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This article proposes an electromagnetic acoustic transducer (EMAT) for selectively improving the purity and amplitude of ultrasonic Lamb waves in non-ferromagnetic plates. The developed EMAT consists of a racetrack coil and a group of periodic permanent magnets (PPMs). Two-dimensional finite element simulations and experiments are implemented to analyze the working mechanism and performance of the PPM EMAT. Thanks to the specific design, the eddy currents increase with increasing wire density and the directions of the magnetic fields and Lorentz forces alternate according to the polarities of the magnet units. Wires laid uniformly beneath the magnets, and the gaps between adjacent magnets generate tangential and normal Lorentz forces, resulting in-plane (IP) and out-of-plane (OP) displacements, respectively. The constructive interference occurs when the wavelength of the generated Lamb wave is twice the spacing of the magnets, leading to large amplitudes of the targeted ultrasonic Lamb waves. Therefore, the PPM EMAT is capable of generating pure symmetric or antisymmetric mode Lamb waves at respective frequencies. The results prove that the developed PPM EMAT can generate pure either S0 or A0 mode Lamb waves at respective frequencies. The increase in wire width and wire density further increases the signal amplitudes. Compared with the case of conventional meander-line-coil (MLC) EMAT, the amplitudes of the A0 and S0 mode Lamb waves of our PPM EMAT are increased to 880% and 328%, respectively.

In Parkinson's disease (PD), wearing off and side effects of long-term medication and complications pose challenges for neurologists. Although Tai Chi is beneficial for many illnesses, its efficacy for PD remains uncertain. The purpose of this review was to evaluate the efficacy and safety of Tai Chi for PD. Randomized controlled trials (RCTs) of Tai Chi for PD were electronically searched by the end of December 2013 and identified by two independent reviewers. The tool from the Cochrane Handbook 5.1 was used to assess the risk of bias. A standard meta-analysis was performed using RevMan 5.2 software. Ten trials with PD of mild-to-moderate severity were included in the review, and nine trials (n = 409) were included in the meta-analysis. The risk of bias was generally high in the blinding of participants and personnel. Improvements in the Unified Parkinson's Disease Rating Scale Part III (mean difference (MD) -4.34, 95% confidence interval (CI) -6.67--2.01), Berg Balance Scale (MD: 4.25, 95% CI: 2.83-5.66), functional reach test (MD: 3.89, 95% CI: 1.73-6.04), Timed Up and Go test (MD: -0.75, 95% CI: -1.30--0.21), stride length (standardized MD: 0.56, 95% CI: 0.03-1.09), health-related quality of life (standardized MD: -1.10, 95% CI: -1.81--0.39) and reduction of falls were greater after interventions with Tai Chi plus medication. Satisfaction and safety were high. Intervention with Tai Chi alone was more effective for only a few balance and mobility outcomes. Tai Chi performed with medication resulted in promising gains in mobility and balance, and it was safe and popular among PD patients at an early stage of the disease. This provides a new evidence for PD management. More RCTs with larger sample size that carefully address blinding and prudently select outcomes are needed. PROSPERO registration number CRD42013004989.

Background Aicardi–Goutières syndrome (AGS) is a severe neurodegenerative disease with clinical features of early-onset encephalopathy and progressive loss of intellectual abilities and motor control. Gene mutations in seven protein-coding genes have been found to be associated with AGS. However, the causative role of these mutations in the early-onset neuropathogenesis has not been demonstrated in animal models, and the mechanism of neurodegeneration of AGS remains ambiguous. Methods Via CRISPR/Cas-9 technology, we established a mutant mouse model in which a genetic mutation found in AGS patients at the ADAR1 coding gene ( Adar ) loci was introduced into the mouse genome. A mouse model carrying double gene mutations encoding ADAR1 and MDA-5 was prepared using a breeding strategy. Phenotype, gene expression, RNA sequencing, innate immune pathway activation, and pathologic studies including RNA in situ hybridization (ISH) and immunohistochemistry were used for characterization of the mouse models to determine potential disease mechanisms. Results We established a mouse model bearing a mutation in the catalytic domain of ADAR1, the D1113H mutation found in AGS patients. With this mouse model, we demonstrated a causative role of this mutation for the early-onset brain injuries in AGS and determined the signaling pathway underlying the neuropathogenesis. First, this mutation altered the RNA editing profile in neural transcripts and led to robust IFN-stimulated gene (ISG) expression in the brain. By ISH, the brains of mutant mice showed an unusual, multifocal increased expression of ISGs that was cell-type dependent. Early-onset astrocytosis and microgliosis and later stage calcification in the deep white matter areas were observed in the mutant mice. Brain ISG activation and neuroglial reaction were completely prevented in the Adar D1113H mutant mice by blocking RNA sensing through deletion of the cytosolic RNA receptor MDA-5. Conclusions The Adar D1113H mutation in the ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the mouse brain.

