The structures of two polysaccharides from Lepidium meyenii and their immunomodulatory effects via activating NF-κB signaling pathway.

Lepidium meyenii Walp., also known as the "Peruvian national treasure", is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii. The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6-α-D-Glc, while branches feature T-α-L-Ara, 1,5-α-L-Ara, and T-α-D-Glc attached to the O-6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6-ß-D-Gal, 1,3,6-ß-D-Gal with a few 1,3-ß-D-GlcpA-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3-ß-D-Gal, T-ß-D-Gal, T-α-L-Ara, 1,5-α-L-Ara, with trace amounts of 1,4-ß-D-Glc and T-ß-D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1ß, TNF-α, and IL-6 from RAW 264.7 cells at concentrations ranging from 50 µg/mL to 400 µg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB-α, p-IκB-α, p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities.

Plasma membrane-localized hexose transporter OsSWEET1b, affects sugar metabolism and leaf senescence.

KEY MESSAGE: OsSWEET1b is a hexose transporter protein, which localized in cell membranes and interacting with itself to form homodimer and knockout of OsSWEET1b resulted in reduced leaves sugar content and accelerating leaf senescence. In the rice genome, the SWEET gene family contains 21 homologous members, but the role of some of them in rice growth and development is still unknown. The function of the sugar transporter OsSWEET1b protein in rice was identified in this research. Expression analysis showed that the expression levels of OsSWEET1b in leaves were higher than that in other tissues. The hexose transport experiment confirmed that OsSWEET1b has glucose and galactose transporter activity in yeast. Subcellular localization indicates that OsSWEET1b protein was targeted to the plasma membrane and BiFC analysis showed that OsSWEET1b interacts with itself to form homodimers. Functional analysis demonstrated that the ossweet1b mutant plants were have reduced the sucrose, glucose, fructose, starch and galactose contents, and induced carbon starvation-related gene expression, which might lead to carbon starvation in leaves at filling stage. The ossweet1b knockout plants showed decreased chlorophyll content and antioxidant enzyme activity, and increased ROS accumulation in leaves, leading to leaf cell death and premature senescence phenotype at filling stage. In ossweet1b mutants, the leaf senescence-related gene expression levels were increased and the abundance of photosynthesis-related proteins was decreased. Loss of OsSWEET1b were affected the starch, sucrose metabolism and carbon fixation in photosynthetic organelles pathway by RNA-seq analysis. The destruction of OsSWEET1b function will cause sugar starvation, decreased photosynthesis and leaf senescence, which leading to reduced rice yield. Collectively, our results suggest that the OsSWEET1b plays a key role in rice leaves carbohydrate metabolism and leaf senescence.

Ultrasound-assisted fermentation for antioxidant peptides preparation from okara: Optimization, stability, and functional analyses.

This study investigated the effects of ultrasound-assisted fermentation (UAF) on the preparation of antioxidant peptides (UAFP) from okara and examined their content, chemical structures, and antioxidant activity. After the optimal ultrasonic processing (time, 20 min; frequency, 45 KHz; power, 120 W/L), the peptide content yield reached the maximum of 12.36 ± 0.02 mg/mL, and their DPPH free radical scavenging rate was 65.15 ± 0.32 %. UAF increased the number of globular aggregates with deeper gullies, a looser structure, and higher porosity. The experiments conducted using the oxidative stress injury model of HepG2 cells showed that okara UAFP promoted cell growth and exerted a protective effect. Moreover, ultrasonic treatment remarkably improved the environmental stability (NaCl, glucose, sodium benzoate, temperature, pH, metal ions) and antioxidant activity of UAFP. Concisely, optimal ultrasonic processing can aid the fermentation of agroindustrial by-products to prepare antioxidant peptides, such as natural food antioxidant peptides from soybean waste.

Determinants of parental self-reported uptake of influenza vaccination in preschool children during the COVID-19 pandemic.

