Endovascular therapy beyond 24 hours for anterior circulation large vessel occlusion or stenosis in acute ischemic stroke: a retrospective study.

Background: To assess the clinical and safety outcomes of endovascular treatment (EVT) administered more than 24 h after the onset of symptoms in patients with acute ischemic stroke resulting from anterior circulation large-vessel occlusion or stenosis (AIS-ACLVO/S). Methods: We enrolled consecutive AIS-ACLVO/S patients who received EVT in our hospital between January 2019 and February 2022 and divided them into two groups based on the time from AIS onset to EVT: EVT < 24 h group and EVT >24 h group. The successful reperfusion (modified thrombolysis in cerebral infarction, [mTICI] ≥2b), 90-day modified Rankin Scale score (mRS), intracranial hemorrhage (ICH), and symptomatic ICH (sICH), as well as mortality, were analyzed in the two groups of patients. Results: A total of 239 patients were included in the study, with 214 patients in the EVT < 24 h group (67.8 ± 0.8 years, 126 males) and 25 patients in the EVT > 24 h group (62.80 ± 2.0 years, 22 males). Both groups were similar in terms of hypertension, diabetes history, responsible vessels, and Alberta stroke program early computed tomography scores (p > 0.05). However, the EVT < 24 h group had significantly higher age, history of atrial fibrillation, proportion of patients receiving intravenous thrombolysis, and NIHSS scores before EVT than the EVT > 24 h group. AIS etiology differed between the groups, with more cases of large artery atherosclerosis in the EVT > 24-h group and more cases of cardioembolism in the EVT < 24-h group. Successful reperfusion (mTICI ≥2b), ICH, and sICH were similar between the groups. The 90-day functional independence rate (mRS ≤ 2) was significantly higher in the EVT > 24-h than in the EVT < 24-h group (80% vs. 39.7%, p < 0.001), while the 90-day mortality rate was lower in the EVT > 24-h group (0% vs. 24.8%, p < 0.001). Conclusion: In our study, we found that EVT beyond 24 h of symptom onset in patients selected with multimodal MR screening, was associated with high functional independence rates and low mortality. Larger or randomized studies are needed to confirm these findings.

A systematic review and meta-analysis of the diagnostic accuracy of metagenomic next-generation sequencing for diagnosing tuberculous meningitis.

Objective: The utility of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains uncertain. We performed a meta-analysis to comprehensively evaluate its diagnostic accuracy for the early diagnosis of TBM. Methods: English (PubMed, Medline, Web of Science, Cochrane Library, and Embase) and Chinese (CNKI, Wanfang, and CBM) databases were searched for relevant studies assessing the diagnostic accuracy of mNGS for TBM. Review Manager was used to evaluate the quality of the included studies, and Stata was used to perform the statistical analysis. Results: Of 495 relevant articles retrieved, eight studies involving 693 participants (348 with and 345 without TBM) met the inclusion criteria and were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver-operating characteristic curve of mNGS for diagnosing TBM were 62% (95% confidence interval [CI]: 0.46-0.76), 99% (95% CI: 0.94-1.00), 139.08 (95% CI: 8.54-2266), 0.38 (95% CI: 0.25-0.58), 364.89 (95% CI: 18.39-7239), and 0.97 (95% CI: 0.95-0.98), respectively. Conclusions: mNGS showed good specificity but moderate sensitivity; therefore, a more sensitive test should be developed to assist in the diagnosis of TBM.

Recent advances in microbiological and molecular biological detection techniques of tuberculous meningitis.

Tuberculous meningitis (TBM) is the most common type of central nervous system tuberculosis (TB) and has the highest mortality and disability rate. Early diagnosis is key to improving the prognosis and survival rate of patients. However, laboratory diagnosis of TBM is often difficult due to its paucibacillary nature and sub optimal sensitivity of conventional microbiology and molecular tools which often fails to detect the pathogen. The gold standard for TBM diagnosis is the presence of MTB in the CSF. The recognised methods for the identification of MTB are acid-fast bacilli (AFB) detected under CSF smear microscopy, MTB cultured in CSF, and MTB detected by polymerase chain reaction (PCR). Currently, many studies consider that all diagnostic techniques for TBM are not perfect, and no single technique is considered simple, fast, cheap, and efficient. A definite diagnosis of TBM is still difficult in current clinical practice. In this review, we summarise the current state of microbiological and molecular biological diagnostics for TBM, the latest advances in research, and discuss the advantages of these techniques, as well as the issues and challenges faced in terms of diagnostic effectiveness, laboratory infrastructure, testing costs, and clinical expertise, for clinicians to select appropriate testing methods.