Background Aicardi-Goutières syndrome (AGS) is a severe infant or juvenile-onset autoimmune disease characterized by inflammatory encephalopathy with an elevated type 1 interferon-stimulated gene (ISG) expression signature in the brain. Mutations in seven different protein-coding genes, all linked to DNA/RNA metabolism or sensing, have been identified in AGS patients, but none of them has been demonstrated to activate the IFN pathway in the brain of an animal. The molecular mechanism of inflammatory encephalopathy in AGS has not been well defined. Adenosine Deaminase Acting on RNA 1 (ADAR1) is one of the AGS-associated genes. It carries out A-to-I RNA editing that converts adenosine to inosine at double-stranded RNA regions. Whether an AGS-associated mutation in ADAR1 activates the IFN pathway and causes autoimmune pathogenesis in the brain is yet to be determined. Methods Mutations in the ADAR1 gene found in AGS patients were introduced into the mouse genome via CRISPR/Cas9 technology. Molecular activities of the specific p.K999N mutation were investigated by measuring the RNA editing levels in brain mRNA substrates of ADAR1 through RNA sequencing analysis. IFN pathway activation in the brain was assessed by measuring ISG expression at the mRNA and protein level through real-time RT-PCR and Luminex assays, respectively. The locations in the brain and neural cell types that express ISGs were determined by RNA in situ hybridization (ISH). Potential AGS-related brain morphologic changes were assessed with immunohistological analysis. Von Kossa and Luxol Fast Blue staining was performed on brain tissue to assess calcification and myelin, respectively. Results Mice bearing the ADAR1 p.K999N were viable though smaller than wild type sibs. RNA sequencing analysis of neuron-specific RNA substrates revealed altered RNA editing activities of the mutant ADAR1 protein. Mutant mice exhibited dramatically elevated levels of multiple ISGs within the brain. RNA ISH of brain sections showed selective activation of ISG expression in neurons and microglia in a patchy pattern. ISG-15 mRNA was upregulated in ADAR1 mutant brain neurons whereas CXCL10 mRNA was elevated in adjacent astroglia. No calcification or gliosis was detected in the mutant brain. Conclusions We demonstrated that an AGS-associated mutation in ADAR1, specifically the p.K999N mutation, activates the IFN pathway in the mouse brain. The ADAR1 p.K999N mutant mouse replicates aspects of the brain interferonopathy of AGS. Neurons and microglia express different ISGs. Basal ganglia calcification and leukodystrophy seen in AGS patients were not observed in K999N mutant mice, indicating that development of the full clinical phenotype may need an additional stimulus besides AGS mutations. This mutant mouse presents a robust tool for the investigation of AGS and neuroinflammatory diseases including the modeling of potential “second hits” that enable severe phenotypes of clinically variable diseases.

This systematic review and meta-analysis aims to: assess the effectiveness and safety of orally administered Chinese herbal medicines (CHMs) as adjuncts to the post-surgical management of chronic rhinosinusitis (CRS); inform clinicians of the current evidence; identify the best available evidence; and suggest directions for further research. Randomised controlled trials (RCTs) were identified from searches of nine databases plus clinical trial registries. Participants were adults and/or children diagnosed with sinusitis or rhinosinusitis, with or without nasal polyps, who had received surgery. Interventions were CHMs used orally following surgery for CRS as additions to conventional post-surgical management. Controls received conventional post-surgical management without CHMs. Studies reported results for Sino-Nasal Outcome Test (SNOT), visual analogue scales (VAS), Lund-Mackay computed tomography score (LM), Lund-Kennedy endoscopic score (LK), mucociliary transport time (MTT), mucociliary transport rate (MTR), mucociliary clearance (MC) or quality of life (QoL). Twenty-one RCTs were included. All used oral CHMs following functional endoscopic sinus surgery (FESS). The pooled results showed no significant difference between groups for SNOT-20 at the end of treatment (EoT) but there was a significant difference at follow up (FU) in favour of additional CHMs. The VAS for total nasal symptoms (VAS-TNS) showed greater improvements in the CHM groups at EoT and FU. Only FU data were reported for LM which showed greater improvement in the CHM groups. LK showed greater improvements at EoT and FU. The measures of mucociliary transport (MTT, MTR, and MC) each showed significantly greater improvement at EoT in the group that received additional CHMs. No study reported QoL. Adverse events were not serious, but reporting was incomplete. The meta-analyses suggested the addition of oral CHMs to conventional management following FESS may improve recovery. However, most studies were not blinded, and substantial heterogeneity was evident in some meta-analyses. Blinded studies are required to further investigate the roles of oral CHMs in post-surgical recovery. Systematic review registration number: The protocol was registered in PROSPERO ( CRD42019119586 ).

