Quantitative susceptibility mapping in rats with minimal hepatic encephalopathy: Does iron overload aggravate cognitive impairment by promoting neuroinflammation?

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. MATERIALS AND METHODS: Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. RESULTS: MHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats. CONCLUSION: MHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.

In Situ Electrospinning of "Dry-Wet" Conversion Nanofiber Dressings for Wound Healing.

Rapid wound dressings provide an excellent solution strategy for the treatment of wounds in emergency situations. In this study, aqueous solvent-based PVA/SF/SA/GelMA nanofiber dressings fabricated by a handheld electrospinning device could deposit quickly and directly on the wound, perfectly fitting wounds with various sizes. Using an aqueous solvent overcame the disadvantage of using the current organic solvents as the medium for rapid wound dressings. The porous dressings had excellent air permeability to ensure smooth gas exchange at the wound site. The distribution range of the tensile strength of the dressings was 9-12 Kpa, and the tensile strain was between 60-80%, providing sufficient mechanical support during wound healing. The dressings could absorb 4-8 times their own weight in solution and could rapidly absorb wound exudates from wet wounds. The nanofibers formed ionic crosslinked hydrogel after absorbing exudates, maintaining the moist condition. It formed a hydrogel-nanofiber composite structure with un-gelled nanofibers and combined the photocrosslinking network to maintain a stable structure at the wound location. The in vitro cell culture assay indicated that the dressings had excellent cell cytocompatibility, and the addition of SF contributed to cell proliferation and wound healing. The in situ deposited nanofiber dressings had excellent potential in the urgent treatment of emergency wounds.

Altered anterior insula-superior frontal gyrus functional connectivity is correlated with cognitive impairment following total sleep deprivation.

Sleep deprivation is an important cause of cognitive impairment, and anterior insular subregions are core brain regions linked to cognitive function. However, the relationship between anterior insular subregions functional connectivity (FC) and the cognitive impairment that occurs following total sleep deprivation (TSD) remains unknown. As such, this study was designed to evaluate how such anterior insular subregions FC alterations are linked with impaired cognitive activity after TSD. This study recruited 20 healthy volunteers who underwent two rounds of resting-state functional magnetic resonance imaging (rs-fMRI), with one being conducted while in a state of rested wakefulness (RW) and the other being conducted following 24 h of TSD. These rs-fMRI data were then used to conduct seed-based FC analyses for the bilateral anterior insular subregions, including the dorsal anterior insula (dAI) and the ventral anterior insula (vAI). The Psychomotor Vigilance Test (PVT) was used to gauge cognitive performance, and associations between altered FC in these anterior insular subregions and PVT performance following TSD were measured using Pearson correlation analyses. Significant changes in the FC of these bilateral insular subregions were observed following 24 h of TSD relative to the RW state. Significantly enhanced FC was evident between the left dAI and right superior frontal gyrus (SFG), right dAI and bilateral SFG and right putamen, and right vAI and left medial SFG. Moreover, the observed enhancement of FC between the left vAI and right SFG functional connectivity was positively correlated with worse PVT performance. These data suggest that altered FC in the anterior insular subregions represents a prominent neuroimaging biomarker associated with cognitive impairment following TSD.

Kearns-Sayre syndrome with rare imaging finding of SLC25A4 Mutation.

Kearns-Sayre Syndrome (KSS) is a subtype of chronic progressive external ophthalmoplegia (CPEO). In this case, A 21-year-old man diagnosed with KSS, and presented with chronic progressive blepharoptosis (ptosis) and external ophthalmoplegia, diffuse depigmentation of the retinal pigment epithelium, and cerebellar ataxia, with a cerebrospinal fluid protein of 254 mg/dL, was reported. Genetic screening revealed a novel mutated gene in SLC25A4 in the patient as well as in his mother: NM_001151:c.170G>C in exon 2. Its imaging finding is a characteristic progressive atrophy of the right cerebellar hemisphere. In conclusion, we found a case of KSS with a novel mutated gene in SLC25A4: NM_001151:c.170G>C in exon 2 as the pathogenic mechanism, and found that KSS can be caused only when the proportion of mutations in the SLC25A4 gene reach a certain degree, and the patient with KSS showed a unique cranial imaging feature of unilateral progressive cerebellar atrophy.

