Research advances in the role of / 临床肝胆病杂志

Alcoholic liver disease (ALD) is one of the most common chronic liver diseases worldwide and includes the different stages of steatosis, steatohepatitis, fibrosis, and liver cirrhosis. Enterococcus faecalis is a common bacterium for nosocomial infection and has a significant impact on the prognosis of patients with alcoholic hepatitis. This review mainly introduces the pathogenesis of ALD and the pathogenic mechanism of E. faecalis , summarizes the research advances in E. faecalis in ALD, and briefly describes the detection and treatment methods for E. faecalis infection in clinical practice. Since there is an extremely high mortality rate in ALD patients with lytic E. faecalis infection, an in-depth understanding of E. faecalis has become an important issue nowadays.

Research progress of human milk exosomes and their effects on intestinal mucosal barrier in neonates / 中华围产医学杂志

Human breast milk-derived exosomes (HMDEs) are newly discovered active signaling vesicles in breast milk, which are rich in nucleic acids, proteins, and lipids. These exosomes play an essential role in the development and maturation of the intestinal mucosal barrier in newborns. In addition, HMDEs possess distinctive properties that allow for remodeling and modification, thereby are expected to provide more efficient prevention and treatment strategies for neonatal intestinal diseases. This article aims to provide a comprehensive review of the origin, isolation, identification, labeling, structural features, composition, and biological functions, and their unique impact on the intestinal mucosal barrier function in newborns.

The value of serum related cytokines in predicting intestinal mucosal injury in severe acute pancreatitis patients / 中国医师杂志

Objective:To analyze the value of serum related cytokines in predicting intestinal mucosal injury in patients with severe acute pancreatitis (SAP) and its correlation with intestinal mucosal injury.Methods:A total of 92 patients with SAP admitted to the First Hospital of Qinhuangdao from January 2020 to December 2021 were included in the study. According to the presence or absence of intestinal mucosal barrier dysfunction, the patients were divided into intestinal mucosal barrier dysfunction group (33 cases) and non-intestinal mucosal barrier dysfunction group (59 cases). Another 100 healthy subjects were selected as the control group. Clinical data of the subjects were collected. Serum levels of procalcitonin (PCT), D-lactic acid (D-L), endotoxin, diamine oxidase (DAO), citrulline and intestinal fatty acid binding protein (I-FABP) of the three groups were compared, and the correlation between the above indexes was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the value of each indicator in predicting intestinal mucosal barrier dysfunction in SAP patients.Results:The levels of serum PCT, D-L, endotoxin, DAO and I-FABP in intestinal mucosal barrier dysfunction group, non-intestinal mucosal barrier dysfunction group and control group showed a downward trend, while the level of serum citrulline showed an upward trend, with statistically significant difference (all P<0.05). Pearson correlation analysis showed that serum citrulline was negatively correlated with serum PCT, D-L, and endotoxin levels ( r=-0.740, -0.629, -0.310, all P<0.05); There was a positive correlation between serum DAO and serum PCT, D-L and endotoxin levels ( r=0.482, 0.779, 0.338, all P<0.05); There was a positive correlation between serum I-FABP and serum PCT, D-L and endotoxin levels ( r=0.613, 0.421, 0.341, all P<0.05). The ROC curve results showed that the area under the curve (AUC) of serum PCT, D-L, endotoxin, DAO, citrulline, and I-FABP predicting intestinal mucosal injury in SAP patients were 0.816, 0.789, 0.732, 0.801, 0.812, and 0.857, respectively. The AUC of the combination of the above indicators predicting intestinal mucosal barrier dysfunction in SAP patients was 0.909, significantly higher than that predicted by each index alone (all P<0.05). Conclusions:The occurrence of intestinal mucosal barrier dysfunction in SAP patients may be related to the increase of serum PCT, D-L, endotoxin, DAO, I-FABP levels and the decrease of citrulline levels. It may be considered to predict the risk of intestinal mucosal injury by detecting the levels of various indicators in patients′ serum.

