Nattokinase as a functional food ingredient:therapeutic applications and mechanisms in age-related diseases

Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.

Functional near-infrared spectroscopy in non-invasive neuromodulation

Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.

Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.

Research progress of TCM regulation of Cajal interstitial cells in the treatment of functional Gastrointestinal diseases

Interstitial cells of Cajal are a different class of cells with unique ultrastructure,molecular phenotype and function,and their main function is to generate slow waves,thereby triggering gastrointestinal pacing and regulating gastrointestinal motility.They play an extremely important physiological role in coordinating the normal activities of the digestive system,and their number,shape and function abnormalities often have a certain impact on gastrointestinal motility.Functional gastrointestinal disease is a type of digestive system disease closely related to gastrointestinal motility.Relevant studies have shown that the pathogenesis of functional gastrointestinal disease is closely related to the abnormal number,morphology and function of Cajal interstitial cells.Regulating the shape and number of interstitial cells of Cajal,maintaining the normal operation of gastrointestinal electrophysiology,inhibiting excessive autophagy and activating related signaling pathways,etc.,can improve gastrointestinal motility,thereby treating functional gastrointestinal diseases.This article will discuss the treatment of functional gastrointestinal diseases from traditional Chinese medicine compound,traditional Chinese medicine monomer,and external treatment of traditional Chinese medicine by regulating Cajal interstitial cells.

Analysis of Cardiac Functional Status and Factors Influencing Adverse Pregnancy Outcomes in Pregnant Women with Combined Heart Disease

Objective:To investigate the cardiac function of pregnant women with complicated heart disease during pregnancy and the factors influencing the adverse pregnancy outcome.Methods:A total of 162 cases of pregnant women with complicated heart disease admitted to the Beijing Anzhen Hospital from October 2021 to December 2023 were selected to compare the occurrence of adverse pregnancy outcomes in pregnant women with complicated heart disease at different levels of cardiac function and to analyze the single and multi factors leading to adverse pregnancy outcomes in pregnant women with complicated heart disease.Results:Among 162 pregnant women with combined heart disease in pregnancy,the highest percentage of heart disease type was congenital heart disease(80/49.38%),and the lowest percentage was other(9/5.56%);the overall incidence of adverse pregnancy outcomes in pregnant women with combined heart disease in pregnancy with cardiac function grades of 3–4 cardiac function(30/68.18%)was higher than that in pregnant women with combined heart disease in cardiac function grades of 1–2(40/33.90%)(P=0.000);age,marital status,hypertension,and past history of all pregnant women were not statistically significant(P>0.05);gestational age,type of heart disease,and cardiac function grading were statistically significant(P<0.05),and these factors were all independent risk factors for adverse pregnancy resolution in pregnant women with combined heart disease(P<0.05).Conclusion:The overall incidence of adverse pregnancy outcomes was higher in pregnant women with heart disease than in those with heart disease grades 1–2,and the number of pregnancies,the type of heart disease,and heart function grades were all independent risk factors for adverse pregnancy outcomes in pregnant women with heart disease.

Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome:A study from China

BACKGROUND Functional constipation(FC)and constipation-predominant irritable bowel syndrome(IBS-C)represent a spectrum of constipation disorders.However,the majority of previous clinical investigations have focused on Western populations,with limited data originating from China.AIM To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population.METHODS Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled.FC and IBS-C diagnoses were established using ROME IV criteria,and patients underwent high-resolution anorectal manometry(ARM)and a colonic transmit test using the Sitz marker study.Constipation-related symptoms were obtained through questionnaires.Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21.The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared.RESULTS No significant differences in sex,age or abdominal discomfort symptoms were observed between IBS-C and FC patients(all P>0.05).The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC(36.63%vs 15.91%,P<0.05),while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group(50%vs 26.73%,P<0.05).Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM.IBS-C patients were found to have a higher prevalence of depression than FC patients(66.30%vs 42.42%,P<0.05).The scores for feelings of guilt,suicide,psychomotor agitation,diurnal variation,obsessive/compulsive disorder,hopelessness,self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients(P<0.05).For IBS-C(χ^(2)=5.438,P<0.05)but not FC,patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time.For IBS-C patients but not FC patients,the threshold of first constant sensation,desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety(r=0.414,r=0.404,and r=0.418,respectively,P<0.05).The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression(69.6%vs 41.9%,χ2=4.054,P<0.05).CONCLUSION Our findings highlight both overlapping and distinctive patterns of colon transit,dyssynergic patterns,anorectal sensation,psychological distress,and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population,providing valuable insights into the pathophysiological underpinnings of these disorders.

