Achromatic CMOS-Integrated Four-Bit Orbital Angular Momentum Mode Detector at Three Wavelengths.

The simultaneous detection of the orbital angular momentum (OAM) and wavelength offers new opportunities for optical multiplexing. However, because of the dispersion of lens functions for Fourier transformation, the mode conversions at distinct wavelengths cannot be achieved in the same plane. Here we propose an ultracompact achromatic complementary metal oxide semiconductor (CMOS)-integrated OAM mode detector. Specifically, a spatial multiplexed scheme, randomly interleaving the phase distributions for distributing the superposed OAM modes into preset positions at distinct wavelengths, is presented. In addition, such a nanoprinted achromatic OAM detector featuring a microscale size and a short focal length can be integrated onto a CMOS chip. Consequently, the four-bit incident light beams at three discrete wavelengths (633, 532, and 488 nm) can be distinguished with a high degree of accuracy evaluated by the average standardized Euclidean distance of ∼0.75 between the analytical and target results. Our results showcase a miniaturized platform for achieving high-capacity information processing.

Orbital angular momentum holographic multicasting for switchable and secure wireless optical communication links.

The physical dimension of orbital angular momentum (OAM) states of light has been successfully implemented as information carrier in wireless optical communication (WOC) links. However, the current OAM data coding strategies in WOC are mainly limited to the temporal domain, rarely involving the degree of freedom of spatial domain to transmit an image directly. Here, we apply OAM holographic multiplexing technology for spatial information encoding in WOC links. Further, we demonstrate the new concept of OAM holographic multicasting, wherein a beam-steering grating has been utilized for information decoding. To distribute the OAM multiplexing information appropriately in the receiving terminal, the beam-steering grating with controllable topological charges and amplitude weighting coefficients of each diffraction order in the spatial frequency domain has been designed. An iterative algorithm has been introduced to obtain the intensity uniformity >98% at target diffraction orders. As such, this scheme experimentally allows four separate users to receive independent images, which can be switched by modulating the topological charges of the beam-steering gratings at each diffraction order. In addition, this leads to a beam-steering grating-encrypted WOC links, wherein the information can only be decoded by the grating phase with 7 pre-set spatial frequency components. Our results mark a new parallel decoding paradigm of OAM multiplexing holography, which opens up the door for future high-capacity and high-security all-optical holographic communications.

Association of dietary isoflavone consumption with subclinical cardiovascular disease in middle-aged and elderly Chinese people.

BACKGROUND AND AIMS: The association between isoflavone (ISF) consumption and cardiovascular disease (CVD) remains controversial because of limited evidence. Carotid atherosclerosis is an established indicator of subclinical CVD. The study aimed to investigate the relationship between dietary ISF intake and subclinical CVD in middle-aged and elderly adults. METHODS AND RESULTS: A total of 873 subjects aged 40-70 years without CVD were enrolled in this cross-sectional study. A restricted cubic spline was used to investigate the association between ISF intake and subclinical CVD risk. The odds ratio (OR) and 95% confidence interval of the risk of subclinical CVD for ISF were estimated by two-segmented logistic regression analysis. In Model 2, there was a non-linear association between ISF intake and the risk of subclinical CVD among women (Pnon-linear = 0.002), with an inverse association below the change point. The nadir for the risk of subclinical CVD among women was 7.26 mg/day (energy-adjusted). Below the change point, an increase of 1 mg ISF/day reduced the risk of subclinical CVD by 15%. There was no significant association between ISF intake and subclinical CVD risk above the change point (OR = 1.01 [0.99, 1.04]). ISF intake was not associated with subclinical CVD risk in men (Model 2: Pnon-linear = 0.224). CONCLUSIONS: Below the change point (7.26 mg/day), women with a higher intake of ISF had a significantly lower risk of subclinical CVD. Encouraging the consumption of ISF-rich foods may help to lower CVD risk in middle-aged and elderly women. TRIAL REGISTRATION: This study is registered at http://www.chictr.org.cn (ChiCTR 1900022445).

Targeting virulence factors as an antimicrobial approach: Pigment inhibitors.

