Dorsal root ganglia control nociceptive input to the central nervous system.

Accumulating observations suggest that peripheral somatosensory ganglia may regulate nociceptive transmission, yet direct evidence is sparse. Here, in experiments on rats and mice, we show that the peripheral afferent nociceptive information undergoes dynamic filtering within the dorsal root ganglion (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using synchronous in vivo electrophysiological recordings from the peripheral and central processes of sensory neurons (in the spinal nerve and dorsal root), ganglionic transplantation of GABAergic progenitor cells, and optogenetics, we demonstrate existence of tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically induced GABA release within DRG from the transplanted GABAergic cells enhanced filtering and alleviated hypersensitivity to noxious stimulation produced by chronic inflammation and neuropathic injury in vivo. These findings support "gating" of pain information by DRGs and suggest new therapeutic approaches for pain relief.

PI4KIIIß-Mediated Phosphoinositides Metabolism Regulates Function of the VTA Dopaminergic Neurons and Depression-Like Behavior.

Phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP2), play a crucial role in controlling key cellular functions such as membrane and vesicle trafficking, ion channel, and transporter activity. Phosphatidylinositol 4-kinases (PI4K) are essential enzymes in regulating the turnover of phosphoinositides. However, the functional role of PI4Ks and mediated phosphoinositide metabolism in the central nervous system has not been fully revealed. In this study, we demonstrated that PI4KIIIß, one of the four members of PI4Ks, is an important regulator of VTA dopaminergic neuronal activity and related depression-like behavior of mice by controlling phosphoinositide turnover. Our findings provide new insights into possible mechanisms and potential drug targets for neuropsychiatric diseases, including depression. Both sexes were studied in basic behavior tests, but only male mice could be used in the social defeat depression model.

Unrevealing Temporal Mechanoluminescence Behaviors at High Frequency via Piezoelectric Actuation.

Mechanoluminescence (ML) materials present widespread applications. Empirically, modulation for a given ML material is achieved by application of programmed mechanical actuation with different amplitude, repetition velocity and frequency. However, to date modulation on the ML is very limited within several to a few hundred hertz low-frequency actuation range, due to the paucity of high-frequency mechanical excitation apparatus. The universality of temporal behavior and frequency response is an important aspect of ML phenomena, and serves as the impetus for much of its applications. Here, we push the study on ML into high-frequency range (∼250 kHz) by combining with piezoelectric actuators. Two representative ML ZnS:Mn and ZnS:Cu, Al phosphors were chosen as the research objects. Time-resolved ML of ZnS:Mn and ZnS:Cu, Al shows unrevealed frequency-dependent saturation and quenching, which is associated with the dynamic processes of traps. From the point of applications, this study sets the cut-off frequency for ML sensing. Moreover, by in-situ tuning the strain frequency, ZnS:Mn exhibits reversible frequency-induced broad red-shift into near-infrared range. These findings offer keen insight into the photophysics nature of ML and also broaden the physical modulation of ML by locally adjusting the excitation frequency.

Si-integrated lanthanide-doped ferroelectrics for a photomemory based on a photochromic reaction.

We describe a Si-integrated photochromic photomemory based on lanthanide-doped ferroelectric Na0.5Bi2.5Nb2O9:Er3+ (NBN:Er) thin films. We show that upconversion emission can be effectively modulated by up to 78% through the photochromic reaction. The coupling between lanthanide upconversion emission and the photochromic effect ensures rewritable and nondestructive readout characteristics. Moreover, integrating photochromic thin films with Si would benefit from its compatibility with the mature complementary metal-oxide semiconductor (CMOS) technique. These results demonstrate the opportunity to develop more compact photochromic photomemories and related photonic devices.

Impact of environmental factors on diversity of fungi in sediments from the Shenzhen River Estuary.