Incidence and Risk Factors of Cranial Nerve Palsy in Patients with Tuberculous Meningitis: A Retrospective Evaluation.

Objective: Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics. Methods: A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM. Results: A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy. Conclusion: The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.

Exploration of the Risk Factors of Anemia in Patients with Tuberculous Meningitis in South China.

Objective: Central nervous system (CNS) infection has a high incidence and mortality worldwide. Tuberculous meningitis (TBM) accounts for approximately 5-6% of all extrapulmonary tuberculosis (TB), and is considered an extremely lethal form of CNS TB, which has become an important threat to human health. Anemia is a common symptom of TB, and its prevalence is generally higher in patients with TBM than in other meningitis patients and healthy individuals. Anemia can increase a person's susceptibility to common infectious diseases, including TB, by compromising the immune system. Information regarding anemia during the hospitalization of TBM is still scarce in China. This study aimed to describe in detail the prevalence of anemia in patients with TBM in Southern China and its association with the clinical forms of TB, as well as other characteristics of these patients. Methods: We conducted a retrospective analysis of patients diagnosed with TBM at two tertiary hospitals in southern China. The demographic characteristics, clinical characteristics, and laboratory results of 114 patients with TBM were collected. Multivariate logistic regression analysis was performed to explore the risk factors for anemia in patients with TBM. Results: Electronic medical record data of adult patients diagnosed with TBM from January 2004 to December 2019 were reviewed. Among 134 patients with TBM, 20 were excluded and 114 were analyzed, of whom 33 had anemic, the prevalence rate of anemia was 28.9%. Among patients with anemia, 51.5% had hypochromic microcytic anemia, 33.3% had normochromic normocytic anemia, and 15.2% had macrocytic anemia. Fever duration, TBM grade III and ESR were found to be independent predictors of anemia. Conclusion: Anemia was highly prevalent in patients with TBM, mainly hypochromic microcytic anemia. Besides, Fever duration, TBM grade III and ESR are predictors of anemia in patients with TBM.

Endovascular treatment over 24 hours after ischemic stroke onset: a single-center retrospective study.

PURPOSE: The aim of this study is to evaluate the safety and effectiveness of endovascular treatment (EVT) for acute ischemic stroke caused by large-vessel obstruction or stenosis (AIS-LVO/S) over 24 h after first AIS symptom recognition (FAISSR). METHODS: A total of 33 AIS-LVO/S cases with EVT over 24 h after FAISSR during the period from January 2019 to February 2022 in our hospital were divided into the 90d mRS ≤ 2 group [favorable outcome (FO) group] and 90d mRS > 2 group [unfavorable outcome (UFO) group] and retrospectively analyzed. RESULTS: The reperfusion was successfully established with EVT in 97% (32/33) of cases, and most (63.6%, 21/33) had 90d mRS ≤ 2 and only 36.4% (12/33) had 90d mRS > 2. Preoperative DWI-ASPECT and ASITN/SIR scores were significantly higher and NIHSS scores were significantly lower in the FO group than those in the UFO group (P < 0.05). In addition, the FAISSR to exacerbation time, FAISSR to groin puncture time, and FAISSR to reperfusion time were significantly longer, and the groin puncture to reperfusion time was significantly shorter in the FO group than those in the UFO group (P < 0.05), but there was no significant difference in the stroke exacerbation to groin puncture time (P > 0.05). The patients with cerebral infarction due to artery dissection had more favorable EVT outcomes, but the patients with posterior cerebral circulation infarction had very poor EVT outcomes. CONCLUSIONS: The FAISSR to groin puncture time over 24 h may not be a taboo for EVT and it may be safe and effective for AIS-LVO/S in anterior cerebral circulation, especially with lower preoperative NIHSS scores.

Diagnostic Accuracy of Interferon-Gamma Release Assays for Tuberculous Meningitis: A Systematic Review and Meta-Analysis.

