated at 1600 rpm. Finally, the trace amounts of PAHs extracted and enriched in the stationary phase were eluted out by the lower mobile phase and determined by gas chromatography-flame ionization detector (GC-FID) or gas chromatography-mass spectrometry (GC-MS). The enrichment and cleanup of PAHs can be fulfilled online by this method with high recoveries (84.1-103.2%) and good reproducibility (RSDs: 4.9-12.2%) for 16 EPA PAHs under the optimized CCC pretreatment conditions. This method has been successfully applied to determine PAHs in lake water where 8 PAHs were detected in the concentration of 40.9-89.9 ng/L. The present method is extremely suitable for the preparation of large volume of environmental water sample for the determination of trace amounts of organic pollutants including PAHs as studied in this paper.