The Regulatory Mechanism of Hypoxia-inducible Factor 1 and its Clinical Significance.

Hypoxia-inducible factor (HIF) is a nuclear protein that plays a crucial role in oxygen homeostasis through its transcriptional activity and thousands of target gene profiles. Through transcriptional and post-transcriptional regulation, the downstream target genes of HIF can trigger multiple pathological responses in the body, including energy metabolism, cytopenia, and angiogenesis. There are three distinct subtypes of HIF: HIF-1, HIF-2, and HIF-3. HIF-1 is a significant regulator of the cellular response to hypoxia, and the balance between its production and degradation is critical for this response. As hypoxia is linked to several disorders, understanding HIF can open up novel avenues for the treatment of many diseases. This review describes the regulatory mechanisms of HIF-1 synthesis and degradation and the clinical significance of the hypoxia-inducible factor pathway in lung injury, kidney disease, hematologic disorders, and inflammation-related diseases.

SIMULATED AEROMEDICAL EVACUATION EXACERBATES ACUTE LUNG INJURY VIA HYPOXIA-INDUCIBLE FACTOR 1Α-MEDIATED BNIP3/NIX-DEPENDENT MITOPHAGY.

ABSTRACT: Background: With the advancement of medicine and the development of technology, the limiting factors of aeromedical evacuation are gradually decreasing, and the scope of indications is expanding. However, the hypobaric and hypoxic environments experienced by critically ill patients in flight can cause lung injury, leading to inflammation and hypoxemia, which remains one of the few limiting factors for air medical evacuation. This study aimed to examine the mechanism of secondary lung injury in rat models of acute lung injury that simulate aeromedical evacuation. Methods: An acute lung injury model was induced in SD rats by the administration of lipopolysaccharide (LPS) followed by exposure to a simulated aeromedical evacuation environment (equivalent to 8,000 feet above sea level) or a normobaric normoxic environment for 4 h. The expression of hypoxia-inducible factor 1α (HIF-1α) was stabilized by pretreatment with dimethyloxalylglycine. The reactive oxygen species levels and the protein expression levels of HIF-1α, Bcl-2-interacting protein 3 (BNIP3), and NIX in lung tissue were measured. Results: Simulated aeromedical evacuation exacerbated pathological damage to lung tissue and increased the release of inflammatory cytokines in serum as well as the reactive oxygen species levels and the protein levels of HIF-1α, BNIP3, and NIX in lung tissue. Pretreatment with dimethyloxalylglycine resulted in increases in the protein expression of HIF-1α, BNIP3, and NIX. Conclusion: Simulated aeromedical evacuation leads to secondary lung injury through mitophagy.

Analysis of birth surveillance results in Baoshan Districtfrom 2013 to 2022 / 预防医学

Objective @#To investigate the fertility level of registered population in Baoshan District, Shanghai Municipality and the incidence of adverse birth outcomes of live births from 2013 to 2022, so as to provide the evidence for improving maternal and child health care strategies. @*Methods@#The data pertaining to live births registered in Baoshan District from 2013 to 2022 were collected through the Shanghai Birth Medical Information System, including the basic information of live births and maternal fertility. The indicators such as fertility level, parity, birth age and incidence of adverse birth outcomes of live births were descriptively analyzed. The trend of crude birth rate and total fertility rate was analyzed by annual percent change (APC). @*Results@#A total of 56 719 live births were registered in Baoshan District from 2013 to 2022. The crude birth rate was 6.54‰, the total fertility rate was 31.78‰, and the sex ratio at birth was 105.61. The crude birth rate showed a downward trend from 2016 to 2022 (APC=-11.054%, P<0.05), and the total fertility rate showed a downward trend from 2017 to 2022 (APC=-10.377%, P<0.05). The proportion of second parity and above showed an increasing trend from 2013 to 2017 (P<0.05) and a decreasing trend from 2017 to 2022 (P<0.05). The maternal childbearing age showed an increasing trend from 2013 to 2022 (P<0.05), the incidence of premature infants and low birth weight infants showed an increasing trend (both P<0.05). The incidence of premature infants and low birth weight infants increased with the rising childbearing age (both P<0.05). @*Conclusions@#The fertility level in Baoshan District was relatively low from 2013 to 2022. The proportion of second parity and above showed an upward trend followed by a downward trend. The incidence of premature infants and low birth weight infants increased with the rising childbearing age.

