Comparison of SGLT2 inhibitors vs. DPP4 inhibitors for patients with metabolic dysfunction associated fatty liver disease and diabetes mellitus.

PURPOSE: This study aimed to examine the potential benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and diabetes mellitus (DM) using a real-world database. METHODS: We analyzed individuals with MAFLD and DM newly initiated on SGLT2 or dipeptidyl peptidase 4 (DPP4) inhibitors from a large-scale administrative claims database. The primary outcome was the change in the fatty liver index (FLI) assessed using a linear mixed-effects model from the initiation of SGLT2 or DPP4 inhibitors. A propensity score-matching algorithm was used to compare the change in FLI among SGLT2 and DPP4 inhibitors. RESULTS: After propensity score matching, 6547 well-balanced pairs of SGLT2 and 6547 DPP4 inhibitor users were created. SGLT2 inhibitor use was associated with a greater decline in FLI than DPP4 inhibitor use (difference at 1-year measurement, - 3.8 [95% CI - 4.7 to - 3.0]). The advantage of SGLT2 inhibitor use over DPP4 inhibitor use for improvement in FLI was consistent across subgroups. The relationship between SGLT2 inhibitors and amelioration of FLI was comparable between individual SGLT2 inhibitors. CONCLUSIONS: Our analysis using large-scale real-world data demonstrated the potential advantage of SGLT2 inhibitors over DPP4 inhibitors in patients with MAFLD and DM.

Combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy in cow's milk allergy: a randomised controlled trial.

Safer and more effective cow milk (CM)-oral immunotherapy that does not induce allergic reactions has not yet been standardised. We sought to explore the efficacy and feasibility of a combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy for treating IgE-mediated cow milk allergy (CMA). We conducted a 24-week, double-blind, randomised (1:1), two-arm, parallel-group, placebo-controlled, phase 2 trial of LP0132 intervention for treating IgE-mediated CMA in children aged 1-18 years (n=60) from January 29, 2018 to July 12, 2019 in Tokyo, Japan. Participants were randomly assigned to the LP0132 group receiving citrus juice fermented with LP0132 or to the control group receiving citrus juice without. Both groups received low-dose slow oral immunotherapy with CM. The primary outcome was improved tolerance to CM, proven by the CM challenge test at 24 weeks. Secondary outcomes were changes in serum biomarkers of serum-specific ß-lactoglobulin-IgE (sIgE) and ß-lactoglobulin-IgG4 (sIgG4). Exploratory outcomes included changes in serum cytokine levels and gut microbiota composition. A total of 61 participants were included. Finally, 31 children were assigned to the LP0132 group and 30 to the control group, respectively. After the intervention, 41.4 and 37.9% of the participants in the LP0132 and control groups, respectively, showed improved tolerance to CM. In serum biomarkers after the intervention, the sIgG4 level was significantly higher, and interleukin (IL)-5 and IL-9 were significantly lower, in the LP0132 group than in the control group. In the gut microbiome, the α-diversity and Lachnospiraceae increased significantly in the LP0132 group, and Lachnospiraceae after the intervention was significantly higher in the LP0132 group than in the control group. In conclusion, low-dose oral immunotherapy with modulating gut microbiota might be a safer and more effective approach for treating cow's milk allergy.

Relativistic magnetic reconnection in laser laboratory for testing an emission mechanism of hard-state black hole system.

Magnetic reconnection in a relativistic electron magnetization regime was observed in a laboratory plasma produced by a high-intensity, large energy, picoseconds laser pulse. Magnetic reconnection conditions realized with a laser-driven several kilotesla magnetic field is comparable to that in the accretion disk corona of black hole systems, i.e., Cygnus X-1. We observed particle energy distributions of reconnection outflow jets, which possess a power-law component in a high-energy range. The hardness of the observed spectra could explain the hard-state x-ray emission from accreting black hole systems.

Recruitment gain of spinal motor neuron pools in cat and human.

