Causal effects of gut microbiota on the prognosis of ischemic stroke: evidence from a bidirectional two-sample Mendelian randomization study.

Background: Increasing research has implicated the possible effect of gut microbiota (GM) on the prognosis of ischemic stroke (IS). However, the precise causal relationship between GM and functional outcomes after IS remains unestablished. Methods: Data on 211 GM taxa from the MiBioGen consortium and data on prognosis of IS from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) network were utilized as summary-level data of exposure and outcome. Four kinds of Mendelian randomization (MR) methods were carried out to ascertain the causal effect of GM on functional outcomes following IS. A reverse MR analysis was performed on the positive taxa identified in the forward MR analysis to determine the direction of causation. In addition, we conducted a comparative MR analysis without adjusting the baseline National Institute of Health Stroke Scale (NIHSS) of post-stroke functional outcomes to enhance confidence of the results obtained in the main analysis. Results: Four taxa were identified to be related to stroke prognosis in both main and comparative analyses. Specifically, genus Ruminococcaceae UCG005 and the Eubacterium oxidoreducens group showed significantly negative effects on stroke prognosis, while the genus Lachnospiraceae NK4A136 group and Lachnospiraceae UCG004 showed protective effects against stroke prognosis. The reverse MR analysis did not support a causal role of stroke prognosis in GM. No evidence of heterogeneity, horizontal pleiotropy, and outliers was found. Conclusion: This MR study provided evidence that genetically predicted GM had a causal link with post-stroke outcomes. Specific gut microbiota taxa associated with IS prognosis were identified, which may be helpful to clarify the pathogenesis of ischemic stroke and making treatment strategies.

The Efficacy and Safety of Manual Therapy for Symptoms Associated with Multiple Sclerosis: A Systematic Review and Meta-Analysis.

Background: Multiple sclerosis (MS) is a chronic neurological autoimmune disease, affecting the psychological and physical health of patients. Manual therapies have been proven to relieve pain, strengthen muscles, and improve bladder and bowel problems with a high safety and low adverse event profile. Previous studies have reported the results of manual therapy in alleviating symptoms associated with MS, but the conclusions were controversial. Objective: The purpose of this meta-analysis is to comprehensively analyze and determine the efficacy and safety of manual therapy in relieving symptoms associated with MS. Methods: Eight electronic databases were searched from inception of the database to April 30, 2021. Randomized controlled trials (RCTs) using manual therapy in patients to relieve symptoms associated with MS were considered eligible for this study. Two reviewers independently extracted data using pre-established standards. Results: Finally, 10 eligible RCTs with 631 subjects were included in this meta-analysis. These data establish that massage therapy can significantly ameliorate fatigue, pain, and spasms, while reflexology was only effective in relieving pain in MS patients. No adverse events were reported in eligible RCTs. Conclusions: The present study provides strong evidence that massage therapy could alleviate fatigue, pain, and spasms in MS patients, while reflexology plays a positive role in relieving pain. Physicians could consider massage therapy or reflexology as a safe and effective complementary and alternative treatment. Larger RCTs with higher methodological quality are needed in the future, which aim to provide more meaningful evidence for further proof of efficacy.

Evaluation methods of a rat sciatic nerve crush injury model.

BACKGROUND: The rat sciatic nerve crush injury model is one of the most commonly used models to research peripheral nerve injury (PNI), however, the evaluation of the model preparation lacks exact standards. This study aimed to investigate accurately assessment methods for research concerning the rat sciatic nerve crush injury. METHODS: The sciatic nerve crush injury model of was performed using the FST toothless forceps. The corresponding locations and pressures of different ratchet strengths were assessed by using CMAP, behavioral, and morphological methods. RESULTS: In each group of PNI, motor and sensory functions were gradually restricted on the injured side of rats as the applied pressure increased. CMAP was more sensitive to nerve injury arising out of the force values obtained from the forceps. CONCLUSIONS: As a sensitive indicator for PNI, the neuroelectrophysiological examination was more likely to reflect the morphological changes of injured nerves. These findings may provide a standardized approach to sciatic crush injury modelling.