In China, the coverage rate of influenza vaccination among the general population is significantly lower than that of high-income countries, with only 2.46% of the population vaccinated. Preschool-aged children are particularly susceptible to influenza viruses, yet the factors that influence parents' willingness to vaccinate their children are not well understood. To address this research gap, we developed a theoretical model grounded in the Unified Theory of Acceptance and Use of Technology (UTAUT), which explores six key factors influencing parental self-reported uptake of influenza vaccination in preschool children: performance expectancy, effort expectancy, social influence, facilitating conditions, knowledge, and behavioral intention. We collected data from 872 parents of children in five major cities in China and employed structural equation modeling to examine the significance of the theoretical model and explore the potential moderating effects of demographic variables on path relationships. Our analysis revealed that several positive factors influenced parents' intention of influenza vaccination for preschool children, including effort expectancy (ß = 0.38), social influence (ß = 0.17), and knowledge (ß = 0.52). Facilitating conditions (ß = 0.34), knowledge (ß = 0.40), and behavioral intention (ß = 0.34) were found to be associated with self-reported uptake. Furthermore, we observed significant moderating effects of the child's gender and age, as well as the guardian's category and income, on the theoretical models. Parents' willingness to vaccinate preschool children against influenza is influenced by both psychological and demographic variables. Further studies are needed to determine if these relationships persist over time and across different regions.

APE1 regulates mitochondrial DNA damage repair after experimental subarachnoid haemorrhage in vivo and in vitro.

BACKGROUND: Subarachnoid haemorrhage (SAH) can result in a highly unfavourable prognosis. In recent years, the study of SAH has focused on early brain injury (EBI), which is a crucial progress that contributes to adverse prognosis. SAH can lead to various complications, including mitochondrial dysfunction and DNA damage. Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein with multifaceted functionality integral to DNA repair and redox signalling. However, the role of APE1 in mitochondrial DNA damage repair after SAH is still unclear. METHODS: Our study involved an in vivo endovascular perforation model in rats and an in vitro neuron oxyhaemoglobin intervention. Then, the effects of APE1 on mitochondrial DNA damage repair were analysed by western blot, immunofluorescence, quantitative real-time PCR, mitochondrial bioenergetics measurement and neurobehavioural experiments. RESULTS: We found that the level of APE1 decreased while the mitochondria DNA damage and neuronal death increased in a rat model of SAH. Overexpression of APE1 improved short-term and long-term behavioural impairment in rats after SAH. In vitro, after primary neurons exposed to oxyhaemoglobin, APE1 expression significantly decreased along with increased mitochondrial DNA damage, a reduction in the subunit of respiratory chain complex levels and subsequent respiratory chain dysfunction. Overexpression of APE1 relieved energy metabolism disorders in the mitochondrial of neurons and reduced neuronal apoptosis. CONCLUSION: In conclusion, APE1 is involved in EBI after SAH by affecting mitochondrial apoptosis via the mitochondrial respiratory chain. APE1 may potentially play a vital role in the EBI stage after SAH, making it a critical target for treatment.

Genomic Surveillance of SARS-CoV-2 Variants That Emerged in South and Southeast Asia during Early 2022.

The continuously emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made the global coronavirus disease 2019 (COVID-19) pandemic unpredictable. Since the beginning of the pandemic, densely populated South and Southeast Asia have suffered great losses due to multiple COVID-19 surges because of vaccine and other medical resource shortages. Therefore, it is crucial to closely monitor the SARS-CoV-2 epidemic and to understand the evolutionary and transmission characteristics of SARS-CoV-2 in these regions. Here, we document the evolution of epidemic strains in the Philippines, Pakistan, and Malaysia from late 2021 to early 2022. Our results confirmed the circulation of at least five SARS-CoV-2 genotypes in these countries in January 2022, when Omicron BA.2, with a detection rate of 69.11%, replaced Delta B.1.617 as the dominant strain. Single-nucleotide polymorphism analysis indicated the distinct evolutionary directions of the Omicron and Delta isolates, with S, Nsp1, and Nsp6 genes potentially playing a significant role in the host adaptation of the Omicron strain. These findings are able to provide insights for predicting the evolutionary direction of SARS-CoV-2 in terms of variant competition, developing multi-part vaccines, and to support the evaluation and adjustment of current surveillance, prevention, and control strategies in South and Southeast Asia.