Granulomatous myopathy co-existent immune-mediated necrotizing myopathy: A case report.

Granulomatous myopathy (GM) is a rare disease characterized by non-caseating inflammation of the skeletal muscle, with sarcoidosis as a common cause. Here, we report a case of GM co-existent immune-mediated necrotizing myopathy (IMNM) in which an anti-signal recognition particle (SRP) antibody was positive and a muscle biopsy showed a non-caseating granulomatous structure, along with myofiber necrosis and inflammatory cell infiltration.

An outbreak of school influenza complicated with mycoplasma pneumoniae infection / 中国学校卫生

Objective@#To describe the clinical features, causal agent and transmission mode of a fever outbreak in a school in Shanghai.@*Methods@#Field epidemiological approaches including case definition development, searching for contacts, distribution of diseases description, environmental sampling and laboratory testing.@*Results@#A total of 16 influenza like cases were included, all concentrated in the one class of grade two, including 15 students and 1 teacher. Among student cases, the incidence rate was 36.59% (15/41), the average age was 7.4 years, the incidence rate was 36.84%(7/19) for boys, 36.36%(8/22) for girls. The clinical course was 5-15 days, with the median of 9 days, and 18.75%(3/16) of the cases stayed studying while sick. The nasopharyngeal swab specimens in 16 cases all tested positive for influenza B, of which 11 tested positive for mycoplasma pneumoniae and 1 case also tested positive for coronavirus OC43. Body temperature, number of mononuclear cells, and treatment time of patients infected with Influenza B and mycoplasma pneumoniae were higher than those of patients infected with influenza B alone( P <0.05). The outbreak lasted for 12 days, all sick students were treated and discharged from hospital, with no severe cases or death, and the outbreak was effectively controlled.@*Conclusion@#This campus cluster outbreak caused by influenza B and mycoplasma pneumoniae. Patients with influenza B with mycoplasma pneumoniae have severe symptoms and a long course of illness, suggesting the importance of early management of the epidemic.

Metabolic response of Lactobacillus acidophilus exposed to amoxicillin.

Drug-induced diarrhea is a common adverse drug reaction, especially the one caused by the widespread use of antibiotics. The reduction of probiotics is one reason for intestinal disorders induced by an oral antibiotic. However, the intrinsic mechanism of drug-induced diarrhea is still unknown. In this study, we used metabolomics methods to explore the effects of the classic oral antibiotic, amoxicillin, on the growth and metabolism of Lactobacillus acidophilus, while scanning electron microscopy (SEM) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were employed to evaluate changes in cell activity and morphology. The results showed that cell viability gradually decreased, while the degree of cell wall rupture increased, with increasing amoxicillin concentrations. A non-targeted metabolomics analysis identified 13 potential biomarkers associated with 9 metabolic pathways. The data showed that arginine and proline metabolism, nicotinate and nicotinamide metabolism, pyrimidine metabolism, glycine, serine and threonine metabolism, beta-alanine metabolism, glycerolipid metabolism, tryptophan metabolism, steroid hormone biosynthesis, and histidine metabolism may be involved in the different effects exerted by amoxicillin on L. acidophilus. This study provides potential targets for screening probiotics regulators and lays a theoretical foundation for the elucidation of their mechanisms.

1H NMR-based urinary metabonomic study of the antidiabetic effects of Rubus Suavissimus S. Lee in STZ-induced T1DM rats.

