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.

Evaluating rehabilitation interventionsin Parkinson's disease with functional MRI:a promising neuroprotective strategy

Parkinson＇s disease （PD） is a progressive neurodegenerative disorder affecting approximately 10 million people world- wide （Planetta et al., 2014; Zigmond and Smeyne, 2014）. The principal clinical features of PD are bradykinesia, rigidity, tremor at rest and postural instability （Planetta et al., 2014）. It is known that both PD itself and the use of anti-parkinson drugs are associated with several non-motor symptoms such as cognitive impairment, neuropsychiatric disturbances and sleep, autonomic, and sensory disorders （Park and Stacy, 2009; Foster et al., 2014）. The histopathological hallmark of PD is the reduction of dopaminergic cells in the substantia nigra pars compacta, causing dopamine deficiency in spe- cific nuclei of the basal ganglia such as the dorsal striatum （Fearnley and Lees, 1991; Planetta et al., 2014）. The disrup- tion of the dopaminergic system has long been regarded as the major cause of PD; however, it has been shown that a widespread involvement of several non-dopaminergic path- ways also contribute to the clinical manifestations of PD （Park et al., 2014）.

The Relationships between Serum Concentration of IGF-I and Left Ventricular Function as well as Coronary Collateral Circulation in Patients with Coronary Artery Disease

Objective To investigate therelationships between serum concentration of insulin -like growth factor - I (IGF-I) and left ventricular function as well as coronary collateral circulation in patients with coronary artery disease (CAD) . Methods In 41 patients with CAD and 15 control subjects without CAD, the concentrations of serum IGF - I were measured using radioimmunoassay. The relationships between the concentration of serum IGF - I and Leaman coronary artery score, Rentrop grade of coronary collateral circulation, left ventricular ejection fraction (LVEF) as well as left ventricular wall motion Cortina score were assessed. Results 1. There was no significant difference in the mean level of serum IGF -I between the CAD group and the control group (107. 92±44.74 ng/ml vs 113.05 ±33. 65 ng/ml, P> 0. 05), but the IGF - I concentrations in the subgroup with collateral circulation were significantly greater than that in the control group (147. 33 ±29. 92 ng/ml vs 113. 05±33. 65 ng/ml, P < 0. 01) or in the subgroup without collateral circulation (147. 33 ±29. 92 ng/ml vs 80. 01±29. 75 ng/ml , P < 0. 01). 2. The serum concentration of IGF -I had no significant correlation to the Leaman coronary artery score. 3. The serum level of IGF -I had significantly positive correlation to both LVEF ( r = 0. 45, P < 0. 001) and the Rentrop grade of coronary collateral circulation ( r = 0. 74, P < 0. 001), and was negatively related to the left ventricular wall motion Cortina score (r = -0. 53, P < 0. 001). 4. The Leaman coronary artery score had no significant correlation to the Rentrop grade of coronary collateral circulation. 5. The Leaman coronary artery score was related to neither the LVEF nor the Cortina score in the whole CAD group. In the subgroup without coronary collateral circulation, however, the Leaman score had significantly negative correlation to LVEF ( r = - 0. 46, P < 0. 05) and positive correlation to the Cortina score (r = 0. 47, P < 0. 05) . Conclusions The serum concentration of IGF -I was associated with both left ventricular function and coronary collateral circulation in patients with CAD. IGF -I may play a role in promoting coronary collateral circulation and in protecting left ventricular function in patients with coronary artery disease.

Neurodegenerative diseases are a function of matrix breakdown:how to rebuild extracellular matrix and intracellular matrix

Matrix within cells,the cytoskeleton,and that which surrounds cells,the extracellular matrix（ECM）,are connected to one another through a number of receptors including those in primary cilia,serving as an important chemical and physical signaling system：Mechanical forces generated through the matrix play a critical role in determining the form and function of tissues（Hughes et al.,2018）.