Comparative efficacy and safety of various mechanical thrombectomy strategies for patients with acute ischemic stroke: a Bayesian network meta-analysis.

Background: Stent retriever, contact aspiration, and combined treatment are crucial mechanical thrombectomy strategies for patients with acute ischemic stroke (AIS). Objectives: The aim of this study was to compare and rank three different mechanical thrombectomy strategies for AIS due to large vessel occlusion by means of a Bayesian network meta-analysis. Design: A systematic review and Bayesian network meta-analysis based on PRISMA guidelines. Data sources and methods: Relevant randomized controlled trials (RCTs) were identified in Embase, MEDLINE, the Cochrane Library database, and Clinicaltrials.gov from inception to 15 March 2022. We used random effect models to estimate corresponding odds ratios (ORs) and rank probabilities using pairwise and Bayesian network meta-analysis. We applied the grading of recommendations assessment, development, and evaluation (GRADE) methodology to rate the certainty of evidence. Results: We identified 10 RCTs enrolling 2098 participants. As for modified Rankin Scale (mRS) 0-2, moderate certainty evidence established all mechanical thrombectomy strategies that were more effective than standard medical treatment [combined: log OR 0.9288, 95% credibility intervals (CrI) 0.1268-1.7246; contact aspiration: log OR 0.9507, 95% CrI 0.3361-1.5688; stent retriever: log OR 1.0919, 95% CrI 0.6127-1.5702]. The same applied to mRS 0-3 (combined: log OR 0.9603, 95% CrI 0.2122-1.7157; contact aspiration: log OR 0.7554, 95% CrI 0.1769-1.3279; stent retriever: log OR 1.0046, 95% CrI 0.6001-1.4789). Combined treatment was superior to stent retriever in substantial reperfusion (log OR 0.8921, 95% CrI 0.2105-1.5907, high certainty). Stent retriever had the highest probability of being optimal for mRS 0-2 and mRS 0-3. Standard medical treatment had the lowest risk of subarachnoid hemorrhage. For all other outcomes, combined treatment was most likely the best treatment. Conclusion: Our results indicated that, with the exception of functional outcome, combined treatment might be the outstanding strategy. Apart from subarachnoid hemorrhage, all three mechanical thrombectomy strategies proved better strategies than standard medical treatment. Registration: PROSPERO (CRD42022351878).

Efficacy and safety of remote ischemic conditioning for acute ischemic stroke: A comprehensive meta-analysis from randomized controlled trials.

BACKGROUND AND PURPOSE: Remote ischemic conditioning (RIC) is a remote, transient, and noninvasive procedure providing temporary ischemia and reperfusion. However, there is no comprehensive literature investigating the efficacy and safety of RIC for the treatment of acute ischemic stroke. In the present study, we performed a comprehensive meta-analysis of the available studies. METHODS: MEDLINE, Embase, the Cochrane Library database (CENTRAL), and ClinicalTrials.gov were searched before Sep 7, 2022. The data were analyzed using Review Manager 5.4.1 software, Stata version 16.0 software, and R 4.2.0 software. Odds ratio (OR), mean difference (MD), and corresponding 95% CIs were pooled using fixed-effects meta-analysis. RESULTS: We pooled 6392 patients from 17 randomized controlled trials. Chronic RIC could reduce the recurrence of ischemic stroke at the endpoints (OR 0.67, 95% CI [0.51, 0.87]). RIC could also improve the prognosis of patients at 90 days as assessed by mRS score (mRS 0-1: OR 1.29, 95% CI [1.09, 1.52]; mRS 0-2: OR 1.22, 95% CI [1.01, 1.48]) and at the endpoints assessed by NIHSS score (MD -0.99, 95% CI [-1.45, -0.53]). RIC would not cause additional adverse events such as death (p = 0.72), intracerebral hemorrhage events (p = 0.69), pneumonia (p = 0.75), and TIA (p = 0.24) but would inevitably cause RIC-related adverse events (OR 26.79, 95% CI [12.08, 59.38]). CONCLUSIONS: RIC could reduce the stroke recurrence and improve patients' prognosis. Intervention on bilateral upper limbs, 5 cycles, and a length of 50 min in each intervention might be an optimal protocol for RIC at present. RIC could be an effective therapy for patients not eligible for reperfusion therapy. RIC would not cause other adverse events except for relatively benign RIC-related adverse events.