Long-term hyperglycemia associated with diabetes mellitus (DM) causes damage to various organs and tissues, including the eyes, kidneys, heart, blood vessels and nerves. Rubus Suavissimus S. Lee (RS), a shrub whose leaves are used in traditional Chinese medicine (TCM), has been shown to exert hypoglycemic effects in DM patients. However, the underlying mechanism is unclear. This was investigated in the present study in a rat model of streptozotocin-induced type 1 diabetes mellitus (T1DM) by 1H NMR analysis. We identify 9 metabolites whose levels were altered in T1DM rats compared to control rats, namely, lactate, acetate, pyruvate, succinate, 2-oxoglutarate, citrate, creatinine, allantoin, and hippurate, which are mostly related to glycolysis/gluconeogenesis, pyruvate metabolism, TCA cycle, and other metabolism. The observed pathologic changes in the levels of these metabolites in T1DM rats were reversed by treatment with RS. Thus, RS exerts effects in T1DM rats by regulating the three abnormal metabolic pathways synergistically. These findings provide supporting evidence for the therapeutic efficacy of this TCM formulation in the treatment of DM.

Lei-gong-gen formula granule attenuates hyperlipidemia in rats via cGMP-PKG signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among the 56 nationalities in China. It is composed of three herbs, namely Centella asiatica (L.) Urb., Eclipta prostrata (L.) L., Smilax glabra Roxb. It has been widely used as health protection tea for many years to prevent cardiovascular and cerebrovascular diseases such as hyperlipidemia and hypertension. AIM OF THE STUDY: This study validated the lipid-lowering effect of LFG in a hyperlipidemia rat model. Then we employed network pharmacology and molecular biological approach to identify the active ingredients of LFG, corresponding targets, and its anti-hyperlipidemia mechanisms. MATERIALS AND METHODS: Hyperlipidemia rat model was established by feeding male Sprague-Dawley rats with high-fat diet for two weeks. LFG (two doses of 10 and 20 g/kg) was administered orally to hyperlipidemia rat model for 4 weeks, twice per day. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were monitored in rats pre and post-treatment. Hematoxylin-eosin staining was applied to observe the pathology and lipid accumulation of liver. We then performed network pharmacology analysis to predict the ingredients, their associated targets, and hyperlipidemia associated targets. Pathway analysis with significant genes was carried out using KEGG pathway. These genes and proteins intersectioned between compound targets and hyperlipidemia targets were further verified with samples from hyperlipidemia rats treated with LFG using Real-time RT-PCR and Western Blot. RESULTS: LFG attenuated hyperlipidemia in rat model, and this was characterized with decreased serum levels of TC, LDL-C, liver wet weight, and liver index. LFG alleviated the hepatic steatosis in hyperlipidemia rats. Network pharmacology analysis identified 53 bioactive ingredients from LFG formula (three herbs), which link to 765 potential targets. 53 hyperlipidemia associated genes were retrieved from public databases. There were 10 common genes between ingredients-targets and hyperlipidemia associated genes, which linked to 20 bioactive ingredients. Among these 10 genes, 3 of them were validated to be involved in LFG's anti-hyperlipidemia effect using Real-time RT-PCR, namely ADRB2 encoding beta-2 adrenergic receptor, NOS3 encoding nitric oxide synthase 3, LDLR encoding low-density lipoprotein receptor. The cGMP-PKG signaling pathway was enriched for hyperlipidemia after pharmacology network analysis with ADRB2, NOS3, and LDLR. Interestingly, expression of cGMP-dependent protein kinase (PKG) was downregulated in hyperlipidemia rat after LFG treatment. Molecular docking study further supported that ferulic acid, histidine, p-hydroxybenzoic acid, and linalool were potential active ingredients for LFG's anti-hyperlipidemia effect. LC-MS/MS analysis confirmed that ferulic acid and p-hydroxybenzoic acid were active ingredients of LFG. CONCLUSION: LFG exhibited the lipid-lowering effect, which might be attributed to downregulating ADRB2 and NOS3, and upregulating LDLR through the cGMP-PKG signaling pathway in hyperlipidemia rat. Ferulic acid and p-hydroxybenzoic acid might be the underlying active ingredients which affect the potential targets for their anti-hyperlipidemia effect.