Background: In this study, we evaluated and compared the accuracy of blood and cerebrospinal fluid (CSF) interferon release tests [interferon-gamma release assays (IGRAs)] in the diagnosis of tuberculous meningitis (TBM) by a meta-analysis of the relevant literature. Methods: We searched for studies published before 2021 in Medline, Embase, the Cochrane database, and Chinese databases. All studies used the QuantiFERON-TB Gold In-Tube and/or T-SPOT.TB method. Blood and/or CSF tests that met the guidelines for the quality assessment of studies with diagnostic accuracy were included. We used the revised diagnostic accuracy study quality assessment to assess the quality of the included studies. Begg's funnel plots were used to assess publication bias in the meta-analysis of the diagnostic studies, and statistical analyses were performed by using Stata (Version 12) software. Results: A total of 12 blood and/or CSF IGRA studies were included in this meta-analysis, with 376 patients and 493 controls. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve (SROC) of the blood IGRAs in the pooled data from 12 studies were 74% (95% CI: 0.65-0.82), 78% (95% CI: 0.68-0.86), 3.38 (95% CI 2.26-5.06), 0.33 (95% CI: 0.23-0.46), 10.25 (95% CI: 5.46-19.25), and 0.83 (95% CI: 0.79-0.86), respectively. For CSF IGRAs, these values for the pooled data from the 10 studies included were 79% (95% CI: 0.71-0.85), 95% (95% CI: 0.88-0.98), 16.30 (95% CI 6.5-40.83), 0.22 (95% CI: 0.16-0.31), 57.93 (95% CI: 22.56-148.78), and 0.91 (95% CI: 0.88-0.93), respectively. Conclusion: CSF IGRAs exhibited a better diagnostic accuracy than blood IGRAs in diagnosing TBM.

A New Scoring System to Differentially Diagnose and Distinguish Tuberculous Meningitis and Bacterial Meningitis in South China.

Background: Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis, and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China. Methods: A retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule. Results: Five characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively. Conclusion: The new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources.

LncRNA HOTAIR Participates in Microglia Activation and Inflammatory Factor Release by Regulating the Ubiquitination of MYD88 in Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the leading causes of death worldwide. Long non-coding RNAs (LncRNAs) have been reported to be closely associated with various diseases, but their roles in TBI has not been fully elucidated. The purpose of this study was to elucidate the underlying mechanism of LncRNA HOTAIR in TBI-induced microglial activation and inflammatory factor release. In vivo mouse TBI model and in vitro microglia activation model were established by Feeney's free-fall impact method and by LPS stimulation, respectively. The expression of LncRNA HOTAIR in activated microglia was detected by qRT-PCR. After shRNA knocked down, the expressions of LncRNA HOTAIR and microglia activation marker Iba-1 in microglia were detected by qRT-PCR and Western blot and by ELISA that detected the concentration of inflammatory factor in cell culture supernatants. The relationship between LncRNA HOTAIR and MYD88 in mouse microglia BV2 cells was observed by RNA pull-down assay. Furthermore, the effect of LncRNA HOTAIR on MYD88 stability was assessed by cycloheximide (CHX)-chase and by immunoprecipitation and ubiquitination assays that analyzed MYD88 ubiquitination. LncRNA HOTAIR was abnormally highly expressed in activated microglia. By Western blot and ELISA, the knockdown of LncRNA HOTAIR in microglia significantly repressed microglia activation and inflammatory factor release. By RNA pull-down assay, LncRNA HOTAIR could bind to MYD88 protein. Besides, by cycloheximide (CHX)-chase and immunoprecipitation and ubiquitination assays, the overexpression of the LncRNA HOTAIR enhanced the stability of MYD88 protein and inhibited Nrdp1-mediated ubiquitination of MYD88 protein. After the transfection of shRNA-HOTAIR and shRNA-HOTAIR+pcDNA-MYD88 into microglia, shRNA-HOTAIR could significantly inhibit the activation of microglia and the release of inflammatory factors, while these effects were reversed after the transfection of pcDNA-MYD88. Our experimental data indicated that LncRNA HOTAIR was highly expressed in activated microglia, and our further studies had found that the interference with LncRNA HOTAIR could repress microglia activation and inflammatory factor release via promoting Nrdp1-mediated ubiquitination of MYD88 protein.

Multiband enhanced second-harmonic generation via plasmon hybridization.