Three Doses of Platelet-Rich Plasma Therapy Are More Effective Than One Dose of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis.

PURPOSE: To compare the efficacy of a single dose of platelet-rich plasma (PRP) with multiple doses of PRP therapy in the treatment of knee osteoarthritis (KOA). METHODS: The PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, and Cochrane Library databases were searched from database inception to May 2022; in addition, the gray literature and bibliographic references were searched. Only randomized controlled trials comparing the effect of a single dose versus multiple doses of PRP for KOA were included. Literature retrieval and data extraction were conducted by 3 independent reviewers. The inclusion and exclusion criteria were based on type of study, research subjects, intervention, outcome, language, and availability of data. Pooled analyses of visual analog scale (VAS) scores, Western Ontario and McMaster Universities Arthritis Index scores, and adverse events were conducted. RESULTS: Seven studies (all randomized controlled trials) of high methodologic quality involving 575 patients were included. The ages of the patients included in this study ranged from 20 to 80 years, and the sex ratio was balanced. Triple-dose PRP therapy resulted in significantly better VAS scores compared with single-dose PRP therapy at 12 months (P < .0001), with no significant change in VAS scores between double-dose PRP and single-dose PRP at 12 months. Regarding adverse events, double-dose (P = .28) and triple-dose (P = .24) therapy showed no significant differences in safety from single-dose therapy. CONCLUSIONS: Although there is a paucity of large high-quality Level I studies, current best evidence suggests that 3 doses of PRP for KOA are more effective than 1 dose of PRP at providing pain relief up to 1 year after administration. LEVEL OF EVIDENCE: Level II, systematic review of Level II studies.

Transcranial direct current stimulation with virtual reality versus virtual reality alone for upper extremity rehabilitation in stroke: A meta-analysis.

Background: Stroke is one of the most prevalent diseases. Motor impairment in patients with stroke frequently affects the upper extremities. Several randomized clinical trials (RCTs) have tried to prove whether or not the combination of transcranial direct current stimulation (tDCS) with virtual reality (VR) is superior to VR alone for upper extremity rehabilitation. Methods: We searched Embase, MEDLINE, the Cochrane Library database, and Clinicaltrials.gov for relevant RCTs published before June 10, 2022. The results were analyzed by using standard mean differences (SMD) and 95% confidence intervals (95% CI). Results: We pooled 120 patients from 4 RCTs. There were no significant improvements in the Fugl-Meyer Upper Extremity scale (SMD = 0.51; 95% CI, -0.04 to 1.06), the Box and Block Test (SMD = 0.42; 95% CI, -0.02 to 0.86), and the Modified Ashworth Scale after the combined treatment of tDCS and VR. But tDCS combined with VR could enhance the Barthel Index scores in patients with stroke compared to VR alone (SMD = 0.49; 95% CI, 0.04 to 0.94). Conclusions: The combination of tDCS and VR can improve the quality of daily living in patients with stroke. No more satisfactory efficacy has been demonstrated in terms of upper extremity function. However, we observe a distinct trend toward significance in some outcomes.

The efficacy and safety of ganaxolone for the treatment of refractory epilepsy: A meta-analysis from randomized controlled trials.