The fascinating and dangerous colored pathogens contain unique chemically pigmented molecules, which give varied and efficient assistance as virulence factors to the crucial reproduction and growth of microbes. Therefore, multiple novel strategies and inhibitors have been developed in recent years that target virulence factor pigments. However, despite the importance and significance of this topic, it has not yet been comprehensively reviewed. Moreover, research groups around the world have made successful progress against antibacterial infections by targeting pigment production, including our serial works on the discovery of CrtN inhibitors against staphyloxanthin production in Staphylococcus aureus. On the basis of the previous achievements and recent progress of our group in this field, this article will be the first comprehensive review of pigment inhibitors against colored pathogens, especially S. aureus infections, and this article includes design strategies, representative case studies, advantages, limitations, and perspectives to guide future research.

Periodic micro-structures in optical microfibers induced by Plateau-Rayleigh instability and its applications.

A periodic micro-structure on optical microfibers induced by Plateau-Rayleigh instability (PRI) was investigated and a potential application for long period gratings (LPGs) fabrication was given. The linear relation between the average periods of micro-structures and the diameters of optical microfibers was demonstrated first. By brushing a glass rod with a Teflon droplet suspended at the end tip along microfibers, a continuous film of Teflon was formed at once, then the film broke up into a series of periodic droplets due to PRI. Periodic Teflon nodes were left after the evaporation of the solvent. A LPG structure based on polymer was finally formed by this method on a microfiber with a diameter of 5.5 µm. An attenuation transmission dip of 15 dB around 1447 nm was achieved. Investigation of the strain and temperature response characteristics of the grating presented a strain sensitivity of -2.5 pm/µÎµ and a temperature sensitivity of -157 pm/°C. The technique proposed here provides a versatile technique for polymer-based LPGs fabrication. Benefiting from the high sensitivities, LPGs based on numerous polymers fabricated in this way could have potential applications in optical and biological sensing.

Suprapedicular Foraminal Endoscopic Approach to Lumbar Lateral Recess Decompression Surgery to Treat Degenerative Lumbar Spinal Stenosis.

BACKGROUND To discuss the strategy of suprapedicular foraminal endoscopic approach to lumbar lateral recess decompression and evaluate the safety and effectiveness of this strategy. MATERIAL AND METHODS Complete clinical information of 52 cases of lumbar lateral recess decompression with therapy of suprapedicular foraminal endoscopic approach were analyzed during the period from February 2010 to April 2014 in the Third Hospital of Hebei. All patients were followed up for 24 months, and VAS, JOA, ODI, and LRD were compared between preoperative and postoperative therapy and changes of FA. Intraoperative and postoperative complications were recorded and the safety of the surgery was evaluated. The surgical "excellent" and "good" rates were evaluated using MacNab score. RESULTS VAS scores for lumbago and leg pain at 3, 6, 12, and 24 months after surgery were significantly lower than before surgery (p<0.05). JOA scores at 12 and 24 months after surgery were significantly higher than before surgery (p<0.05). ODI at 12 and 24 months after surgery were significantly lower than before surgery (p<0.05). LRD after surgery was higher (p<0.05), and FA was lower than before surgery. CONCLUSIONS Use of the suprapedicular foraminal endoscopic approach to lumbar lateral recess decompression is safe and effective, and this minimally invasive treatment can achieve satisfactory results, especially for elderly patients with complicated underlying diseases.

[Detection of Syrup Adulterants in Prepackaged Pure Pineapple Juice by Fourier-Transform Infrared Spectroscopy and Chemometric Analysis].

This study was performed to establish a method that can quickly and accurately identify adulterated syrup in the pure pineapple juice. A attenuated total internal refraction-fourier transform infrared spectroscopy was used to collect the range of 900 -1 500 cm(-1) infrared spectra of 234 samples pure pineapple juice and adulterated syrup by beet syrup, rice syrup and cassava syrup. By using linear discriminant analysis and support vector machine for the identification model, comparing the full spectral and selected wavelengths based on principal component analysis loading plots of the two models to identify adulteration. Studies showed that the correct rate of validation set by linear discriminant analysis and support vector machine model on full spectral were both higher than 88%, variables were significantly reduced from 312 to 8 after selecting the eight characteristic wavelengths, the correct rate of validation set by linear discriminant analysis model was up to 96.15% and support vector machine was increase to 94.87%. The results demonstrated that the model built using a attenuated total internal refraction-fourier transform infrared spectroscopy in combination with chemometric methods after selected characteristic wavelengths could be used for the identification of the adulterated syrup in the pure pineapple juice.