The output from a motor nucleus is determined by the synaptic input to the motor neurons and their intrinsic properties. Here, we explore whether the source of synaptic inputs to the motor neurons (cats) and the age or post-stroke conditions (humans) may change the recruitment gain of the motor neuron pool. In cats, the size of Ia EPSPs in triceps surae motor neurons (input) and monosynaptic reflexes (MSRs; output) was recorded in the soleus and medial gastrocnemius motor nerves following graded stimulation of dorsal roots. The MSR was plotted against the EPSP thereby obtaining a measure of the recruitment gain. Conditioning stimulation of sural and peroneal cutaneous afferents caused significant increase in the recruitment gain of the medial gastrocnemius, but not the soleus motor neuron pool. In humans, the discharge probability of individual soleus motor units (input) and soleus H-reflexes (output) was performed. With graded stimulation of the tibial nerve, the gain of the motor neuron pool was assessed as the slope of the relation between probability of firing and the reflex size. The gain in young subjects was higher than in elderly subjects. The gain in post-stroke survivors was higher than in age-matched neurologically intact subjects. These findings provide experimental evidence that recruitment gain of a motor neuron pool contributes to the regulation of movement at the final output stage from the spinal cord and should be considered when interpreting changes in reflex excitability in relation to movement or injuries of the nervous system.

Rates of asymptomatic respiratory virus infection across age groups.

Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population.

Effect of Bacillus subtilis C-3102 on loose stools in healthy volunteers.

Ingestion of Bacillus subtilis C-3102 spores (C-3102) has relieved the symptoms of diarrhoea in piglets and changed the composition of gut microbiota in humans. Recently, it was suggested that the composition of the human gut microbiota affects stool consistency. In this study, a double-blind, randomised, placebo-controlled trial was conducted to assess the preventive effects of chronic diarrhoea in healthy volunteers with loose stools by ingestion of C-3102. The results showed that oral doses of C-3102 tablets significantly decreased the Bristol Stool Scale score and stool frequency, and also significantly improved abdominal sounds. With regard to gut microbiota, the relative abundance of Lachnospira, Actinomyces and SMB53 were significantly changed. This study shows that C-3102 could be effective for treating loose stools (Trial registration: UMIN000022583, http://tinyurl.com/ya4refqn ).

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.

Dynamics of M1 macrophages in oral mucosal lesions during the development of acute graft-versus-host disease in rats.

The role of macrophage infiltrates in oral mucosal acute graft-versus-host disease (AGVHD) remains unclear, although clinical studies suggest that macrophage infiltration correlates directly with the severity of AGVHD. In this study, we investigated the role of M1 macrophage infiltration in the oral mucosa of rats with AGVHD. Lewis rat spleen cells were injected into (Lewis × Brown Norway) F1 rats to induce systemic GVHD. Tongue samples were evaluated using histology, immunohistochemistry, dual immunofluorescence, real-time reverse transcription-polymerase chain reaction, Transwell migration assays and Stamper-Woodruff binding assays. At the onset of oral mucosal AGVHD, dual immunofluorescence and migration assays revealed that M1 macrophages had accumulated in the basement membrane (BM) region via the laminin/CD29 ß1 integrin pathway. Macrophage-secreted matrix metalloproteinase-2 was related to BM degradation. The adhesion of macrophages to the oral epithelium could be inhibited by pretreating macrophages with a CC chemokine receptor 2 (CCR2) antibody and/or pretreating lesion sections with monocyte chemoattractant protein-1 (MCP-1) antibody. Our data show that the migration and adhesion of M1 macrophages are associated with oral mucosal AGVHD, which is mediated in part by both laminin/CD29 ß 1 intern and MCP-1/CCR2 pathways. Therefore, our study provides additional support for the contribution of macrophage infiltrate to the development of oral mucosal AGVHD.