Carbomer hemorrhoid gel for the treatment of second-degree internal hemorrhoid bleeding / 中国基层医药

Objective:To investigate the clinical efficacy of carbomer hemorrhoid gel in the treatment of second-degree internal hemorrhoid bleeding.Methods:A total of 160 anorectal outpatients with second-degree internal hemorrhoid bleeding who received treatment in Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine from January 2017 to January 2021 were included in this study. They were randomly divided into an observation group and a control group ( n = 80/group). In the observation group, carbomer hemorrhoid gel was used to plug the anus, while in the control group, a hemorrhoid suppository was used to plug the anus. All patients were treated for 7 days. Clinical efficacy was compared between the two groups. Results:After 4 days of treatment, the bleeding score in the observation group was lower than that in the control group [1(0) point vs. 2(1) points, Z = -6.70, P < 0.05). After 7 days of treatment, the bleeding score in the observation group was significantly lower than that in the control group [0(1) point vs. 1(1) point, Z = -4.73, P < 0.05]. After 4 days of treatment, there was no significant difference in the size score of the hemorrhoids between the two groups ( P > 0.05). After 4 days of treatment, the size score of hemorrhoids in the control group did not differ significantly compared with before treatment ( P > 0.05). After 4 days of treatment, the size score of hemorrhoids in the observation group differed significantly compared with before treatment ( Z = -3.16, P < 0.05). After 7 days of treatment, the size score of the hemorrhoids in the observation group was lower than that in the control group [1(1) point vs. 1(0) point, Z = -4.48, P < 0.05]. The total response rate in the observation group was significantly higher than that in the control group [97.5% (78/80) vs. 75% (60/80), Z = -4.50, P < 0.05]. Conclusion:Carbomer hemorrhoid gel is a new drug used to treat hemorrhoids. It has a new dosage form, has no stimulation to the rectum, and is safe to use. Carbomer hemorrhoid gel is highly effective on second-degree internal hemorrhoid bleeding and deserves clinical popularization.

Study on improvement effects and mechanism of rhein on immunoglobulin A nephropathy / 中国药房

OBJECTIVE To study the improvement effects and mechanism of rhein on immunoglobulin A nephropathy （IgAN） model rat based on signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS Rats were randomly divided into normal control group， IgAN model group and rhein treatment group， with 10 rats in each group. IgAN model group and rhein treatment group were given combination of bovine serum albumin+lipopolysaccharide+carbon tetrachloride to induce IgAN model. Since the 7th week， rhein treatment group rats were intragastrically given relevant medicine， and normal control group and model group rats were given equal amount of normal saline intragastrically， for consecutive 4 weeks. After the last administration， the count of urine sediment erythrocyte， 24 h-urine total protein （UTP）， the levels of immunoglobulin A （IgA） in serum and secretory immunoglobulin A （sIgA） in intestinal mucosa were detected. The pathological changes of Peyer’s patch in renal cortex and intestinal mucosa and IgA deposition in renal cortex were observed. The expressions of interleukin-17 （IL-17）， IL- 6 and transforming growth factor β （TGF-β） in Peyer’s patch of intestinal mucosa in rats were detected. The expressions of STAT3 and related orphan receptor γt （RORγt） mRNA in Peyer’s patch were detected. The expressions of p-STAT3 and RORγt proteins in Peyer’s patch were detected. RESULTS Compared with normal control group， the count of urine sediment erythrocyte， 24 h-UTP， the levels of IgA in serum and sIgA in intestinal mucosa were increased significantly in IgAN model group （P＜0.01）； enlarged renal corpuscles， dilated renal sacs， obvious intratubular mesangial hyperplasia and fibrosis were observed in renal cortex； the volume and germinal center of Peyer’s patch in intestinal mucosa increased； IgA deposition of renal cortex zxyylxk20220103） was obvious； the expressions of IL-17， IL-6 and TGF-β in Peyer’s patch， mRNA expressions of STAT3 and RORγt， protein expressions of p-STAT3 and RORγt were increased significantly （P＜0.01）. Compared with IgAN model group，above indexes were decreased significantly in rhein treatment group （P＜0.01）， pathological damage of renal cortex was improved， the volume of Peyer’s patch and germinal center of intestinal mucosa were reduced， and IgA deposition in renal cortex was weakened. CONCLUSIONS Rhein can improve IgAN model rats， the mechanism of which may be associated with inhibiting STAT3 signaling pathway and regulating immune function of Peyer’s patch in intestinal mucosa.

