Increased Frequency Of Defecation Research Articles

Response to PD-1 inhibitor in SMARCB1‑deficient undifferentiated rectal carcinoma with low TMB, proficient MMR and BRAF V600E mutation: a case report and literature review

Background Despite major advancements, effective treatment for patients with SMARCB1-deficient cancers has remained elusive. Here, we report the first case of a SMARCB1-deficient undifferentiated carcinoma in the rectum expressing high PD-L1 and responding to a PD-1 inhibitor, as well as with low tumor mutation burden (TMB), proficient mismatch repair (MMR) and BRAF V600E mutation.Case presentation A 35-year-old man visited our hospital complaining of increased defecation frequency, bloody stools and weight loss of 3 kg for one month. Colonoscopy revealed an ulcerated and irregular mass approximately 8–12 cm from the anus. Surgical resection was performed. Histopathological findings revealed that the tumor cells had poor connectivity with each other; each cell had eosinophilic cytoplasm and a polymorphic nucleus. Brisk mitotic activity and necrosis were frequently observed in the tumor cells. Immunohistochemical examination showed that the tumor cells were negative for SMARCB1. The tumor proportion score (TPS) of PD-L1 (22C3) expression was 95%, and the combined positive score (CPS) was 100; the tumor was mismatch repair (MMR) proficient. Next-generation sequencing showed a low tumor mutation burden (TMB), as well as the BRAF V600E mutation. The final diagnosis was SMARCB1-deficient undifferentiated carcinoma. Chemotherapy was useless in this case. His tumor recurred during chemotherapy, and he then received targeted therapy with tirelizumab, an inhibitor of PD-1. At present, his general condition is good. A recent computed tomography (CT) scan showed that the tumor had disappeared, indicating that the immunotherapy was effective. Astonishingly, his most recent follow-up was in August, and his condition continued to improve with the tumor has disappeared.ConclusionSMARCB1‑deficient undifferentiated carcinoma in the rectum is extremely rare, and it has aggressive histological malignancy and poor progression. The observed response to PD-1 inhibitors suggests a role for prospective use of SMARCB1 alterations as a predictive marker for immune checkpoint blockade.

Effects of Prebiotic Yeast Mannan on Gut Health and Sleep Quality in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study.

Human gut health is closely related to sleep. We aimed to evaluate the efficacy of yeast mannan (YM) in improving bowel habits and sleep quality, along with metabolomics in fecal samples. A total of 40 healthy adults (age range, 22-64 years) with discomfort in defecation were enrolled and randomly allocated to receive either YM (n = 20; 1.1 g/day) or placebo (n = 20) for four weeks. Participants recorded their defecation habits throughout the test periods. Sleep electroencephalogram (EEG) recording using an EEG device and fecal sampling were performed pre- and post-treatment. The YM group significantly increased defecation frequency and stool volumes compared to the placebo group. After 4 weeks of treatment, the non-REM sleep stage 3 (N3) duration in the YM group was significantly higher than that in the placebo group. YM ingestion significantly lengthened total time in bed (TIB) and significantly shortened N3 latency compared to placebo intake during the trial. The metabolomics analysis found a total of 20 metabolite differences between the YM and placebo groups. As a result of stepwise linear regression, changes in fecal propionate and gamma-aminobutyric acid (GABA) levels were identified as the primary factors explaining changes in TIB and N3 latency, respectively. Our findings suggest that the prebiotic YM could be beneficial to gut health and sleep quality.

L-Fucose promotes enteric nervous system regeneration in type 1 diabetic mice by inhibiting SMAD2 signaling pathway in enteric neural precursor cells