FAM83D promotes epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer.

PURPOSE: FAM83D has been proposed to act as an oncoprotein in several types of human cancer. Its role and mode of action in human non-small cell lung cancer (NSCLC) metastasis and its impact on chemotherapy are as yet, however, poorly understood. METHODS: FAM83D expression was measured in NSCLC cells and normal lung epithelial cells, as well as in primary NSCLC tissues and corresponding adjacent non-cancerous tissues, using qRT-PCR, Western blotting and immunohistochemistry. FAM83D was stably overexpressed in BEAS2B cells or silenced in A549 and H1299 cells using retroviral or lentiviral vectors. The growth capacity of NSCLC cells was evaluated using MTT and colony formation assays. Epithelial-mesenchymal transition (EMT) was assessed using Western blotting and immunofluorescence. NSCLC cell invasive capacities were assessed using scratch wound healing and Boyden chamber assays. NSCLC cell viability in response to cisplatin treatment was assessed using MTT assays in vitro and a xenograft model in vivo. RESULTS: We found that FAM83D expression levels were significantly elevated in NSCLC cells and tissues, and positively correlated with tumor progression and a poor prognosis. Exogenous FAM83D overexpression promoted, while FAM83D silencing inhibited NSCLC cell proliferation, EMT and invasion. FAM83D silencing also reduced cisplatin resistance. Concordantly, we found that NSCLC patients with a low FAM83D expression benefited most from chemotherapy. Mechanistically, we found that FAM83D activated the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Pharmacological treatment with either AKT or mTOR inhibitors reverted FAM83D-induced tumorigenic phenotypes. CONCLUSIONS: Our results suggest a role of FAM83D in NSCLC development. In addition, our results indicate that NSCLC patients exhibiting FAM83D overexpression are likely to benefit from AKT and/or mTOR inhibitor treatment.

Altered effective connectivity network in patients with insular epilepsy: A high-frequency oscillations magnetoencephalography study.

OBJECTIVE: The project aimed to determine the alterations in the effective connectivity (EC) neural network in patients with insular epilepsy based on interictal high-frequency oscillations (HFOs) from magnetoencephalography (MEG) data. METHODS: We studied MEG data from 22 insular epilepsy patients and 20 normal subjects. Alterations in spatial pattern and connection properties of the patients with insular epilepsy were investigated in the entire brain network and insula-based network. RESULTS: Analyses of the parameters of graph theory revealed the over-connectivity and small-world configuration of the global connectivity patterns observed in the patients. In the insula-based network, the insular cortex ipsilateral to the seizure onset displayed increased efferent and afferentEC. Left insular epilepsy featured strong connectivity with the bilateral hemispheres, whereas right insular epilepsy featured increased connectivity with only the ipsilateral hemisphere. CONCLUSIONS: Patients with insular epilepsy display alterations in the EC network in terms of both whole-brain connectivity and the insula-based network during interictal HFOs. SIGNIFICANCE: Alterations of interictal HFO-based networks provide evidence that epilepsy networks, instead of epileptic foci, play a key role in the complex pathophysiological mechanisms of insular epilepsy. The dysfunction of HFO networks may prove to be a novel promising biomarker and the cause of interictal brain dysfunctions in insular epilepsy.

Dynamic urinary metabolomics analysis based on UHPLC-Q-TOF/MS to investigate the potential biomarkers of blood stasis syndrome and the effects of Danggui Sini decoction.