Probiotics in Crohn's disease remission: a systematic review

Crohn's disease (CD) is an inflammatory condition that can affect the entire gastrointestinal tract due to an exacerbated and inadequate immune system response. Objective. This study aimed to conduct a systematic review, through clinical trials, about the use of probiotics in humans with CD. Materials and methods. Research was carried out in the PubMed, Scopus and Science Direct databases using the keywords "Crohn's disease" and "probiotics". We conducted the review by searching clinical trials published from 2000 to December 2019. Results. Of 2,164 articles found, only nine were considered eligible for this review. The studies investigated patients with CD at different stages of the pathology, and in three studies the potential effect of probiotics in the active phase was observed; in two, in the remission phase; and in four, after intestinal surgery. The sample size of the studies ranged from 11 to 165 individuals and the age of the participants between 5 and 71 years. Gram-positive bacteria were used in six clinical interventions and in two studies yeasts were used. As for the significant results obtained with the treatment with probiotics, in one study there was beneficial clinical effects in patients and, in another, there was an improvement in intestinal permeability. Conclusion. Currently, it is not possible to establish a recommendation for probiotic therapy to control CD due to the few clinical trials with significant results. There is a need for more research on clinical intervention with probiotics in CD to clarify the action, define doses and time of use(AU)

La enfermedad de Crohn (EC) es una afección inflamatoria que puede afectar todo el tracto gastrointestinal debido a una respuesta del sistema inmunitario exacerbada e inadecuada. Objetivo. Realizar una revisión sistemática, a través de ensayos clínicos, sobre el uso de probióticos en humanos con EC. Materiales y métodos. La investigación se realizó en las bases de datos PubMed, Scopus y Science Direct utilizando las palabras clave "enfermedad de Crohn" y "probióticos". La revisión se hizo en ensayos clínicos publicados desde 2000 hasta diciembre 2019. Resultados. De 2164 artículos encontrados, solo nueve fueron considerados elegibles. Los estudios investigaron pacientes con EC en diferentes etapas de la patología, y en tres estudios se observó el efecto potencial de los probióticos en la fase activa; en dos, en remisión; y en cuatro, tras cirugía intestinal. El tamaño de la muestra fue entre 11 y 165 individuos y la edad entre 5 y 71 años. Se utilizaron bacterias grampositivas en seis intervenciones clínicas y en dos estudios se utilizaron levaduras. En cuanto a los resultados significativos obtenidos con el tratamiento con probióticos, en un estudio hubo efectos clínicos beneficiosos en los pacientes y, en otro, hubo una mejora en la permeabilidad intestinal. Conclusión. Actualmente, no es posible establecer una recomendación de terapia con probióticos para el control de la EC debido a los pocos ensayos clínicos con resultados significativos. Existe la necesidad de más investigación sobre la intervención clínica con probióticos en EC para aclarar la acción, definir dosis y tiempo de uso(AU)

Research progress on mechanism of intestinal mucosal mechanical barrier injury associated with severe acute pancreatitis / 中华肝胆外科杂志

Severe acute pancreatitis (SAP) is closely related to intestinal mucosal barrier dysfunction, in which intestinal epithelial mechanical barrier injury is the structural basis of SAP-related intestinal mucosal dysfunction. Among the molecular mechanisms of injury factors, inflammatory mediators and cytokines, produced by SAP waterfall inflammation, are the main factors of intestinal mucosal barrier injury. This article briefly describes the effects of SAP on intestinal mechanical barrier injury and its molecular mechanism in order to provide ideas for the treatment of SAP.