A framework for assessing carbon effect of land consolidation with life cycle assessment: A case study in China.

Ecological transformation is an inevitable trend for the development of land consolidation (LC) worldwide, and the research on carbon effect of LC is an important theoretical basis for promoting the construction of Eco-LC. However, there is currently a lack of analysis of the carbon effect based on the whole process of LC, ignoring the stage elements and temporal factors. This study applied Life Cycle Assessment (LCA) method to construct a research framework and accounting system for carbon footprint assessment of LC, and explored the carbon effect in a typical land consolidation project area (LCPA) of China. Results showed that: (a) The carbon effect of the project area was characterized as carbon emission during the whole life cycle of LC. Carbon footprint before and after LC was 3.251 tCE·ha-1·a-1 and 2.401 tCE·ha-1·a-1 respectively. The carbon storage reduced and the carbon footprint is declined by 0.850 tCE·ha-1·a-1. (b) Carbon effect varied among different stages of LC. The Benefit Period (BP) was the only stage that was manifested as carbon absorption (-14.65%), while all the other stages were manifested as carbon emission. Among them, as to the carbon emission, the Construction Period (CP) played a decisive role with the most proportion (102.74%), followed by DP and RP, and the carbon effect of PP was negligible. (c) The dominant factors of carbon effect at different stages were also different. During CP, cement contributed the most to the carbon emission in this case. During RP, carbon sequestration effect of cropland proved to be the most significant. During RP, the carbon sequestration effect of cultivated land and the carbon emission effect of unused land were the most prominent. During BP, the carbon sequestration capacity of farmland ecosystems proved to be greater than the carbon emissions from agricultural activities. This study contributes to providing certain theoretical guidance and method reference for the realization of Low-Carbon LC project planning, with this comprehensive and reliable method.

Sampling for DUS Test of Flower Colors of Ranunculus asiaticus L. in View of Spatial and Temporal Changes of Flower Colorations, Anthocyanin Contents, and Gene Expression Levels.

Sampling for DUS test of flower colors should be fixed at the stages and sites that petals are fully colored, and besides, flower colorations are uniform among individuals and stable for a period of time to allow testers to get consistent results. It remains a problem since spatial and temporal flower colorations are reported a lot but their change traits are little discussed. In this study, expression state, uniformity and stability of color phenotypes, anthocyanin contents, and gene expression levels were taken into account based on measurements at 12 development stages and three layers (inner, middle, and outer petals) of two varieties of Ranunculus asiaticus L. to get their best sampling. Our results showed that, outer petals of L9⁻L10 (stage 9⁻stage 10 of variety 'Jiaoyan zhuanhong') and C5⁻C6 (stage 5⁻stage 6 of variety 'Jiaoyan yanghong') were the best sampling, respectively. For DUS test, it is suggested to track flower colorations continuously to get the best sampling as well as representative colors since different cultivars had different change traits, and moreover, full expression of color phenotypes came later and lasted for a shorter duration than those of anthocyanin contents and gene expressions. Our innovation exists in following two points. Firstly, a model of change dynamic was introduced to illustrate the change traits of flower colorations, anthocyanin contents, and gene expressions. Secondly, genes used for expression analysis were screened on account of tentative anthocyanins, which were identified based on comparison between liquid chromatography⁻mass spectrometry (LC⁻MS) results and molecular mass and mass fragment pattern (M²) of each putative anthocyanin and their fragments deduced in our previous study. Gene screening in this regard may also be interest for other non-model plant genera with little molecular background.