In this study, to explore the relationship between environmental factors and fungal diversity in the Shenzhen River ecosystem, multiple methods including chemical analysis, culture isolation, qPCR analysis of fungal ITS region and ITS-based Illumina next-generation-sequencing were integrated. A total of 115 isolates were finally isolated and could be classified into 23 genera. Top three abundant genera isolated were Meyerozyma (18 strains), Aspergillus (17 strains) and Penicillium (14 strains). Based on the Illumina sequencing approach, 829 OTUs were affiliated to seven phyla, 17 known classes, and 162 genera, indicating the Shenzhen estuary sediments are rich in fungal diversity. The major fungal genera were Meyerozyma, Trichoderma and Talaromyces. Environmental factors showed a gradient change in Shenzhen estuary, and fungal abundance was only significantly correlated with NH4+. Shannon index was significantly correlated with pH and IC (P < 0.05). Principal coordinate analysis based on OTU level grouped into three clusters among sampling sites along with the IC and pH gradient. Functional guilds analysis suggests most of the fungi in this studying area were almost all saprotrophs, suggesting a large number of saprophytic fungi may play a significant role in the organic matter decomposition and nutrient cycling process. In summary, this study will deepen our understanding of fungi community in Shenzhen River ecosystem and their distribution and potential function shaped by environmental factors.

Impact of Maternal Preoperative Hemoglobin Levels on Intraoperative Hemorrhage Risk in Placenta Accrete Spectrum Disorders: A Retrospective Cross-Sectional Study.

BACKGROUND Placenta accreta spectrum (PAS) disorders involve abnormal adhesion or invasion of chorionic villi through the myometrium and uterine serosa. Maternal anemia during pregnancy is common and may contribute to complications during delivery, particularly with abnormal placentation. This study examines the association between preoperative maternal hemoglobin levels and the risk of intraoperative massive hemorrhage in pregnant women with PAS disorders. MATERIAL AND METHODS A retrospective study included 538 consecutive participants (mean age=31.12±4.68 years) who underwent cesarean sections and met the diagnostic criteria for PAS disorders. Logistic regression analysis was performed to investigate the relationship between maternal preoperative hemoglobin levels and the risk of massive intraoperative hemorrhage (blood loss ≥1500 mL). RESULTS The incidence of intraoperative massive hemorrhage among patients with PAS disorders was 38.66%. The mean preoperative maternal hemoglobin level was 10.99±1.39 g/dL, and overall anemia incidence (<11 g/dL) was 48.88% in our study. After adjusting for potential confounders, a non-linear relationship was observed between preoperative maternal hemoglobin levels and the risk of intraoperative massive hemorrhage. When the preoperative hemoglobin level of pregnant women was below 11.5 g/dL (OR=0.52, 95% CI 0.39-0.70), the lower hemoglobin level significantly increased the risk of intraoperative hemorrhage. CONCLUSIONS Maternal preoperative hemoglobin levels were inversely associated with the risk of massive intraoperative hemorrhage in PAS disorders. A non-linear relationship was identified, with a turning point at 11.5 g/dL. These findings emphasize the importance of monitoring and managing maternal hemoglobin levels to mitigate the risk of intraoperative hemorrhage in pregnant women with PAS disorders.

Mechanically induced enhancement and modulation of upconversion photoluminescence by bending lanthanide-doped perovskite oxides.

We report experimental studies of the bending strain impact on the upconversion processes in Yb3+, Er3+, and Mn2+ co-doped BaTiO3 (BTO) thin films with mica as the flexible substrate. Bending strain induces strong enhancement and modulation of the upconversion emission in doped BTO thin films. Because the unshielded 3d5 configuration of Mn2+ is more susceptible to crystal field changes, the introduction of an Mn2+ ion further promotes the strain-induced modulation effect. The upconversion intensity is amplified by six times at bending strain ε = 1.83% in BTO:Yb3+/Er3+/Mn2+ thin films. These results demonstrate the opportunity of rendering an upconversion emission through integrating lanthanide-doped ferroelectric films with flexible mica, especially by incorporating an Mn2+ ion.