Effects of different doses of dexmedetomidine in patients undergoing heart valve replacement / 中国医师进修杂志

Objective:To investigate the effects of different doses of dexmedetomidine on intestinal mucosal barrier function, cognitive function and brain protection in patients undergoing heart valve replacement.Methods:The clinical data of 135 patients with heart valve replacement from April 2019 to April 2020 in the First Affiliated Hospital of Chengdu Medical College were retrospectively analyzed. Among them, 54 patients received low-dose of dexmedetomidine after induction of anesthesia (low-dose group), 38 patients received high-dose of dexmedetomidine (high-dose group), and 43 patients did not use dexmedetomidine (control group). Before surgery (T 1), 1 h after surgery (T 2), end of surgery (T 3) and 72 h after surgery (T 4), the levels of intestinal mucosal barrier function indexes D-lactate and diamine oxidase (DAO) were detected by spectrophotometry, the levels of brain injury indexes central nervous system specific protein (S100β) and neuron-specific enolase (NSE) were detected by double antibody sandwich enzyme-linked immunosorbent assay; before surgery and 3 d after surgery, the cognitive function was assessed by the mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scale before and 3 days after surgery. Result:There was no statistical difference in T 1, T 2 and T 4 D-lactic acid among 3 groups ( P>0.05); the T 3 D-lactic acid in low-dose group was significantly lower than that in high-dose group and the control group: (7.87 ± 1.59) mg/L vs. (8.99 ± 1.82) and (9.32 ± 1.74) mg/L, the high-dose group was significantly lower than the control group, and there were statistical differences ( P<0.05). There was no statistical difference in T 1 and T 2 DAO among 3 groups ( P>0.05); the T 3 and T 4 DAO in low-dose group was significantly lower than that in high-dose group and control group: (2.77 ± 0.23) kU/L vs. (3.58 ± 0.25) and (4.30 ± 0.26) kU/L, (2.08 ± 0.25) kU/L vs. (2.40 ± 0.20) and (2.71 ± 0.23) kU/L, the high-dose group was significantly lower than the control group, and there were statistical differences ( P<0.05). There were no statistical differences in MMSE score and MoCA score before surgery among 3 groups ( P>0.05); the MMSE score and MoCA score 3 d after surgery in low-dose group were significantly higher than those in high-dose group and control group: (22.76 ± 0.54) scores vs. (21.41 ± 0.47) and (20.21 ± 0.43) scores, (24.90 ± 0.51) scores vs. (24.01 ± 0.48) and (23.12 ± 0.49) scores, the high-dose group was significantly higher than the control group, and there were statistical differences ( P<0.05). There was no statistical difference in T 1, T 2 and T 4 S100β among 3 groups ( P>0.05); the T 3 S100β in low-dose group was significantly lower than that in high-dose group and control group: (4.09 ± 2.01) μg/L vs. (5.48 ± 1.10) and (6.10 ± 1.58) μg/L, and there were statistical differences ( P<0.05). There was no statistical difference in T 1 and T 4 NSE among 3 groups ( P>0.05); the T 2 and T 3 NSE in low-dose group was significantly lower than that in high-dose group and control group: (17.20 ± 4.13) μg/L vs. (20.29 ± 3.77) and (22.35 ± 3.80) μg/L, (19.40 ± 3.92) μg/L vs. (23.46 ± 5.26) and (25.18 ± 5.32) μg/L, and there were statistical differences ( P<0.05). Conclusions:Administration of 0.5 μg/(kg·h) dexmedetomidine during heart valve replacement under cardiopulmonary bypass can reduce intestinal mucosal damage, protect brain against injury in a certain degree, and improve cognitive function.