Synthesis of tricyclic quinazolinones via intramolecular cyclization of 3-(2-aminoalkyl)-2-(phenylamino)quinazolin-4(3H)-ones.

Bioactive tricyclic quinazolines class of 3,4-dihydro-1H-pyrimido[2,1-b]quinazolin-6(2H)-ones I and 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones II were synthesized by the formic acid-catalyzed intramolecular cyclization of 3-(2-aminoalkyl)-2-(phenylamino)quinazolin-4(3H)-ones 1 in high yields. A plausible mechanism of the cyclization step is proposed.

Rosiglitazone via PPARγ-dependent suppression of oxidative stress attenuates endothelial dysfunction in rats fed homocysteine thiolactone.

To explore whether rosiglitazone (RSG), a selective peroxisome proliferator-activated receptor γ (PPARγ) agonist, exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hrs significantly reduced cell viabilities assayed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, as well as enhanced productions of reactive oxygen species, activation of nuclear factor kappa B, and increased intercellular cell adhesion molecule-1 secretion. Pre-treatment of cells with RSG (0.001-0.1 mM), pyrollidine dithiocarbamate (PDTC, 0.1 mM) or apocynin (0.1 mM) for 1 hr reversed these effects induced by HTL. Furthermore, co-incubation with GW9662 (0.01 mM) abolished the protective effects of RSG on HTL-treated cells. In ex vivo experiments, exposure of isolated aortic rings from. rats to HTL (1 mM) for 1 hr dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced release of nitric oxide and activity of superoxide dismutase, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with RSG (0.1, 0.3, 1 mM), PDTC or apocynin normalized the disorders induced by HTL. In vivo analysis indicated that administration of RSG (20 mg/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed HTL (50 mg/kg/d) for 8 weeks. RSG improves endothelial functions in rats fed HTL, which is related to PPARγ-dependent suppression of oxidative stress.

Clinical efficacy and safety of traditional Chinese medicine combined with Western Medicine in patients with diabetic acute ischemic stroke.

OBJECTIVE: To observe the clinical efficacy and safety of Traditional Chinese Medicine (TCM) combined with Western Medicine (WM) in patients with diabetic acute ischemic stroke. METHODS: Ninety patients with diabetic acute ischemic stroke were randomly divided into a treatment group and a control group. The 45 patients in the treatment group were given standardized treatment with TCM combined with WM. They received corresponding oral Chinese decoctions three times daily, according to their TCM syndromes, along with basic western medical treatment. The 45 patients in the control group were given non-standardized treatment with TCM combined with WM. They received an oral Chinese decoction for promotion of blood circulation to inhibit hemostasis, regardless of their TCM syndromes, along with basic western medical treatment. The treatments lasted for 4 weeks. Scores were evaluated on the National Institutes of Health Stroke Scale (NIHSS) score, activity of daily life (ADL) scores, and TCM symptoms before treatment and 2 and 4 weeks after treatment. RESULTS: Analysis of variance for repeated measurements showed that there were significant differences in NIHSS and ADL score before and after treatment in both groups (P < 0.05). There were also significant differences between the scores at 2 and 4 weeks after treatment. There were significant differences in TCM syndrome scores before and after treatment in both groups (P < 0.05). There were also significant differences between the scores at 2 and 4 weeks after treatment. The X2 test showed no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). CONCLUSION: Standardized treatment was superior to non-standardized treatment for clinical efficacy of TCM combined with WM in patients with diabetic acute ischemic stroke, and the superiority was more obvious in improving neural dysfunction, ADL score, and TCM symptoms. The adverse reactions were similar in the two treatment groups.

Iron overload regulates cognitive function in rats with minimal hepatic encephalopathy by inducing an increase in frontal butyrylcholinesterase activity.

