Non-invasive biomagnetic assessment of gastrointestinal motility in a loperamide-induced constipation model

Constipation is a disorder of the gastrointestinal (GI) and some of the main etiological mechanisms are directly related to changes in GI physiology. The capacity to carry out paired assessments and measure GI parameters under the influence of constipation is a relevant point in selecting a suitable methodology. We aimed to perform a non-invasive investigation of gastrointestinal motility in constipated rats using the alternating current biosusceptometry system (ACB). The animals were split into two groups: the pre-induction stage (CONTROL) and post-induction loperamide stage (LOP). We assessed GI motility parameters using the ACB system. Colon morphometric and immunohistochemical analyses were performed for biomarkers (C-kit) for interstitial cells of Cajal (ICC). Our results showed a significant increase in gastrointestinal transit in the LOP group in addition to a reduction in the dominant frequency of gastric contraction and an arrhythmic profile. A change in colonic contractility profiles was observed, indicating colonic dysmotility in the LOP group. We found a reduction in the number of biomarkers for intestinal cells of Cajal (ICC) in the LOP group. The ACB system can evaluate transit irregularities and their degrees of severity, while also supporting research into novel, safer, and more efficient treatments for constipation.

Sampling reflex as a new manometric marker in the diagnosis of defecation disorders: systematic review

Introduction: Distension of the rectum wall and subsequent momentary relaxation of the internal anal sphincter (IAS) trigger a reflex called the rectoanal inhibitory reflex (RAIR). This same rectal distension causes a reflex contraction of the external anal sphincter (EAS), responsible for conscious continence called rectoanal excitatory reflex (RAER). This set of reflexes are named sampling reflex. Objectives: The sampling reflex is necessary to initiate defecation or flatulence. The objective of this study is to evaluate the sampling reflex and its practical applicability as a manometric marker of the main defecation disorders. Methodology: This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) items. The development method consisted of searching for articles in the research platforms BVS, PubMed, Cochrane Library, SciELO and ScienceDirect and for the selection of articles the Rayyan Platform was used. The articles resulting from the search strategies were added to the platform and five collaborators were invited for the blind selection. Finally, 6 articles were included in the final review. Results: An intact sampling reflex allows the individual to facilitate discrimination between flatus and stool and to choose whether to discharge or retain rectal contents. On the other hand, an impaired sampling reflex can predispose an individual to incontinence. Therefore, it was observed that patients with defecation disorders had an impaired sampling reflex, since it was found that constipated patients have incomplete opening of the IAS, lower amplitude of RAIR and increase of RAER. Most incontinent patients present a failure in the recruitment of the EAS, a decrease in the RAER and an increase in the RAIR, in duration and amplitude. (AU)

Diferencias en la duración del reflejo rectoanal inhibitorio en pacientes con constipación funcional refractaria y mielomeningocele / Differences in rectoanal inhibitory reflex duration between patients with refractory functional constipation and myelomeningocele

Introducción. Habitualmente, durante la manometría anorrectal, en lo correspondiente al reflejo rectoanal inhibitorio (RRAI) solo se pesquisa su presencia o ausencia. Estudios han reportado que su análisis detallado puede brindar datos de interés. Nuestra hipótesis es que la medición del RRAI puede dar información para reconocer causas orgánicas (médula anclada, lipoma, etc.) en pacientes en los que previamente se consideró como de causa funcional. Objetivos. Comparar la duración del reflejo rectoanal inhibitorio en la manometría anorrectal de pacientes con constipación funcional refractaria (CFR) y mielomeningocele (MMC). Población y métodos. Estudio observacional, transversal, analítico (2004-2019). Pacientes constipados crónicos con incontinencia fecal funcional y orgánica (mielomeningocele). Se les realizó manometría anorrectal con sistema de perfusión de agua y se midió la duración del RRAI con diferentes volúmenes (20, 40 y 60 cc). Grupo 1 (G1): 81 CFR. Grupo 2 (G2): 54 MMC. Se excluyeron pacientes con retraso madurativo, esfínter anal complaciente, agenesia sacra y aquellos no colaboradores. Resultados. Se incluyeron 135 sujetos (62 varones). La mediana de edad fue G1:9,57 años; G2: 9,63 años. Duración promedio G1 vs. G2 con 20 cc: 8,89 vs. 15,21 segundos; con 40 cc: 11.41 vs. 21,12 segundos; con 60 cc: 14,15 vs. 26,02 segundos. La diferencia de duración del RRAI entre ambos grupos con diferentes volúmenes fue estadísticamente significativa (p = 0,0001). Conclusión. La duración del RRAI aumenta a mayor volumen de insuflación del balón en ambas poblaciones. Pacientes con MMC tuvieron mayor duración del RRAI que aquellos con CFR. En los pacientes con RRAI prolongado, debe descartarse lesión medular.