Polydatin improves intestinal barrier injury after traumatic brain injury in rats by reducing oxidative stress and inflammatory response via activating SIRT1-mediated deacetylation of SOD2 and HMGB1 / 南方医科大学学报

OBJECTIVE@#To investigate the protective effect against intestinal mucosal injury in rats following traumatic brain injury (TBI) and explore the underlying mechanism.@*METHODS@#SD rat models of TBI were established by fluid percussion injury (FPI), and the specimens were collected at 12, 24, 48, and 72 h after TBI. Another 15 rats were randomly divided into shamoperated group (n=5), TBI with saline treatment (TBI+NS) group (n=5), and TBI with PD treatment (TBI+PD) group (treated with 30 mg/kg PD after TBI; n=5). Body weight gain and fecal water content of the rats were recorded, and after the treatments, the histopathology of the jejunum was observed, and the levels of D-lactic acid (D-LAC), diamine oxidase (DAO), ZO-1, claudin-5, and reactive oxygen species (ROS) were detected. Lipid peroxide (LPO) and superoxide dismutase (SOD) 2 content, jejunal pro-inflammatory factors (IL-6, IL-1β, and TNF- α), Sirt1 activity, SOD2 and HMGB1 acetylation level were also determined after the treatments.@*RESULTS@#The rats showed significantly decreased body weight and fecal water content and progressively increased serum levels of D-LAC and DAO after TBI (P < 0.05) with obvious jejunal injury, significantly decreased expression levels of ZO-1 and claudin-5, lowered SOD2 and Sirt1 activity (P < 0.05), increased expression levels of LPO, ROS, and pro-inflammatory cytokines, and enhanced SOD2 and HMGB1 acetylation levels (P < 0.05). Compared with TBI+NS group, the rats in TBI+PD group showed obvious body weight regain, increased fecal water content, reduced jejunal pathologies, decreased D-LAC and DAO levels (P < 0.05), increased ZO-1, claudin-5, SOD2 expression levels and Sirt1 activity, and significantly decreased ROS, LPO, pro-inflammatory cytokines, and acetylation levels of SOD2 and HMGB1 (P < 0.05).@*CONCLUSION@#PD alleviates oxidative stress and inflammatory response by activating Sirt1-mediated deacetylation of SOD2 and HMGB1 to improve intestinal mucosal injury in TBI rats.

Ruifuping pectin protects against intestinal mucosal injury in the rat exertional heat stroke model / 中华危重病急救医学