SLP-2: a potential new target for improving mitochondrial function in Parkinson's disease

Parkinson＇s disease （PD） is a progressive neurodegenerative disease, which is generally considered a multifactorial disorder that arises owing to a combination of genes and environmental factors. While most cases are idiopathic, in about 10% of the patients a genetic cause can be detected, ascribable to mutations in more than a dozen genes. PD is characterized clinically by tremor, rigidity, reduced mo- tor activity （bradykinesia）, and postural instability and pathological- ly by loss of dopaminergic （DA） neurons in the substantia nigra pars compacta, loss of DA innervation in the striatum, and the presence of a-synuclein positive aggregates in the form of Lewy bodies. The symptomatic treatment of PD with levodopa, which aims at replac- ing dopamine, remains the gold standard, and no neuroprotective or disease-modifying therapy is available. During treatment, the disease continues to progress, and long-term use of levodopa has import- ant limitations including motor complications termed dyskinesias. Therefore, a pharmacological therapy able to prevent or halt the neu- rodegenerative process is urgently required.

Chloride channels in vascular function and disease

Vascular smooth muscle cells（VSMCs） are the major component of vascular wall which are often stretched and compressed by pounding intravascular pressure.These mechanical signals are usually transformed to electrical signals by the opening or closing of ion channels in VSNCs and endothelial cells.Intravascular pressure causes a graded membrane potential depolarization of the VSMCs and leads to vasoconstriction（i.e.,myogenic response）,independent of the vascular endothelium. Although the important role of cation channels including L-type Ca2+ channels,K+ channels,and TRP channels in the regulation of vascular tone has been well established the functional roles played by Cl- channels in the regulation of the membrane potential and vascular tone remain essentially obscure. Recent emerging evidence implicates very important roles of Cl- channels in vascular function ranging from the control of membrane potential equilibrium, vascular contraction and relaxation to the regulation of intracellular pH,cell volume homeostasis,cell proliferation,migration,and apoptosis.

Gait improvement after treadmill training in ischemic stroke survivors A critical review of functional MRI studies

Stroke survivors often present with abnormal gait, movement training can improve the walking performance post-stroke, and functional MRI can objectively evaluate the brain functions before and after movement training. This paper analyzes the functional MRI changes in patients with ischemic stroke after treadmill training with voluntary and passive ankle dorsiflexion. Functional MRI showed that there are some changes in some regions of patients with ischemic stroke including primary sensorimotor cortex, supplementary motor area and cingulate motor area after treadmill training. These findings suggest that treadmill training likely improves ischemic stroke patients＇ lower limb functions and gait performance and promotes stroke recovery by changing patients＇ brain plasticity; meanwhile, the novel treadmill training methods can better training effects.

The Level of Serum Intact Terminal Peptide of Procollagen and Its Clinical Significance in Patients with Chronic Keshan Disease

Objectives To evaluate the changes of serum intact terminal peptide of procollagen in patients with chronic Keshan disease (KD) and investigate their clinical significance. Methods The concentrations of serum intact N-terminal peptide of type procollagen (P NP) and intact N-terminal peptide of type procollagen were measured by radioimmunoassay in 35 patients with chronic KD and 31 normal control. Doppler ultrasounds was used to determine several parameters of left ventricular systole and diastole functions. Results The concentration of serum P NP (74.07±16.74)μg/L and the ratio of P NP/ P NP (18.02 ±4.60) in chronic KD were significantly increased as compared to the control (39.63±12.07 μg/L, 12.12±4.24; P< 0.001). Serum P NP (4.19±0.64)μg/L in chronic KD was higher than that in the control (3.36±0.65 μg/L,P < 0.001) too. The higher of serum concentration of P NP and the ratio of P NP/ P NP, the worse of cardiac function in patients with chronic KD. A negative correlation was found between serum P NP/ P NP, P NP and VE/VA, LVEF (γ=-0.4502, -0.4608, P< 0.01 and γ=-0.3936, -0.3904, respectively; P<0.05). Conclusions These findings suggested that tissue synthesis of collagen type and type was abnormally increased in chronic KD. On the other hand, our results indicated that P NP and P NP were related to several functional alterations of the left ventricle. Serum procollagen peptide measurements might therefore provide indirectly diagnostic information on myocardial fibrosis associated with chronic KD.