Blood stasis syndrome (BSS) is one of the common syndromes in traditional Chinese medicine (TCM). It involves abnormal blood circulation, which can progress to produce many severe diseases. Danggui Sini decoction (DSD) is a classical TCM prescription frequently used to treat BSS by decreasing blood stasis and improving blood circulation. However, understanding of the therapeutic mechanism of DSD during the development of BSS is still limited, as the development of BSS is a slow dynamic process. Therefore, a dynamic urinary metabolomics analysis based on ultra-high-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (UHPLC-Q-TOF/MS) combined with multivariate statistical analysis was used to explore the distinctive metabolic patterns of BSS development and the efficacy of DSD. The dynamic changes of endogenous metabolites over time revealed the progression of BSS and allowed the overall efficacy of DSD in rats with BSS to be evaluated. The effects of the DSD compatibilities were also explored. A total of 21 metabolites were identified during the development of BSS. They are involved in the metabolic pathways of tryptophan metabolism, phenylalanine metabolism, riboflavin metabolism, nicotinate and nicotinamide metabolism, pentose and glucuronate interconversions, histidine metabolism, steroid hormone biosynthesis, and starch and sucrose metabolism. A receiver operating characteristic (ROC) curve analysis showed that 10 metabolites with an area under the curve (AUC) value >0.9, which can be used as potential biomarkers for the diagnosis of BSS. In conclusion, a dynamic urinary metabolomics approach was applied to identify potential biomarkers of the development of BSS and to clarify the therapeutic mechanism of DSD in BSS. The results could provide a theoretical basis for further research on the therapeutic mechanism of DSD.

The study of neuroprotective effect of ferulic acid based on cell metabolomics.

Ferulic acid (FA), a naturally derived phenolic compound, has antioxidant and antidepressant-like effects. It is still a challenge to study its mechanism due to the complexity of the pathophysiology of depression. In this study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to perform metabolomics studies based on biochemical changes in differentiated rat pheochromocytoma (PC12) cells treated with corticosterone-induced neurological damage after FA treatment. A total of 31 metabolites were identified as potential biomarkers for corticosterone-induced PC12 cells injury. Among them, 24 metabolites were regulated after FA treatment. Pathway analysis revealed that these metabolites were mainly involved in the amino acid metabolism, energy metabolism and glycerophospholipid metabolism. In addition, based on the results of metabolomics, three cell signaling pathways related to glutamate were discovered. To further study the interactions between FA and major targets in three signaling pathways, a molecular docking method was employed. The results showed that FA had the strongest binding power with protein kinase B (AKT). Furthermore, the result of mRNA changes analyzed by quantitative real time RT-PCR indicated that AKT and protein kinase A (PKA) in the signaling pathway were up regulated after treatment with FA compared with model group. This study shows that strategies based on cell metabolomics associated with molecular docking and molecular biology is a helpful tool to elucidate the neuroprotective mechanism of FA.

Iron dysregulation in vascular dementia: Focused on the AMPK/autophagy pathway.

Recent researches suggested that iron dysregulation play an important role in the pathogenesis of vascular dementia (VD). Iron deposition had been found in hippocampus in vascular dementia model in recent research. Nevertheless, the underlying mechanisms of iron deposition and its neurotoxicity in vascular dementia was still unclear. Thus, our research was aimed at whether the neurotoxicity of iron was associated with autophagy regulation. We established a chronic cerebral hypoperfusion model in the rat brain in order to mimic the vascular dementia using permanent bilateral common carotid artery occlusion (2VO). The preparation of iron overloaded rats model by intraperitoneal injection of iron dextran. Following, we tested the learning and memory function of each group using Morris Water Maze. Consequently, we analyzed the iron content and iron transport related molecules (TFR1, DMT1) in hippocampus. Furthermore, we examined the effect of iron deposition on autophagy-related molecules including AMPK, Beclin1 and LC3 and the number of autophagosomes in hippocampus. Last, we tested the apoptosis of neurons in hippocampus. We found that iron deposition in hippocampus in model groups which accompanied the decline of learning and memory function. And the expression of TFR1 and DMT1 were up-regulated in model groups. Moreover, iron deposition up-regulated the expression of AMPK, Beclin1 and LC3 and increase the number of autophagosomes in hippocampus. And the expression of Bax was up-regulated and Bcl-2 was down-regulated in iron deposition groups. To sum up, our data suggested that iron deposition increased AMPK/autophagy pathway associated molecules in the hippocampus and promoted neuronal apoptosis, which might be a new pathogenesis in vascular dementia.