Causal associations between modifiable risk factors and intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a common degenerative condition, which is thought to be a major cause of lower back pain (LBP). However, the etiology and pathophysiology of IVDD are not yet completely clear. PURPOSE: To examine potential causal effects of modifiable risk factors on IVDD. STUDY DESIGN: Bidirectional Mendelian randomization (MR) study. PATIENT SAMPLE: Genome-wide association studies (GWAS) with sample sizes between 54,358 and 766,345 participants. OUTCOME MEASURES: Outcomes included (1) modifiable risk factors associated with IVDD use in the forward MR; and (2) modifiable risk factors that were determined to have a causal association with IVDD in the reverse MR, including smoking, alcohol intake, standing height, education level, household income, sleeplessness, hypertension, hip osteoarthritis, HDL, triglycerides, apolipoprotein A-I, type 2 diabetes, fasting glucose, HbA1c, BMI and obesity trait. METHODS: We obtained genetic variants associated with 33 exposure factors from genome-wide association studies. Summary statistics for IVDD were obtained from the FinnGen consortium. The risk factors of IVDD were analyzed by inverse variance weighting method, MR-Egger method, weighted median method, MR-PRESSO method and multivariate MR Method. Reverse Mendelian randomization analysis was performed on risk factors found to be caustically associated with IVDD in the forward Mendelian randomization analysis. The heterogeneity of instrumental variables was quantified using Cochran's Q statistic. RESULTS: Genetic predisposition to smoking (OR=1.221, 95% CI: 1.068-1.396), alcohol intake (OR=1.208, 95% CI: 1.056-1.328) and standing height (OR=1.149, 95% CI: 1.072-1.231) were associated with increased risk of IVDD. In addition, education level (OR=0.573, 95%CI: 0.502-0.654)and household income (OR=0.614, 95%CI: 0.445-0.847) had a protective effect on IVDD. Sleeplessness (OR=1.799, 95%CI: 1.162-2.783), hypertension (OR=2.113, 95%CI: 1.132-3.944) and type 2 diabetes (OR=1.069, 95%CI: 1.024-1.115) are three important risk factors causally associated with the IVDD. In addition, we demonstrated that increased levels of triglycerides (OR=1.080, 95%CI:1.013-1.151), fasting glucose (OR=1.189, 95%CI:1.007-1.405), and HbA1c (OR=1.308, 95%CI:1.017-1.683) could significantly increase the odds of IVDD. Hip osteoarthritis, HDL, apolipoprotein A-I, BMI and obesity trait factors showed bidirectional causal associations with IVDD, therefore we considered the causal associations between these risk factors and IVDD to be uncertain. CONCLUSIONS: This MR study provides evidence of complex causal associations between modifiable risk factors and IVDD. It is noteworthy that metabolic disturbances appear to have a more significant effect on IVDD than biomechanical alterations, as individuals with type 2 diabetes, elevated triglycerides, fasting glucose, and elevated HbA1c are at higher risk for IVDD, and the causal association of obesity-related characteristics with IVDD incidence is unclear. These findings provide new insights into potential therapeutic and prevention strategies. Further research is needed to clarify the mechanisms of these risk factors on IVDD.

Orbital angular momentum-mediated machine learning for high-accuracy mode-feature encoding.

Machine learning with optical neural networks has featured unique advantages of the information processing including high speed, ultrawide bandwidths and low energy consumption because the optical dimensions (time, space, wavelength, and polarization) could be utilized to increase the degree of freedom. However, due to the lack of the capability to extract the information features in the orbital angular momentum (OAM) domain, the theoretically unlimited OAM states have never been exploited to represent the signal of the input/output nodes in the neural network model. Here, we demonstrate OAM-mediated machine learning with an all-optical convolutional neural network (CNN) based on Laguerre-Gaussian (LG) beam modes with diverse diffraction losses. The proposed CNN architecture is composed of a trainable OAM mode-dispersion impulse as a convolutional kernel for feature extraction, and deep-learning diffractive layers as a classifier. The resultant OAM mode-dispersion selectivity can be applied in information mode-feature encoding, leading to an accuracy as high as 97.2% for MNIST database through detecting the energy weighting coefficients of the encoded OAM modes, as well as a resistance to eavesdropping in point-to-point free-space transmission. Moreover, through extending the target encoded modes into multiplexed OAM states, we realize all-optical dimension reduction for anomaly detection with an accuracy of 85%. Our work provides a deep insight to the mechanism of machine learning with spatial modes basis, which can be further utilized to improve the performances of various machine-vision tasks by constructing the unsupervised learning-based auto-encoder.