BackgroundDiabetes can lead to extensive damage to the enteric nervous system (ENS), causing gastrointestinal motility disorders. However, there is currently a lack of effective treatments for diabetes-induced ENS damage. Enteric neural precursor cells (ENPCs) closely regulate the structural and functional integrity of the ENS. L-Fucose, is a dietary sugar that has been showed to effectively ameliorate central nervous system injuries, but its potential for ameliorating ENS damage and the involvement of ENPCs in this process remains uncertain.MethodsGenetically engineered mice were generated for lineage tracing of ENPCs in vivo. Using diabetic mice in vivo and high glucose-treated primary ENPCs in vitro, the effects of L-Fucose on the injured ENS and ENPCs was evaluated by assessing gastrointestinal motility, ENS structure, and the differentiation of ENPCs. The key signaling pathways in regulating neurogenesis and neural precursor cells properties, transforming growth factor-β (TGF-β) and its downstream signaling pathways were further examined to clarify the potential mechanism of L-Fucose on the injured ENS and ENPCs.ResultsL-Fucose improved gastrointestinal motility in diabetic mice, including increased defecation frequency (p < 0.05), reduced total gastrointestinal transmission time (p < 0.001) and bead expulsion time (p < 0.05), as well as enhanced spontaneous contractility and electric field stimulation-induced contraction response in isolated colonic muscle strips (p < 0.001). The decrease in the number of neurons and glial cells in the ENS of diabetic mice were reversed by L-Fucose treatment. More importantly, L-Fucose treatment significantly promoted the proportion of ENPCs differentiated into neurons and glial cells both in vitro and in vivo, accompanied by inhibiting SMAD2 phosphorylation.ConclusionsL-Fucose could promote neurogenesis and gliogenesis derived from ENPCs by inhibiting the SMAD2 signaling, thus facilitating ENS regeneration and gastrointestinal motility recovery in type 1 diabetic mice.7Zzihak_jncvcnfCNwCPXsVideo

Arecoline alleviated loperamide induced constipation by regulating gut microbes and the expression of colonic genome

This study aimed to investigate the effects of arecoline on constipation by intervening at different times to explore its preventive and therapeutic effects. Symptoms related to constipation, gut microbes, short-chain fatty acid (SCFA) content in the cecum, and gene expression in the colon were measured to examine the effect of arecoline on relieving constipation. The results showed that arecoline intervention alleviated loperamide-induced constipation, as evidenced by significantly shortened intestinal transit time, increased fecal water content, improved small bowel propulsion, and increased defecation frequency. In addition, arecoline significantly reduced the levels of gastrointestinal regulatory peptides such as somatostatin and vasoactive intestinal peptide in the serum, thereby regulating intestinal peristalsis. Histopathological analysis showed that arecoline ameliorated intestinal injury caused by constipation. Gut microbial analysis indicated that arecoline altered the taxonomic composition and levels of its metabolite SCFAs in the gut microbiota. Furthermore, the colonic transcriptome results indicated that genes expression related to intestinal diseases were significantly down-regulated by arecoline intervention. In conclusion, the results of the correlation analysis propose a possible mechanism of arecoline in alleviating constipation by modulating the gut microbes and their metabolites and regulating the gut genome.

Effects of acupuncture on gut microbiota and short-chain fatty acids in patients with functional constipation: a randomized placebo-controlled trial.

Objective: To comprehensively evaluate the effect of acupuncture on gut microbiota, identify specific microbes closely related to the clinical efficacy of acupuncture, and explored the role of short-chain fatty acids (SCFAs). Methods: A randomized placebo-controlled trial was conducted with 80 FC patients and 28 healthy controls (HCs). FC patients randomly received 16 acupuncture (n = 40) or sham acupuncture (n = 40) sessions over 4weeks; HCs received no treatment. The change in the proportion of patients with mean weekly complete spontaneous bowel movements (CSBMs) was considered as the primary outcome measure. Moreover, the composition and the predictive metabolic function of the gut microbiota from feceal samples were analyzed by 16S rRNA gene sequencing, while feceal SCFAs were identified via gas chromatography-mass spectrometry (GC-MS). Results: Compared to sham acupuncture, acupuncture significantly increased the proportion of CSBM responders, and improved spontaneous bowel movements (SBMs), straining, stool consistency, and quality of life. Moreover, Sequencing of 16S rRNA genes revealed that acupuncture improved β-diversity and restored the composition of gut microbiota. Specifically, the abundance of beneficial bacteria such as g_Lactobacillus increased while that of pathogenic bacteria such as g_Pseudomonas decreased after acupuncture, which were significantly correlated with alleviated symptoms. Moreover, ten microbes including g_Coprobacter, g_Lactobacillus, and g_Eubacterium_coprostanoligenes_group might be considered acupuncture-specific microbes, and formed a stable interaction network. Additionally, GC-MS analysis indicated that acupuncture increased the content of butyrate acid in the gut, which was positively correlated with an increase in defecation frequency and a decrease in acupuncture-related pathogens. Finally, acupuncture specific-microbes including g_Coprobacter, g_Lactobacillus, g_Pseudomonas, g_Eubacterium_coprostanoligenes_group, g_Erysipelotrichaceae_UCG.003, g_Prevotellaceae_UCG.001, and g_Rolstonia could accurately predict the clinical efficacy of acupuncture (AUC = 0.918). Conclusion: Acupuncture could effectively improve clinical symptoms in FC patients, and was associated with gut microbiota reshaping and increased butyrate acid levels. Moreover, key microbial genera such as g_Coprobacter and g_Lactobacillus was predictive of acupuncture efficacy in treating FC. Future studies are required to validate the causal relationship between key microbial genera and acupuncture clinical efficacy, and should explore further metabolic pathways for designing personalized treatment strategies. Clinical Trial Registration: http://www.chictr.org.cn, Identifier: ChiCTR2100048831.