OBJECTIVE: Epilepsy is one of the most common and refractory neurological disorders globally. Ganaxolone, a neuroactive steroid that enhances GABAergic inhibition, has been tested in many trials for the resolution of refractory epilepsy. Based on these, our study implemented a meta-analysis to evaluate the general benefit of ganaxolone for refractory epilepsy. METHODS: EMBASE, Medline, Scopus, Cochrane Library, and Clinicaltrials.gov were searched for relevant randomized controlled trials (RCTs) up to June 20, 2022. The risk ratio (RR) and standard mean difference (SMD) were analyzed using dichotomous and continuous outcomes, respectively with a random effect model. Trial sequential analysis (TSA) was also performed to judge the reliability of results. RESULTS: We totally collected 659 patients from four RCTs to evaluate the efficacy and safety of ganaxolone. As results showed, ≥50% reduction in mean seizure frequency has improved significantly compared with placebo (RR = 1.60, 95%CI: 1.02-2.49, p = 0.04, I2  = 30%), which is supported by TSA. However, the percentage of seizure-free days shows no statistical significance (p = 0.36). For safety outcomes, adverse events (AEs), serious adverse events, and AE leading to study drug discontinuation all revealed no obvious difference between ganaxolone and placebo (p > 0.05). SIGNIFICANCE: Based on our research, we have observed that ganaxolone is safe and has potential efficacy in the treatment of refractory epilepsy, waiting for further studies.

Rapid prediction of winter wheat yield and nitrogen use efficiency using consumer-grade unmanned aerial vehicles multispectral imagery.

Rapid and accurate assessment of yield and nitrogen use efficiency (NUE) is essential for growth monitoring, efficient utilization of fertilizer and precision management. This study explored the potential of a consumer-grade DJI Phantom 4 Multispectral (P4M) camera for yield or NUE assessment in winter wheat by using the universal vegetation indices independent of growth period. Three vegetation indices having a strong correlation with yield or NUE during the entire growth season were determined through Pearson's correlational analysis, while multiple linear regression (MLR), stepwise MLR (SMLR), and partial least-squares regression (PLSR) methods based on the aforementioned vegetation indices were adopted during different growth periods. The cumulative results showed that the reciprocal ratio vegetation index (repRVI) had a high potential for yield assessment throughout the growing season, and the late grain-filling stage was deemed as the optimal single stage with R2, root mean square error (RMSE), and mean absolute error (MAE) of 0.85, 793.96 kg/ha, and 656.31 kg/ha, respectively. MERIS terrestrial chlorophyll index (MTCI) performed better in the vegetative period and provided the best prediction results for the N partial factor productivity (NPFP) at the jointing stage, with R2, RMSE, and MAE of 0.65, 10.53 kg yield/kg N, and 8.90 kg yield/kg N, respectively. At the same time, the modified normalized difference blue index (mNDblue) was more accurate during the reproductive period, providing the best accuracy for agronomical NUE (aNUE) assessment at the late grain-filling stage, with R2, RMSE, and MAE of 0.61, 7.48 kg yield/kg N, and 6.05 kg yield/kg N, respectively. Furthermore, the findings indicated that model accuracy cannot be improved by increasing the number of input features. Overall, these results indicate that the consumer-grade P4M camera is suitable for early and efficient monitoring of important crop traits, providing a cost-effective choice for the development of the precision agricultural system.

Exploring loss and grief during the COVID-19 pandemic: A scoping review of qualitative studies.

INTRODUCTION: The COVID-19 pandemic has brought about multiple losses to various groups, namely patients, families and healthcare professionals. Grief, which is the reaction to these losses, could cause strain on these individuals' physical and mental health if not identified and managed early. This scoping review analysed loss, grief and how they were managed among these groups during the pandemic. METHOD: This scoping review utilised the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement extension for Scoping Reviews (PRISMA-ScR) and the Joanna Briggs Institute framework for scoping reviews. Only qualitative studies relating to loss and grief and their management were included. Of 166 studies screened, 69 were included in the study. Qualitative analysis and data coding of each record were conducted through qualitative data analysis software. RESULTS: Losses included the death of family members, patients, colleagues and others. They also included the loss of usual routines, lifestyles and physical health. The grief experienced was multidimensional, affecting mainly the emotional, physical, social and existential realms. Anger, guilt and fear resulted from unsatisfactory farewells, issues with funerals, social isolation, financial strain and stigmatisation. Management strategies could be categorised into 5 themes: communication, finance, counselling, education and spiritual care. CONCLUSION: Loss and grief identification and management among patients, family members and healthcare professionals are critically important during this COVID-19 pandemic. Current operating guidelines have proven insufficient in managing loss and grief. Innovative strategies are essential to tackle the many dimensions of loss and grief. Nevertheless, further research is necessary to better understand the effectiveness of implemented policies.