[Preparation of monoclonal antibodies against the envelope protein extracellular domain of Zika virus in mice].

Objective To prepare monoclonal antibodies against the envelope protein extracellular domain (Eecto) of Zika virus (ZIKV) in mice. Methods A prokaryotic expression plasmid, pET28a-ZIKV-Eecto of ZIKV Eecto, was constructed, transformed into Escherichia coli BL21 and induced by isopropyl ß-D-thiogalactoside (IPTG). The recombinant Eecto protein was expressed in the form of inclusion bodies, and purified proteins were obtained through denaturation, renaturation and ultrafiltration. After three rounds of immunization with the Eecto protein, the serum of BALB/c mice was obtained and the titer of polyclonal antibodies in serum was determined. The reactivity of polyclonal antibodies was analyzed with Western blotting and immunofluorescence assay in HEK293T cells expressing the ZIKV prME. Spleen cells from mice with higher antibody titers were prepared and fused with SP2/0 myeloma cells. The hybridoma cells secreting antibodies were screened through the limited dilution method, and the ascites containing antibody were harvested for titer measurement and subclass analysis. The Eecto from the envelope proteins of Japanese encephalitis virus (JEV), Yellow fever virus (YFV), Dengue virus (DENV1-4), and Tick borne encephalitis virus (TBEV) were coated and used to analyze the cross-reactivity of ZIKV monoclonal antibodies by ELISA. Further specificity analysis was conducted on antibodies with high titers and strong specificity. Results The plasmid pET28a-ZIKV-Eecto was successfully constructed. The purified Eecto protein was obtained with good immunogenicity. Four monoclonal antibodies were prepared and screened, namely 1D6, 4F11, 4H7, and 4F8. Among them, 1D6, 4H7, and 4F8 are IgG (K) type antibodies, and 4F11 is an IgM (K) antibody. The ascitic fluid titer of 1D6 was higher than 1:108. Antibodies 1D6 and 4H7 are ZIKV-specific and showed no cross-reactivity with other Flaviviruses. Conclusion The mice monoclonal antibodies against ZIKV-Eecto are produced successfully, which will provide experimental materials for the establishment of ZIKV detection methods and the study of its pathogenesis.

Integration of Proteomic and Metabolomic Data Reveals the Lipid Metabolism Disorder in the Liver of Rats Exposed to Simulated Microgravity.

Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based quantitative proteomics techniques, as well as non-targeted metabolomics techniques based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), to comprehensively analyse the relative expression levels of proteins and the abundance of metabolites associated with lipid accumulation in rat liver tissues under simulated microgravity conditions. The differential analysis revealed 63 proteins and 150 metabolites between the simulated microgravity group and the control group. By integrating differentially expressed proteins and metabolites and performing pathway enrichment analysis, we revealed the dysregulation of major metabolic pathways under simulated microgravity conditions, including the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, steroid hormone biosynthesis and butanoate metabolism, indicating disrupted liver metabolism in rats due to weightlessness. Finally, we examined differentially expressed proteins associated with lipid metabolism in the liver of rats exposed to stimulated microgravity. These findings contribute to identifying the key molecules affected by microgravity and could guide the design of rational nutritional or pharmacological countermeasures for astronauts.

Rational design of a high-affinity fluorescent probe for visualizing monitoring the amyloid ß clearance effect of anti-Alzheimer's disease drug candidates.