Brain Functional Networks with Dynamic Hypergraph Manifold Regularization for Classification of End-Stage Renal Disease Associated with Mild Cognitive Impairment

The structure and function of brain networks have been altered in patients with end-stage renal disease(ESRD).Manifold regularization(MR)only considers the pairing relationship between two brain regions and cannot represent functional interactions or higher-order relationships between multiple brain regions.To solve this issue,we developed a method to construct a dynamic brain functional network(DBFN)based on dynamic hypergraph MR(DHMR)and applied it to the classification of ESRD associated with mild cognitive impairment(ESRDaMCI).The construction of DBFN with Pearson’s correlation(PC)was transformed into an optimization model.Node convolution and hyperedge convolution superposition were adopted to dynamically modify the hypergraph structure,and then got the dynamic hypergraph to form the manifold regular terms of the dynamic hypergraph.The DHMR and L_(1) norm regularization were introduced into the PC-based optimization model to obtain the final DHMR-based DBFN(DDBFN).Experiment results demonstrated the validity of the DDBFN method by comparing the classification results with several related brain functional network construction methods.Our work not only improves better classification performance but also reveals the discriminative regions of ESRDaMCI,providing a reference for clinical research and auxiliary diagnosis of concomitant cognitive impairments.

Global Functional Network Connectivity Disturbances in Parkinson’s Disease with Mild Cognitive Impairment by Resting-State Functional MRI

Examining the spontaneous BOLD activity to understand the neural mechanism of Parkinson’s disease(PD)with mild cognitive impairment(MCI)is a focus in resting-state functional MRI(rs-fMRI)studies.This study aimed to investigate the alteration of brain functional connectivity in PD with MCI in a systematical way at two levels:functional connectivity analysis within resting state networks(RSNs)and functional network connectivity(FNC)analysis.Using group independent component analysis(ICA)on rs-fMRI data acquired from 30 participants(14 healthy controls and 16 PD patients with MCI),16 RSNs were identified,and functional connectivity analysis within the RSNs and FNC analysis were carried out between groups.Compared to controls,patients with PD showed decreased functional connectivity within putamen network,thalamus network,cerebellar network,attention network,and self-referential network,and increased functional connectivity within execution network.Globally disturbed,mostly increased functional connectivity of FNC was observed in PD group,and insular network and execution network were the dominant network with extensively increased functional connectivity with other RSNs.Cerebellar network showed decreased functional connectivity with caudate network,insular network,and self-referential network.In general,decreased functional connectivity within RSNs and globally disturbed,mostly increased functional connectivity of FNC may be characteristics of PD.Increased functional connectivity within execution network may be an early marker of PD.The multi-perspective study based on RSNs may be a valuable means to assess functional changes corresponding to specific RSN,contributing to the understanding of the neural mechanism of PD.