Effects of lornoxicam combining with fentanyl on postoperative arrhythmia and platelet function in patients with coronary artery disease after abdominal surgery

To investigate the effects of patient-controlled intravenous analgesia (PCIA) with lornoxicam and fentanyl on arrhythmia and the expression of platelet membrane glycoproteins in patients with coronary artery disease (CAD) after abdominal surgery.Methods Eighty ASA Ⅱ or Ⅲ patients with CAD aged 51～66 yrs weighing 59～68 kg presenting for abdominal surgery participated in this study.CAD was diagnosed by clinical symptoms and ischemic changes on ECG.The patients were premedicated with intramuscular henobarbital 0.1 g and scopolamine 0.3 mg.Anesthesia was induced with fentanyl,droperidol,propofol and vecuronium and maintained with propofol,fentanyl and vecuronium.The patients received PCIA after operation.The PCIA solution contained fentanyl 0.9 mg and droperidol 5 mg in 100 ml of normal saline (N.S.) in group A (n=40) or lornoxicam 56 mg,fentanyl 0.2 mg and droperidol 5 mg in 100 ml N.S. in group B (n=40).In group A the loading dose was fentanyl 0.05 mg and group B lornoxicam 4 mg.PCIA included a background infusion at 2 ml·h -1 and a bolus of 0.5 ml with a 15 min lock-out.VAS(0=no pain,10= worst pain) was used to measure pain intensity.In addition to BP,HR and SpO2 monitoring ECG was continuously monitored with a Holter monitor after operation.Blood samples were taken from peripheral vein before and 6 h after operation and on the 1st,2nd,7th and 8th postoperative days for determination of the expression of CD 62p ,CD 63 and CD 41 /CD 61 on the platelet membrane,platelet count,prothrombin time (PT) thrombin time (TT) and partial thromboplastin time (PTT).Results The two groups were comparable with respect to sex,age,body weight,severity of CAD,duration of operation and intraoperative blood loss.The patients received no blood transfusion during operation.There was no significant difference in VAS score,platelet count,PT,TT and PTT between the two groups.The incidence of atrial and ventricular premature beat on ECG and the expression of CD 41 /CD 61 ,CD 62p and CD 63 on the platelet membrane were significantly lower in group B than in group A on the 7th and 8th postoperative days(P<0.05 or 0.01).Conclusion Postoperative PCIA with lornoxicam and fentanyl can more effectively reduce the incidence of postoperative arrhythmia in patients with CAD.Suppression of activation of platelets by lornoxicam may contribute to the mechanism.10 refs,3 tabs.

Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong（EX-HN1）, Yintang（EX-HN3）, Neiguan（PC6）, Taixi（KI3）, Fenglong（ST40）, and Taichong（LR3）, or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.

The pleiotropic vasoprotective functions of high density lipoproteins(HDL)

The pleiotropic functions of circulating high density lipoprotein（HDL） on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflammation,endothelial activation and apoptosis in peripheral vessels. Although not expressed in the central nervous system, HDL has nevertheless emerged as a potential resilience factor for dementia in multiple epidemiological studies. Animal model data specifically support a role for HDL in attenuating the accumulation of P-amyloid within cerebral vessels concomitant with reduced neuroinflammation and improved cognitive performance. As the vascular contributions to dementia are increasingly appreciated, this review seeks to summarize recent literature focused on the vasoprotective properties of HDL that may extend to cerebral vessels, discuss potential roles of HDL in dementia relative to brainderived lipoproteins, identify gaps in current knowledge, and highlight new opportunities for research and discovery.