Introduction. Usually, during anorectal manometry, only the presence or absence of rectoanal inhibitory reflex (RAIR) is investigated. Studies have reported that a detailed analysis may provide data of interest. Our hypothesis is that RAIR measurement may provide information to detect organic causes (tethered cord, lipoma, etc.) in patients in whom a functional cause had been previously considered. Objectives. To compare RAIR duration in anorectal manometry between patients with refractory functional constipation (RFC) and myelomeningocele (MMC). Population and methods. Observational, analytical, cross-sectional study (2004­2019). Patients with chronic constipation and functional and organic fecal incontinence (myelomeningocele). The anorectal manometry was performed with a water-perfused system, and the duration of RAIR was measured with different volumes (20, 40, and 60 cc). Group 1 (G1): 81 RFC. Group 2 (G2): 54 MMC. Patients with developmental delay, compliant anal sphincter, sacral agenesis and non-cooperative patients were excluded. Results. A total of 135 individuals were included (62 were male). Their median age was 9.57 years in G1 and 9.63 years in G2. Average duration in G1 versus G2 with 20 cc: 8.89 versus 15.21 seconds; 40 cc: 11.41 versus 21.12 seconds; 60 cc: 14.15 versus 26.02 seconds. The difference in RAIR duration with the varying volumes was statistically significant (p = 0.0001). Conclusion. RAIR duration was longer with increasing balloon inflation volumes in both populations. RAIR duration was longer in patients with MMC than in those with RFC. Spinal injury should be ruled out in patients with prolonged RAIR.

Incidence of intestinal constipation during the COVID-19 pandemic period in medical students from a private institution in São Paulo, SP

Introduction: Chronic intestinal constipation (CIC) presents an incidence of 2.6 to 30.7% in the overall population and due to the social reality imposed by the coronavirus pandemic, some behavior changes in the Brazilian population occurred that might or not be associated with alterations of CIC prevalence. Objective: To assess CIC incidence in medical students before and during the COVID-19 pandemic in Brazil in a private higher educational institution in the city of São Paulo, state of São Paulo. Methods: Clinic data were collected through Google Forms software from the same students seeking to analyze the variables before (year of 2019) and during the coronavirus pandemic. The data were: age, sex, body mass index, constipation referred in a subjective way and confirmed through the ROME III criteria, feces consistency and anxiety and/or depression during the pandemic. Results: A total of 126 medical students from a private higher education institution from São Paulo, SP were included. The average age was 22.9 years old, 70.6% were female and the average BMI was 23.3 kg/m2. Regarding the ROME III criteria, 32.5% presented >2 in 2019 and 42.1% during the pandemic. Concerning the feces consistency, 31.75 and 35.71% presented dry Bristol 1 feces or in both periods, respectively. Conclusion: It was observed an increase in the prevalence of chronic intestinal constipation in medical students from a private higher education institution from São Paulo, state of São Paulo, during the COVID-19 pandemic, as well as dryness in the feces. (AU)