This systematic review aims to assess the effects and safety of Chinese herbal medicines (CHMs) in the management of rhinosinusitis (RS); inform clinicians of the current state of the evidence; identify the best available evidence; and suggest further directions for research. Five English and four Chinese language databases, and four clinical trial registries were searched. Eligible studies were randomised controlled trials (RCTs). Participants were diagnosed with RS based on established criteria. Test interventions were CHMs administered orally and/or nasally, excluding injections and displacement techniques. Control interventions included placebos, no additional treatment, and conventional non-invasive treatments including pharmacotherapies and/or nasal irrigation, and/or inhalations. Polyposis and post-surgical recovery were excluded. Outcomes were Sino-Nasal Outcome Test (SNOT), visual analogue scales (VAS), Lund-Mackay computed tomography score (LM), Lund-Kennedy Endoscopic score (LK), Mucociliary transport time (MTT), Mucociliary transport rate (MTR), quality of life and adverse events (AEs). Risk of bias used the Cochrane tool. Meta-analysis in Review Manager 5.4.1 used random effects for mean difference (MD) or risk ratio (RR) with 95% confidence intervals. Heterogeneity was assessed as I 2 . Thirty-four RCTs were included, 30 of chronic RS (CRS) and four of acute RS (ARS). These enrolled 3,752 participants. Five RCTs blinded participants. For CRS, comparisons with placebo showed greater improvements in the CHM groups for SNOT-20 and VAS-TNS (total nasal symptoms). Blinded comparisons with pharmacotherapies showed no differences between groups in the degree of improvement for SNOT-20, VAS-TNS, and LM, suggesting these CHMs had similar effects, at least in the short term. In ARS, pooled results found improved scores on VAS-TNS and LK suggesting a benefit for combining these CHMs with pharmacotherapies. Limitations included inadequacies in study design and methodological reporting, and insufficient reporting of AEs. Heterogeneity in some pooled results precluded strong conclusions. Further well-designed studies are needed to test whether the results are replicable. Systematic review registration number: PROSPERO ( CRD42019119586 ).

Migraine is a disabling, recurrent headache disorder with complex comorbidities. Conventional treatments for migraine are unsatisfactory, with side effects and limited effectiveness. Chinese herbal medicine (CHM) has been used as an alternative or complementary treatment option for migraine in China. Currently, the existing evidence of benefit of CHM for migraine has been generated from randomised clinical trials using standardised intervention with a focus on internal validity hence with limited external validity. Moreover, CHM individualised intervention design, patients' preferences and concerns, and clinicians' experience are critical to clinical decision making and therapeutic success. This real-world observational study aims to gather practice-based evidence of effects and safety of CHM for migraine in the context of integrating Chinese medicine diagnostic procedures, patients' preferences and matters relevant to clinical decision making. The study is being undertaken at the Guangdong Provincial Hospital of Chinese Medicine (GPHCM) from December 2020 to May 2022. We anticipate that approximately 400 adult migraineurs will be enrolled and observed on their migraine severity, analgesic consumption, quality of life, anxiety, depression and insomnia at baseline and then every four weeks over 12 weeks. Treatments, diagnostic information, and patient-reported most bothersome symptoms will be collected from patient clinical records. Patient's demographic data, preferences and concerns on CHM treatments will also be gathered at baseline and be analysed. Factors related to clinical outcomes will be explored with multiple correlation and multivariable regression analyses. Effects of CHM will be evaluated using generalised estimated equation, based on clinical outcome data. This study will provide comprehensive evidence of CHM for migraine in the context of evidence-based practice. ChiCTR2000041003.

