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.

Post-cholecystectomy symptoms were caused by persistence of a functional gastrointestinal disorder

AIM： To classify gallstone disease as a basis for assessment of post-choleolstectomy symptoms.METHODS： One hundred and fifty three patients with a clinical and ultrasonographic diagnosis of gallstones filled out a structured questionnaire on abdominal pain symptoms and functional gastrointestinal disorder （FGID） before and at six months after cholecystectomy. Symptom frequency groups （SFG） were categorized according to frequency of pain attacks. According to certain pain characteristics in gallstone patients, a gallstone symptom score was accorded on a scale from one to ten. A visual analogue scale was used to quan- tify pain. Operative specimens were examined for size and magnitude of stone contents as well as presence of bacteria. Follow-up took place after six months with either a consultation or via a mailed questionnaire. Results were compared with those obtained pre-operatively to describe and analyze symptomatic outcome.RESULTS： SFG groups were categorized as severe （24.2%）, moderate （38.6%）, and mild （22.2%） attack frequency, and a chronic pain condition （15%）. Pain was cured or improved in about 90% of patients and two-thirds of patients obtained complete symptom re- lief. Patients with the most frequent pain episodes were less likely to obtain symptom relief. FGID was present in 88% of patients pre-operatively and in 57% postoperatively （P = 0.244）. Those that became asymptomatic or improved with regard to pain also had most relief from FGID （P = 0.001）. No pre-operative FGID meant almost complete cure.CONCLUSION： Only one third of patients with FGID experienced postoperative relief, indicating that FGID was a dominant cause of post-cholecystectomy symptoms.

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.

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）.

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）.

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.

Irritable bowel syndrome and small intestinal bacterial overgrowth:Meaningful association or unnecessary hype

Irritable bowel syndrome (IBS) is a common condition characterized by abdominal pain or discomfort, bloating, and altered stool form and passage. Small intestinal bacterial overgrowth (SIBO) is a condition in which there is overgrowth of bacteria in small bowel in excess of 105 colony forming units per milliliter on culture of the upper gut aspirate. Frequency of SIBO varied from 4%-78% among patients with IBS and from 1%-40% among controls. Higher frequency in some studies might be due to fallacious criteria [post-lactulose breath-hydrogen rise 20 PPM above basal within 90 min (early-peak)]. Glucose hydrogen breath test (GHBT) has a low sensitivity to diagnose SIBO. Hence, studies based on GHBT might have under-estimated frequency of SIBO. Therefore, it is important to analyze these studies carefully to evaluate whether the reported association between IBS and SIBO is over or under-projected. This review evaluates studies on association between SIBO and IBS, discordance between different studies, their strength and weakness including methodological issues and evidence on therapeutic manipulation of gut flora on symptoms of IBS.

Can probiotics benefit children with autism spectrum disorders?

Children with autism are commonly affected by gastrointestinal problems such as abdominal pain, constipation and diarrhea. In recent years, there has been a growing interest in the use of probiotics in this population, as it hypothetically may help to improve bowel habits and the behavioral and social functioning of these individuals. The gut microbiome plays an important role in the pathophysiology of organic as well as functional gastrointestinal disorders. Microbial modification with the use of antibiotics, probiotics, and fecal transplantation have been effective in the treatment of conditions such as recurrent Clostridium difficile infection, pouchitis, and irritable bowel syndrome. The present review presents a number of reported clinical, immunological and microbiomerelated changes seen in children with autism compared to normally developed children. It also discusses gut inflammation, permeability concerns, and absorption abnormalities that may contribute to these problems. Most importantly, it discusses evidence, from human and animal studies, of a potential role of probiotics in the treatment of gastrointestinal symptoms in children with autism.

Non-pharmacological treatments in the irritable bowel syndrome

INTRODUCTIONThe irritable bowel syndrome (IBS) is a gastrointestinal disorder characteried by chronic lower abdominal pain and disordered defaecation associated with bloating ,tenesmus and extra-intestinal symptoms including and functional upper gastrointestinal symptoms .Currently there is nounifying hypothesis which adepuately explains the pathogenesis of the disorder although a number of physiological and psychological abmormalites have been described.

Elevated pro-inflammatory and lipotoxic mucosal lipids characterise irritable bowel syndrome

AIM： To investigate the pathophysiology of irritable bowel syndrome （IBS） by comparing the global mucosal metabolic profiles of IBS patients with those of healthy controls. METHODS： Fifteen IBS patients fulfilling the Rome II criteria, and nine healthy volunteers were included in the study. A combined lipidomics （UPLC/MS） and metabolomics （GC × GC-TOF） approach was used to achieve global metabolic profiles of mucosal biopsies from the ascending colon. RESULTS： Overall, lipid levels were elevated in patients with IBS. The most significant upregulation was seen for pro-inflammatory lysophosphatidylcholines. Other lipid groups that were significantly upregulated in IBS patients were lipotoxic ceramides, glycosphingolipids, and di-and triacylglycerols. Among the meo tabolites, the cyclic ester 2（3H）-furanone was almost 14-fold upregulated in IBS patients compared to healthy subjects （P = 0.03）. CONCLUSION： IBS mucosa is characterised by a distinct pro-inflammatory and lipotoxic metabolic profile. Especially, there was an increase in several lipid species such as lysophospholipids and ceramides.