Beta-amyloid (Aß), the most pivotal pathological hallmark for Alzheimer's disease (AD) diagnosis and drug evaluation, was recognized by TZ095, a high-affinity fluorescent probe developed by rational molecular design. With a TICT mechanism, TZ095 exhibited remarkable affinity with Aß aggregates (Kd = 81.54 nM for oligomers; Kd = 66.70 nM for fibril) and substantial fluorescence enhancement (F/F0 = 44), enabling real-time monitoring of Aß in live cells and nematodes. Significantly, this work used TZ095 to construct a new protocol that can quickly and conveniently monitor Aß changes at the cellular and nematode levels to evaluate the anti-AD efficacy of candidate compounds, and four reported Aß-lowering drug candidates were administrated for validation. Imaging data demonstrated that TZ095 can visually and quantitatively track the effect of Aß elimination after drug treatment. Furthermore, TZ095 excelled in ex vivo histological staining of 12-month-old APP/PS1 mouse brains, accurately visualizing Aß plaques. Integrating CUBIC technology, TZ095 facilitated whole-brain, 3D imaging of Aß distribution in APP/PS1 mice, enabling high-resolution in situ analysis of Aß plaques. Collectively, these innovative applications of TZ095 offer a promising strategy for rapid, convenient, and real-time monitoring of Aß levels in preclinical therapeutic assessments.

[Preparation of mouse monoclonal antibodies against the ectodomain of Western equine encephalitis virus E2 (E2ecto) protein].

Objective To prepare mouse monoclonal antibodies against the ectodomain of E2 (E2ecto) glycoprotein of Western equine encephalitis virus (WEEV). Methods A prokaryotic expression plasmid pET-28a-WEEV E2ecto was constructed and transformed into BL21 (DE3) competent cells. E2ecto protein was expressed by IPTG induction and presented mainly as inclusion bodies. Then the purified E2ecto protein was prepared by denaturation, renaturation and ultrafiltration. BALB/c mice were immunized with the formulated E2ecto protein using QuickAntibody-Mouse5W as an adjuvant via intramuscular route, boosted once at an interval of 21 days. At 35 days post-immunization, mice with antibody titer above 1×104 were inoculated with E2ecto intraperitoneally, and spleen cells were fused with SP2/0 cells three days later. Hybridoma cells secreting specific monoclonal antibodies were screened by the limited dilution method, and ascites were prepared after intraperitoneal inoculation of hybridoma cells. The subtypes and titers of the antibodies in ascites were assayed by ELISA. The biological activity of the mAb was identified by immunofluorescence assay(IFA) on BHK-21 cells which were transfected with eukaryotic expression plasmid pCAGGS-WEEV-CE3E2E1. The specificity of the antibodies were evaluated with E2ecto proteins from EEEV and VEEV. Results Purified WEEV E2ecto protein was successfully expressed and obtained. Four monoclonal antibodies, 3G6G10, 3D7G2, 3B9E8 and 3D5B7, were prepared, and their subtypes were IgG2c(κ), IgM(κ), IgM(κ) and IgG1(κ), respectively. The titers of ascites antibodies 3G6G10, 3B9E8 and 3D7G2 were 105, and 3D5B7 reached 107. None of the four antibody strains cross-reacted with other encephalitis alphavirus such as VEEV and EEEV. Conclusion Four strains of mouse mAb specifically binding WEEV E2ecto are successfully prepared.

Natural Linoleic Acid from Marine Fungus Eutypella sp. F0219 Blocks KEAP1/NRF2 Interaction and Ameliorates MASLD by Targeting FABP4.

Ectopic lipid accumulation induced lipotoxicity plays a crucial role in exacerbating the development of metabolic dysfunction-associated steatotic liver disease (MASLD), which affects over 30% of the worldwide population and 85% of the obese population. The growing demand for effective therapeutic agents highlights the need for high-efficacy lipotoxicity ameliorators and relevant therapeutic targets in the fight against MASLD. This study aimed to discover natural anti-lipotoxic and anti-MASLD candidates and elucidate the underlying mechanism and therapeutic targets. Utilizing palmitic acid (PA)-induced HepG-2 and primary mouse hepatocyte models, we identified linoleic acid (HN-002), a ligand of fatty acid binding protein 4 (FABP4), from the marine fungus Eutypella sp. F0219. HN-002 dose-dependently prevented lipid overload-induced hepatocyte damage and lipid accumulation, inhibited fatty acid esterification, and ameliorated oxidative stress. These beneficial effects were associated with improvements in mitochondrial adaptive oxidation. HN-002 treatment enhanced lipid transport into mitochondria and oxidation, inhibited mitochondrial depolarization, and reduced mitochondrial ROS (mtROS) level in PA-treated hepatocytes. Mechanistically, HN-002 treatment disrupted the interaction between KEAP1 and NRF2, leading to NRF2 deubiquitylation and nuclear translocation, which activated beneficial metabolic regulation. In vivo, HN-002 treatment (20 mg/kg/per 2 days, i. p.) for 25 days effectively reversed hepatic steatosis and liver injury in the fast/refeeding plus high-fat/high-cholesterol diet induced MASLD mice. These therapeutic effects were associated with enhanced mitochondrial adaptive oxidation and activation of NRF2 signaling in the liver. These data suggest that HN-002 would be an interesting candidate for MASLD by improving mitochondrial oxidation via the FABP4/KEAP1/NRF2 axis. The discovery offers new insights into developing novel anti- MASLD agents derived from marine sources.