Parkinson's disease (PD) is a progressive neurodegenerative condition. Chinese medicine therapies have demonstrated effectiveness for PD in controlled settings. However, the utilization of Chinese medicine therapies for PD in real-world clinical practice and the characteristics of patients seeking these therapies have not been thoroughly summarized. The study retrospectively analyzed initial patient encounters (PEs) with a first-listed diagnosis of PD, based on electronic medical records from Guangdong Provincial Hospital of Chinese Medicine between July 2018 and July 2023. A total of 3,206 PEs, each corresponding to an individual patient, were eligible for analyses. Approximately 60% of patients made initial visits to the Chinese medicine hospital after receiving a PD diagnosis, around 4.59 years after the onset of motor symptoms. Over 75% of the patients visited the Internal Medicine Outpatient Clinic at their initial visits, while a mere 13.85% visited PD Chronic Care Clinic. Rest tremor (61.98%) and bradykinesia (52.34%) are the most commonly reported motor symptoms, followed by rigidity (40.70%). The most commonly recorded non-motor symptoms included constipation (31.88%) and sleep disturbance (25.27%). Integration of Chinese medicine and conventional medicine therapies was the most common treatment method (39.15%), followed by single use of Chinese herbal medicine (27.14%). The most frequently prescribed herbs for PD included Fisch. ( ), Bunge ( ), Koidz. ( ), (Oliv.) Diels ( ), (Gaertn.) DC. ( ), Pall. ( ), DC. ( ), L. ( / ), C. A. Mey. ( ), and (Schw.) Wolf ( ). These herbs contribute to formulation of (BZYQT). Patients typically initiated Chinese medical care after the establishment of PD diagnosis, ~4.59 years post-onset of motor symptoms. The prevalent utilization of CHM decoctions and patented Chinese herbal medicine products, underscores its potential in addressing both motor and non-motor symptoms. Despite available evidence, rigorous clinical trials are needed to validate and optimize the integration of CHM, particularly BZYQT, into therapeutic strategies for PD.

The generation of test vectors is a key technique that affects the efficiency and fault detection rate of the boundary scan test. Aiming at the local optimal solution problem of the current common test vectors generation algorithm, this paper proposes a test vectors generation algorithm based on improved GA-AO* model, through which the test vectors are generated by using the idea of heuristic search and backtracking correction. In order to speed up the heuristic search, this paper designed a heuristic function with both prior and posterior parameters to describe the influence of typical faults on the failure probability index of the test vectors. At the same time, this paper used a genetic algorithm (GA) to determine the specific values of the posterior parameters iteratively. Finally, through theoretical analysis and physical verification, compared with the test vector generated by the traditional method, the test vector generated by this method is optimized on the prior failure probability index and performs better in the physical experiment.

Objectives: To assess the clinical evidence for integrative herbal medicine therapy in the management of chemotherapy-induced peripheral neuropathy (CIPN) and hand-foot syndrome (HFS) resulting from treatments for colorectal cancer (CRC). Design: Randomized controlled trials (RCTs) were identified from major English and Chinese databases. Participants had been diagnosed with CRC by pathology and had received or were undergoing chemotherapy. Interventions included herbal medicines administered orally or topically. Controls were placebo, supportive care or conventional chemotherapy for CRC. Methods followed the Cochrane handbook. Meta-analyses were grouped by study design, outcome measure, severity, and chemotherapy. Random-effects models with 95% confidence intervals were used. Heterogeneity was assessed as I2. Results: Sixty-three RCTs (4286 participants) were included. Five used a placebo in the control groups. Fifty-eight studies tested oral herbal medicine, and 5 tested topical herbal medicine. Data were available for CIPN (60 studies) and HFS (12 studies). Fifty-seven studies combined orally administered herbal medicine with chemotherapy compared with the same chemotherapy. For CIPN, 33 studies used World Health Organization (WHO) criteria, 7 used Levi’s criteria, and 10 used the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). These were analyzed separately. For grades III + IV CIPN, there was a significant reduction in the integrative groups for WHO (relative risk [RR] 0.42 [0.23, 0.77], I2 = 0%) and Levi’s (RR 0.28 [0.11, 0.69], I2 = 0%) but not NCI-CTCAE (RR 0.65 [0.37, 1.13], I2 = 26.4%). Hand and foot baths showed no differences for Levi’s grades III + IV CIPN but a significant reduction in all grades (RR 0.69 [0.50, 0.95], I2 = 68.8%). For HFS (all grades) there was a significant reduction in the integrative groups for WHO (RR 0.62 [0.41, 0.96], I2 = 22%) but not for NCI-CTCAE (RR 0.93 [0.55, 1.55], I2 = 75.7%). Sensitivity analyses explored sources of heterogeneity. Conclusions: Integrative herbal therapy appeared to reduce CIPN and HFS in people receiving chemotherapy for CRC. However, the strength of the evidence was limited by lack of blinding in most studies, potential for bias, and relatively short study durations.