Investigating the protective effects of Astragalus polysaccharides on cyclophosphamide-induced bone marrow suppression in mice and bone mesenchymal stem cells.

BACKGROUND: This study determines the role and mechanism of APS in cyclophosphamide-induced myelosuppression in mice and bone mesenchymal stem cells (BMSCs) cell model. METHODS: Cy-induced myelosuppression mice and BMSCs cell model were established. Fifty C57BL/6 mice (weighing 20 ± 2 g) were randomly divided into five groups. Femur and tibia samples, bone marrow samples, and blood samples were collected 3 days after the last injection of Cy. Histopathology changes and cell apoptosis were detected. Cell viability, apoptosis, cycle distribution, reactive oxygen species activity, osteogenesis ability, and protein levels were detected. γ-H2AX and senescence-associated ß-galactosidase activity expression was detected by immunofluorescence. Cy-induced senescence and Wnt/ß-catenin related protein levels were detected using western blotting. RESULTS: The results showed that APS effectively induced Cy-induced histological injury and cell apoptosis rate. After treated with APS, ROS and ALP levels were significantly increased. In BMSCs, cell viability, apoptosis, and cell cycle distribution were also influenced by APS treatment. Compared with the control group, cell viability was significantly increased, the cell apoptosis rate was decreased while the number of cells remained in the G0-G1 phase was increased. Meanwhile, ROS levels were significantly increased in APS group. Cell senescence and Wnt/ß-catenin related protein (γ-H2AX, SA-ß-gal, p21, p16, p-ß-catenin/ ß-catenin, c-Myc, and AXIN2) levels were also altered both in vivo and in vitro. Interestingly, the effects of APS were reversed by BML-284. CONCLUSION: Our results indicate that APS protected Cy-induced myelosuppression through the Wnt/ß-catenin pathway and APS is a potential therapeutic drug for Cy-induced myelosuppression.

Dynamics and concordance alterations of regional brain function indices in vestibular migraine: a resting-state fMRI study.

BACKGROUND: Prior MRI studies on vestibular migraine (VM) have revealed abnormalities in static regional intrinsic brain activity (iBA) and dynamic functional connectivity between brain regions or networks. However, the temporal variation and concordance of regional iBA measures remain to be explored. METHODS: 57 VM patients during the interictal period were compared to 88 healthy controls (HC) in this resting-state functional magnetic resonance imaging (fMRI) study. The dynamics and concordance of regional iBA indices, including amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo), were examined by utilizing sliding time-window analysis. Partial correlation analyses were performed between clinical parameters and resting-state fMRI indices in brain areas showing significant group differences. RESULTS: The VM group showed increased ALFF and ReHo dynamics, as well as increased temporal concordance between ALFF and ReHo in the bilateral paracentral lobule and supplementary motor area relative to the HC group. We also found decreased ReHo dynamics in the right temporal pole, and decreased ALFF dynamics in the right cerebellum posterior lobe, bilateral angular gyrus and middle occipital gyrus (MOG) in the VM group compared with the HC group. Moreover, a positive correlation was observed between ALFF dynamics in the left MOG and vertigo disease duration across all VM patients. CONCLUSION: Temporal dynamics and concordance of regional iBA indices were altered in the motor cortex, cerebellum, occipital and temporoparietal cortex, which may contribute to disrupted multisensory processing and vestibular control in patients with VM. ALFF dynamics in the left MOG may be useful biomarker for evaluating vertigo burden in this disorder.

Associations of Combined Lifestyle Factors with MAFLD and the Specific Subtypes in Middle-Aged and Elderly Adults: The Dongfeng-Tongji Cohort Study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the crucial pathogenesis for intra-hepatic and extra-hepatic diseases, especially in elderly adults. Lifestyle management may be a modifiable cost-effective measure for MAFLD prevention, but the evidence is limited. A total of 23,408 middle-aged and elderly individuals were included in a longitudinal study from 2008 to 2018. Combined lifestyle scores (range 0-6) were evaluated by BMI, smoking, drinking, diet, physical activity, and sleep. Logistic regression models were used to calculate ORs for the risks of MAFLD and specific subtypes. The mean age of participants was 61.7 years, and 44.5% were men. Compared with poor lifestyle (scores 0-2), ORs (95% CIs) of the ideal lifestyle (scores 5-6) were 0.62 (0.57-0.68) for MAFLD, 0.31 (0.28-0.34) for MAFLD with excess weight and obesity, 0.97 (0.75-1.26) for MAFLD with diabetes, and 0.56 (0.51-0.62) for MAFLD with metabolic dysregulation. Additionally, lifestyle improvement was associated with lower risks of MAFLD (OR, 0.76; 95% CI, 0.68-0.86), MAFLD with excess weight and obesity (OR, 0.72; 95% CI, 0.63-0.81), MAFLD with diabetes (OR, 0.74; 95% CI, 0.54-1.02) and MAFLD with metabolic dysregulation (OR, 0.49; 95% CI, 0.43-0.55), respectively. Our findings suggest that adherence to a combined healthy lifestyle was associated with lower risks of MAFLD, particularly in excess weight/obese individuals or those with metabolic dysregulation.