The effect of transvaginal prolapse surgery on anorectal function

Objective: Pelvic floor dysfunction can manifest as a spectrum including anorectal dysfunction, vaginal prolapse, and urinary incontinence. Sacrospinous fixation is a procedure performed by gynecologists to treat vaginal prolapse. The present study aims to evaluate the impact of transvaginal prolapse surgery on anorectal function. Materials and Methods: We conducted a retrospective review of patients undergoing sacrospinous fixation surgery for vaginal prolapse between 2014 to 2020. Those with anorectal dysfunction who had also been evaluated by the colorectal service preoperatively and postoperatively were included for analysis. These patients were assessed with symptom-specific validated questionnaires. The effect of surgery on constipation and fecal incontinence symptoms was analyzed. Results: A total of 22 patients were included for analysis. All patients underwent transvaginal sacrospinous fixation, and 95.4% also had posterior colporrhaphy for vaginal prolapse. There were a statistically significant improvements in the Fecal Incontinence Severity Index (FISI), the St. Mark's Incontinence Score (Vaizey), the embarrassment and lifestyle components of the Fecal Incontinence Quality of Life Score, the Constipation Scoring System, the Obstructed Defecation Score, and components of the Patient Assessment of Constipation Quality of Life score. Conclusion: Transvaginal prolapse surgery leads to a favorable effect on anorectal function, with improvements in both obstructed defecation and fecal incontinence scores in this small series. (AU)

Colonoscopic laxative instillation for the fecal-loaded colon: a case series

Context: Postoperative, critically ill, and elderly patients often have fecal loading or impaction. In a few such patients, disimpaction of fecalomas and colon cleansing are difficult. Bowel obstruction, megacolon, lower gastrointestinal bleeding, and gut perforation are complications that may ensue. Oral laxatives or enemas may only be partially effective. Surgical intervention may be needed for salvage or to treat complications. Series and Design: Fourteen hospitalized cases with defecation disorder due to fecal loading of the colon were enrolled for retrospective analysis. Colonoscopic instillation of mannitol and/or lactulose was undertaken as an intervention when the use of oral laxatives was either ineffective or unfeasible, and enema had yielded poor results. Results: Ten patients had satisfactory outcomes for fecal clearance, whereas four patients with poor or incomplete responses underwent repeat interventions or surgery. No significant complications were encountered due to this therapy. Conclusion: Colonoscopic instillation of mannitol or lactulose in fecal-loaded critically ill patients results in a safe and satisfactory fecal clearance. (AU)

A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China / 中西医结合学报

OBJECTIVE@#Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients.@*METHODS@#A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process.@*RESULTS@#We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for selection of therapeutic drugs.@*CONCLUSION@#This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC. Please cite this article as: Wei DJ, Li HJ, Lyu ZP, Lyu AP, Bian ZX, Zhong LL. A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China. J Integr Med. 2023; 21(6): 550-560.

Clinical observation of acupuncture at Huiyin (CV 1) for chronic severe functional constipation / 中国针灸

OBJECTIVE@#To compare the effect of acupuncture at Huiyin (CV 1) and oral administration of western medication in treatment of chronic severe functional constipation (CSFC).@*METHODS@#A total of 64 patients with CSFC were randomly divided into an acupuncture group (32 cases, 5 cases dropped off) and a western medication group (32 cases, 4 cases dropped off). Both groups were given routine basic treatment. The acupuncture group was treated by directly puncture of 20-30 mm at Huiyin (CV 1), once a day for the first 4 weeks, 5 times a week, once every other day for the next 4 weeks, 3 times a week, totally for 8 weeks. The western medication group was treated with 2 mg prucalopride succinate tablets orally before breakfast every day for 8 weeks. The average number of weekly spontaneous bowel movement (SBM) of the two groups were observed before treatment and 1-8 weeks into treatment. The constipation symptom score before and after treatment, and in follow-up of 1 month after treatment, as well as quality of life [patient assessment of constipation quality of life questionnaire (PAC-QOL) score and the proportion of patients of PAC-QOL score difference before and after treatment≥1] before and after treatment were compared in the two groups. The clinical effects of the two groups were evaluated after treatment and in follow-up.@*RESULTS@#Compared before treatment, the average number of weekly SBM in the two groups was increased 1-8 weeks into treatment (P<0.05). The average number of weekly SBM in the acupuncture group was less than that in the western medication group 1 week into treatment (P<0.05), and the average number of weekly SBM in the observation group was more than that in the western medication group 4-8 weeks into treatment (P<0.05). The scores of constipation symptom after treatment and in follow-up and scores of PAC-QOL after-treatment in the two groups were lower than those before treatment (P<0.05), and those in the acupuncture group were lower than the western medication group (P<0.05). The proportion of patients of PAC-QOL score difference before and after treatment≥1 in the acupuncture group was higher than that in the west medication group (P<0.05). The total effective rates after treatment and in follow-up in the acupuncture group were 81.5% (22/27) and 78.3% (18/23), respectively, which were better than 42.9% (12/28) and 43.5% (10/23) in the western medication group (P<0.05).@*CONCLUSION@#Acupuncture at Huiyin (CV 1) can effectively increase the number of spontaneous defecation in patients with CSFC, reduce constipation symptoms, improve the quality of life, and the effect after treatment and in follow-up is better than oral western medication.