Shelter crowding and increased incidence of acute respiratory infection in evacuees following the Great Eastern Japan Earthquake and tsunami.

Although outbreaks of acute respiratory infection (ARI) at shelters are hypothesized to be associated with shelter crowding, no studies have examined this relationship. We conducted a retrospective study by reviewing medical records of evacuees presenting to one of the 37 clinics at the shelters in Ishinomaki city, Japan, during the 3-week period after the Great Eastern Japan Earthquake and tsunami in 2011. On the basis of a locally weighted scatter-plot smoothing technique, we categorized 37 shelters into crowded (mean space <5·5 m2/per person) and non-crowded (⩾5·5 m2) shelters. Outcomes of interest were the cumulative and daily incidence rate of ARI/10 000 evacuees at each shelter. We found that the crowded shelters had a higher median cumulative incidence rate of ARI [5·4/10 000 person-days, interquartile range (IQR) 0-24·6, P = 0·04] compared to the non-crowded shelters (3·5/10 000 person-days, IQR 0-8·7) using Mann-Whitney U test. Similarly, the crowded shelters had an increased daily incidence rate of ARI of 19·1/10 000 person-days (95% confidence interval 5·9-32·4, P < 0·01) compared to the non-crowded shelters using quasi-least squares method. In sum, shelter crowding was associated with an increased incidence rate of ARI after the natural disaster.

Serum glycopeptidolipid core IgA antibody levels in patients with chest computed tomography features of mycobacterium aviumintracellulare complex pulmonary disease.

Measurement of serum glycopeptidolipid core IgA antibody (GPL antibody) was recently reported to show a high sensitivity and specificity for diagnosing Mycobacterium avium-intracellulare complex (MAC) pulmonary disease (MAC-PD), but its clinical value has not been confirmed. This study aims to evaluate the seropositive rate in patients with suspected MAC-PD based on chest computed tomography (CT), and to examine whether GPL antibody reflects the extent of lung involvement on CT or the number of bacteria in sputum, retrospectively. Among 66 patients with suspected MAC-PD on CT, 36 patients were negative for MAC by culture and 30 were positive. Sputum grades of MAC were evaluated by fluorochrome microscopy of sputum smears. The lungs were divided into six regions to assess the extent of disease. Serum levels of GPL antibody were measured with an enzyme immunoassay (cut-off value >0.7 U/ml). The GPL antibody positive rate was 19.4% among patients who were negative for MAC by culture versus 73.3% among culture–positive patients. The serum level of GPL antibody was significantly correlated with the sputum smear grade (r=0.43, p less than 0.05) and was also correlated with the number of lung regions showing MAC-PD features on CT (r=0.43, less than 0.05). Some MAC-PD patients may have CT features of MAC with positive level of GPL antibody, although the diagnosis cannot be confirmed by culture. GPL antibody levels reflect the pulmonary burden of MAC, as assessed from the sputum smear grade and number of involved regions on chest CT.

Nitric oxide confers cisplatin resistance in human lung cancer cells through upregulation of aldo-keto reductase 1B10 and proteasome.

In this study, we show that exposure of human lung cancer A549 cells to cisplatin (cis-diamminedichloroplatinum, CDDP) promotes production of nitric oxide (NO) through generation of reactive oxygen species (ROS) and resulting upregulation of inducible NO synthase (iNOS). The incubation of the cells with a NO donor, diethylenetriamine NONOate, not only reduced the CDDP-induced cell death and apoptotic alterations (induction of CCAAT-enhancer-binding protein homologous protein and caspase-3 activation), but also elevated proteolytic activity of 26S proteasome, suggesting that the activation of proteasome function contributes to the reduction of CDDP sensitivity by NO. Monitoring expression levels of six aldo-keto reductases (AKRs) (1A1, 1B1, 1B10, 1C1, 1C2, and 1C3) during the treatment with the NO donor and subsequent CDDP sensitivity test using the specific inhibitors also proposed that upregulation of AKR1B10 by NO is a key process for acquiring the CDDP resistance in A549 cells. Treatment with CDDP and NO increased amounts of nitrotyrosine protein adducts, indicative of peroxynitrite formation, and promoted the induction of AKR1B10, inferring a relationship between peroxynitrite formation and the enzyme upregulation in the cells. The treatment with CDDP or a ROS-related lipid aldehyde, 4-hydroxy-2-nonenal, facilitated the iNOS upregulation, which was restored by increasing the AKR1B10 expression. In contrast, the facilitation of NO production by CDDP treatment was hardly observed in AKR1B10-overexpressing A549 cells and established CDDP-resistant cancer cells (A549, LoVo, and PC3). Collectively, these results suggest the NO functions as a key regulator controlling AKR1B10 expression and 26S proteasome function leading to gain of the CDDP resistance.