Intervening Effects of Total Alkaloids of Corydalis saxicola Bunting on Rats With Antibiotic-Induced Gut Microbiota Dysbiosis Based on 16S rRNA Gene Sequencing and Untargeted Metabolomics Analyses.

Gut microbiota dysbiosis induced by antibiotics is strongly connected with health concerns. Studying the mechanisms underlying antibiotic-induced gut microbiota dysbiosis could help to identify effective drugs and prevent many serious diseases. In this study, in rats with antibiotic-induced gut microbiota dysbiosis treated with total alkaloids of Corydalis saxicola Bunting (TACS), urinary and fecal biochemical changes and cecum microbial diversity were investigated using 16S rRNA gene sequencing analysis and untargeted metabolomics. The microbial diversity results showed that 10 genera were disturbed by the antibiotic treatment, and two of them were obviously restored by TACS. The untargeted metabolomics analysis identified 34 potential biomarkers in urine and feces that may be the metabolites that are most related to the mechanisms underlying antibiotic-induced gut microbiota dysbiosis and the therapeutic effects of TACS treatment. The biomarkers were involved in six metabolic pathways, comprising pathways related to branched-chain amino acid (BCAA), bile acid, arginine and proline, purine, aromatic amino acid, and amino sugar and nucleotide sugar metabolism. Notably, there was a strong correlation between these metabolic pathways and two gut microbiota genera (g__Blautia and g__Intestinibacter). The correlation analysis suggested that TACS might synergistically affect four of these metabolic pathways (BCAA, bile acid, arginine and proline, and purine metabolism), thereby modulating gut microbiota dysbiosis. Furthermore, we performed a molecular docking analysis involving simulating high-precision docking and using molecular pathway maps to illuminate the way that ligands (the five main alkaloid components of TACS) act on a complex molecular network, using CYP27A1 (a key enzyme in the bile acid synthesis pathway) as the target protein. This study provides a comprehensive overview of the intervening effects of TACS on the host metabolic phenotype and gut microbiome in rats with gut microbiota dysbiosis, and it presents new insights for the discovery of effective drugs and the best therapeutic approaches.

Detection and localization of interictal ripples with magnetoencephalography in the presurgical evaluation of drug-resistant insular epilepsy.

Precise noninvasive presurgical localization of insular epilepsy is important. The objective of the present study was to detect and localize interictal high-frequency oscillations (HFOs) in patients with insular epilepsy at the source levels using magnetoencephalography (MEG). We investigated whether HFOs can delineate epileptogenic areas. We analysed MEG data with new accumulated source imaging (HFOs, 80-250 Hz ripples during spikes) and conventional dipole modelling (spikes) methods for localizing epileptic foci. We evaluated the relationship of the resection of focal brain regions containing interictal HFOs and the spikes with the postsurgical seizure outcome. Interictal HFOs were localized in the insular epileptogenic zone (EZ) in 18 out of 21 patients undergoing surgical treatment for clinically diagnosed insular epilepsy. While dipole clusters of spikes were involved in the insular EZ in 15 patients. Both the HFOs and the dipole cluster were localized in the insula in 14 patients. The seizure-free percentage was 87% for the resection of brain regions generating HFOs, whereas 80% for the resection of brain regions generating spikes. There was a much higher chance of freedom from seizures with complete resection of the HFO-generating regions than with partial resection or no resection (P = 0.031). No such difference was seen for spike-generating regions. Our results suggest that HFOs from insular epilepsy could be noninvasively detected and quantitatively assessed with MEG technology. MEG HFOs (ripples during spikes) may be valuable for the localization of the epileptogenic zone in insular epilepsy.

A study for the mechanism of sensory disorder in restless legs syndrome based on magnetoencephalography.