Insights into multisource sludge distributed in the Yangtze River basin, China: Characteristics, correlation, treatment and disposal.

Sludge is the by-product of wastewater treatment process. Multisource sludge can be defined as sludge from different sources. Based on the sludge properties of five typical cities in the Yangtze River basin, including Jiujiang, Wuhu, Lu'an, Zhenjiang and Wuhan, this study investigated and summarized the characteristic variations and distribution differences of multiple indicators and substances from municipal sludge, dredged sludge, and river and lake sediments. The results demonstrated pH of multisource sludge was relatively stable in the neutral range. Organic matter and water content among municipal sludge were high and varied considerably between different wastewater treatment plants. Dredged sludge had an obviously higher sand content and wider particle distribution, which could be considered for graded utilization depending on its size. The nutrients composition of river and lake sediments was usually stable and special, with lower nitrogen and phosphorus content but higher potassium levels. The sources of heavy metals and persistent organic pollutants in multisource sludge were correlated, generally much higher among municipal sludge than dredged sludge and river and lake sediments, which were the most important limitation for final land utilization. Despite various properties of multisource sludge, the final fate and destination have some overall similarities, which need to be supplemented and improved by standards and laws. The study provided a preliminary analysis of suitable technical routes for municipal sludge, dredged sludge, river and lake sediments based on their different characteristics respectively, which was of great significance for multisource sludge co-treatment and disposal in the future of China.

Genes in pediatric pulmonary arterial hypertension and the most promising BMPR2 gene therapy.

Pulmonary arterial hypertension (PAH) is a rare but progressive and lethal vascular disease of diverse etiologies, mainly caused by proliferation of endothelial cells, smooth muscle cells in the pulmonary artery, and fibroblasts, which ultimately leads to right-heart hypertrophy and cardiac failure. Recent genetic studies of childhood-onset PAH report that there is a greater genetic burden in children than in adults. Since the first-identified pathogenic gene of PAH, BMPR2, which encodes bone morphogenetic protein receptor 2, a receptor in the transforming growth factor-ß superfamily, was discovered, novel causal genes have been identified and substantially sharpened our insights into the molecular genetics of childhood-onset PAH. Currently, some newly identified deleterious genetic variants in additional genes implicated in childhood-onset PAH, such as potassium channels (KCNK3) and transcription factors (TBX4 and SOX17), have been reported and have greatly updated our understanding of the disease mechanism. In this review, we summarized and discussed the advances of genetic variants underlying childhood-onset PAH susceptibility and potential mechanism, and the most promising BMPR2 gene therapy and gene delivery approaches to treat childhood-onset PAH in the future.

BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma.

Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell-like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas. SIGNIFICANCE: Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1-BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma. See related commentary by Beytagh and Weiss, p. 2730. See related article by Mo et al., p. 2906.