Control of upconversion luminescence by tailoring energy migration in doped perovskite superlattices.

We describe an experimental investigation of photon upconversion (UC) in a series of perovskite BaTiO3/SrTiO3 superlattices doped with different lanthanide compositions. We show that UC emission can be effectively enhanced by precisely incorporating a set of lanthanide ions into separated layers rather than homogeneously distributing the dopant ions in the host lattice. The use of an inert layer in the superlattice can suppress deleterious energy cross-relaxation. Furthermore, UC emission can be rendered by controlling the energy migration mediated by the Yb-doped sublattice. These results demonstrate the opportunity to modulate energy migration and transfer processes through the rational design of superlattice structures.

Junctophilin-4 facilitates inflammatory signalling at plasma membrane-endoplasmic reticulum junctions in sensory neurons.

KEY POINTS: Rat somatosensory neurons express a junctional protein, junctophilin-4 (JPH4) JPH4 is necessary for the formation of store operated Ca2+ entry (SOCE) complex at the junctions between plasma membrane and endoplasmic reticulum in these neurons. Knockdown of JPH4 impairs endoplasmic reticulum Ca2+ store refill and junctional Ca2+ signalling in sensory neurons. In vivo knockdown of JPH4 in the dorsal root ganglion (DRG) sensory neurons significantly attenuated experimentally induced inflammatory pain in rats. Junctional nanodomain Ca2+ signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms. ABSTRACT: Junctions of endoplasmic reticulum and plasma membrane (ER-PM junctions) form signalling nanodomains in eukaryotic cells. ER-PM junctions are present in peripheral sensory neurons and are important for the fidelity of G protein coupled receptor (GPCR) signalling. Yet little is known about the assembly, maintenance and physiological role of these junctions in somatosensory transduction. Using fluorescence imaging, proximity ligation, super-resolution microscopy, in vitro and in vivo gene knockdown we demonstrate that a member of the junctophilin protein family, junctophilin-4 (JPH4), is necessary for the formation of store operated Ca2+ entry (SOCE) complex at the ER-PM junctions in rat somatosensory neurons. Thus we show that JPH4 localises to the ER-PM junctional areas and co-clusters with SOCE proteins STIM1 and Orai1 upon ER Ca2+ store depletion. Knockdown of JPH4 impairs SOCE and ER Ca2+ store refill in sensory neurons. Furthermore, we demonstrate a key role of the JPH4 and junctional nanodomain Ca2+ signalling in the pain-like response induced by the inflammatory mediator bradykinin. Indeed, an in vivo knockdown of JPH4 in the dorsal root ganglion (DRG) sensory neurons significantly shortened the duration of nocifensive behaviour induced by hindpaw injection of bradykinin in rats. Since the ER supplies Ca2+ for the excitatory action of multiple inflammatory mediators, we suggest that junctional nanodomain Ca2+ signalling maintained by JPH4 is an important contributor to the inflammatory pain mechanisms.

Delineating an extracellular redox-sensitive module in T-type Ca2+ channels.

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1-IS2 and IS3-IS4 loops of domain I and a cluster of extracellular cysteines in the IS1-IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species-producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1-IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1-IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.