Safety and efficacy of tyrosine kinase inhibitors for the treatment of multiple sclerosis: A systematic review and meta-analysis from randomized controlled trials.

Background: Multiple sclerosis (MS), an autoimmune disease, is characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Drugs targeting tyrosine kinase, a critical component of immune cell receptor signaling, have been developed to treat MS. However, the exact efficacy and safety of tyrosine kinase inhibitors (TKIs) are still controversial, and comprehensive analysis with a high level of evidence is needed. Methods: Medline, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials (RCTs) evaluating TKIs versus placebo for MS were searched up to April 1st, 2022. The risk ratio (RR) and mean difference (MD) or standard mean difference (SMD) were analyzed using dichotomous outcomes and continuous outcomes, respectively, with a random effect model. Results: A total of 1,043 patients derived from four clinical trials were included to investigate the efficacy and safety of TKI therapy for MS. According to our analysis, TKIs decreased the cumulative number of gadolinium-enhancing lesions on T1-weighted MRI with the application of high dose (SMD = -0.61, 95% CI: -0.93 to -0.30, P = 0.0001). Meanwhile, TKIs prevented the expanded disability status scale (EDSS) from rising (MD = -0.10, 95% CI: -0.19 to -0.00, P = 0.046). In terms of MS relapse, TKIs have not revealed an obvious statistical difference compared with placebo (RR = 0.96, 95% CI: 0.55-1.65, P = 0.8755). However, more adverse events seem to occur in the TKIs group, both for adverse events (RR = 1.12, 95% CI: 1.05-1.19, P = 0.0009) and serious adverse events (RR = 1.91, 95% CI: 1.30-2.81, P = 0.001). Conclusion: Tyrosine kinase inhibitors have shown promise in treating MS. Generally, TKIs that attain the effective dose demonstrate definite efficacy and have tolerable side effects. More clinical trials and validation are needed, and we anticipate that TKIs will be a viable alternative for MS patients.

Efficacy of Neurostimulations for Upper Extremity Function Recovery after Stroke: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Neurostimulations for the post-stroke recovery of upper extremity function has been explored in previous research, but there remains a controversy about the superiority of different neurostimulations. METHODS: Randomized controlled trials (RCTs) were searched in MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov, from 1 January 2000 to 1 June 2022. A conventional pair-wise meta-analysis with a random-effect model was used to evaluate direct evidence. Bayesian random effect models were used for network meta-analysis. The grading of the recommendations assessment, development and evaluation (GRADE) approach was applied to assess the clinical quality of the results. RESULTS: A total of 88 RCTs, which enrolled 3491 participants, were included. For the Fugl-Meyer Assessment-Upper Extremity score change from the baseline to the longest follow-up, the following interventions showed a significant difference: VNS (MD = 4.12, 95%CrI: 0.54 to 7.80, moderate certainty), cNMES (MD = 3.98, 95%CrI: 1.05 to 6.92, low certainty), FES (MD = 7.83, 95%CrI: 4.42 to 11.32, very low certainty), drTMS (MD = 7.94, 95%CrI: 3.71 to 12.07, moderate certainty), LFrTMS (MD = 2.64, 95%CrI: 1.20 to 4.11, moderate certainty), HFrTMS (MD = 6.73, 95%CrI: 3.26 to 10.22, moderate certainty), and iTBS combined with LFrTMS (MD = 5.41, 95%CrI: 0.48 to 10.35, moderate certainty). CONCLUSIONS: The neurostimulations above the revealed significant efficacy for improving the upper limb function after stroke eased the suffering of the patient.