Background and aims: This study aimed to investigate the effect of iron overload on acetylcholinesterase activity in the frontal lobe tissue of rats with minimal hepatic encephalopathy (MHE) and its relation to cognitive ability. By elucidating the potential mechanisms of cognitive impairment, this study may offer insights into novel therapeutic targets for MHE. Materials and methods: Twelve Sprague-Dawley rats were purchased and randomly assigned to either the experimental or control group with six rats in each group. Following the induction of MHE, the Morris Water Maze (MWM) was utilized to assess spatial orientation and memory capacity. Subsequently, Magnetic Resonance Imaging (MRI) scans were performed to capture Quantitative Susceptibility Mapping (QSM) images of all rats' heads. Results: Compared to the control group rats, the MHE model rats showed significantly reduced learning and memory capabilities as well as spatial orientation abilities (P < 0.05). Furthermore, the susceptibility values in the frontal lobe tissue of MHE model rats was significantly higher than that of the control group rats (P < 0.05), and the corresponding BuChE activity in the frontal lobe extract of model rats was significantly increased while BuChE activity in the peripheral blood serum was significantly decreased compared to the control group rats (P < 0.05). Meanwhile, our findings indicate a significant positive correlation between latency period and BuChE activity with susceptibility values in the MHE group. Conclusion: The changes in BuChE activity in frontal lobe extract may be related to changes in spatial orientation and behavioral changes in MHE, and iron overload in the frontal lobe tissue may regulate changes in BuChE activity, BuChE levels appear to be iron-dependent.

Regulatory mechanism of Sarmentosin and Quercetin on lipid accumulation in primary hepatocyte of GIFT tilapia (Oreochromis niloticus) with fatty liver.

Sarmentosin (SA) and Quercetin (QC) are two active components of Sedum Sarmentosum Bunge, which is a traditional Chinese herbal medicine. This study aimed to investigate the role and regulatory mechanism of SA and QC in fatty liver of Genetic Improvement of Farmed Tilapia (GIFT) tilapia. GIFT tilapia were randomly divided into two groups with three replicates per treatment (30 fish in each replicate): normal diet group (average weight 3.51±0.31 g) and high-fat diet group (average weight 3.44±0.09 g). After 8 weeks feeding trial, growth index, lipid deposition, and biochemical indexes were measured. Lipid deposition, and lipid and inflammation-related gene expression were detected in a primary hepatocyte model of fatty liver of GIFT tilapia treated with SA or QC. Our results showed that high-fat diet caused lipid deposition and peroxidative damage in the liver of GIFT tilapia. The cell counting kit-8 assay results indicated that 10 µM SA and 10 µM of QC both had the least effect on hepatocyte proliferation. Moreover, both 10 µM of SA and 10 µM of QC showed lipolytic effects and inhibited the expression of lipid-related genes (FAS, Leptin, SREBP-1c, and SREBP2) in fatty liver cells. Interestingly, QC induced autophagosome-like subcellular structure and increased the expression of IL-8 in fatty liver cells. In conclusion, this study confirmed that SA and QC improved fatty liver caused by high-fat diet, providing a novel therapeutic approach for fatty liver of GIFT tilapia.

Microstructural white matter changes in chronic migraine patients with liver-yang hyperactivity and qi-blood deficiency syndrome: a diffusion tensor imaging study.

White matter alterations in patients with chronic migraine (CM) have been reported. Traditional Chinese medicine (TCM) syndromes are clinical syndromes proposed by TCM doctors based on long-term clinical observation and classification of the clinical symptoms and signs of CM patients. This study aimed to analyze the whole-brain diffusion tensor imaging (DTI) data of CM patients with different types of TCM syndromes. Sixteen CM patients diagnosed with liver-yang hyperactivity (LH) syndrome and 16 CM patients with qi-blood deficiency (QD) syndrome were recruited in this study. Thirty-one healthy controls (HCs) were also enrolled. All subjects underwent DTI and T1-weighted MRI acquisition. Thirty HCs and 30 CM patients (LH group: n = 15; QD group: n = 15) were included in the final analysis. No significant difference was observed in the DTI indexes between CM patients and HCs, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). The mean FAs of the left tapetum and the mean MD values for the right medial lemniscus and the right inferior cerebellar peduncle were significantly different in the LH and HC groups. The mean AD values for the right cingulate gyrus and the left uncinate fasciculus, as well as the mean RD for the right inferior cerebellar peduncle and the left tapetum, were also significantly different between these two groups. CM patients with LH and QD syndrome showed altered FA and diffusivity in comparison to healthy controls, suggesting that there may be significant white matter microstructural alterations in these patients.