Involvement of IP3-receptor activation in endothelin-1-induced Ca(2+) influx in rat pulmonary small artery.

We examined the endothelin-1 (ET-1)-induced increase in the intracellular free Ca(2+) concentration ([Ca(2+)]i) in fura-2-loaded rat pulmonary small arteries. ET-1 (30 nM) elicited a long-lasting increase in [Ca(2+)]i in physiological salt solution (PSS). In subsequent experiments, arteries were pretreated with BQ-788, an ETB-specific blocker, to allow us to focus on responses mediated via the ETA receptor, the existence of which was confirmed by immunohistochemistry. In Ca(2+)-free PSS, ET-1 evoked a small transient increase in [Ca(2+)]i, indicating Ca(2+) release from the SR (sarcoplasmic reticulum). After a switch to PSS (containing 2mM CaCl2), ET-1 elicited a long-lasting increase in [Ca(2+)]i that was not inhibited by 1 µM nicardipine, an L-type Ca(2+)-channel inhibitor, suggesting involvement of a Ca(2+)-influx pathway independent of that channel. In arteries preincubated with 30 µM cyclopiazonic acid (CPA) or 2 µM thapsigargin (TG), the ET-1-induced Ca(2+)-release was greatly reduced, and the induced Ca(2+)-influx was attenuated. U-73122, a phospholipase C (PLC) inhibitor, had inhibitory effects similar to those of CPA and TG on the ET-1-induced Ca(2+)-release and Ca(2+)-influx, whereas U-73343, an inactive analogue of U-73122, had no such effects. Two putative membrane-permeable IP3-receptor blockers, 2-aminoethoxydiphenyl borate (2APB, 50 µM) and Xestospongin C (20 µM), (a) almost completely inhibited the ET-1-induced Ca(2+)-release and Ca(2+)-influx, and (b) reduced the ET-1-induced contraction. These results indicate that in rat pulmonary small arteries, ET-1 induces receptor-operated Ca(2+) influx via the ETA receptor, and that this influx interacts with InsP3-receptor activation.

Myogenic tone is impaired at low arterial pressure in mice deficient in the low-voltage-activated CaV 3.1 T-type Ca(2+) channel.

AIM: Using mice deficient in the CaV 3.1 T-type Ca(2+) channel, the aim of the present study was to elucidate the molecular identity of non-L-type channels involved in vascular tone regulation in mesenteric arteries and arterioles. METHODS: We used immunofluorescence microscopy to localize CaV 3.1 channels, patch clamp electrophysiology to test the effects of a putative T-type channel blocker NNC 55-0396 on whole-cell Ca(2+) currents, pressure myography and Ca(2+) imaging to test diameter and Ca(2+) responses of the applied vasoconstrictors, and Q-PCR to check mRNA expression levels of several Ca(2+) handling proteins in wild-type and CaV 3.1(-/-) mice. RESULTS: Our data indicated that CaV 3.1 channels are important for the maintenance of myogenic tone at low pressures (40-80 mm Hg), whereas they are not involved in high-voltage-activated Ca(2+) currents, Ca(2+) entry or vasoconstriction to high KCl in mesenteric arteries and arterioles. Furthermore, we show that NNC 55-0396 is not a specific T-type channel inhibitor, as it potently blocks L-type and non-L-type high-voltage-activated Ca(2+) currents in mouse mesenteric vascular smooth muscle cell. CONCLUSION: Our data using mice deficient in the CaV 3.1 T-type channel represent new evidence for the involvement of non-L-type channels in arteriolar tone regulation. We showed that CaV 3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions in vivo. Moreover, CaV 3.1 channels are not involved in Ca(2+) entry and vasoconstriction to large depolarization with, for example, high KCl. Finally, we caution against using NNC 55-0396 as a specific T-type channel blocker in native cells expressing high-voltage-activated Ca(2+) channels.