Microsurgical Management of Posterior Circulation Aneurysms: A Retrospective Study on Epidemiology, Outcomes, and Surgical Approaches.

Posterior circulation aneurysms have been regarded as the most challenging for endovascular coiling and microsurgical occlusion. The role of microsurgical treatment is gradually being overlooked and diminishing in the trend of endovascular treatment. As microsurgical occlusion of posterior circulation aneurysms is decreasing, we present our relevant experience to evaluate treatment options and surgical approaches. A retrospective study was conducted in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University between 2016 and 2021. Patients with posterior circulation aneurysms treated by clipping, bypass, and trapping were enrolled and followed up for at least six months. We included 50 patients carrying 53 posterior circulation aneurysms, 43 of whom had aneurysm ruptures. The posterior cerebral artery and posterior inferior cerebellar artery were the most common aneurysm locations. Direct clipping was performed in 43 patients, while bypass and trapping was performed in six patients. The retrosigmoid, far-lateral, and midline or paramedian suboccipital approaches were performed for those aneurysms in the middle and lower thirds. Aneurysms in the upper third required the lateral supraorbital approach, pterional approach, subtemporal approach, and occipital craniotomy. The lateral supraorbital approach was utilized in seven patients for aneurysms above the posterior clinoid process. Thirty-four patients recovered well with modified Rankin score 0-3 at discharge. No patient experienced aneurysm recurrence during the mean follow-up period of 3.57 years. Microsurgery clipping and bypass should be considered in conjunction with endovascular treatment as a treatment option in posterior circulation aneurysms. The lateral supraorbital approach is a feasible, safe, and simple surgical approach for aneurysms above the posterior clinoid process.

High-dose versus low-dose inhaled levodopa (CVT-301) in patients with Parkinson disease for the treatment of OFF episodes: a meta-analysis of randomized controlled trials.

BACKGROUND: Levodopa is the most commonly used first-line drug for Parkinson's disease. However, during the period of medication, the generation of motor fluctuations affects the life quality of patients. CVT-301, as an inhaled levodopa for the treatment of OFF episodes, rose in response to this condition. METHODS: We systematically searched Medline, EMBASE, Cochrane Library, and Clinicaltrials.gov for relevant randomized controlled trials, from the earliest available date to February 12, 2022, to evaluate the efficacy of high and low dose of inhaled levodopa in patients with Parkinson's disease. RESULTS: A total of six multicenter, randomized controlled trials with 1166 patients were included. Compared with placebo, CVT-301 has a statistically significant effect on the treatment of Parkinson's patients with OFF episodes of medication interval. The UPDRS Part III score decreased more significantly in the high-dose group 30 minutes after administration than the low-dose group (WMD = - 4.51; 95% CI, - 7.34 to - 1.68; p = 0.002). More patients in the high-dose group achieved and maintained an on state up to 60 min after receiving study medication (RR = 1.17; 95% CI, 1.08 to 1.27; p < 0.001). And more patients were proved with improved PGIC scores in the high-dose group (RR = 1.13; 95% CI, 1.05 to 1.21; p = 0.001). CONCLUSIONS: High doses CVT-301 can improve the motor function of the patient to some extent. There seems no risk of increasing adverse reactions.

Metabolomic analysis of serum from pure coronary artery ectasia patients based on UPLC-QE/MS technique.