Boosting nonlinear frequency-conversion efficiencies in hybrid metal-dielectric nanostructures generally requires the enhancement of optical fields that interact constructively with nonlinear dielectrics. Inevitably for localized surface plasmons, spectra subject to this enhancement tend to span narrowly. As a result, because of the spectral mismatch of resonant modes at frequencies participating in nonlinear optical processes, strong nonlinear signal generations endure the disadvantage of rapid degradations. Here, we experimentally design a multiband enhanced second-harmonic generation platform of three-dimensional metal-dielectric-metal nanocavities that consist of thin ZnO films integrated with silver mushroom arrays. Varying geometric parameters, we demonstrate that the introduction of ZnO materials in intracavity regions enables us to modulate fundamental-frequency-related resonant modes, resulting in strong coupling induced plasmon hybridization between localized and propagating surface plasmons. Meanwhile, ZnO materials can also serve as an efficient nonlinear dielectric, which provides a potential to obtain a well-defined coherent interplay between hybridized resonant modes and nonlinear susceptibilities of dielectric materials at multi-frequency. Finally, not only is the conversion efficiency of ZnO materials increased by almost two orders of magnitude with respect to hybrid un-pattered systems at several wavelengths over a 100-nm spectral range but also a hybrid plasmon-light coupling scheme in three-dimensional nanostructures can be developed.

Magnetic Tunnel Junction Applications.

Spin-based devices can reduce energy leakage and thus increase energy efficiency. They have been seen as an approach to overcoming the constraints of CMOS downscaling, specifically, the Magnetic Tunnel Junction (MTJ) which has been the focus of much research in recent years. Its nonvolatility, scalability and low power consumption are highly attractive when applied in several components. This paper aims at providing a survey of a selection of MTJ applications such as memory and analog to digital converter, among others.

Illuminating nanostructured gold electrode: surface plasmons or electron ejection?

Recently, the photoelectric effect in metals in electrolyte environments has aroused the interest of researchers. However, direct evidence for surface plasmons-enhanced electrochemical reactions involving classic outer-sphere reactions of reversible redox couples is seldom reported. We used a surface plasmons-active gold-mushroom-array as a working electrode and observed enhanced faradaic current from ferrocenemethanol following illumination with a xenon lamp. The photoelectric current behaved differently in the presence and absence of oxygen in the solution. The preliminary results are discussed with consideration of the possible mechanisms of electron transfer, although they are very complex, due to the lack of direct evidence. Some consideration was also taken of the research on photoelectrochemical reactions on metallic electrodes.

Millifluidic chip with a modular design used as a sample pretreatment cartridge for flour and flour food products.

The integration of sample pretreatment remains one of the hurdles towards a rapid, automated micro total analytical system (µ-TAS) for real samples. In this paper, a modular design, which was used for sample preparation, has been developed as the polydimethylsiloxane (PDMS) millifluidic chips with channels at a millimeter level. Multiple functional units, including extraction, filtration, mixing and solid phase extraction (SPE), for sample pretreatment were integrated in one chip. In this chip, each functional unit was connected by pump tubings and one-way valves in series to form a fully automated system. Based on the modular design, multiple functional units have been combined in different sequences according to practical needs. In addition, the proposed system has characteristics of miniaturization, portability, and real-time application. Herein, spiked benzoyl peroxide (BPO) in flour samples was used as a model compound to study the system's performances. With a portable integrated Raman spectrometer for detection, the detection limit of BPO was 0.017gkg-1, with a linear relationship from 0.025 to 0.5gkg-1. This modular design was demonstrated to be effective and it can be expanded for pretreatment of other food samples.

Enhancing the Bipolar Redox Cycling Efficiency of Plane-Recessed Microelectrode Arrays by Adding a Chemically Irreversible Interferent.

The individual electrochemical anodic responses of dopamine (DA), epinephrine (EP), and pyrocatechol (CT) were investigated at arrays of recessed gold disk-microelectrodes arrays (MEAs) covered by a gold plane electrode and compared to those of their binary mixture (CT and EP) when the top-plane electrode was operated as a bipolar electrode or as a collector. The interferent species (EP) displays a chemically irreversible wave over the same potential range as the chemically reversible ones of DA or CT. As expected, in the generator-collector (GC) mode, EP did not contribute to the redox cycling amplification that occurred only for DA or CT. Conversely, in the bipolar mode, the presence of EP drastically increased the bipolar redox cycling efficiency of DA and CT. This evidenced that the chemically irreversible oxidation of EP at the anodic poles of the top plane floating electrode provided additional electron fluxes that were used to more efficiently reduce the oxidized DA or CT species at the cathodic poles. This suggests an easy experimental strategy for enhancing the bipolar efficiency of MEAs up to reach a performance identical to that achieved when the same MEAs are operated in a GC mode.