Design, synthesis, and biological evaluation of acetophenone derivatives as dual binding acetylcholinesterase inhibitors.

As part of a project aimed at developing new agents for potential application in Alzheimer's disease, a new series of acetophenone derivatives which possess alkylamine side chains were designed, synthesized and assayed as acetylcholinesterase (AChE) inhibitors that could simultaneously bind to the peripheral and catalytic sites of the enzyme. The compounds were synthesized, and the inhibitory activities toward AChE and butyrylcholinesterase (BuChE) in vitro were determined using a modified Ellman method. Of the compounds tested, 6 derivatives were found to inhibit AChE in the micromolar range. The best compound, 2e, had an 1C50 of 0.13 microM. A detailed molecular modeling study was performed to explore the interaction of 2e with AChE.

Design and oxidative desulfurization of Ag/Ti heterometallic clusters based on Hard-Soft Acid-Base principle.

Hard-Soft Acid-Base (HSAB) principle plays an important guiding role in the design and synthesis of novel clusters and coordination compounds, in which "soft acids prefer to react with soft bases, while hard acids have an affinity for hard bases". Based on HSAB principle, four Ag/Ti heterometallic clusters, including Ag2Ti10, Ag2Ti11 with "Ti-encapsulated Ag" configurations, and two "Ag-encapsulated Ti" structures Ag2Ti2 and Ag2Ti12, were synthesized under solvothermal conditions. In addition, Ag2Ti12 exhibited an efficient and stable catalytic activity for sulfide oxidation. This work provides not only a new structural model for the modulation of the catalytic oxidative desulfurization properties of Ag/Ti heterometallic clusters but also a new insight of the utilization of phosphine-containing ligands to regulate the structure of Ag/Ti heterometallic clusters.

Diversity-oriented synthesis of P-stereogenic and axially chiral monodentate biaryl phosphines enabled by C-P bond cleavage.

Chiral monodentate biaryl phosphines (MOPs) have attracted intense attention as chiral ligands over the past decades. However, the creation of structurally diverse chiral MOPs with both P- and axial chirality is still in high demand but challenging. Here, we show a distinct strategy for diversity-oriented synthesis of structurally diverse MOPs containing both P- and axial chirality enabled by enantioselective C-P bond cleavage. The key chiral PdII intermediates, generated through the stereoselective oxidative addition of C-P bond, could be trapped by alkynes, R3Si-Bpin, diboron esters or reduced by H2O/B2pin2, leading to enantioenriched structurally diverse MOPs in excellent diastereo- and enantioselectivities. Based on the outstanding properties of the parent scaffolds, the P- and axially chiral monodentate biaryl phosphines serve as excellent catalysts in asymmetric [3 + 2] annulation of MBH carbonate affording the chiral functionalized bicyclic imide.

Comparison of the effects of remimazolam tosylate and propofol on postoperative delirium among older adults undergoing major non-cardiac surgery: protocol for a randomised controlled trial.

INTRODUCTION: Postoperative delirium (POD) is a common cognitive disturbance in elderly individuals that is characterised by acute and fluctuating impairments in attention and awareness. Remimazolam tosylate is a novel, ultrashort-acting benzodiazepine, and there is limited evidence of its correlation with the incidence of early POD. The aim of this study is to evaluate the incidence of POD after anaesthesia induction and maintenance with remimazolam tosylate or propofol in elderly patients undergoing major non-cardiac surgery. METHODS AND ANALYSIS: This is a single-centre, randomised controlled trial. 636 elderly patients undergoing major non-cardiac surgery will be enrolled and randomised at a 1:1 ratio to receive total intravenous anaesthesia with either remimazolam tosylate or propofol. The primary outcome is the incidence of POD within 5 days after surgery. Delirium will be assessed twice daily by the 3 min Diagnostic Interview for the Confusion Assessment Method or the Confusion Assessment Method for the intensive care unit (ICU) for ICU patients. Secondary outcomes are the onset and duration of delirium, cognitive function at discharge and within 1-year postoperatively, postoperative analgesia within 5 days, chronic pain at 3 months, quality of recovery and postoperative inflammatory biomarker levels. ETHICS AND DISSEMINATION: The study was approved by the institutional ethics committee of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (approval No. 22/520-3722). Written informed consent will be obtained from each patient before enrolment. The results of this trial will be presented at scientific conferences and in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ChiCTR2300067368.