BACKGROUND: Coronary artery ectasia (CAE) is a cardiovascular disorder characterized by abnormal coronary artery dilation and disturbed coronary flow. The exact pathophysiology of CAE is still unclear. We aimed to investigate differences in metabolomic profiles between CAE patients and healthy controls. METHODS: Radial artery blood samples were collected from 14 pure CAE patients, 12 mixed CAE patients with atherosclerosis, and 14 controls with normal angiography. Differential serum metabolites were analyzed by untargeted ultra-high performance liquid chromatography-mass spectrometry. Serum ICAM-1, VEGF, ROS, and glutathione levels were also measured. RESULTS: Ten metabolites distinguished pure CAE patients from controls and mixed CAE, including 1-cyano-2-hydroxy-3-butene, 2,3-dihydro-6-methyl-5-(5-methyl-2-furanyl)-1H-pyrrolizine, 2-propionylpyrrole, 2-pyrrolidinone, 3-(2-furanylmethylene)pyrrolidine, D-alanine, furanofukinin, o-ethyltoluene, rotundine A, and SM(d18:1/18:1(9Z)). Related metabolic pathways include amino acid metabolism, sphingolipid dysfunction, energy metabolism, mitochondrial dysfunction, and oxidative stress. Serum concentrations of ICAM-1, VEGF and ROS were significantly elevated in CAE patients compared to controls, while glutathione decreased significantly in CAE patients. Moreover, ICAM-1 levels were negatively correlated with 2-propionylpyrrole, and VEGF levels were negatively correlated with SM(d18:1/18:1(9Z)), while GSH and ROS levels were correlated with the abundance of SM(d18:1/18:1(9Z)), further confirming systemic inflammation and oxidative stress in CAE. CONCLUSIONS: This is the first report describing differential serum metabolomic profiles of pure CAE patients compared to mixed CAE and healthy controls, which revealed 10 potential biomarkers that can provide an early diagnosis of pure CAE. These discriminatory metabolites and related metabolic pathways can help to better understand the pathogenesis of pure CAE.

Strategies of Targeting Inflammasome in the Treatment of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ dysfunction resulting from the production of multiple autoantibodies and adaptive immune system abnormalities involving T and B lymphocytes. In recent years, inflammasomes have been recognized as an important component of innate immunity and have attracted increasing attention because of their pathogenic role in SLE. In short, inflammasomes regulate the abnormal differentiation of immune cells, modulate pathogenic autoantibodies, and participate in organ damage. However, due to the clinical heterogeneity of SLE, the pathogenic roles of inflammasomes are variable, and thus, the efficacy of inflammasome-targeting therapies is uncertain. To provide a foundation for the development of such therapeutic strategies, in this paper, we review the role of different inflammasomes in the pathogenesis of SLE and their correlation with clinical phenotypes and propose some corresponding treatment strategies.

The efficacy and safety of atogepant for the prophylactic treatment of migraine: evidence from randomized controlled trials.

BACKGROUND: Migraine is a common neurovascular disorder that has a severe impact on the individual daily life. Atogepant (AGN-241689) is an orally ingested, small-molecule drugs belonging to calcitonin gene-related peptide receptor antagonist, which has been initiated for the prophylactic treatment of migraine. However, there is no comprehensive literature to study the efficacy and safety of atogepant for the treatment of migraine. In this article, we present a meta-analysis of the available studies. METHODS: MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov were searched before October 20, 2021 for any relevant literature. Eventually, three randomized clinical trials (RCTs) with 2,466 patients were included in our study. RESULTS: We pooled 2,466 patients from 3 RCTs and primary outcome was mean monthly migraine days, the secondary endpoints were monthly headache days, acute medication use days per month and ≥ 50% reduction in monthly migraine days, baseline to end of trials. It was found that atogepant (10 mg, 30 mg, 60 mg once a day) led to a significant reduction in monthly migraine days (P < 0.00001, P < 0.00001, P = 0.007), monthly headache days (P < 0.00001, P < 0.00001, P = 0.001), and monthly medication use days (P < 0.00001, P < 0.00001, P = 0.0001), and an increase in the proportion of people with ≥ 50% reduction in monthly migraine days (P = 0.0008, P = 0.02, P = 0.04) in comparison with placebo. Moreover, there were no significant differences (P > 0.05) in outcomes of adverse events between atogepant and placebo. CONCLUSIONS: Atogepant has shown good efficacy and safety in the prophylactic treatment of migraine, and further studies are expected.