Efficacy and safety of naldemedine treatment for opioid-induced constipation in gastrointestinal cancer: a retrospective analysis.

Gastrointestinal cancers are one of the most common cancer cases worldwide. Cancer treatment is multidisciplinary, which includes opioid pain management. Opioid analgesics cause opioid-induced constipation (OIC) with the onset of effect. Naldemedine, a peripheral opioid receptor antagonist, is an OIC-modifying agent, but no focused efficacy and safety analysis has been conducted for its use in gastrointestinal cancers. We retrospectively evaluated patients with gastrointestinal cancer treated with naldemedine at ten institutions in Japan from June 2017 to August 2019. Patients with gastrointestinal cancer who initiated treatment with opioids during hospitalization and were treated with naldemedine for the first time were included in the study. The gastrointestinal cancer types included were esophageal, gastric, small bowel, and colorectal cancers. We assessed the defecation frequency before and after the initiation of naldemedine use. Responders were defined as patients who defecated three or more times/week, with an increase from the baseline of one or more bowel movements/week over seven days after starting naldemedine. Thirty-three patients were observed for one week before and after starting naldemedine. Twentyone patients had an increase in defecation frequency of at least three times per week or at least once per week above the baseline. The response rate was 63.6% (95% CI: 46.6-77.9%). The median number of bowel movements for a week before and after the initiation of naldemedine treatment was 3 (range, 0-13) and 7 (range, 1-39), respectively, in the overall population (n=33), with a significant increase in defecation frequency following naldemedine administration (Wilcoxon signed rank test, P<0.005). Diarrhea was the predominant gastrointestinal symptom, with 13 (39.4%) patients experiencing grade 1 and none experiencing grade 3 or grade 4 adverse events. The frequency of other grade 1 adverse events was low abdominal pain in two patients, nausea in two patients, and anorexia in one patient, without any grade 2-4 adverse events. The results of the study suggest that naldemedine is effective and safe in clinical practice for gastrointestinal cancer treatment.

Eluxadoline-Loaded Eudragit Nanoparticles for Irritable Bowel Syndrome with Diarrhea: Formulation, Optimization Using Box-Behnken Design, and Anti-Diarrheal Activity.

Eluxadoline (ELD), a recently approved drug, exhibits potential therapeutic effects in the management and treatment of IBS-D. However, its applications have been limited due to poor aqueous solubility, leading to a low dissolution rate and oral bioavailability. The current study's goals are to prepare ELD-loaded eudragit (EG) nanoparticles (ENPs) and to investigate the anti-diarrheal activity on rats. The prepared ELD-loaded EG-NPs (ENP1-ENP14) were optimized with the help of Box-Behnken Design Expert software. The developed formulation (ENP2) was optimized based on the particle size (286 ± 3.67 nm), PDI (0.263 ± 0.01), and zeta potential (31.8 ± 3.18 mV). The optimized formulation (ENP2) exhibited a sustained release behavior with maximum drug release and followed the Higuchi model. The chronic restraint stress (CRS) was successfully used to develop the IBS-D rat model, which led to increased defecation frequency. The in vivo studies revealed a significant reduction in defecation frequency and disease activity index by ENP2 compared with pure ELD. Thus, the results demonstrated that the developed eudragit-based polymeric nanoparticles can act as a potential approach for the effective delivery of eluxadoline through oral administration for irritable bowel syndrome diarrhea treatment.

Surgical Options for Appropriate Length of J-Pouch Construction for Better Outcomes and Long-term Quality of Life in Patients with Ulcerative Colitis after Ileal Pouch-Anal Anastomosis.