Changing face of irritable bowel syndrome

Recent years have witnessed tremendous progress in our understanding of irritable bowel syndrome （IBS）. It is evident that this is a truly global disease associated with significant symptoms and impairments in personal and social functioning for afflicted individuals. Advances in our understanding of gut flora-mucosal interactions, the enteric nervous system and the brain-gut axis have led to substantial progress in the pathogenesis of symptoms in IBS and have provided some hints towards the basic etiology of this disorder, in some subpopulations, at the very least. We look forward to a time when therapy will be addressed to pathophysiology and perhaps, even to primary etiology. In the meantime, a model based on a primary role for intestinal inflammation serves to integrate the various strands, which contribute to the presentation of IBS

Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors

AIM: To determine the bowel symptoms associated with diabetes and diabetes-related factors after excluding gastrointestinal (GI) organic diseases.METHODS: Participants were 4738 (603 diabetic and 4135 non-diabetic) patients who underwent colonoscopy and completed a questionnaire. On the day of pre-colonoscopy, 9 symptoms (borborygmus, abdominal distension, increased flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were prospectively evaluated on a 7-point Likert scale. The test-retest reliability of the bowel symptom scores from the baseline and second questionnaires was analyzed using kappa statistics. Associations between bowel symptom scores and diabetes or diabetes-related factors were analyzed by a rank-ordered logistic model adjusted for related confounders, and odds ratios (ORs) were estimated.RESULTS: In multivariate analysis, constipation [adjusted odds ratio (AOR) = 1.57, CI: 1.33-1.85, P < 0.01] and hard stools (AOR = 1.56, CI: 1.33-1.84, P < 0.01) were associated with diabetes, and fecal urgency (AOR = 1.16, CI: 0.99-1.37, P = 0.07) and incomplete evacuation (AOR = 1.16, CI: 1.00-1.36, P = 0.06) were marginally associated with diabetes. These symptoms remained associated even after excluding organic GI diseases on colonoscopy. Test-retest reliability of symptom score with a mean duration of 3.2 mo was good (mean kappa, 0.69). Associations of symptoms with diabetes-related factors were found; constipation with HbA1c ≥ 8.0% (AOR = 2.11, CI: 1.19-3.73), body mass index (BMI) < 25 (AOR = 2.11, CI: 1.22-3.66), and insulin use (AOR = 1.90, CI: 1.08-3.36); hard stools with diabetes duration (AOR = 1.03, CI: 1.00-1.07); fecal urgency with BMI < 25 (AOR = 1.73, CI: 1.00-2.98); and incomplete evacuation with BMI < 25 (AOR = 2.60, CI: 1.52-4.43), serum creatinine level (AOR = 1.27, CI: 1.10-1.47), and insulin use (AOR = 1.92, CI: 1.09-3.38).CONCLUSION: Diabetes is associated with constipation, hard stools, fecal urgency, and incomplete evacuation, and poor glycemic control, duration, leanness, and nephropathy affect the risk of these symptoms.

Nodular lymphoid hyperplasia: A marker of low-grade inflammation in irritable bowel syndrome?

AIM To evaluate the prevalence of nodular lymphoid hyperplasia(NLH) in adult patients undergoing colonoscopy and its association with known diseases. METHODS We selected all cases showing NLH at colonoscopy in a three-year timeframe, and stratified them into symptomatic patients with irritable bowel syndrome(IBS)-type symptoms or suspected inflammatory bowel disease(IBD), and asymptomatic individuals undergoing endoscopy for colorectal cancer screening.Data collection included medical history and final diagnosis. As controls, we considered all colonoscopies performed for the aforementioned indications during the same period.RESULTS One thousand and one hundred fifty colonoscopies were selected. NLH was rare in asymptomatic individuals(only 3%), while it was significantly more prevalent in symptomatic cases(32%). Among organic conditions associated with NLH, the most frequent was IBD, followed by infections and diverticular disease. Interestingly, 31% of IBS patients presented diffuse colonic NLH. NLH cases shared some distinctive clinical features among IBS patients: they were younger, more often female, and had a higher frequency of abdominal pain, bloating, diarrhoea, unspecific inflammation, self-reported lactose intolerance and metal contact dermatitis. CONCLUSION About 1/3 of patients with IBS-type symptoms or suspected IBD presented diffuse colonic NLH, which could be a marker of low-grade inflammation in a conspicuous subset of IBS patients.

Perceived risk as a barrier to appropriate diagnosis of irritable bowel syndrome

AIM: To evaluate perceived risk, diagnostic testing, and acceptance of a diagnosis of irritable bowel syndrome (IBS) among the Korean laypersons.

Gastrointestinal manifestations of endocrine disease

The hormonal interactions among the systems throughout the body are not fully understood; many vague clinical symptoms may in fact be manifestations of underlying endocrine diseases. The aim of the following review is to discuss gastrointestinal manifestations of surgically correctable endocrine diseases, focusing on abnormalities of thyroid function, cancer and finally autoimmune diseases. We also review manifestations of pancreatic endocrine tumors, and multiple endocrine neoplasia.

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.

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.

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.