Increased colon transit time and faecal load in irritable bowel syndrome

BACKGROUND Irritable bowel syndrome(IBS)is a bowel disorder involving abdominal pain or discomfort along with irregularity of stool form and passage frequency.The pathophysiology is poorly understood and seems to be multifactorial.Investigations of possible causes of IBS have included only a few colonic transit studies and no simultaneous determination of the colonic faecal content.AIM To compare colon transit time and faecal load between IBS-patients and healthy control subjects.METHODS The study included 140 patients with IBS,with a mean age of 50.0 years.The control group comprised 44 healthy persons with a mean age of 43.4 years,who were selected at random from the National Civil Register.Both the patient group and the control group underwent a marker study to measure colon transit time(CTT)and to calculate a faecal loading score.The patient group underwent treatment with a combined prokinetic regime,after which their CTT and faecal loading were reassessed.Analyses were performed to compare measurements between the control group and the patient group before and after treatment.RESULTS Compared to healthy controls,IBS-patients exhibited a significantly prolonged mean CTT(45.48 h vs 24.75 h,P=0.0002)and significantly greater mean faecal loading scores in all colonic segments(P<0.001).Among IBS patients,we found no significant differences between the 48 h and 96 h radiographs.Among patients exhibiting increased CTT and faecal loading,approximately half exhibited a palpable mass in the right iliac fossa.After intervention with a prokinetic treatment,the mean CTT among IBS patients was reduced from 45.48 h to 34.50 h(P=0.091),with the post-treatment CTT not significantly differing from the CTT among control subjects(P=0.095).The faecal loading score among IBS patients did not significantly differ before and after treatment(P=0.442).The posttreatment faecal loading score in IBS patients remained significantly higher compared to that in controls(5.3 vs 4.3,P=0.014).After treatment,half of the IBSpatients were relieved of bloating,while the majority no longer experienced abdominal pain and achieved a daily consistent stool.CONCLUSION IBS-patients exhibited prolonged CTT and heavier faecal loading.These assessments may aid in diagnosis.Faecal retention may contribute to IBS symptoms,which can be treated using a prokinetic regime.

Outcomes of anatomical versus functional testing for coronary artery disease

Background Many patients have symptoms suggestive of coronary artery disease （CAD） and are often eval- uated with the use of diagnostic testing, although there are limited data from randomized trials to guide care.

Correlation between Diastolic Function and Mass and Geometry of Left Ventricle in Essential Hypertension

Object Diastolic function' s assessment is vital in order to produce information relevant to patients' functional class, management and prognosis. We sought to investigate diastolic dysfunction in essential hypertension (EH) with or without coronary heart disease (CAD) using color M - mode Doppler echocardiography and to study the relation between diastolic dysfunction and left ventricular mass index (LVMI) and geometry of LV, and to demonstrate partly the cause of increased cardiovascular risk of an echocardiographic pattern of LV geometry. Methods36 normal subjects (Group Ⅰ) and 107 patients with essential hypertension (Group II) were studied using color M - mode Doppler echocardiography. Four different LV anatomic adaptation to hypertension were i-dentified by categorizing patients according to values of end - diastolic relative wall thickness (RWT) and LVMI. We measured the rate of propagation of peak early filling flow velocity (Vp), time delay (TD) of the peak early filling flow velocity from mitral tips to the apex and Vp/E. Results The geometry of LV was classified into four types according to the LVMI and RWT. The normal limits of LVMI and RWT were obtained from the upper limits of the 95 % confidence interval from mean of LVMI and RWT in healthy control group respectively, which were 115.2 g/m2 and 0. 44. The definition of each type was as follows: Type I (normal group): LVMI≤115. 2 g/m2 and RWT≤ 0.44; Type Ⅱ (concentric remodeling): LVMI≤ 115. 2 g/m2 and RWT > 0. 44; Type III (eccentric hypertrophy): LVMI> 115.2 g/m2 and RWT≤0.44; Type Ⅳ (concentric hypertrophy): LVMI> 115.2 g/m2 and RWT>0.44. Most parameters of diastolic function in each geometry type differed significantly from those in the control group, but the difference among each geometry type was not significant. When compared with type Ⅰ, there was a tendency that TD was longer and Vp/E smaller in Type Ⅱ, Ⅲ and Ⅳ groups. The correlation between LVMI and Vp and TD had statistical significance ( P < 0. 01); the correlation coefficients were-0.21 and 0.29, respectively. Conclusions There is diastolic dysfunction in different LV geometry in patients with essential hypertension, even in patients with LV normal geometry there is diastolic dysfunction. LVMI has negative correlation to Vp, and positive correlation to TD. It may indicate that the greater the LVMI is, the worse the LV diastolic function.