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as a radical surgery for refractory ulcerative colitis (UC). Definite results on the appropriate pouch length for an evaluation of the risk-to-benefit ratio regarding technical complications and long-term quality of life (QOL) are still scarce. Data on UC patients who underwent IPAA from 2008 to 2022 in four well-established pouch centers affiliated to China UC Pouch Center Union were collected. A total of 208 patients with a median follow-up time of 6.0 years (interquartile range, 2.3 to 9.0 years) were enrolled. The median lengths of the patients' short and long pouches were 14.0 cm (interquartile range, 14.0 to 15.0 cm) and 22.0 cm (interquartile range, 20.0 to 24.0 cm), respectively. Patients with a short J pouch configuration were less likely to achieve significantly improved long-term QOL (p=0.015) and were prone to develop late postoperative complications (p=0.042), such as increased defecation frequency (p=0.003) and pouchitis (p=0.035). A short ileal pouch was an independent risk factor for the development of late postoperative complications (odds ratio, 3.100; 95% confidence interval, 1.519 to 6.329; p=0.002) and impaired longterm QOL improvement (odds ratio, 2.221; 95% confidence interval, 1.218 to 4.050, p=0.009). The length of the J pouch was associated with the improvement in long-term QOL and the development of late post-IPAA complications. A long J pouch configuration could be a considerable surgical option for pouch construction.

Effects of Bifidobacterium animalis subspecies lactis supplementation on gastrointestinal symptoms: systematic review with meta-analysis.

The effects of probiotics on gastrointestinal (GI) symptoms have been increasingly investigated, particularly that of Bifidobacterium animalis. Clinical trials so far have shown differing evidence regarding these effects in healthy adults. To synthesize the published evidence on the effects of B. animalis subspecies lactis on GI symptoms (GIS) in healthy adults. A search of the Medline, Embase, Lilacs, Scopus, Web of Science, ProQuest, and Google Scholar databases was conducted for reports on randomized controlled trials published up to October 2021. Population characteristics and data on colonic transit time (CTT), stool consistency, defecation frequency, abdominal pain, bloating, flatulence, volunteer compliance, and adverse events were extracted. A random-effects model was used to estimate the effect of probiotic treatment on these variables. In total, 1551 studies were identified, of which 14 were included in the qualitative synthesis and 13 in the meta-analysis. Overall, probiotic supplementation increased defecation frequency (standardized mean difference [SMD], 0.26; 95%CI, 0.13-0.39). Subgroup analysis revealed a decrease in CTT (SMD, -0.34; 95%CI, -0.62 to -0.07) in short-term treatment (≤14 d) and an improvement in stool consistency (SMD, 0.76; 95%CI, 0.44-1.08) in individuals without GIS. No improvement in abdominal pain and bloating was found. B. animalis subspecies lactis supplementation may increase defecation frequency and, in short-term treatment, may reduce CTT in healthy adults and improve stool consistency in individuals without GIS. More high-quality randomized controlled trials are needed to develop a clinical protocol for the use of this strain to improve these symptoms. PROSPERO registration no. CRD42020154060.

A randomized controlled trial of abdominal massage and prone positioning as a proactive nursing strategy for feeding intolerance among preterm with non-invasive ventilation

Background: Feeding intolerance among preterm infants is a significant contributing factor to their prolonged hospitalization in the neonatal intensive care unit. This condition is further exacerbated by the use of noninvasive ventilation. The aim of this study is to examines the effectiveness of utilizing abdominal massage and prone positioning on the incidence of feeding intolerance in preterm infants receiving noninvasive ventilation in the neonatal intensive care unit. The study employed a randomized controlled trial with an equivalent control group pretest and posttest design to investigate the subject matter. The research was conducted in the neonatal intensive care unit affiliated with the Specialized Pediatric Hospital in Benha city, Egypt. The research was carried out on a sample of 75 premature infants, divided into three groups: 25 subjects who received abdominal massage, 25 who were placed in a prone position, and 25 who served as a control group. The study monitored feeding intolerance parameters, including gastric residue, abdominal distension, and vomiting, on both the first (pre) and seventh (post) days. The findings indicate a statistically significant distinction (P≤ 0.001) between the first and seventh day of the trial in both the abdominal massage group and prone positioning group, as compared to the control group, in relation to the feeding intolerance parameter. This was evidenced by an increase in defecation frequency, a reduction in gastric residue, a decrease in vomits and regurgitations, a relief in abdominal distention, an absence of bradycardia, and a decrease in abdominal circumference. Furthermore, a significant positive correlation was observed between the application of abdominal massage and the utilization of prone positioning in relation to the parameter of feeding intolerance. In conclusion, the study found that the implementation of abdominal massage and prone positioning had a significant impact on the incidence of feeding intolerance in preterm infants receiving noninvasive ventilation. As a result, the author recommends that nursing professionals consider these interventions as proactive measures for addressing feeding intolerance in this preterm.