Transcriptional Regulation of Voltage-Gated Sodium Channels Contributes to GM-CSF-Induced Pain.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the production of granulocyte and macrophage populations from the hematopoietic progenitor cells; it is one of the most common growth factors in the blood. GM-CSF is also involved in bone cancer pain development by regulating tumor-nerve interactions, remodeling of peripheral nerves, and sensitization of damage-sensing (nociceptive) nerves. However, the precise mechanism for GM-CSF-dependent pain is unclear. In this study, we found that GM-CSF is highly expressed in human malignant osteosarcoma. Female Sprague Dawley rats implanted with bone cancer cells develop mechanical and thermal hyperalgesia, but antagonizing GM-CSF in these animals significantly reduced such hypersensitivity. The voltage-gated Na+ channels Nav1.7, Nav1.8, and Nav1.9 were found to be selectively upregulated in rat DRG neurons treated with GM-CSF, which resulted in enhanced excitability. GM-CSF activated the Janus kinase 2 (Jak2)-signal transducer and activator of transcription protein 3 (Stat3) signaling pathway, which promoted the transcription of Nav1.7-1.9 in DRG neurons. Accordingly, targeted knocking down of either Nav1.7-1.9 or Jak2/Stat3 in DRG neurons in vivo alleviated the hyperalgesia in male Sprague Dawley rats. Our findings describe a novel bone cancer pain mechanism and provide a new insight into the physiological and pathological functions of GM-CSF.SIGNIFICANCE STATEMENT It has been reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a key role in bone cancer pain, yet the underlying mechanisms involved in the GM-CSF-mediated signaling pathway in nociceptors is not fully understood. Here, we showed that GM-CSF promotes bone cancer-associated pain by enhancing the excitability of DRG neurons via the Janus kinase 2 (Jak2)-signal transducer and activator of transcription protein 3 (Stat3)-mediated upregulation of expression of nociceptor-specific voltage-gated sodium channels. Our study provides a detailed understanding of the roles that sodium channels and the Jak2/Stat3 pathway play in the GM-CSF-mediated bone cancer pain; our data also highlight the therapeutic potential of targeting GM-CSF.

Volume-regulated Cl- current: contributions of distinct Cl- channels and localized Ca2+ signals.

The swelling-activated chloride current (ICl,swell) is induced when a cell swells and plays a central role in maintaining cell volume in response to osmotic stress. The major contributor of ICl,swell is the volume-regulated anion channel (VRAC). Leucine-rich repeat containing 8A (LRRC8A; SWELL1) was recently identified as an essential component of VRAC, but the mechanisms of VRAC activation are still largely unknown; moreover, other Cl- channels, such as anoctamin 1 (ANO1), were also suggested to contribute to ICl,swell. In this present study, we investigated the roles of LRRC8A and ANO1 in activation of ICl,swell; we also explored the role of intracellular Ca2+ in ICl,swell activation. We used a CRISPR/Cas9 gene editing approach, electrophysiology, live fluorescent imaging, selective pharmacology, and other approaches to show that both LRRC8A and ANO1 can be activated by cell swelling in HEK293 cells. Yet, both channels contribute biophysically and pharmacologically distinct components to ICl,swell, with LRRC8A being the major component. Cell swelling induced oscillatory Ca2+ transients, and these Ca2+ signals were required to activate both the LRRC8A- and ANO1-dependent components of ICl,swell. Both ICl,swell components required localized rather than global Ca2+ for activation. Interestingly, while intracellular Ca2+ was necessary and sufficient to activate ANO1, it was necessary but not sufficient to activate LRRC8A-mediated currents. Finally, Ca2+ transients linked to the ICl,swell activation were mediated by the G protein-coupled receptor-independent PLC isoforms.

Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals.

Ca(2+)-activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin-1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca(2+) sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca(2+) for activation. However, global Ca(2+) levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca(2+) transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co-localize with sources of intracellular Ca(2+) signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca(2+) release sites of the intracellular Ca(2+) stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.

Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions.

[Application of optogenetic technique in pain research].

Chronic pain represents a major clinical issue which so far is still in shortage of selective and effective treatment. Multiple components are involved in the pain processing, including peripheral, spinal and supraspinal levels of the nervous system. The core to fight the pain problem effectively is to have a good understanding of nociceptive mechanism and the neurobiology of pain perception. Optogenetic technique allows selective activation of subpopulation neurons and provides possibility for better understanding of complex pathway and modulation mechanism in nervous system. Here we review the researches to date that used optogenetic tools for studying pain pathway, and we also provide a brief overview of some new development in optogenetic techniques that may have great potentials in pain research.