A comparative study of raw Aurantii Fructus Immaturus and bran-fried products on dryness of rats with slow-transit constipation / 中国中药杂志

The differences in dryness between raw Aurantii Fructus Immaturus(AFI) and bran-fried products were investigated based on a slow-transit constipation(STC) model. Seventy healthy SPF-grade rats were randomly divided into a blank group(K), a positive drug group(Y), a model group(M), low-and high-dose raw AFI groups(SD and SG), and low-and high-dose bran-fried AFI groups(FD and FG). During the experiment, it was found that compared with the K group, the groups with drug treatment had little effect on the daily body weight of the STC rats. The first defecation time of black stool in the M group was significantly higher than that in the K group, and the 24-hour fecal output significantly decreased starting from the 13th day, indicating successful modeling. The SG group showed a significant increase in the first defecation time, fecal water content, urine output, and water intake than other groups with drug treatment. The FG group had the highest fecal output than other groups with drug treatment. The FD group had the highest salivary secretion than other groups with drug treatment. The levels of cAMP/cGMP, VIP, 5-HT, AQP1, and AQP5 were measured in each group with drug treatment, and the expression of c-Kit and SCF mRNA in gastric antrum tissue and AQP3 mRNA in the kidney and colon were detected by RT-PCR. The results showed that the SD and SG groups had a more significant impact on AQP1, AQP5, and other water channel indexes in STC rats than the FD and FG groups. The FD and FG groups had a more significant impact on c-Kit, SCF, VIP, 5-HT, and other gastrointestinal motility indicators than the SD and SG groups. This study, through in vitro biological observations, immunological detection, and gene expression analysis, found that raw AFI had strong dryness property, while bran-fried AFI could alleviate its dryness property.

Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling / 中国结合医学杂志

OBJECTIVE@#To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).@*METHODS@#According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.@*RESULTS@#EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.@*CONCLUSION@#EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.

Effects of bilateral erector spinae plane block for posterior lumbar spine surgery in elderly patients / 中南大学学报(医学版)

OBJECTIVES@#With the rapid development of aging population, the number of elderly patients undergoing posterior lumbar spine surgery continues to increase. Lumbar spine surgery could cause moderate to severe postoperative pain, and the conventional opioid-based analgesia techniques have many side effects, which are barriers to the recovery after surgery of the elderly. Previous studies have demonstrated that erector spinae plane block (ESPB) could bring about favorable analgesia in spinal surgery. As far as the elderly are concerned, the analgesic and recovery effects of ESPB on posterior lumbar spine surgery are not completely clear. This study aims to observe the effects of bilateral ESPB on elderly patients undergoing posterior lumbar spine surgery, and to improve the anesthesia techniques.@*METHODS@#A total of 70 elderly patients of both sex, who were selected from May 2020 to November 2021, scheduled for elective posterior lumbar spine surgery, and in the age of 60-79 years, with American Society of Anesthesiologists class Ⅱ-Ⅲ, were divided into a ESPB group and a control (C) group using a random number table method, with 35 patients each. Before general anesthesia induction, 20 mL 0.4% ropivacaine was injected to the transverse process of L3 or L4 bilaterally in the ESPB group and only saline in the C group. The score of Numerical Rating Scale (NRS) indicating pain at rest and on movement within 48 h after operation, time of first patient control analgesia (PCA), cumulative consumptions of sufentanil within 48 hours, Leeds Sleep Evaluation Questionnaire (LSEQ) scores on the morning of day 1 and day 2 after operation, Quality of Recovery-15 (QoR-15) scores at 24 and 48 h after operation, full diet intake times, perioperative adverse reactions such as intraoperative hypotension, postoperative dizziness, nausea, vomiting, and constipation were compared between the 2 groups.@*RESULTS@#A total of 70 patients were enrolled and 62 subjects completed the study, including 32 in the ESPB group and 30 in the C group. Compared with the C group, the postoperative NRS scores at rest at 2, 4, 6, and 12 h and on movementat at 2, 4, and 6 h were lower, time of first PCA was later, sufentanil consumptions were significantly decreased during 0-12 h and 12-24 h after operation, LSEQ scores on the morning of day 1 and QoR-15 scores at 24 and 48 h after operation were higher, full diet intakes achieved earlier in the ESPB group (all P<0.05). There were no significant differences in the incidences of intraoperative hypotension, postoperative dizziness, nausea, vomiting, and constipation between the 2 groups (all P>0.05).@*CONCLUSIONS@#Providing favorable analgesic effects with reduced opioids consumption, bilateral ESPB for posterior lumbar spine surgery in the elderly patients could also improve postoperative sleep quality, promote gastrointestinal functional restoration, and enhance recovery with few adverse reactions.