The Efficacy and Safety of Ginkgo Terpene Lactone Preparations in the Treatment of Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: This meta-analysis aimed to assess the efficacy and safety of ginkgo terpene lactone preparations including ginkgo diterpene lactone meglumine injection, ginkgolide injection, and ginkgolide B injection for ischemic stroke (IS). Methods: We searched the randomized controlled trials (RCTs) with publication date earlier than 31 August 2021 in PubMed, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals Database (VIP), Chinese Biomedical Literature Database (CBM), Wanfang Database, Embase, and the Cochrane Library. RevMan 5.3 software was applied to analyze the data and generate the forest plot and funnel plot. Meanwhile, publication bias was also assessed by Egger's test with STATA 12 software. Results: A total of 28 RCTs were eligible for inclusion. Among them, 23 RCTs were used to evaluate the efficacy of ginkgo terpene lactone preparations as the main treatment intervention for IS. To be specific, ginkgo diterpene lactone meglumine injection was superior to control drug in improving clinical efficacy [RR = 1.18, 95% CI (1.12, 1.24), Z = 6.36, p < 0.001] and neurological function [MD = -1.42, 95% CI (-1.91, -0.93), Z = 5.66, p < 0.001]. However, the effectiveness of the ginkgolide B injection group was equivalent to that of the control group. Additionally, ginkgolide injection achieved better clinical efficacy [RR = 1.10, 95% CI (1.02, 1.18), Z = 2.36, p = 0.02], but the changes of neurological function deficit was not obviously different between two groups [MD = -0.43, 95% CI (-4.32, 3.46), Z = 0.22, p = 0.83]. Furthermore, meta-analysis of five trials on ginkgo diterpene lactone meglumine injection combined with recombinant tissue plasminogen activator (rt-PA) thrombolytic therapy for acute IS showed that combination therapy was better in improving clinical efficacy [OR = 1.91, 95% CI (1.13, 3.22), Z = 2.41, p = 0.02] and neurological function [MD = -3.31, 95% Cl (-3.64,-2.98), Z = 19.63, p < 0.001]. Importantly, no serious adverse drug reactions/adverse drug events (ADRs/ADEs) were reported. Conclusion: Ginkgo terpene lactone preparations have good therapeutic effects on patients with IS. For acute IS, ginkgo diterpene lactone meglumine injection can be used as a complementary therapy to improve the clinical efficacy of rt-PA.

Characterized profiles of gut microbiota in morphine abstinence-induced depressive-like behavior.

Morphine is the most widely used analgesic for pain management worldwide. Abstinence of morphine could lead to neuropsychiatric symptoms, including depression. Gut microbiota is believed to contribute to the development of depression. However, the characteristics and potential role of gut microbiota in morphine abstinence-induced depression remain unclear. In the present study, we first established morphine abstinence-induced depressive behavior in mice. After dividing the mice into depressive and non-depressive groups, the gut microbiota of the mice was detected by 16S rRNA gene sequencing. The difference in the diversities and abundance of the gut microbiota were analyzed between groups. Then, the representative microbial markers that could distinguish each group were identified. In addition, gene function prediction of the operational taxonomic units (OTUs) with differential abundance between the depressive and non-depressive groups after morphine abstinence was conducted. Our results suggested that four weeks of abstinence from morphine did not change the richness of the gut microbiota. However, morphine abstinence influenced the gut microbial composition. Several specific genera of gut microbiota were identified as markers for each group. Interestingly, gene function prediction found that the fatty acid metabolism pathway was enriched in the OUTs in the depressive group compared with the non-depressive group after morphine abstinence. Our data suggested that gut microbiota dysbiosis was associated with morphine abstinence-induced depressive behavior, possibly by implicating the fatty acid metabolism pathway.