In spite of the relatively high incidence rate, the etiology and pathogenesis of restless legs syndrome (RLS) are still unclear. Long-term drug treatments fail to achieve satisfying curative effects, which is reflected by rebound and augmentation of related symptoms. An electrophysiological endophenotype experiment was done to investigate the mechanism of somatosensory disorder among RLS patients. Together with 15 normal subjects as the control group, with comparable ages and genders to the RLS patients, 15 primitive RLS patients were scanned by Magnetoencephalography (MEG) under natural conditions; furthermore, the somatosensory evoked magnetic field (SEF) with single and paired stimuli, was also measured. Compared to the control group, the SEF intensities of RLS patients' lower limbs were higher, and the paired-pulse depression (PPD) for SEF in RLS patients was attenuated. It was also revealed by time-frequency analysis of somatosensory induced oscillation (SIO) in RLS patients, that 93.3% of somatosensory induced Alpha (8-12 Hz) oscillations were successfully elicited, while 0% somatosensory induced Gamma (30-55 Hz) oscillations were elicited; which was significantly different from the control group. Additionally, in RLS patients exhibit increased excitability of the sensorimotor cortex, a remarkable abnormality existing in early somatosensory gating control (GC) and an attenuated inhibitory interneuron network, which consequently results in a compensatory mechanism through which RLS patients increase their attention-driven lower limb sensory gating control via somatosensory-induced Alpha (8-12 Hz) oscillation. This hyperexcitability, partially due to an electrocortical disinhibition, may have an important therapeutical implication, and become an important target of neuromodulatory interventions.

Comparative analysis of the compatibility effects of Danggui-Sini Decoction on a blood stasis syndrome rat model using untargeted metabolomics.

Danggui-Sini Decoction (DSD) is one of the most widely used traditional Chinese medicine formulae (TCMF) for treating various diseases caused by cold coagulation and blood stasis due to its effect of nourishing blood to warm meridians in clinical use. However, studies of the mechanism of how it dispels blood stasis and its compatible regularity are challenging because of the complex pathophysiology of blood stasis syndrome (BSS) and the complexity of DSD, with multiple active ingredients acting on different targets. Observing variations of endogenous metabolites in rats with BSS after administering DSD may further our understanding of the mechanism of BSS and the compatible regularity of DSD. In this study, to understand the pathogenesis of BSS and assess the compatibility effects of DSD, an ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry-based untargeted metabolomics approach was used. Serum metabolic profiles in rats with BSS that was induced by an ice water bath associated with subcutaneous injection of epinephrine hydrochloride were compared with the intervention groups which were administered with DSD or its compatibility. Using pattern recognition analysis, a clear separation between the BSS model and control group was observed; DSD and its compatibility intervention groups were clustered closer toward the control than the model group, which corroborates results of hemorheology studies. In addition, 20 metabolites were considered as potential biomarkers associated with the development of BSS. Nine metabolites were regulated by DSD in intervening blood stasis, they were considered to be correlated with the effect of nourishing blood to warm meridians. Additionally, the results suggested that the intervention effect of DSD on BSS may involve regulating four pathways, namely, arachidonic acid metabolism, glycerophospholipid metabolism, bile acid biosynthesis, and pyruvate metabolism. Moreover, each functional unit (monarch, minister, and assistant) in DSD regulates different metabolites and metabolic pathways to achieve different effects on dispelling blood stasis; however, their intervention efficacies are inferior to the holistic formula, which may be due to the synergism of the bioactive ingredients in seven herbs of DSD. This study demonstrated that metabolomics is a powerful tool for evaluating the efficacy and compatibility effects of traditional Chinese medicine (TCM).

Partial Least Square Aided Beamforming Algorithm in Magnetoencephalography Source Imaging.