Kiwifruit (Actinidia spp.) Dietary Consumption for Constipation: A Systematic Review and Meta-Analysis

The aim of this systematic review is to understand if kiwifruit dietary consumption can effectively improve constipation and intestinal function. PubMed, EMBASE, and Cochrane Library were systematically searched for relevant studies from inception up to September 2021. After database search, nine clinical studies were considered eligible for inclusion. Most trials were characterised by a limited number of study participants (median: 20, min: 11, max: 79) and had a cross-over design. On average, study participants ate from two to four kiwifruits a day for a period varying from three days to four weeks. Included trials almost exclusively involved young or middle-aged adults with a high female-to-male ratio, whereas direct evidence for elderly people (&gt;65 years old) is scant. Moderate quality evidence indicated that kiwifruit dietary consumption can improve complete bowel movements per week and decrease stool consistency in both healthy subjects and patients with constipation due to irritable bowel syndrome, probably owing to the fruit fibre and water content. Kiwifruit dietary consumption can also have beneficial effects beyond intestinal motility, such as a mild anti-inflammatory and antioxidant effect on the gut barrier, due to a combined activity of all its nutrients (enzymes, vitamins, minerals). When only patients affected by constipation were considered, kiwifruit consumption was likely associated with a short-term significant increase in defecation frequency but not always with significant changes in stool consistency. These results were also supported by studies characterised by the highest methodological quality and confirmed by the meta-analysis about the effects of kiwifruit-based interventions on defecation frequency (g = 0.576; 95% CI: (0.174; 0.978); p = 0.012). Further investigations on the topic are recommended to strengthen the consistency of current evidence with larger trials.

Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle.

The etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is complicated and closely related to neurotransmission in the gastrointestinal (GI) tract. Developing new strategies for treating this disease is a major challenge for IBS-D research. Berberine hydrochloride (BBH), the derivative of berberine, is a herbal constituent used to treat IBS. Previous studies have shown that BBH has potential anti-inflammatory, antibacterial, analgesic, and antidiarrheal effects and a wide range of biological activities, especially in regulating the release of some neurotransmitters. A modified IBS-D rat model induced by chronic restraint stress was used in all experiments to study the effects of BBH on the GI tract. This study measured the abdominal withdrawal reflex (AWR) response to graded colorectal distention (CRD; 20, 40, 60, and 80 mmHg) and observed the fecal areas of stress-induced IBS-D model. Experiments were conducted using organ bath techniques, which were performed in vitro using strips of colonic longitudinal smooth muscle. Inhibitory and excitatory neurotransmitter agents were added to each organ bath to observe contractile responses on the strips and the treatment effect exerted by BBH. The IBS-D rat model was successfully induced by chronic restraint stress, which resulted in an increased defecation frequency and visceral hypersensitivity similar to that of humans. BBH could reduce 4-h fecal areas and AWR response to CRD in IBS-D. The stress-induced IBS-D model showed upregulated colonic mRNA expression levels of 5-hydroxytryptamine-3A receptor and downregulated expression levels of neuronal nitric oxide synthase. Meanwhile, BBH could reverse this outcome. The responses of substances that regulate the contraction induced by related neurotransmission in the longitudinal smooth muscle of IBS-D colon (including the agonist of acetylcholine, carbachol; NOS inhibitor, L-NAME; and P2Y1 receptor antagonist, MRS2500) can be inhibited by BBH. In summary, BBH promotes defecation frequency and visceral hypersensitivity in IBS-D and exerts inhibitory effects on contractile responses in colonic longitudinal smooth muscle. Thus, BBH may represent a new therapeutic approach for treating IBS-D.

A survey on the prevalence of diarrhea in a Portuguese population of police working dogs

BackgroundDiarrhea is considered the most common clinical sign of chronic gastrointestinal disease in dogs and affects a considerable portion of working and sporting dogs. We aimed to determine the prevalence of diarrhea in police working dogs and evaluate the relationship between feeding, activity level, and animal characteristics with clinical signs. In an observational, prospective study, information on 188 dogs was collected. For each patient, age, sex, breed, specific mission, number of animals at the same housing location, and activity level was recorded. A body condition (BCS) and canine inflammatory bowel disease activity index (CIBDAI) scores were determined, and feces classified according to the Bristol Stool Form Scale. The Kruskal-Wallis test was used to compare recorded data between breeds, mission, age, and sex. Multiple regression was run to predict BCS score, increased defecation frequency, diarrhea, CIBDAI scores, Bristol stool scores, diarrhea from activity level, number of animals at the same housing location, breed, and mission. A p < 0.05 was set.ResultsAnimals in the sample (male n = 96, female n = 92) had a mean age of 5.2 ± 3.2 years and a bodyweight of 24.1 ± 7.2 kg. Four main dog breeds were represented, 80 Belgian Malinois Shepherd Dogs, 52 German Shepherd Dogs, 25 Labrador Retrievers, and 19 Dutch Shepherd Dog. A prevalence of diarrhea of 10.6% was determined, with 4% of dogs having liquid diarrhea. Dogs classified as “extremely active” were more likely to have a low BCS, and the level of activity contributed to diarrhea and BCS prediction.ConclusionPolice working dogs frequently experience diarrhea episodes, which lead to clinical disease and performance loss. Investigation of aetiologies is required.