The efficacy and safety of Tuina for diabetic gastroparesis: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic gastroparesis (DGP) is one of the most common complication of diabetes. At present, despite the increasing number of clinical researches of treatment with Tuina have been reported, there are no systematic reviews of Tuina therapy for DGP. Therefore, it is of great significance to evaluate its safety and efficacy as a complementary and alternative therapy. METHODS AND ANALYSIS: Randomized controlled trials (RCTs) of Tuina therapy in the treatment of DGP will be retrieved from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP), Medline, and Clinical Trial Register (CTR). We will consider articles published in English or Chinese between database initiation and October 2021. Research selection, data extraction, risk of bias assessment, and meta-analyses will be independently completed by 2 researchers. Our researchers will use Revman 5.3 software, provided by the Cochrane Collaborative Network for conducting systematic reviews and meta-analysis. RESULTS: This systematic review provides a high-quality synthesis to assess the effectiveness and safety of Tuina therapy for treating DGP. CONCLUSION: The conclusions of our study will provide evidence to determine whether Tuina therapy is an effective and safe intervention for patients with DGP. SYSTEMATIC REVIEW REGISTRATION: : INPLASY2021110019.

Therapeutic effect and safety of Tuina on sciatica: A protocol for systematic review and meta-analysis∗.

BACKGROUND: Sciatica is one of the common pain symptoms in the human body, also known as radiating leg pain. Sciatica is increasingly occurring due to poor posture and lack of physical exercise all over the world. At present, many studies have indicated that Tuina can improve the clinical symptoms and functional status of sciatica. However, there is currently no relevant systematic review to evaluate and report this clinical scientific issue. Consequently, this study will conduct a meta-analysis on the effectiveness and safety of Tuina therapy for sciatica. METHODS AND ANALYSIS: Randomized controlled trials (RCTs) related to Tuina treatment of sciatica will be retrieved from the Chinese and English databases and Clinical Trial Register. These databases include China National Knowledge Infrastructure, Wan Fang Database, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, PubMed, Embase, Web of Science, Cochrane Library, and Medline, etc. We will consider articles published in English or Chinese between database initiation and October 2021. Our team will use Review Manager Software 5.3 software provided by the Cochrane Collaborative Network to conduct this systematic review and meta-analysis. RESULTS: This study provides a comprehensive evaluation of the effectiveness and safety of Tuina therapy for sciatica. CONCLUSION: The conclusion of our study will provide scientific evidence and reference to determine whether Tuina is an effective and safe intervention for patients with sciatica. REGISTRATION NUMBER: INPLASY2021100034.

A novel label-free upconversion fluorescence resonance energy transfer-nanosensor for ultrasensitive detection of protamine and heparin.

A novel label-free fluorescence nanosensor was developed for ultrasensitive detection of protamine and heparin based on fluorescence resonance energy transfer (FRET) between NaYF4:Yb,Er upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs). The FRET system was formed by the electrostatic adsorption of AuNPs on UCNPs, and the fluorescence of UCNPs was significantly quenched. When protamine was added to the mixture of UCNPs-AuNPs, the AuNPs interacted with protamine and then desorbed from the surface of UCNPs and aggregated, resulting in the recovery of the fluorescence of UCNPs. On the addition of both protamine and heparin, the FRET system formed owing to the stronger interaction between heparin and protamine than that with AuNPs, leading to a marked fluorescence quenching of UCNPs. The concentrations of protamine and heparin were proportional to the changes of the fluorescence of UCNPs. The linear response range was obtained over the concentration ranges of 0.02 to 1.2µg/ml and 0.002 to 2.0µg/ml with low detection limits of 6.7 and 0.7ng/ml for protamine and heparin, respectively. Simultaneous measurement of protamine and heparin in human serum can be achieved, suggesting that the nanosensor can be used in a complex biological sample matrix.

A "turn-on" fluorescent sensor for ultrasensitive detection of melamine based on a new fluorescence probe and AuNPs.

In this study, we synthesized a new fluorescence probe which was used to detect melamine by coupling with gold nanoparticles (AuNPs). The new fluorescence probe has good optical stability and high fluorescence intensity, which can greatly improve the detection sensitivity. Compared to the traditional fluorophore, it is less dependent on the pH value. It has a very strong fluorescence emission peak at 550 nm, which has larger overlap with the absorption peak of AuNPs. When the probe incubates with the AuNPs, the fluorescence of the probe can be effectively quenched by AuNPs. Adding melamine into a probe-AuNPs mixture caused aggregation of AuNPs and released the adsorbed probe; the fluorescence intensity of the probe was recovered. By measuring the changes of the fluorescence intensity of the probe, the detection of melamine can be realized. Under optimized conditions, the linear response to melamine is in the range of 1.0 × 10(-8)-4.0 × 10(-6) mol L(-1) and lowers the detection limit down to 3.0 nmol L(-1) with the sensor. This method can detect melamine in milk and milk-based productions.

Water-dispersible silicon dots as a peroxidase mimetic for the highly-sensitive colorimetric detection of glucose.

We demonstrate that photoluminescent Si-dots exhibit intrinsic peroxidase-like activity, and can catalyze the oxidization of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2, and produce a color change. This strategy can be used to detect glucose with high sensitivity and selectivity.