A Novel CT-Based Radiomics Features Analysis for Identification and Severity Staging of COPD.

RATIONALE AND OBJECTIVES: To evaluate the role of radiomics based on Chest Computed Tomography (CT) in the identification and severity staging of chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: This retrospective analysis included 322 participants (249 COPD patients and 73 control subjects). In total, 1395 chest CT-based radiomics features were extracted from each participant's CT images. Three feature selection methods, including variance threshold, Select K Best method, and least absolute shrinkage and selection operator (LASSO), and two classification methods, including support vector machine (SVM) and logistic regression (LR), were used as identification and severity classification of COPD. Performance was compared by AUC, accuracy, sensitivity, specificity, precision, and F1-score. RESULTS: 38 and 10 features were selected to construct radiomics models to detect and stage COPD, respectively. For COPD identification, SVM classifier achieved AUCs of 0.992 and 0.970, while LR classifier achieved AUCs of 0.993 and 0.972 in the training set and test set, respectively. For the severity staging of COPD, the mentioned two machine learning classifiers can better differentiate less severity (GOLD1 + GOLD2) group from greater severity (GOLD3 + GOLD4) group. The AUCs of SVM and LR is 0.907 and 0.903 in the training set, and that of 0.799 and 0.797 in the test set. CONCLUSION: The present study showed that the novel radiomics approach based on chest CT images that can be used for COPD identification and severity classification, and the constructed radiomics model demonstrated acceptable performance.

Magnetic resonance imaging radiomics to differentiate ovarian sex cord-stromal tumors and primary epithelial ovarian cancers.

Objective: To evaluate the diagnostic ability of magnetic resonance imaging (MRI) based radiomics and traditional characteristics to differentiate between Ovarian sex cord-stromal tumors (SCSTs) and epithelial ovarian cancers (EOCs). Methods: We consecutively included a total of 148 patients with 173 tumors (81 SCSTs in 73 patients and 92 EOCs in 75 patients), who were randomly divided into development and testing cohorts at a ratio of 8:2. Radiomics features were extracted from each tumor, 5-fold cross-validation was conducted for the selection of stable features based on development cohort, and we built radiomics model based on these selected features. Univariate and multivariate analyses were used to identify the independent predictors in clinical features and conventional MR parameters for differentiating SCSTs and EOCs. And nomogram was used to visualized the ultimately predictive models. All models were constructed based on the logistic regression (LR) classifier. The performance of each model was evaluated by the receiver operating characteristic (ROC) curve. Calibration and decision curves analysis (DCA) were used to evaluate the performance of models. Results: The final radiomics model was constructed by nine radiomics features, which exhibited superior predictive ability with AUCs of 0.915 (95%CI: 0.869-0.962) and 0.867 (95%CI: 0.732-1.000) in the development and testing cohorts, respectively. The mixed model which combining the radiomics signatures and traditional parameters achieved the best performance, with AUCs of 0.934 (95%CI: 0.892-0.976) and 0.875 (95%CI: 0.743-1.000) in the development and testing cohorts, respectively. Conclusion: We believe that the radiomics approach could be a more objective and accurate way to distinguish between SCSTs and EOCs, and the mixed model developed in our study could provide a comprehensive, effective method for clinicians to develop an appropriate management strategy.

The role of butyrylcholinesterase in the regulation of cognitive dysfunction in minimal hepatic encephalopathy: A potential blood marker of disease evolution.