Lifestyle and Chronic Constipation in Medical Students.

Aim Constipation is one of the most common complaints of the digestive system indicated with an increase in defecation frequency, difficulty in defecation, and hard and strained defecation. Environmental, personal, and genetic factors may be affecting constipation although the affecting factors have not yet been thoroughly explained. The aim of this study was to investigate constipation frequency and lifestyles in medical students. Method The population was selected among medical students for the study, which was planned as a survey study. Demographic data of all the participants and the factors suggested to affect constipation were questioned and analyzed. Results The study covered a total of 425 medical students. Among the students reporting constipation, 2.86% were in their first year of medical school, while 7.53% were in the third year and 9.09% were in the sixth year. The rate of students reporting constipation and familial history was statistically significant. While regular eating habits were reported in the first and third years, this rate was much lower in the sixth year group working at clinical departments. The results of our study did not reveal any significant relationship between daily intake of water and constipation. There was, however, a significant relationship between stress and constipation. Conclusion The results of our study showed that medical education did not curb constipation frequency. We believe that stress is significant in constipation. The data we collected indicate that regular eating habits and excess liquid intake are not as effective as suggested in the treatment of constipation.

Fermented milk containing Lactobacillus casei Zhang and Bifidobacterium animalis ssp. lactis V9 alleviated constipation symptoms through regulation of intestinal microbiota, inflammation, and metabolic pathways

Studies suggest that probiotics and fermented milk can improve defecation in constipated patients. However, the mechanism of fermented milk containing probiotics on constipation remains poorly understood. Volunteers with chronic constipation symptoms were recruited and given 200 g/d of fermented milk containing Lactobacillus casei Zhang and Bifidobacterium animalis ssp. lactis V9 (PFM) for 4 wk. Clinical symptoms, cytokines, metagenomics, and metabolomics were evaluated in constipated participants before and after PFM intervention. After PFM intervention, we observed significant improvement of constipation symptoms. In the serum samples, the anti-inflammatory cytokine IL-10 increased and the proinflammatory cytokine C-reactive protein and lipopolysaccharides decreased. Metagenomics results showed that the increase of B. animalis was correlated with an increase in defecation frequency. Fatty acid biosynthesis and bile acid biosynthesis in stool samples as well as carnitine shuttle, vitamin E metabolism, and ascorbate and aldarate metabolism were identified as significantly altered metabolic pathways. Acylcarnitine, located on the carnitine shuttle pathway, had a significantly positive correlation with defecation frequency. It was speculated that PFM may contribute to alleviating constipation symptoms through 3 potential mechanisms: fine-tuning gastrointestinal microbiota, fighting inflammation, and regulating metabolic pathways.

The role of physical therapy in the treatment of children with chronic functional constipation

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Clinical efficacy of laparoscopic stomach intestinal pylorus sparing surgery in the treatment of severe obesity