Objective:To evaluate the intestinal function in rats with exertional heat stroke (EHS) and explore the protective role of Ruifuping pectin (RFP) against heat related intestinal mucosal injury.Methods:One hundred and twenty healthy special pathogen free (SPF) male Sprague-Dawley (SD) rats were randomly divided into normothermic control group, EHS model group, hyperthermic plus drinking water group (H 2O+EHS group) and hyperthermic plus pectin group (RFP+EHS group) with 30 rats in each group. The rats in the H 2O+EHS group and RFP+EHS group were given water 20 mL/kg or RFP 20 mL/kg orally for 5 days during adaptive training period. After 1 week, the temperature control range was adjusted to (37±1)℃ using the temperature control treadmill, and the rat model of EHS was reproduced by one-time high temperature exhaustive exercise. No rehydration intervention was given during the training adaptation period in the EHS model group. The rats in the normothermic control group were maintained to room temperature (25±2)℃ and humidity (55±5)% without other treatment. Behavior tests including withdraw response, righting, and muscle strength were performed immediately after onset of EHS. Blood of inferior vena cava was collected, and the serum inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β, IL-10)] and activity of diamine oxidase (DAO) were detected by enzyme linked immunosorbent assay (ELISA). The intestinal mucosa was collected, after hematoxylin-eosin (HE) staining, and Chiu score was performed to assess EHS induced pathological changes under light microscope. Results:The rats in the EHS model group had behavioral, inflammatory and pathological changes, such as delayed withdraw response and righting, decreased forelimb pulling, increased inflammatory index, and obvious intestinal mucosal injury, which indicated that the reproduction of the EHS model was successful. There was no significant difference in above parameters between the H 2O+EHS group and the EHS model group except that the inflammatory index in the RFP+EHS group was improved. Compared with the EHS model group, the withdraw reflex to pain and righting after RFP pretreatment in the RFP+EHS group were significantly improved (righting score: 1.4±0.2 vs. 0.3±0.2, withdraw reflex to pain score: 1.0±0.1 vs. 0.2±0.1, both P < 0.05), the muscle strength was significantly increased (N: 13.0±0.5 vs. 8.2±0.6, P < 0.01). The levels of pro-inflammatory factors in the RFP+EHS group were significantly lower than those in the EHS model group [TNF-α (ng/L): 67.5±9.2 vs. 194.3±13.7, IL-6 (ng/L): 360.0±54.1 vs. 981.2±84.4, IL-1β (ng/L): 33.7±9.0 vs. 88.7±6.1, all P < 0.01], while the level of anti-inflammatory factor IL-10 was higher than that in the EHS model group (ng/L: 208.7±10.5 vs. 103.7±7.0, P < 0.01). The degree of intestinal mucosal injury in the RFP+EHS group was less severe than that in the EHS model group, and the Chiu score and DAO were significantly lower than those in the EHS model group [Chiu score: 1.5±0.2 vs. 3.8±0.0, DAO (U/L): 83.7±6.7 vs. 128.7±10.5, both P < 0.05]. Conclusions:High temperature training can damage the intestinal barrier function, and induce endotoxemia and systemic inflammatory response syndrome (SIRS) in rats. Oral prophylactic RFP can protect the intestinal barrier function, alleviate SIRS, and promote the recovery of basic nerve reflex and muscle strength after the occurrence of EHS in rats.

Effect of acupoint thread-embedding on tight junction of intestinal mucosa epithelium in rats with ulcerative colitis / 中国针灸

OBJECTIVE@#To observe the effect of acupoint thread-embedding on tight junction of intestinal mucosal epithelial barrier in rats with ulcerative colitis (UC) under the state of "deficiency and stasis", and to explore its mechanism.@*METHODS@#Sixty male SD rats were randomly divided into a control group (@*RESULTS@#Compared with the control group, in the model group the body weight was decreased (@*CONCLUSION@#The thread-embedding could repair the tight junction of intestinal mucosa epithelium and reduce the permeability of intestinal mucosa epithelium, which may be related to the decrease of the expression of CaMKⅡ, MLCK and other protein kinases.

Inflammatory Bowel Disease and Irritable Bowel Syndrome / 胃肠病学

Some studies suggested that patients with irritable bowel syndrome (IBS) are more likely to develop inflammatory bowel disease (IBD) than the general population, which may lead to over-examination in some IBS patients. On the other hand, patients with IBD often have IBS-like symptoms, which may in turn lead to a delay diagnosis of IBD. Therefore, whole digestive tract examination must be carried out to exclude IBD in patients with IBS-like symptoms and having "high risk factors". The incidence of IBS increased in patients with IBD in remission. Such IBS in IBD patients should also be diagnosed and treated in time.

Mechanism of action of intestinal flora in hepatic encephalopathy and related treatment methods / 临床肝胆病杂志

At present, hepatic encephalopathy has a relatively high mortality and thus greatly affects patients’ quality of life. This article describes the changes of intestinal flora in patients with hepatic encephalopathy and analyzes the mechanism of action of intestinal flora in hepatic encephalopathy and related treatment methods. It is pointed out that the development of hepatic encephalopathy is closely associated with intestinal flora, and clinical treatment by regulating intestinal flora has achieved a marked effect in patients with hepatic encephalopathy. In the future, the research on intestinal flora in patients with hepatic encephalopathy can be deepened to provide better regimens for the treatment of hepatic encephalopathy.