Background and aims: Patients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE. Materials and methods: We enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA. Results: BuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05). Conclusion: The altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE.

Decreased brain noradrenaline in minimal hepatic encephalopathy is associated with cognitive impairment in rats.

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication in patients with cirrhosis. Alterations in monoamine neurotransmitters have been associated with the pathogenesis of MHE. We investigated the levels of hippocampal noradrenergic neurotransmitter in a rat model of thioacetamide-induced chronic liver failure-related MHE, and their role in cognitive impairment. MATERIALS: 18 male Sprague-Dawley (SD) rats were equally divided in MHE and control groups. A rat model of MHE was established by intraperitoneal injection of thioacetamide (TAA) for 12 weeks. Cognitive function was assessed using the Morris water maze (MWM) test and locomotor activity and exploratory behavior assessed with open field test. The concentration of hippocampal noradrenaline (NE) was detected by ELISA, and the magnetic susceptibility value in the hippocampus was detected by quantitative susceptibility mapping. Hippocampal iron content was quantified by Prussian blue staining. RESULTS: MHE rats performed significantly poorer than their control counterparts in the MWM test, as seen by decreased number of platform crossings and time in the target quadrant, and increased path length to reach the target zone (P < 0.05 for all parameters). In the open field test, the MHE group exhibited lower locomotor activity and exploratory behavior than the control group (P < 0.05 for all parameters). We detected pronounced iron staining in the hippocampus of MHE rats, whereas no iron-stained particles were found in control rats. We observed an imbalance of inflammatory (increased pro- and decreased anti-) cytokines in the hippocampus of MHE rats. Further analysis of the data showed that the level of hippocampal noradrenaline in MHE rats was significantly lower than that of control rats (P < 0.05). We observed a correlation between the level of inflammatory cytokine and noradrenaline land susceptibility value in the rat hippocampus of the MHE group. CONCLUSION: Our results suggest that MHE associated with TAA-induced chronic liver failure is associated with alterations in noradrenergic neurotransmission. We propose that iron imbalance in the brain might lead to reduction in the levels of noradrenaline, and cognitive impairment.

Monomethyl lithospermate alleviates ischemic stroke injury in middle cerebral artery occlusion mice in vivo and protects oxygen glucose deprivation/reoxygenation induced SHSY-5Y cells in vitro via activation of PI3K/Akt signaling.

Stroke is a fatal neurological disease, which seriously threatens human health and life. Ischemic stroke (IS) is the most common type of stroke in clinic. Its pathogenesis is very complex, mainly caused by nerve damage caused by brain blood supply disorder. Previous studies have confirmed that natural products play important roles in improving neurological disorders. Furthermore, our previous results also suggested that Shenxiong Tongmai granule, a clinically used herbal medicines' prescription, has a good ameliorating effect on IS. In the present study, we found that Monomethyl lithospermate (MOL), a constituent of Shenxiong Tongmai granule, significantly improved the neurological damage in middle cerebral artery occlusion (MCAO) rats. MOL can significantly improve the neurological deficit score of MCAO rats, and improve the damage of hippocampal neurons caused by ischemia-reperfusion (IR). At the same time, we also found that MOL could reduce the level of oxidative stress in the brain tissues of MCAO rats. Furthermore, the oxygen and glucose deprivation/Reoxygenation (OGD/R)-induced SHSY-5Y cell model was established in vitro to investigate the pharmacological activity and molecular mechanisms of MOL in improving the nerve injury of IS rats. The results showed that MOL could increase the cell viability of SHSY-5Y cells, inhibit the mitochondrial membrane potential (MMOP) collapse and suppress apoptosis. In addition, MOL also ameliorated the elevated oxidative stress level caused by OGR/R treatment in SHSY-5Y cells. Further mechanistic studies showed that MOL could activate the PI3K/AKT pathway via promoting the phosphorylation of PI3K and AKT in MCAO rats and OGR/R-induced SHSY-5Y cells, which could be partially blocked by addition of PI3K/AKT pathway inhibitor of LY294002. Taken together, our current study suggested that MOL exerts a protective effect against neural damage caused by IS in vivo and in vitro by activating the PI3K/AKT pathway.

Safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy individuals: protocol for a systematic review and meta-analysis.

INTRODUCTION: COVID-19 has spread with high morbidity and mortality worldwide. Many inactivated SARS-CoV-2 vaccines are being tested at various clinical trial stages for the control and prevention of COVID-19. We aim to comprehensively and objectively evaluate the safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy individuals through a systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS AND ANALYSIS: We will search electronic databases of PubMed, the Cochrane Library, Web of Science and EMBASE for RCTs from inception to 31 December 2021. We will also search conference abstracts, reference lists, and grey literature of all available records. Two reviewers will independently screen and extract information from the literature. Bias and the quality of included studies will be evaluated with the risk-bias assessment tool provided by the Cochrane Collaboration. Statistical analysis will be performed using Cochrane's Review Manager (RevMan), V.5.3. ETHICS AND DISSEMINATION: Ethics approval and patient informed consent are not required because we will be including published literature only. The findings of this research will be disseminated in a peer-reviewed journal and likely through other scientific events such as conferences, seminars and symposia. PROSPERO REGISTRATION NUMBER: CRD42021266285.

Network meta-analysis on efficacy and safety of different anti-CGRP monoclonal antibody regimens for prophylaxis and treatment of episodic migraine.

BACKGROUND: Currently, studies have shown that anti-CGRP monoclonal antibodies are effective drugs for the prophylaxis and treatment of episodic migraine. Therefore, for the first time, we classified and concluded 10 treatment regimens according to the different doses, drugs, routes of administration, and courses of treatment, so as to provide a reference for further clinical studies. METHODS: We studied relevant randomized controlled trials (RCTs) published before August 2020 on PubMed, Embase, Ovid MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials. RESULTS: Eleven RCTs involving 6397 patients were included in our analysis. Network meta-analysis results suggested that in the comparison of the average migraine days per month, Erenumab  (140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) were superior to placebo, Erenumab(7 mg), and the difference was statistically significant; Fremanezumab (225 mg, 675 mg) was superior to Erenumab (21 mg, 70 mg), and the difference was statistically significant; in the comparison of average medication days of acute migraine-specific drug per month, Erenumab (70 mg, 140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) was superior to placebo, and Erenumab (140 mg) and Galcanezumab (120 mg, 240 mg) were superior to Erenumab (70 mg), and the difference was statistically significant; there was no statistically significant difference in the average migraine days in the last month or in the medication days of acute migraine-specific drug. CONCLUSION: Fremanezumab (225 mg) and Galcanezumab (120 mg) may be the best clinical protocol after a comprehensive assessment.

Damage to the central nucleus of the thalamus via atypical Holmes tremor: a case report.

Holmes tremor (HT) is a rare symptomatic movement disorder characterized by a combination of resting, postural, and action tremors. HT is usually caused by lesions in the brain stem, thalamus, and cerebellum, and the pathogenesis is believed to be related to the nigrostriatal pathway and/or the cerebello-thalamo-cortical pathway. Many medications have been used to treat HT with various degrees of effectiveness. We herein present a case involving an elderly woman who developed atypical HT 23 months after cerebral hemorrhage. The atypical HT manifested as a tremor of the right limb with involuntary flexion of the distal five fingers of the right upper limb. Imaging findings suggested the existence of an old hemorrhage in the left thalamus. Specifically, diffusion tensor imaging data of the whole brain and multimodal three-dimensional medical imaging revealed significant white matter microstructural changes in the centromedian nucleus of the left thalamus. Treatment with high-dose oral levodopa was not efficient, but the symptoms gradually decreased in severity and disappeared 1 month after switching to oral clonazepam treatment.