Risk factors for infantile atopic dermatitis and recurrent wheezing.

BACKGROUND: The pathogenic mechanisms of atopic dermatitis (AD) and recurrent wheezing (RW) during infancy are not fully understood. OBJECTIVE: We evaluated immunological markers associated with AD and RW during infancy. METHODS: We followed a cohort (n = 314) from birth to 14 months of age. Some of the participants underwent a physical examination and blood test at 6 and 14 months of age. Univariate and multivariate logistic regression analysis and receiver operating characteristic curve analysis were performed to find which immunological markers could be risk factors for AD and RW. RESULTS: Of 16 immunological markers found in cord blood, only immunoglobulin (Ig) E was associated with AD at 6 months of age (adjusted OR [aOR], 1.607). None of the markers was associated with AD or RW at 14 months of age. Of 23 immunological markers at 6 months of age, total IgE (aOR, 1.018) and sensitization to egg white (aOR, 23.246) were associated with AD at 14 months of age. Phytohemagglutinin (PHA)-induced production of interleukin (IL) 4 from peripheral blood mononuclear cells (PBMCs) (aOR, 1.043) was associated with RW at 14 months of age. CONCLUSION: Cord blood IgE was a risk factor for AD at 6 months of age. Total IgE and sensitization to egg white at 6 months of age were risk factors for AD at 14 months of age. PHA-induced IL-4 production in PBMCs at 6 months of age was a risk factor for RW at 14 months of age.

Genogroup distribution of F-specific coliphages in wastewater and river water in the Kofu basin in Japan.

AIMS: To determine the genogroup distribution of F-specific coliphages in aquatic environments using the plaque isolation procedure combined with genogroup-specific real-time PCR. METHODS AND RESULTS: Thirty water samples were collected from a wastewater treatment plant and a river in the Kofu basin in Japan on fine weather days. F-specific coliphages were detected in all tested samples, 187 (82%) of 227 phage plaques isolated were classified into one of the 4 F-specific RNA (F-RNA) coliphage genogroups and 24 (11%) plaques were F-specific DNA coliphages. Human genogroups II and III F-RNA coliphages were more abundant in raw sewage than animal genogroups I and IV, excluding one sample that was suspected to be heavily contaminated with sporadic heavy animal faeces. The secondary-treated sewage samples were highly contaminated with genogroup I F-RNA coliphages, probably because of different behaviours among the coliphage genogroups during wastewater treatment. The river water samples were expected to be mainly contaminated with human faeces, independent of rainfall effects. CONCLUSIONS: A wide range of F-specific coliphage genogroups were successfully identified in wastewater and river water samples. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results clearly show the usefulness of the genogroup-specific real-time PCR for determining the genogroups of F-specific coliphages present in aquatic environments.

Effect of κ-opioid receptor agonist on the growth of non-small cell lung cancer (NSCLC) cells.