Phosphoinositide kinases play key roles in norepinephrine- and angiotensin II-induced increase in phosphatidylinositol 4,5-bisphosphate and modulation of cardiac function.

The seemly paradoxical Gq agonist-stimulated phosphoinositide production has long been known, but the underlying mechanism and its physiological significance are not known. In this study, we studied cardiac phosphoinositide levels in both cells and whole animals under the stimulation of norepinephrine (NE), angiotensin II (Ang II), and other physiologically relevant interventions. The results demonstrated that activation of membrane receptors related to NE or Ang II caused an initial increase and a later fall in phosphatidylinositol 4,5-bisphosphate (PIP2) levels in the primary cultured cardiomyocytes from adult rats. The possible mechanism underlying this increase in PIP2 was found to be through an enhanced activity of phosphatidylinositol 4-kinase IIIß, which was mediated by an up-regulated interaction between phosphatidylinositol 4-kinase IIIß and PKC; the increased activity of phosphatidylinositol 4-phosphate 5-kinase γ was also involved for NE-induced increase of PIP2. When the systolic functions of the NE/Ang II-treated cells were measured, a maintained or failed contractility was found to be correlated with a rise or fall in corresponding PIP2 levels. In two animal models of cardiac hypertrophy, PIP2 levels were significantly reduced in hypertrophic hearts induced by isoprenaline but not in those induced by swimming exercise. This study describes a novel mechanism for phosphoinositide metabolism and modulation of cardiac function.

Characterization of the effects of Cl⁻ channel modulators on TMEM16A and bestrophin-1 Ca²âº activated Cl⁻ channels.

The Ca(2+) activated Cl(-) channels (CaCCs) play a multitude of important physiological functions. A number of candidate proteins have been proposed to form CaCC, but only two families, the bestrophins and the TMEM16 proteins, recapitulate the properties of native CaCC in expression systems. Studies of endogenous CaCCs are hindered by the lack of specific pharmacology as most Cl(-) channel modulators lack selectivity and a systematic comparison of the effects of these modulators on TMEM16A and bestrophin is missing. In the present study, we studied seven Cl(-) channel inhibitors: niflumic acid (NFA), NPPB, flufenamic acid (FFA), DIDS, tannic acid, CaCCinh-A01 and T16Ainh-A01 for their effects on TMEM16A and bestrophin-1 (Best1) stably expressed in CHO (Chinese hamster ovary) cells using patch clamp technique. Among seven inhibitors studied, NFA showed highest selectivity for TMEM16A (IC50 of 7.40 ± 0.95 µM) over Best1 (IC50 of 102.19 ± 15.05 µM). In contrast, DIDS displayed a reverse selectivity inhibiting Best1 with IC50 of 3.93 ± 0.73 µM and TMEM16A with IC50 of 548.86 ± 25.57 µM. CaCCinh-A01 was the most efficacious blocker for both TMEM16A and Best1 channels. T16Ainh-A01 partially inhibited TMEM16A currents but had no effect on Best1 currents. Tannic acid, NPPB and FFA had variable intermediate effects. Potentiation of channel activity by some of these modulators and the effects on TMEM16A deactivation kinetics were also described. Characterization of Cl(-) channel modulators for their effects on TMEM16A and Best1 will facilitate future studies of native CaCCs.

GABAB receptors inhibit low-voltage activated and high-voltage activated Ca(2+) channels in sensory neurons via distinct mechanisms.