Use of machine learning models to predict prognosis of combined pulmonary fibrosis and emphysema in a Chinese population.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is a novel clinical entity with a poor prognosis. This study aimed to develop a clinical nomogram model to predict the 1-, 2- and 3-year mortality of patients with CPFE by using the machine learning approach, and to validate the predictive ability of the interstitial lung disease-gender-age-lung physiology (ILD-GAP) model in CPFE. METHODS: The data of CPFE patients from January 2015 to October 2021 who met the inclusion criteria were retrospectively collected. We utilized LASSO regression and multivariable Cox regression analysis to identify the variables associated with the prognosis of CPFE and generate a nomogram. The Harrell's C index, the calibration curve and the area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the performance of the nomogram. Then, we performed likelihood ratio test, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA) to compare the performance of the nomogram with that of the ILD-GAP model. RESULTS: A total of 184 patients with CPFE were enrolled. During the follow-up, 90 patients died. After screening out, diffusing lung capacity for carbon monoxide (DLCO), right ventricular diameter (RVD), C-reactive protein (CRP), and globulin were found to be associated with the prognosis of CPFE. The nomogram was then developed by incorporating the above five variables, and it showed a good performance, with a Harrell's C index of 0.757 and an AUC of 0.800 (95% CI 0.736-0.863). Moreover, the calibration plot of the nomogram showed good concordance between the prediction probabilities and the actual observations. The nomogram also improved the discrimination ability of the ILD-GAP model compared to that of the ILD-GAP model alone, and this was substantiated by the likelihood ratio test, NRI and IDI. The significant clinical utility of the nomogram was demonstrated by DCA. CONCLUSION: Age, DLCO, RVD, CRP and globulin were identified as being significantly associated with the prognosis of CPFE in our cohort. The nomogram incorporating the 5 variables showed good performance in predicting the mortality of CPFE. In addition, although the nomogram was superior to the ILD-GAP model in the present cohort, further validation is needed to determine the clinical utility of the nomogram.

Chronic acrylamide exposure resulted in dopaminergic neuron loss, neuroinflammation and motor impairment in rats.

Acrylamide (ACR) as a by-product of Maillard reaction is widely present in food. Although ACR is known to exhibit neurotoxicity, most studies about ACR neurotoxicity are currently short-term high-dose providing limited reference value for human exposure. The present study aims to determine the effects of chronic ACR exposure on dopaminergic neurons in rat nigra and the potential mechanism from the perspective of NLRP3 inflammasome-mediated neuroinflammation. The SD rats were maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. ACR exposure caused motor dysfunction in rats, which was associated with dopaminergic neuron loss, α-Synuclein (α-Syn) accumulation and decreased brain-derived neurotrophic factor (BDNF) in nigra. ACR activated microglia by increasing Iba-1+, Iba-1+CD68+ positive cells and the percentage of ameboid-shaped ones in rat nigra. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3 and caspase-1 and inflammatory cytokine IL-1ß. ACR chronic exposure increased the risk of Parkinson's disease (PD) like dopaminergic neuron depletion in nigra potentially through NLRP3 inflammasome-mediated neuroinflammtion.

Propagation Structure of Intrinsic Brain Activity in Migraine without Aura.

Previous studies have revealed highly reproducible patterns of temporally lagged brain activity in healthy human adults. However, it is unknown whether temporal organization of intrinsic activity is altered in migraines or if it relates to migraine chronification. In this resting-state functional magnetic resonance imaging study, temporal features of intrinsic activity were investigated using resting-state lag analysis, and 39 episodic migraine patients, 17 chronic migraine patients, and 35 healthy controls were assessed. Temporally earlier intrinsic activity in the hippocampal complex was revealed in the chronic migraine group relative to the other two groups. We also found earlier intrinsic activity in the medial prefrontal cortex in chronic compared with episodic migraines. Both migraine groups showed earlier intrinsic activity in the lateral temporal cortex and sensorimotor cortex compared with the healthy control group. Across all patients, headache frequency negatively correlated with temporal lag of the medial prefrontal cortex and hippocampal complex. Disrupted propagation of intrinsic activity in regions involved in sensory, cognitive and affective processing of pain may contribute to abnormal brain function during migraines. Decreased time latency in the lateral temporal cortex and sensorimotor cortex may be common manifestations in episodic and chronic migraines. The temporal features of the medial prefrontal cortex and hippocampal complex were associated with migraine chronification.

Research on Village Type Identification and Development Strategy under the Background of Rural Revitalization: A Case of Gaochun District in Nanjing, China.

In the context of rural revitalization, it is of great significance for the implementation of a Rural Revitalization Strategy to carry out the research on scientifically identifying village types and clarifying the differences and pluralistic trends within villages. Taking Gaochun District of Nanjing in China as an example, this paper constructs an index system of development level and reconstruction intensity from a dynamic and static perspective, uses the polygon area method to calculate the comprehensive score of each index, divides village types based on the combination of development level and reconstruction intensity, and then puts forward the differentiated development strategies of various villages. The results show that the identification method of village types based on combined features is multi-dimensional and comprehensive, and the recognition results are more in line with the objective reality. Villages in Gaochun district have a medium overall development level and high overall reconstruction intensity. There are a large number of low-value villages with development level and high-value villages with reconstruction intensity. According to the three-step strategy of village type identification, the list of characteristic villages, the location of villages and the characteristics of index combination, five village types were identified: the characteristic protection type, the urban-suburban integration type, the agglomeration and upgrading type, the improvement and development type, and the relocation and merger type.