BACKGROUND: It is becoming increasingly recognised that opioids are responsible for tumour growth. However, the effects of opioids on tumour growth have been controversial. METHODS: The effects of κ-opioid receptor (KOR) agonist on the growth of non-small cell lung cancer (NSCLC) cells were assessed by a cell proliferation assay. Western blotting was performed to ascertain the mechanism by which treatment with KOR agonist suppresses tumour growth. RESULTS: Addition of the selective KOR agonist U50,488H to gefitinib-sensitive (HCC827) and gefitinib-resistant (H1975) NSCLC cells produced a concentration-dependent decrease in their growth. These effects were abolished by co-treatment with the selective KOR antagonist nor-BNI. Furthermore, the growth-inhibitory effect of gefitinib in HCC827 cells was further enhanced by co-treatment with U50,488H. With regard to the inhibition of tumour growth, the addition of U50, 488H to H1975 cells produced a concentration-dependent decrease in phosphorylated-glycogen synthase kinase 3ß (p-GSK3ß). CONCLUSION: The present results showed that stimulation of KOR reduces the growth of gefitinib-resistant NSCLC cells through the activation of GSK3ß.

The effect of adaptive iterative dose reduction on image quality in 320-detector row CT coronary angiography.

OBJECTIVE: To evaluate the effect of adaptive iterative dose reduction (AIDR) on image noise and image quality as compared with standard filtered back projection (FBP) in 320-detector row CT coronary angiography (CTCA). METHODS: 50 patients (14 females, mean age 68 ± 9 years) who underwent CTCA (100 kV or 120 kV, 400-580 mA) within a single heartbeat were enrolled. Studies were reconstructed with FBP and subsequently AIDR. Image noise, vessel contrast and contrast-to-noise ratio (CNR) in the coronary arteries were evaluated. Overall image quality for coronary arteries was assessed using a five-point scale (1, non-diagnostic; 5, excellent). RESULTS: All the examinations were performed in a single heartbeat. Image noise in the aorta was significantly lower in data sets reconstructed with AIDR than in those reconstructed with FBP (21.4 ± 3.1 HU vs 36.9 ± 4.5 HU; p<0.001). No significant differences were observed between FBP and AIDR for the mean vessel contrast (HU) in the proximal coronary arteries. Consequently, CNRs in the proximal coronary arteries were higher in the AIDR group than in the FBP group (p<0.001). The mean image quality score was improved by AIDR (3.75 ± 0.38 vs 4.24 ± 0.38; p<0.001). CONCLUSION: The use of AIDR reduces image noise and improves image quality in 320-detector row CTCA.

Effects of denervation at ileocecal junction and ileocecal resection in dogs.

BACKGROUND: To investigate neural regulation at the ileocecal junction (ICJ) and motility changes after ileocecal resection (ICR). Previous studies showed normal basal motility at the ICJ directly by force transducers in dogs, but these observations were limited to normal contractile activity. METHODS: Continuous strain gauge recordings of stomach, terminal ileum, ileocecal sphincter (ICS), and colon were performed in dogs. The dogs were divided into four groups, namely control (CONT), extrinsic denervation at ICJ (ED), intrinsic denervation at ICJ (ID), and ICR groups. Colonic activity was recorded 2 h before a meal, in the early postprandial period (first 2 h), and in the late postprandial period (4-6 h after a meal). The meal lasted 5 min. KEY RESULTS: Motility index was significantly increased at the ICS (P = 0.0056) and proximal colon (P = 0.0059) after feeding. However, such changes were not observed in the ED and ID groups. The amplitude of contractions at proximal colon in the interdigestive state was significantly decreased by ED. In the ID and ICR groups, the numbers of nonmigrating contractions were significantly decreased (P < 0.05), and colonic migrating motor complex (CMMC) ratio was significantly higher than that of the CONT group (P < 0.001). The dogs in these two groups had diarrhea. CONCLUSIONS & INFERENCES: Gastrocolonic response at the ICJ may require both intrinsic and extrinsic innervation. When ID was performed, CMMC ratio increased. As a result, intraluminal water absorption may have decreased. ID may be one of the causes of diarrhea after ICR.