Strategy for increasing the electrode density of microelectrode arrays by utilizing bipolar behavior of a metallic film.

Recessed microelectrode arrays and plane-recessed microelectrode arrays (MEAs) with different center-to-center distances are designed and fabricated using lithographic technology. By comparing electrochemical behavior of plane-recessed MEAs with that of recessed MEAs, bipolar phenomenon of the metallic plane film is revealed. Redox cycling can occur when the top plane electrode was floating; that is, the bipolar behavior of the unbiased top plane electrode may perform locally as a collector and enlarge the concentration gradient of Ru(NH3)6Cl3 and thus promote an apparent generator/collector electrochemical response of the microdisk electrode in the MEAs configuration. By utilizing the bipolar behavior, the center-to-center distance of MEAs required for achieving steady-state current could decrease without favoring at the same time the overlapping of diffusion layers of microelectrodes, and thus, the electrode density of MEAs can be increased. Therefore, the bipolar behavior of the metallic film can increase both the current response of an individual microdisk and the electrode density of microdisks without losing the characteristics of a microelectrode. By just fabricating a thin layer of metallic film on the plane and leaving it floating without potential control, recessed MEAs used in this work can achieve the increase of detection sensitivity by more than 1 order of magnitude.

Luminescence efficiency enhancement of BaZr(BO3)2:Eu with Si or Al addition.

Si4+ and Al3+ doped BaZr(BO3)2:Eu phosphors were prepared by solidstate reaction. BaZr(BO3)2:Eu3+, BaZr(BO3)2:Eu3+, Si4+ and BaZr(BO3)2:Eu3+, Al3+ were characterized by X-ray diffraction spectra (XRD) and photoluminescence spectra. After codoped with Si or Al, the charge-transfer state (CTS) band of Eu3+-O(2-) shows blue shift accompanied by increasing intensity due to shorter ionic radius and stronger electro negativity of Si or Al compared with Zr4+. The high value of asymmetric ratio R(2-1) and omega2 of BaZr(BO3)2:Eu3+ with Si or Al codoping indicates a less symmetrical local structure of Eu3+. This implies that the quantum efficiencies of the 5D0 level of these complexes can be enhanced by doping with Si and Al respectively. Calculation of the Judd-Ofelt parameters of Eu3+ under different crystal fields gives similar results.

A micro surface tension alveolus (MISTA) in a glass microchip.

We have designed a non-membrane micro surface tension alveolus (MISTA) in a glass microchip for direct gas exchange and micro gradient control. Hemoglobin (Hb) in the liquid phase indicates the rapid gas gradient changes of O2 and CO2 shifted by the difference in pressure between the liquid and the gas.

PMMA/PDMS valves and pumps for disposable microfluidics.

Poly(methyl methacrylate) (PMMA) is gaining in popularity in microfluidic devices because of its low cost, excellent optical transparency, attractive mechanical/chemical properties, and simple fabrication procedures. It has been used to fabricate micromixers, PCR reactors, CE and many other microdevices. Here we present the design, fabrication, characterization and application of pneumatic microvalves and micropumps based on PMMA. Valves and pumps are fabricated by sandwiching a PDMS membrane between PMMA fluidic channel and manifold wafers. Valve closing or opening can be controlled by adjusting the pressure in a displacement chamber on the pneumatic layer via a computer regulated solenoid. The valve provides up to 15.4 microL s(-1) at 60 kPa fluid pressure and seals reliably against forward fluid pressure as high as 60 kPa. A PMMA diaphragm pump can be assembled by simply connecting three valves in series. By varying valve volume or opening time, pumping rates ranging from nL to microL per second can be accurately achieved. The PMMA based valves and pumps were further tested in a disposable automatic nucleic acid extraction microchip to extract DNA from human whole blood. The DNA extraction efficiency was about 25% and the 260 nm/280 nm UV absorption ratio for extracted DNA was 1.72. Because of its advantages of inexpensive, facile fabrication, robust and easy integration, the PMMA valve and pump will find their wide application for fluidic manipulation in portable and disposable microfluidic devices.