Predictors of Maternal Death Among Women With Pulmonary Hypertension in China From 2012 to 2020: A Retrospective Single-Center Study.

Background: Previous studies have suggested that pregnant women with pulmonary hypertension (PH) have high maternal mortality. However, indexes or factors that can predict maternal death are lacking. Methods: We retrospectively reviewed pregnant women with PH admitted for delivery from 2012 to 2020 and followed them for over 6 months. The patients were divided into two groups according to 10-day survival status after delivery. Predictive models and predictors for maternal death were identified using four machine learning algorithms: naïve Bayes, random forest, gradient boosting decision tree (GBDT), and support vector machine. Results: A total of 299 patients were included. The most frequent PH classifications were Group 1 PH (73.9%) and Group 2 PH (23.7%). The mortality within 10 days after delivery was 9.4% and higher in Group 1 PH than in the other PH groups (11.7 vs. 2.6%, P = 0.016). We identified 17 predictors, each with a P-value < 0.05 by univariable analysis, that were associated with an increased risk of death, and the most notable were pulmonary artery systolic pressure (PASP), platelet count, red cell distribution width, N-terminal brain natriuretic peptide (NT-proBNP), and albumin (all P < 0.01). Four prediction models were established using the candidate variables, and the GBDT model showed the best performance (F1-score = 66.7%, area under the curve = 0.93). Feature importance showed that the three most important predictors were NT-proBNP, PASP, and albumin. Conclusion: Mortality remained high, particularly in Group 1 PH. Our study shows that NT-proBNP, PASP, and albumin are the most important predictors of maternal death in the GBDT model. These findings may help clinicians provide better advice regarding fertility for women with PH.

Subchronic Acrylamide Exposure Activates PERK-eIF2α Signaling Pathway and Induces Synaptic Impairment in Rat Hippocampus.

Acrylamide (ACR), a well-documented neurotoxicant to humans, is extensively found in starchy foods. More than 30% of the typical daily calorie intake comes from ACR-containing foods. Epidemiological and toxicological studies have found that ACR exposure is associated with mild cognitive change in men and experimental animals. However, there is limited information on the mechanisms by which ACR exposure induces memory deficits. The aberrant activation of the PKR-like ER kinase (PERK)-eukaryotic initiation factor 2α (eIF2α) signaling pathway is emerging as a major common theme in cognitive decline. The present study is designed to explore the effect of subchronic ACR exposure on the PERK signaling and the synaptic impairment to elucidate the potential mechanism of ACR-induced cognitive dysfunction in rat. ACR exposure at 5 and 10 (mg/kg)/day by gavage for 14 weeks results in gait abnormality and cognitive impairment in rats, which were accompanied by neuronal loss, glial cell proliferation, and synaptic ultrastructure damage in the hippocampus. ACR reduced the expression of phosphorylated cAMP response element-binding protein (P-CREB), brain-derived neurotrophic factor (BDNF), and synaptic vesicle proteins synapsin-1 and synaptophysin synthesis. ACR also excessively activates the PERK-eIF2α signaling, resulting in overexpression of C/EBP homologous protein (CHOP) and activating transcription factor 4 (ATF4). This work helps to propose a possible mechanism of subchronic exposure of ACR-induced neurotoxicity.

Characteristics of zooplankton community structure and its relationship with environmental factors in the South Yellow Sea.

A total of 91 species of zooplankton were sampled from the South Yellow Sea in the summer and autumn of 2019. Copepods were the predominant arthropods. The summer sample (81) contained higher species diversity than the autumn (70). In both seasons, Calanus sinicus, Sagitta enflata, S. crassa, Doliolum denticulatum, and Macrura larva were dominant species. The average abundance of zooplankton in summer and autumn was 424.9 and 52.6 ind./m3, respectively, and the biomass was 207.7 and 107.6 mg/m3, respectively. The Shannon-Wiener index (H') in summer was higher than that in autumn, while the Pielou index (J') and Margalef index (D') were lower than those in autumn. BIOENV showed that water temperature (ST), dissolved oxygen (DO), turbidity (Tur), and tetrabromobisphenol A (TBBPA) affected the zooplankton community structure in the South Yellow Sea. The concentration of TBBPA increased from offshore to nearshore, with a significant negative impact on diversity in summer.