El consumo de dos kiwis diarios podría mejorar el hábito intestinal en personas con estreñimiento crónico / Daily consumption of two kiwifruits could improve bowel habits in people with chronic constipation

A partir del caso de una paciente con síndrome de intestino irritable a predominio de estreñimiento cuyos síntomas mejoraron con el consumo regular de kiwi, el médico de familia se planteó la pregunta de si el kiwi podría mejorar los síntomas asociados a constipación crónica en comparación con el tratamiento habitual. Tras realizar una búsqueda de estudios que analizaran los efectos del consumo de kiwi sobre el hábito intestinal, fueron seleccionados tres artículos que permiten concluir que el consumo de esta fruta tiene una eficacia superior al placebo y comparable al psyllium y las pasas de ciruela para mejorar los síntomas de personas con estreñimiento crónico. (AU)

Based on the case of a patient with constipation-predominant irritable bowel syndrome whose symptoms improved with regular consumption of kiwi, the family doctor wondered if kiwi could improve symptoms associated with chronic constipation compared to usual treatment. After conducting a search for studies that analyzed the effects of kiwi consumption on intestinal habit, three articles were selected that allow us to conclude that the consumption of this fruit has an efficacy superior to placebo and comparable to psyllium and plum raisins to improve the symptoms of people with chronic constipation. (AU)

Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma / 中国中药杂志

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.

Effect of electroacupuncture on enteric neuronal autophagy in functional constipation mice / 中国针灸

OBJECTIVES@#To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy.@*METHODS@#A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry.@*RESULTS@#Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group.@*CONCLUSIONS@#Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.

Genetic testing and prenatal diagnosis for a Chinese pedigree affected with Waardenburg syndrome type 4C due to heterozygous deletion of SOX10 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree featuring congenital profound syndromic deafness and chronic constipation, and provide prenatal diagnosis for a high-risk fetus.@*METHODS@#Whole-exome sequencing was carried out to analyze the sequences of genes associated with hereditary deafness, and multiplex ligation-dependent probe amplification (MLPA) was used to verify the candidate variant in the proband's parents and the fetus.@*RESULTS@#The proband was found to have harbored a heterozygous deletion of SOX10, a pathogenic gene associated with Waardenburg syndrome type 4C (WS4C). The same deletion was found in her mother (with profound syndromic deafness and chronic constipation) and the fetus, but not in her father with normal hearing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the SOX10 gene deletion was predicted to be a pathogenic variant (PVS1+PM2_Supporting+PP1+PP4).@*CONCLUSION@#The pedigree was diagnosed with WS4C, which has conformed to an autosomal dominant inheritance. Deletion of the entire SOX10 gene, as a loss-of-function variant, probably underlay its pathogenesis. Above finding has facilitated genetic counseling and prenatal diagnosis for this family.

Zhizhu Decoction Alleviates Intestinal Barrier Damage via Regulating SIRT1/FoxO1 Signaling Pathway in Slow Transit Constipation Model Mice / 中国结合医学杂志

OBJECTIVE@#To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC).@*METHODS@#A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot.@*RESULTS@#Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01).@*CONCLUSION@#ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.