Objective To investigate the clinical efficacy of laparoscopic stomach intestinal pylorus sparing surgery (SIPS) in the treatment of severe obesity. Methods The retrospective and descriptive study was conducted. The clinical data of 5 patients with severe obesity who were admitted to the China-Japan Union Hospital Affiliated to Jilin University from October to November 2018 were collected. There was 1 male and 4 females, aged from 18 to 55 years, with an average age of 33 years. All the 5 patients underwent laparoscopic SIPS. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was performed by outpatient examination, telephone interview and Wechat up to February 2019, including general condition, changes in body weight, body mass index, waistline, blood pressure, percentage of excess weight loss, fasting plasma glucose, glycosylated hemoglobin, blood lipid, and uric acid at 3 months after surgery. Measurement data with normal distribution were represented as Mean±SD, and they were tested with Hotelling T2 test. Measurement data with skewed distribution were represented as M (range). Results (1) Surgical situations: 5 patients underwent successfully laparoscopic SIPS under clear surgical field, without obvious bleeding, conversion to open surgery or perioperative death. The operation time was 240 minutes (range, 165-345 minutes). (2) Postoperative situations: the time to initial out-of-bed activity, time to first and flatus, and time to initial drinking and liquid intake were 2 days (range, 2-3 days), 3 days (range, 2-3 days), and 3 days (range, 3-4 days), respectively. On the third day after surgery, all the 5 patients were confirmed anastomotic patency, without gastric leakage, stenosis, or obstruction by upper gastrointestinal contrast. The abdominal drainage-tube was removed on the fourth day after feeding without obvious discomfort and foreign substances extraction from the drainage-tube. The duration of postoperative hospital stay was 6 days (range, 6-7 days). (3) Follow-up: 5 patients with severe obesity were successfully followed up for 3 months. During the follow-up, one patient had significantly increased frequency of defecation, roughly 5-8 times a day, especially after eating greasy food. According to the dietary guidance of the case manager, diarrhea was improved significantly after reducing the intake of oily food. Of the 5 patients with severe obesity, color doppler ultrasonography examination revealed that cholestasis was found in 2 patients at 3 months after operation, which may be related to significant weight loss, ratio imbalance of bile acid to and cholesterol, intestinal microbiota, injury of vagus nerve, significant increasing in mucin of gallbladder, and without oral ursodeoxycholic acid as prescribed by the doctor. The body weight, body mass index, waistline, systolic blood pressure, and diastolic blood pressure of 5 patients with severe obesity were (100±15)kg, (36±4)kg/m2, (111±10)cm, (130±12)mmHg (1 mmHg=0.133 kPa), and (78±14)mmHg at 3 months after operation, respectively, showing significant differences compared with these of preoperation (F=61.631, 75.558, 87.045, 9.501, 16.248, P<0.05). The percentage of excess weight loss was 44%±9%. Among the 5 patients with severe obesity, the fasting plasma glucose of 2 patients with type 2 diabetes mellitus decreased from 9.55 mmol/L and 13.49 mmol/L to 5.18 mmol/L and 5.62 mmol/L after operation, respectively. Level of glycated hemoglobin decreased from 10.0% and 9.9% to 5.2% and 6.2% after operation, respectively. In the 2 patients with hyperlipidemia, one patient with hypertriglyceride had level of triglyceride, total cholesterol, and low density lipoprotein increased from preoperative 2.24 mmol/L, 4.84 mmol/L and 2.92 mmol/L to 2.47 mmol/L, 6.68 mmol/L and 5.51 mmol/L after operation, another patient with hypercholesterol had cholesterol level decreased from preoperative 5.97 mmol/L to postoperative 5.75 mmol/L after operation. In the 3 patients with hyperuricemia, two patients had the uric acid decreased from 404 μmol/L and 484 μmol/L to 319 μmol/L and 417 μmol/L after operation, respectively, one had the uric acid increased from 531 μmol/L to 674 μmol/L after operation. Conclusions Laparoscopic SIPS has a significant short-term effect on patients with severe obesity, but its long-term safety and efficacy need to be further followed up. Key words: Obesity; Type 2 diabetes mellitus; Stomach intestinal pylorus sparing surgery; Biliopancreatic diversion surgery; Laparoscopy

Differential Effects of Lactobacillus casei Strain Shirota on Patients With Constipation Regarding Stool Consistency in China.

Background/AimsProbiotics are expected to confer benefits on patients with constipation, but how probiotics act on constipated patients with variable stool consistencies remains unclear. We investigated the effect of Lactobacillus casei strain Shirota (LcS) on constipation-related symptoms, especially stool consistency, of constipated patients.MethodsConstipated patients meeting the Rome III criteria were divided into 3 groups according to the Bristol Stool Form Scale (BSFS): hard (hard stool [HS], BSFS < 3), normal (normal stool [NS], ≤ 3 BSFS ≤ 4), and soft (soft stool [SS], 4 < BSFS ≤ 5) stools. Subjects in each group consumed a probiotic beverage containing 1010 colony-forming units of LcS daily for 28 days.ResultsLcS intervention significantly alleviated constipation-related symptoms and increased defecation frequency in all subjects. Four weeks of LcS supplementation softened the hard stools in HS, hardened the soft stools in SS, and did not alter the ideal stool consistency in NS. The short-chain fatty acid (SCFA) concentrations were highest in SS, followed by NS and HS. LcS intervention increased the stool SCFA levels in HS but reduced or did not alter the levels in NS and SS. LcS intervention increased the Pseudobutyrivibrio and Roseburia abundances in HS and decreased the Pseudobutyrivibrio abundance in SS.ConclusionsLcS supplementation improved the constipation-related symptoms in constipated subjects. Differences in baseline stool consistency could result in different anti-constipation effects of LcS intervention. LcS balanced the stool consistency—softened the HS and hardened the SS. These effects could be associated with modulation of the gut microbiota and SCFA production.