Targeted clean extraction of phosphorus from waste activated sludge: From a new perspective of phosphorus occurrence states to an innovative approach through acidic cation exchange resin.

Waste activated sludge (WAS) is an important source of non-renewable phosphorus (P) recovery. Given the factor that the occurrence states of phosphorus in WAS determines its recovery efficiency, the spatial distribution and chemical speciation of phosphorus were comprehensively and simultaneously analyzed by in-situ and step-by-step extraction methods for the first time. It was confirmed that the phosphorus in solid phase of WAS could be mainly divided into three parts: polyphosphate in cells, extracellular polymeric substances (EPS)-bound P, and phosphate precipitated with metals (P-precipitates) in extracellular inorganic minerals. Among these forms, EPS-bound P (mainly orthophosphate, Ortho-P) and P-precipitates (mainly Ca-P, Fe-P, Al-P, and Mg-P) were the major forms of phosphorus in WAS, accounting for 65%-82% of total phosphorus (TP). Owing to the acid solubility of P-precipitates, acid extraction could be a potentially effective means for phosphorus recovery. However, the co-solution of metals may hinder the phosphorus recovery and the EPS-bound P cannot be recovered by acid extraction. To enhance phosphorus release from EPS and reduce metal interference, a targeted clean extraction technology using acidic cation exchange resin (ACER) was also developed. The results showed that a low dosage ACER could effectively extract EPS-bound P and P-precipitates, and the content of phosphorus in the extract exceeded 50% of TP. Compared with acid extraction, the release efficiency of TP increased by 13%-23%, and the dissolved metal content decreased by more than 90% in the extract by ACER. This was attributed to the acidification and metal capture by ACER. Finally, more than 90% of Ortho-P in the extract was recovered as calcium phosphate, which alleviated the depletion of phosphorus resources.

High concentration powder carrier bio-fluidized bed process: A new perspective for domestic wastewater treatment.

The nitrogen removal mechanism of the high concentration powder carrier bio-fluidized bed (HPB) process was investigated with actual domestic wastewater. The micron-size (10-70 µm) powder carriers were diatomite and Fe-C. Results showed diatomite enriched the relative abundances of ammonia-oxidizing bacteria and nitrite-oxidizing bacteria, accordingly increasing the rate of nitrification. Even a 100% increase of genes associated with the ammonia oxidation was achieved. Fe-C enhanced the rate of substrate utilization mainly by increasing the activity of the electron transfer system. Hydrocyclone separator, as a key device of HPB, was able to recover the carriers with high efficiency (recovery efficiency of 72.66 ─ 82.50% after 75 days), thus, indirectly improving the functionality of the carriers. Furthermore, it could renew the surface of microbial aggregations, consequently improving the adsorption capacity to substrates. HPB could provide the feasibility of shortening the hydraulic retention time and expanding the capacity of wastewater treatment plants.

Prediction of long-term mortality by using machine learning models in Chinese patients with connective tissue disease-associated interstitial lung disease.

BACKGROUND: The exact risk assessment is crucial for the management of connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. In the present study, we develop a nomogram to predict 3­ and 5-year mortality by using machine learning approach and test the ILD-GAP model in Chinese CTD-ILD patients. METHODS: CTD-ILD patients who were diagnosed and treated at the First Affiliated Hospital of Zhengzhou University were enrolled based on a prior well-designed criterion between February 2011 and July 2018. Cox regression with the least absolute shrinkage and selection operator (LASSO) was used to screen out the predictors and generate a nomogram. Internal validation was performed using bootstrap resampling. Then, the nomogram and ILD-GAP model were assessed via likelihood ratio testing, Harrell's C index, integrated discrimination improvement (IDI), the net reclassification improvement (NRI) and decision curve analysis. RESULTS: A total of 675 consecutive CTD-ILD patients were enrolled in this study, during the median follow-up period of 50 (interquartile range, 38-65) months, 158 patients died (mortality rate 23.4%). After feature selection, 9 variables were identified: age, rheumatoid arthritis, lung diffusing capacity for carbon monoxide, right ventricular diameter, right atrial area, honeycombing, immunosuppressive agents, aspartate transaminase and albumin. A predictive nomogram was generated by integrating these variables, which provided better mortality estimates than ILD-GAP model based on the likelihood ratio testing, Harrell's C index (0.767 and 0.652 respectively) and calibration plots. Application of the nomogram resulted in an improved IDI (3- and 5-year, 0.137 and 0.136 respectively) and NRI (3- and 5-year, 0.294 and 0.325 respectively) compared with ILD-GAP model. In addition, the nomogram was more clinically useful revealed by decision curve analysis. CONCLUSIONS: The results from our study prove that the ILD-GAP model may exhibit an inapplicable role in predicting mortality risk in Chinese CTD-ILD patients. The nomogram we developed performed well in predicting 3­ and 5-year mortality risk of Chinese CTD-ILD patients, but further studies and external validation will be required to determine the clinical usefulness of the nomogram.