Abnormal characterization of dynamic functional connectivity in Alzheimer’s disease

Numerous studies have shown abnormal brain functional connectivity in individuals with Alzheimer’s disease(AD)or amnestic mild cognitive impairment(aMCI).However,most studies examined traditional resting state functional connections,ignoring the instantaneous connection mode of the whole brain.In this case-control study,we used a new method called dynamic functional connectivity(DFC)to look for abnormalities in patients with AD and aMCI.We calculated dynamic functional connectivity strength from functional magnetic resonance imaging data for each participant,and then used a support vector machine to classify AD patients and normal controls.Finally,we highlighted brain regions and brain networks that made the largest contributions to the classification.We found differences in dynamic function connectivity strength in the left precuneus,default mode network,and dorsal attention network among normal controls,aMCI patients,and AD patients.These abnormalities are potential imaging markers for the early diagnosis of AD.

Acupuncture enhances brain function in patients with mild cognitive impairment: evidence from a functional-near infrared spectroscopy study

Mild cognitive impairment(MCI)is a precursor to Alzheimer’s disease.It is imperative to develop a proper treatment for this neurological disease in the aging society.This observational study investigated the effects of acupuncture therapy on MCI patients.Eleven healthy individuals and eleven MCI patients were recruited for this study.Oxy-and deoxy-hemoglobin signals in the prefrontal cortex during working-memory tasks were monitored using functional near-infrared spectroscopy.Before acupuncture treatment,working-memory experiments were conducted for healthy control(HC)and MCI groups(MCI-0),followed by 24 sessions of acupuncture for the MCI group.The acupuncture sessions were initially carried out for 6 weeks(two sessions per week),after which experiments were performed again on the MCI group(MCI-1).This was followed by another set of acupuncture sessions that also lasted for 6 weeks,after which the experiments were repeated on the MCI group(MCI-2).Statistical analyses of the signals and classifications based on activation maps as well as temporal features were performed.The highest classification accuracies obtained using binary connectivity maps were 85.7%HC vs.MCI-0,69.5%HC vs.MCI-1,and 61.69%HC vs.MCI-2.The classification accuracies using the temporal features mean from 5 seconds to 28 seconds and maximum(i.e,max(5:28 seconds))values were 60.6%HC vs.MCI-0,56.9%HC vs.MCI-1,and 56.4%HC vs.MCI-2.The results reveal that there was a change in the temporal characteristics of the hemodynamic response of MCI patients due to acupuncture.This was reflected by a reduction in the classification accuracy after the therapy,indicating that the patients’brain responses improved and became comparable to those of healthy subjects.A similar trend was reflected in the classification using the image feature.These results indicate that acupuncture can be used for the treatment of MCI patients.

Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease

Crohn’s disease(CD)is a chronic,non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease(IBD).CD is prone to relapse,and its incidence displays a persistent increase in developing countries.However,the pathogenesis of CD is poorly understood,with some studies emphasizing the link between CD and the intestinal microbiota.Specifically,studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD.Furthermore,investigations have shown whitematter lesions and neurologic deficits in patients with IBD.Based on these findings,brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging(BOLD-f MRI).BOLD-f MRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates.Therefore,biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients.To further study this phenomenon,brain changes of CD patients can be detected non-invasively,effectively and accurately by BOLD-f MRI combined with magnetic resonance spectroscopy(MRS).This approach can further shed light on the mechanisms of the occurrence and development of neurological CD.Overall,this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis.

On Chinese-English Translation of Disease and Syndrome Terms in Shang Han Lun from the Perspective of Functional Equivalence Theory

Shang Han Lun is one of the most famous and important traditional medical books in China,so many translation versions of it have emerged.Based on the comparison of examples taken from two of these translation versions,Young Jie De ' s Shang Han Lun Explained and Huang Hai s Introduction to Treatise on Exogenous Febrile Disease,the paper points out that Nida s Functional Equivalence Theory provides a new idea for the translation of Disease and Syndrome Terms in TCM that literal translation,liberal translation and transliteration can be adopted appropriately to make readers of translation versions understand TCM accurately and easily.

Contribution of ghrelin to functional gastrointestinal disorders' pathogenesis

Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis,exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin's gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin's relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.

Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome

Several studies indicate a significant degree of overlap between irritable bowel syndrome(IBS)and gastroesophageal reflux disease(GERD).Likewise,both functional heartburn(FH)and IBS are functional digestive disorders that may occur in the same patients.However,data establishing a solid link between FH and IBS are lacking,mainly because the clinical definition of FH has undergone substantial changes over the years.The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS.In particular,several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH(as defined by the RomeⅢcriteria)from GERD via pathophysiological investigations.Independent of these critical issues,there is preliminary evidence supporting a significantdegree of FH-IBS overlap.This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications,particularly to distinguish FH from GERD.This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.

Irritable bowel syndrome and functional constipation management with integrative medicine: A systematic review

BACKGROUND Irritable bowel syndrome(IBS)and functional constipation(FC)are two commonly encountered functional gastrointestinal disorders in clinical practice and are usually managed with Western medicines in cooperation with traditional Chinese medicine(TCM)interventions.Although clinical practice guidelines(CPGs)have been developed to assist clinicians with their decisions,there are still gaps in management with regard to integrative medicine(IM)recommendations.AIM To comprehensively review the currently available CPGs and to provide a reference for addressing the gaps in IBS and FC management.METHODS We searched mainstream English and Chinese databases and collected data from January 1990 to January 2019.The search was additionally enriched by manual searches and the use of publicly available resources.Based on the development method,the guidelines were classified into evidence-based(EB)guidelines,consensus-based(CB)guidelines,and consensus-based guidelines with no comprehensive consideration of the EB(CB-EB)guidelines.With regard to the recommendations,the strength of the interventions was uniformly converted to a 4-point grading scale.RESULTS Thirty CPGs met the inclusion criteria and were captured as data extraction sources.Most Western medicine(WM)CPGs were developed as EB guidelines.All TCM CPGs and most IM CPGs were identified as CB guidelines.Only the 2011 IBS and IM CPG was a CB-EB set of guidelines.Antispasmodics and peppermint oil for pain,loperamide for diarrhea,and linaclotide for constipation polyethylene glycol and lactulose as osmotic laxatives,bisacodyl and sodium picosulfate as stimulant laxatives,lubiprostone and linaclotide as prosecretory agents,and prucalopride were strongly recommended or recommended in FC.TCM interventions were suggested based on pattern differentiation,while the recommendation level was considered to be weak or insufficient.CONCLUSION WM CPGs generally provide a comprehensive management algorithm,although there are still some gaps that could be addressed with TCM.Specific high-quality trials are needed to enrich the evidence.

Diets, functional foods, and nutraceuticals as alternative therapies for inflammatory bowel disease: Present status and future trends

Inflammatory bowel disease(IBD) is a serious health concern among western societies. The disease is also on the rise in some East Asian countries and in Australia. Health professionals and dietitians around the world are facing an unprecedented challenge to prevent and control the increasing prevalence of IBD. The current therapeutic strategy that includes drugs and biological treatments is inefficient and are associated with adverse health consequences. In this context, the use of natural products is gaining worldwide attention. In vivo studies and clinical evidence suggest that wellplanned dietary regimens with specific nutrients can alleviate gastrointestinal inflammation by modulating inflammatory cytokines, such as tumor necrosis factor α(TNF-α), interleukin 1(IL-1), IL-6, IL-1β, and IL-10. Alternatively, the avoidance of high-fat and highcarbohydrate diets is regarded as an effective tool to eliminate the causes of IBD. Many functional foods and bioactive components have received attention for showing strong therapeutic effects against IBD. Both animal and human studies suggest that bioactive functional foods can ameliorate IBD by downregulating the pro-inflammatory signaling pathways, such as nuclear factor κB, STAT1, STAT6, and pro-inflammatory cytokines, including IL-1β, IL-4, IL-6, COX-2, TNF-α, and interferon γ. Therefore, functional foods and diets have the potential to alleviate IBD by modulating the underlying pathogenic mechanisms. Future comprehensive studies are needed to corroborate the potential roles of functional foods and diets in the prevention and control of IBD.