Beamforming techniques have played a prominent role in source imaging in neuroimaging and in locating epileptogenic zones. However, existing vector-beamformers are sensitive to noise on localization of epileptogenic zones. In this study, partial least square (PLS) was used to aid the minimum variance beamforming approach for source imaging with magnetoencephalography (MEG) arrays, and verified its effectiveness in simulated data and epilepsy data. First, PLS was employed to extract the components of the MEG arrays by maximizing the covariance between a linear combination of the predictors and the class variable. Noise was then removed by reconstructing the MEG arrays based on those components. The minimum variance beamforming method was used to estimate a source model. Simulations with a realistic head model and varying noise levels indicated that the proposed approach can provide higher spatial accuracy than other well-known beamforming methods. For real MEG recordings in 10 patients with temporal lobe epilepsy, the ratios of the number of spikes localized in the surgical excised region to the total number of spikes using the proposed method were higher than that of the dipole fitting method. These localization results using the proposed method are more consistent with the clinical evaluation. The proposed method may provide a new imaging marker for localization of epileptogenic zones.

Investigation of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced liver fibrosis in rats by 1H-NMR-based metabonomics and network pharmacology approaches.

Liver fibrosis is a common consequence of chronic liver diseases resulting from multiple etiologies. Furthermore, prolonged unresolved liver fibrosis may gradually progress to cirrhosis, and eventually evolve into hepatocellular carcinoma (HCC). Corydalis saxicola Bunting (CS), a type of traditional Chinese folk medicine, has been reported to have hepatoprotective effects on the liver. However, the exact mechanism of how it cures liver fibrosis requires further elucidation. In this work, an integrated approach combining proton nuclear magnetic resonance (1H-NMR)-based metabonomics and network pharmacology was adopted to elucidate the anti-fibrosis mechanism of CS. Metabonomic study of serum biochemical changes by carbon tetrachloride (CCl4)-induced liver fibrosis in rats after CS treatment were performed using 1H-NMR analysis. Metabolic profiling by means of partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl4 was reduced after CS treatment. As a result, lipids, leucine, alanine, acetate, O-acetyl-glycoprotein and creatine were significantly restored after CS treatment, which regulated valine, leucine and isoleucine metabolism; arginine and proline metabolism; lipid metabolism and pyruvate metabolism. Additionally, 157 potential targets of CS and 265 targets of liver fibrosis were identified by means of network pharmacology. Subsequently, 5 target proteins, which are the intersection of potential CS targets and liver fibrosis targets, indicated that CS has potential anti-fibrosis effects through regulating alanine aminotransferase (ALT) activity, the farnesoid X receptor (FXR), cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1) and angiotensinogen. Chelerythrine and sanguinarine were the potential active compounds in CS for treating liver fibrosis through regulating ALT activity. This study is the first report to study the anti-fibrosis effects of CS on the basis of combining a metabonomics and network pharmacology approaches, and it may be a potentially powerful tool to study the efficacy and mechanisms of traditional Chinese folk medicines.

A Stacked Sparse Autoencoder-Based Detector for Automatic Identification of Neuromagnetic High Frequency Oscillations in Epilepsy.

High-frequency oscillations (HFOs) are spontaneous magnetoencephalography (MEG) patterns that have been acknowledged as a putative biomarker to identify epileptic foci. Correct detection of HFOs in the MEG signals is crucial for the accurate and timely clinical evaluation. Since the visual examination of HFOs is time-consuming, error-prone, and with poor inter-reviewer reliability, an automatic HFOs detector is highly desirable in clinical practice. However, the existing approaches for HFOs detection may not be applicable for MEG signals with noisy background activity. Therefore, we employ the stacked sparse autoencoder (SSAE) and propose an SSAE-based MEG HFOs (SMO) detector to facilitate the clinical detection of HFOs. To the best of our knowledge, this is the first attempt to conduct HFOs detection in MEG using deep learning methods. After configuration optimization, our proposed SMO detector is outperformed other classic peer models by achieving 89.9% in accuracy, 88.2% in sensitivity, and 91.6% in specificity. Furthermore, we have tested the performance consistency of our model using various validation schemes. The distribution of performance metrics demonstrates that our model can achieve steady performance.