Microbial production of lactic acid from food waste: Latest advances, limits, and perspectives.

A significant amount of food waste (FW) is produced every year. If it is not disposed of timeously, human health and the ecological environment can be negatively affected. Lactic acid (LA), a high value-added product, can be produced by fermentation from FW as a substrate, realizing the concurrent treatment and recycling of FW, which has attracted increasing research interest. In this paper, the latest advances and deficiencies were presented from the following aspects: microorganisms involved in LA fermentation and the metabolic pathways of Lactobacillus, fermentation conditions, and methods of enhanced biotransformation and LA separation. The limitations of the LA fermentation of FW are mainly associated with low LA concentration and yield, the low purity of L(+)-LA, and the high separation costs. The establishment of biorefineries of FW with lactic acid as the target product is the future development direction, but there are still many research studies to be done.

Alterations in Effective Connectivity of the Hippocampus in Migraine without Aura.

PURPOSE: Neuroimaging studies on migraine have revealed structural and functional alterations in the hippocampus, a region involved in pain processing and stress response. This study was designed to investigate whether effective connectivity of this region is disrupted in migraine and relates to chronicity of this disease. PATIENTS AND METHODS: In 39 episodic migraine (EM) patients, 17 chronic migraine (CM) patients, and 35 healthy controls, we investigated differences in the directional influences between the hippocampus and the rest of the brain by combining resting-state functional magnetic resonance imaging and Granger causality analysis (GCA), with bilateral hippocampus as seed regions. The associations between directional influences and the clinical variables were also examined. RESULTS: Comparing each patient group to the control group, we found increased and decreased negative influence on the hippocampus exerted by the bilateral visual areas and right dorsolateral prefrontal cortex (dlPFC), respectively. The hippocampus showed increased positive influence on the right posterior insula and medial prefrontal cortex (mPFC), as well as increased negative influence on the left cerebellum in CM patients relative to EM patients and healthy controls. Furthermore, across all patients, the migraine frequency exhibited a positive and negative association with causal influence from the hippocampus to mPFC and left cerebellum, respectively. CONCLUSION: Migraine patients have abnormal effective connectivity between the hippocampus and multiple brain regions involved in the sensory and cognitive processing of pain. Disrupted directional influences to the hippocampus exerted by dlPFC and bilateral visual areas were common features of EM and CM patients. Directional influences from the hippocampus to mPFC and left cerebellum may be useful imaging biomarkers for assessing migraine frequency.

[Evidence of clinical randomized controlled trial study in treatment of acute cerebral infarction with traditional Chinese medicine in recent five years].

To systematically search and sort out the clinical randomized controlled trial(RCT) on the prevention and treatment of acute cerebral infarction with traditional Chinese medicine(TCM) by using the method of evidence map, and to understand the evidence distribution of related studies. CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Cochrane Library and Web of Science were retrieved from January 2016 to September 2020, and literatures related to the prevention and treatment of acute cerebral infarction with traditional Chinese medicine were included. Text description combined with table and bubble chart were used to analyze the distribution characteristics of evidence. A total of 1 102 clinical articles in recent five years were retrieved. The annual trend of clinical study publication, study size, TCM therapy category and main scheme, and study literature quality were analyzed. We find that TCM treatment of acute cerebral infarction has become a hot topic of clinical research, the number of literature showed a trend of increased year by year, various means of intervention of TCM in the treatment of the advantages of increasingly highlight. Follow-up clinical research should highlight the characteristics of TCM: in the analysis of outcome indicators; increase the neuropsychological patients after stroke and cognitive ability, and the theory of combined treatment of TCM disease when thoughts; At the same time, the quality of clinical research needs to be improved. At present, there is still a lack of unified standards for the production of evidence map. This study is the first to explore the application of evidence map to summarize and display the clinical research status of TCM treatment of acute cerebral infarction, and combine it with the setting of priority areas of TCM clinical research, so as to provide a reference basis for determining the priority topic selection of TCM treatment optimization research.