TLX knockdown in the dorsal dentate gyrus of juvenile rats differentially affects adolescent and adult behaviour

The orphan nuclear receptor TLX is predominantly expressed in the central nervous system and is an important factor regulating the maintenance and self-renewal of neural stem cells from embryonic development through adulthood. In adolescence and adulthood, TLX expression is restricted to the neurogenic niches of the brain: the dentate gyrus of the hippocampus and the subventricular zone. The adolescent period is critical for maturation of the hippocampus with heightened levels of neurogenesis observed in rodents. Therefore, we investigated whether lentiviral silencing of TLX expression (TLX knockdown) in the dorsal dentate gyrus of juvenile rats incurred differential impairments in behaviour during late adolescence and adulthood. Our results showed that knockdown of TLX in the dorsal dentate gyrus led to a decrease in cell proliferation in the dorsal but not ventral dentate gyrus.At a behavioural level we observed differential effects in adolescence and adulthood across a number of parameters. A hyperactive phenotype was present in adolescent but not adult TLX knockdown rats, and an increase in immobility during adolescence and in swimming frequency during adulthood was observed in the forced swim test. There was an increased defecation frequency in the open field during adulthood but not adolescence.There were no changes in cognitive performance on hippocampus-dependent tasks or in anxiety-related behaviours. In conclusion, silencing of TLX in the dorsal dentate gyrus led to impairments in hippocampal-independent behaviours which either did not persist or were reversed during adulthood. The current data highlight the temporal importance and function of the nuclear receptor TLX during development.

Treatment of anastomotic tubular stricture after anterior resection of rectal cancer

To investigate the treatment of colorectal anastomotic tubular stricture after anterior resection of rectal cancer. A retrospective study on 23 cases of anastomotic tubular stricture after anterior resection of rectal cancer from 2008 to 2017 at the Division of Colorectal Surgery, Department of General Surgery of Peking Union Medical College Hospital was performed. The general conditions of the patients, surgical procedures of rectal cancer, perioperative treatment, specific conditions of anastomotic stricture, treatment methods and outcomes were summarized and analyzed. Anastomotic tubular stricture was defined as follows: (1) The length of scar stenosis was >1 cm with thickening anastomotic intestinal wall and a 12 mm diameter colonoscopy could not pass through the anastomosis; (2) Patients were often accompanied by left abdominal pain when exhaust and defecation, increased frequency of defecation, fecal thinning and difficulty in defecation; (3) Anastomotic stricture was indicated by anal examination, colonoscopy, transanal proctography, and rectal MRI. Among 2035 patients undergoing anterior resection of rectal cancer from 2008 to 2017, 23 patients (1.1%) had anastomotic tubular stricture after operation, including 20 males and 3 females with age of 36 to 78 (58.3±10.2) years old. The anastomotic distance from the anal verge was less than 6 cm in 7 cases, 6 to 10 cm in 12 cases, and more than 10 cm in 4 cases. Twelve patients received radiotherapy, among whom 6 patients received neoadjuvant chemoradiation before surgery, and 6 patients received postoperative radiotherapy and chemotherapy. The initial treatment after anastomotic stricture: 9 cases (39.1%) underwent balloon dilation; 1 case(4.3%) underwent stenting; 1 case (4.3%) underwent transanal endoscopic microsurgery (TEM); 7 cases (30.5%) underwent permanent stoma and 5 patients (21.7%) underwent digestive tract reconstruction. Of the 12 patients receiving radiotherapy, 4 cases initially failed to undergo balloon dilatation; 1 case initially received a bare stent to relieve obstruction due to intestinal obstruction, but had re-stricture 1 month after stent removal, then was followed by permanent stoma surgery; 7 cases underwent resection of stenosis and permanent stoma, because the remaining intestine was too short for anastomosis. Of the 11 patients without radiotherapy, 5 patients were treated with balloon dilatation to relieve stenosis; 1 patient was initially treated with TEM, while posterior urethra was injured intraoperatively, and the urinary fistula finally healed with indwelling catheter; 5 patients underwent resection of the anastomotic stenosis, and no stenosis occurred after reconstruction of digestive tract, but 1 patient suffered from intraoperative presacral bleeding. Balloon dilatation is considered an effective treatment of anastomotic tubular stricture following anterior resection of rectal cancer, but with the risk of re-stenosis. Stricture resection and digestive tract reconstruction can be a radical way to improve stricture but with high risk of complications.