Chinese surgical diagnosis and treatment consensus on slow transit constipation (2023 edition) / 中华胃肠外科杂志

In recent years, advancements have been made in both basic and surgical research of slow-transit constipation (STC). However, compelling references for surgeons in the clinical practice of STC have been lacking, particularly on preoperative evaluation and the choice of surgical procedures. In order to further standardize the diagnosis, assessment and surgical management of STC, Chinese Medical Doctor Association Anorectal Doctor Branch and its Functional Diseases Committee selected relevant experts in the field of STC surgery in China to form the Editorial and Review Committee of the Expert Consensus on Diagnosis, Evaluation and Surgical Management of STC in China. By meticulously reviewing relevant literature from both domestic and international sources and integrating the clinical expertise of the panel of experts, the committee has formulated 20 recommendations. These recommendations aim to establish standardized processes for surgical diagnosis and treatment of STC, ultimately elevating the overall diagnostic and therapeutic standards for STC across China.

Chinese expert consensus on colonic and anorectal manometry (2023 edition) / 中华胃肠外科杂志

Colonic and anorectal manometry includes anorectal manometry and colonic manometry. Anorectal manometry is a common method to evaluate anorectal function, which can objectively reflect the pathological and physiological abnormalities of outlet obstructive constipation and fecal incontinence, as well as the impact of anorectal surgery on continence. Colonic manometry is a new type of colon motility detection method developed in recent years. It can record the peristalsis and contraction of the whole colon through a pressure measuring catheter, which helps physicians further evaluate various colonic diseases. However, various factors such as testing equipment, operating standards, and evaluation parameters are difficult to unify. There is no consensus on the operation and interpretation of colorectal anal pressure measurement. Under the guidance of the Anorectal Branch of Chinese Medical Doctor Association, in collaboration with Clinical Guidelines Committee, Anorectal Branch of Chinese Medical Doctor Association, Anorectal motility disorders Committee , Colorectal Surgeons Branch of Chinese Medical Doctor Association, Colonic Branch of China international exchange and promotive association for medical and healthcare, Tianjin Union Medical Center is leading the organization of domestic experts in this field. Based on searching relevant literature and combining clinical experience at home and abroad, after multiple discussions, the "Chinese expert consensus on colonic and anorectal manometry" has been prepared. This consensus discusses the indications, contraindications, pre examination management and technical procedures, treatment of complications, and interpretation of examination reports for colonic and anorectal manometry , aiming to guide the standardized clinical practice of colonic and anorectal manometry.

Association Between Constipation and a Reduction in Lower Limb Muscle Strength in Preoperative Patients with Thoracic Spinal Tumors / 中国医学科学杂志(英文版)

Objective To investigate the clinical symptoms experienced by patients with thoracic spinal tumors and verify the associated symptoms that are predictive of a decline in muscle strength in the lower limbs. Methods A single-center, retrospective cross-sectional study was conducted on in-patients diagnosed with epidural thoracic spinal tumors between January 2011 and May 2021. The study involved a review of electronic medical records and radiographs and the collection of clinical data. The differences in clinical manifestations between patients with constipation and those without constipation were analyzed. Binary logistic regression analyses were performed to identify risk factors associated with a decline in muscle strength in the lower limbs.Results A total of 227 patients were enrolled, including 131 patients with constipation and 96 without constipation. The constipation group had a significantly higher proportion of patients who experienced difficulty walking or paralysis compared to those without constipation prior to surgery (83.2% vs. 17.7%, χ2 = 99.035,P < 0.001). Constipation (OR = 9.522, 95%CI: 4.150-21.849, P < 0.001) and urinary retention (OR = 14.490, 95%CI: 4.543-46.213, P < 0.001) were independent risk factors for muscle strength decline in the lower limbs. Conclusions The study observed that patients with thoracic spinal tumors who experienced constipation symptoms had a higher incidence of lower limb weakness. Moreover, the analysis revealed that constipation and urinary retention were independent risk factors associated with a preoperative decline in muscle strength of lower limbs.