Selective role of autophagy in neuronal function and neurodegenerative diseases

Proteostasis is critical for neuronal maintenance and survival, and its imbalance leads to neurodegeneration with the hallmark of protein misfolding and aggregation. Macroautophagy becomes a major route for the clearance of protein aggregates that are normally poor substrates for the proteasome, the other protein quality-control machinery. As a flux process, macroautophagy （hereafter referred to as autophagy） involves the formation of the autophagosome, a double-membrane vesicle for engulfing unwanted cellular components such as protein aggregates, and the fusion of autophagosomes with lysosomes that contain many potent proteases for final degradation.

Epidemiologic study of the irritable bowel syndrome in Beijing: stratified randomized study by cluster sampling

OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) in Beijing and its risk factors. METHODS: Phase I: a screening for IBS in Beijing area according to symptoms using both Manning (modified including constipation) and Rome criteria. 2486 subjects were studied by cluster sampling of the inhabitant groups according to a stratified design of urban, suburban and rural areas, and sample size of each area studied was in proportion to the population of the area. Selection of the inhabitant groups was made by simple random sampling. Age of subjects enrolled in the study was 18-70 years. All subjects fulfilling the selection criteria were requested to fill in a questionnaire assisted by trained doctors or medical students during the visit to their families. Phase II: an aliquot of patients who fulfilled at least the Manning criteria were further selected according to their scoring series to undergo detail clinical examination in the hospital including laboratory examination, abdominal ultrasonography, colonoscopy or/and barium enema to exclude organic disease of the colon. Prevalence of IBS of the population was then adjusted by the rate of correct diagnosis during Phase II study. Study using Minnesota Multi-Personality Indices (MMPI) was done in some cases. Probable risk factors were explored by comparing their frequencies among IBS group and non-IBS group using chi 2 and logistic analysis of multifactors. RESULTS: The adjusted point prevalence of IBS in Beijing is 7.26% according to Manning criteria, and is 0.82% according to Rome criteria. There is a higher prevalence rate in city (10.50%) than in rural areas (6.14%) by stratified analysis (P

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

Impaired structure and function of the hippocampus is a valuable predictor of progression from amnestic mild cognitive impairment（a MCI） to Alzheimer＇s disease（AD）. As a part of the medial temporal lobe memory system,the hippocampus is one of the brain regions affected earliest by AD neuropathology,and shows progressive degeneration as a MCI progresses to AD. Currently,no validated biomarkers can precisely predict the conversion from a MCI to AD. Therefore,there is a great need of sensitive tools for the early detection of AD progression. In this review,we summarize the specifi c structural and functional changes in the hippocampus from recent a MCI studies using neurophysiological and neuroimaging data. We suggest that a combination of advanced multi-modal neuroimaging measures in discovering biomarkers will provide more precise and sensitive measures of hippocampal changes than using only one of them. These will potentially affect early diagnosis and disease-modifying treatments. We propose a new sequential and progressive framework in which the impairment spreads from the integrity of fibers to volume and then to function in hippocampal subregions. Meanwhile,this is likely to be accompanied by progressive impairment of behavioral and neuropsychological performance in the progression of a MCI to AD.