Label-free silicon quantum dots as fluorescent probe for selective and sensitive detection of copper ions.

In this work, label-free silicon quantum dots (SiQDs) were used as a novel fluorescence probe for the sensitive and selective detection of Cu(2+). The fluorescence of the SiQDs was effectively quenched by H2O2 from the reaction of ascorbic acid with O2, and hydroxyl radicals from Fenton reaction between H2O2 and Cu(+). The fluorescence intensity of SiQDs was quenched about 25% in 15 min after the addition of H2O2 (1mM). While the SiQDs was incubated with AA (1mM) and Cu(2+) (1 µM) under the same conditions, the fluorescence intensity of SiQDs decreased about 55%. Obviously, the recycling of Cu(2+) in the test system may lead to a dramatical decrease in the fluorescence of SiQDs. Under the optimized experimental conditions, the rate of fluorescence quenching of SiQDs was linearly dependent on the Cu(2+) concentration ranging from 25 to 600 nM with the limit of detection as low as 8 nM, which was much lower than that of existing methods. Moreover, the probe was successfully applied to the determination of Cu(2+) in different environmental water samples and human hair.

Gold nanoparticle coupled with fluorophore for ultrasensitive detection of protamine and heparin.

Here we report a novel label-free fluorescent sensor for ultrasensitive detection of protamine and heparin based on the high quenching ability of gold nanoparticles to the fluorescence of fluorescein. The fluorescence was significantly quenched when fluorescein molecules were attached to the surface of gold nanoparticles by electrostatic interaction. Upon addition of protamine, the fluorescein molecules were detached from the surface of the gold nanoparticles due to the stronger adsorption of protamine on the surface of AuNPs, and resulting in the recovery of the fluorescein molecules fluorescence. Heparin is able to bind with Protamine specifically. In the presence of heparin, the interaction of heparin with protamine makes the AuNPs de-aggregate and the fluorescein molecules re-attach to the AuNPs, which lead to marked fluorescence quench again. By measuring the changes in the fluorescence of the fluorescein molecules, the concentration of protamine and heparin were sequentially determined. The linear response range was obtained over the concentration range from 0 to 0.8 µg/mL and 4 to 1.6 µg/mL with the low detection limit 0.0067 µg/mL and 0.0013 µg/mL for protamine and heparin, respectively.

A label-free silicon quantum dots-based photoluminescence sensor for ultrasensitive detection of pesticides.

Sensitive, rapid, and simple detection methods for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents are in urgent demand. A novel label-free silicon quantum dots (SiQDs)-based sensor was designed for ultrasensitive detection of pesticides. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce betaine and H2O2 which can quench the photoluminescence (PL) of SiQDs. Upon the addition of pesticides, the activity of AChE is inhibited, leading to the decrease of the generated H2O2, and hence the PL of SiQDs increases. By measuring the increase in SiQDs PL, the inhibition efficiency of pesticide to AChE activity was evaluated. It was found that the inhibition efficiency was linearly dependent on the logarithm of the pesticides concentration. Consequently, pesticides, such as carbaryl, parathion, diazinon, and phorate, were determined with the SiQDs PL sensing method. The lowest detectable concentrations for carbaryl, parathion, diazinon, and phorate reached 7.25 × 10(-9), 3.25 × 10(-8), 6.76 × 10(-8), and 1.9 × 10(-7) g/L, respectively, which were much lower than those previously reported. The detecting results of pesticide residues in food samples via this method agree well with those from high-performance liquid chromatography. The simple strategy reported here should be suitable for on-site pesticides detection, especially in combination with other portable platforms.

Green synthesis of carbon dots with down- and up-conversion fluorescent properties for sensitive detection of hypochlorite with a dual-readout assay.

High quality carbon dots (C-dots) with down- and up-conversion fluorescence have been synthesized through low-temperature carbonization using sweet pepper as the carbon source. The C-dots with a quantum yield (QY) of 19.3% exhibit superior photophysical properties, for example, narrow and symmetric emission spectra, large stock shifts, resistance to photobleaching, and excitation-dependent fluorescence behavior. The excellent C-dots serve as useful fluorescent probes for hypochlorite (ClO(-)) detection by both down- and up-conversion fluorescence. Two consecutive linear ranges allow a wide determination of ClO(-) concentrations with a low detection limit of 0.05 µmol L(-1) and 0.06 µmol L(-1) (S/N = 3) for down- and up-conversion fluorescence measurements, respectively. The proposed detection method is advantageous because it is simple, sensitive, dual-signalling model and low-cost and has potential extensive applications in environmental and biological assays.