Diagnosis and management of functional symptoms in inflammatory bowel disease in remission

Inflammatory bowel disease(IBD) patients in remission may suffer from gastrointestinal symptoms that resemble irritable bowel syndrome(IBS). Knowledge on this issue has increased considerably in the last decade, and it is our intention to review and summarize it in the present work. We describe a problematic that comprises physiopathological uncertainties, diagnostic difficulties, as IBS-like symptoms are very similar to those produced by an inflammatory flare, and the necessity of appropriate management of these patients, who, although in remission, have impaired quality of life. Ultimately, from almost a philosophical point of view, the presence of IBS-like symptoms in IBD patients in remission supposes a challenge to the traditional functional-organic dichotomy, suggesting the need for a change of paradigm.

Alteration of functional connectivity in patients with Alzheimer’s disease revealed by resting-state functional magnetic resonance imaging

The main symptom of patients with Alzheimer’s disease is cognitive dysfunction. Alzheimer’s disease is mainly diagnosed based on changes in brain structure. Functional connectivity reflects the synchrony of functional activities between non-adjacent brain regions, and changes in functional connectivity appear earlier than those in brain structure. In this study, we detected resting-state functional connectivity changes in patients with Alzheimer’s disease to provide reference evidence for disease prediction. Functional magnetic resonance imaging data from patients with Alzheimer’s disease were used to show whether particular white and gray matter areas had certain functional connectivity patterns and if these patterns changed with disease severity. In nine white and corresponding gray matter regions, correlations of normal cognition, early mild cognitive impairment, and late mild cognitive impairment with blood oxygen level-dependent signal time series were detected. Average correlation coefficient analysis indicated functional connectivity patterns between white and gray matter in the resting state of patients with Alzheimer’s disease. Functional connectivity pattern variation correlated with disease severity, with some regions having relatively strong or weak correlations. We found that the correlation coefficients of five regions were 0.3–0.5 in patients with normal cognition and 0–0.2 in those developing Alzheimer’s disease. Moreover, in the other four regions, the range increased to 0.45–0.7 with increasing cognitive impairment. In some white and gray matter areas, there were specific connectivity patterns. Changes in regional white and gray matter connectivity patterns may be used to predict Alzheimer’s disease;however, detailed information on specific connectivity patterns is needed. All study data were obtained from the Alzheimer’s Disease Neuroimaging Initiative Library of the Image and Data Archive Database.

Emotion processing in Parkinson's disease: a blood oxygenation level-dependent functional magnetic resonance imaging study

Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease.

Pathophysiology of functional heartburn based on Rome Ⅲ criteria in Japanese patients

AIM:To investigate the pathophysiology of functional heartburn(FH) in Japanese patients.METHODS:A total of 111 patients with proton pump inhibitor(PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedancep H(24MII-p H) testing.The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease(QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease(FSSG), the gastrointestinal symptoms rating scale(GSRS), SF-36, and the Cornell Medical Index(CMI).The subjects were classified into FH and endoscopy-negative reflux disease(ENRD) groups based on the Rome Ⅲ criteria.RESULTS:Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time(p H-POS) and 34 with hypersensitive esophagus(HE) were included in the ENRD group.The FH group included 22 patients with no reflux involvement.Sex, age, and body mass index did not differ significantly between the groups.The mean SF-36 values were < 50(normal) for all scales in these groups, with no significant differences.The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms.The QUEST and the FSSG scores did not differ significantly between the groups.Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the p H-POS(n=4),HE(n=8),and FH(n=5)groups,with no significant differences.CONCLUSION:Clinical characteristics of the FH and PPI-refractory ENRD groups were similar.Therefore,esophageal function should be examined via manometry and 24MII-p H testing to differentiate between them.