Growing evidence suggests that mammalian peripheral somatosensory neurons express functional receptors for gamma-aminobutyric acid, GABAA and GABAB. Moreover, local release of GABA by pain-sensing (nociceptive) nerve fibres has also been suggested. Yet, the functional significance of GABA receptor triggering in nociceptive neurons is not fully understood. Here we used patch-clamp recordings from small-diameter cultured DRG neurons to investigate effects of GABAB receptor agonist baclofen on voltage-gated Ca(2+) currents. We found that baclofen inhibited both low-voltage activated (LVA, T-type) and high-voltage activated (HVA) Ca(2+) currents in a proportion of DRG neurons by 22% and 32% respectively; both effects were sensitive to Gi/o inhibitor pertussis toxin. Inhibitory effect of baclofen on both current types was about twice less efficacious as compared to that of the µ-opioid receptor agonist DAMGO. Surprisingly, only HVA but not LVA current modulation by baclofen was partially prevented by G protein inhibitor GDP-ß-S. In contrast, only LVA but not HVA current modulation was reversed by the application of a reducing agent dithiothreitol (DTT). Inhibition of T-type Ca(2+) current by baclofen and the recovery of such inhibition by DTT were successfully reconstituted in the expression system. Our data suggest that inhibition of LVA current in DRG neurons by baclofen is partially mediated by an unconventional signaling pathway that involves a redox mechanism. These findings reinforce the idea of targeting peripheral GABA receptors for pain relief.

Acupuncture combined with mirror therapy for post-stroke dyskinesia: A meta-analysis and systematic review.

BACKGROUND: Dyskinesia is one of the most common complications of stroke. Acupuncture therapy (AT) and mirror therapy (MT) are promising rehabilitation measures for the treatment of post-stroke dyskinesia. Although some studies suggested that AT and MT are effective and safe for dyskinesia, the effects, and safety remain uncertain due to lacking strong evidence. The purpose of this study is to investigate the efficacy and safety of AT combined with MT in the treatment of post-stroke dyskinesia. METHODS: We searched the following databases: PubMed, Web of Science, Cochrane Library, EMBASE, Medline, China Knowledge Network, WANFANG, and China Biomedical Literature Database, from inception to 1 January 2023 to identify eligible studies. Total effective rate, the Fugl-Meyer assessment scale (FMA) upper and lower limb scores, modified Barthel index scores, Berg balance scale, modified Ashworth scale, and adverse reactions were adopted as outcome indicators. The Grading of Recommendations Assessment Development and Evaluation system was used by 2 independent reviewers to assess the quality of evidence for the outcome indicators included in the study. The statistical analysis was conducted by RevMan V.5.4 software. RESULTS: A total of 24 randomized controlled studies included 2133 patients with post-stroke dyskinesia were included. The total effective rate of AT combined with MT was more advantageous in the treatment of post-stroke dyskinesia (relative risk = 1.31, 95% confidence interval [CI] [1.22-1.42], Z = 6.96, P < .0001). AT combined with MT was more advantageous for FMA upper limb score (mean difference [MD] = 6.67, 95% CI [5.21-8.13], Z = 8.97, P < .00001) and FMA lower limb score (MD = 3.72, 95% CI [2.81-4.63], Z = 7.98, P < .00001). Meta-analysis showed that AT combined with MT for post-stroke dyskinesia had a more advantageous modified Barthel index score (MD = 9.51, 95% CI [7.44-11.58], Z = 9.01, P < .00001). CONCLUSION: AT combined with MT is effective in improving motor function and daily living ability of patients, especially in improving muscle spasms. However, these results should be regarded with caution given the low quality of evidence for the evaluation results.

Effects of health-related dispositions on citizens' appraisals toward the COVID-19 pandemic and protective behavior.

In this study, health risk attitude and health locus of control were included as dispositional factors in the Protection Motivation Theory (PMT) to explain people's protective behavior in the context of COVID-19 pandemic. Empirical data involved two waves of data with a sample of 526 adults with full-time jobs from Beijing, China, and structural equation model results confirmed a partial successful extension of the PMT. Specifically, health risk attitude had a direct effect on citizens' protective behavior, but without an indirect effect mediated by threat appraisal toward the COVID-19 pandemic; health locus of control did not directly associate with citizens' protective behavior, but had an indirect effect on it fully via coping appraisal toward the COVID-19 pandemic. Thus, the PMT has been extended by adding a distal dispositional factor on the impact of coping appraisal on protective behavior. Implications for advancing the government's anti-epidemic strategy are discussed.