Outcomes of implanting porcine small intestinal submucosa mesh in rabbit vesicovaginal space / 中华妇产科杂志

Objective@#To assess surgical outcomes of implanted porcine small intestinal submucosa (SIS) mesh in the rabbit vesicovaginal space (VVS) and explore its application value in pelvic floor reconstruction surgery.@*Methods@#Sixteen male rabbits were randomly divided into four groups, and each group had four rabbits. All groups of rabbits were implanted with SIS mesh in the vesicovaginal space. They were humanely killed after a postoperative period of 7, 30, 90 and 180 days by group. The grafted area was removed with the surrounding bladder and vaginal tissues. The specimens were embedded in paraffin and then stained with HE and Masson's trichrome stains for visual observations, cells counts, and assessment of tissues and collagen fibers.@*Results@#(1) After HE staining, a large number of inflammatory response cells mainly eosinophils and lymphocytes infiltrated around the SIS mesh in 7 days group, and neovascularization was observed, the infiltration area of inflammatory response cells further increased in 30 days group, the infiltration area of inflammatory response cells significantly reduced in 90 days group, while the inflammatory response basically subsided in 180 days group. (2) After Masson's trichromestaining, the collagen structure of SIS mesh in 7 days group was clear and intact. While, the collagen structure of SIS mesh was partially degraded in 30 days group, the SIS meshes of 4 rabbits were completely degraded, but the collagen fragments of SIS remained in 90 days group. In 180 days group, the SIS mesh of all rabbits was degraded, and one of them had the formation of new collagen fibers.@*Conclusions@#SIS mesh implanted into the VVS of rabbits can lead to a transient non infective inflammatory reaction, which could be completely degraded and a small amount of new collagen fibers could be produced after 180 days of implantation. Which shown that SIS mesh should be used cautiously in pelvic floor reconstruction surgery.

Exploration of Prevention and Treatment of COVID-19 by Regulating Mucosal Immune System with Traditional Chinese Medicine / 中国实验方剂学杂志

Patients with low immune function are prone to novel coronavirus infection, which is consistent with the traditional Chinese medicine (TCM) concept of deficiency of vital Qi and invasion of toxin. At present, it is necessary to focus on the development of antiviral drugs, but it is also urgent to study the preparation for regulating the immune system. Mucosal tissue is an important barrier of human immune system. It has an independent immune system with unique functions and structures. It is the body's first line of defense against infection, and is in direct contact with external antigens (such as food, symbiotic bacteria, viruses, etc.). In the resistance to viruses and infections, the mucosal immune system (such as respiratory mucosa, intestinal mucosa, etc.) plays an extremely important role, which can eliminate foreign pathogenic microorganisms or other foreign antigens, so that the virus does not invade the body tissue and cause damage to the body. There are more and more reports on the therapeutic effects of TCM through the mucosal immune system. This paper aims to explore the relationship between mucosal immunity and coronavirus disease-2019 (COVID-19) and the intervention mechanism of TCM, so as to provide useful research methods and therapeutic ideas for the prevention and treatment of COVID-19.

A suplementação com quercetina previne mudanças em células imunorreativas à serotonina e caspase-3 do jejuno de ratos diabéticos / Quercetin supplementation prevents changes in the serotonin and caspase-3 immunoreactive cells of the jejunum of diabetic rats

ABSTRACT BACKGROUND: Serotonin (5-HT) is present in the epithelial enterochromaffin cells (EC), mast cells of the lamina propria and enteric neurons. The 5-HT is involved in regulating motility, secretion, gut sensation, immune system and inflammation. OBJECTIVE: Evaluate the effects of diabetes and quercetin supplementation on serotoninergic cells and its cell loss by apoptosis in jejunal mucosa of streptozotocin-induced diabetic rats (STZ-rats). METHODS: Twenty-four male Wistar rats were divided into four groups: normoglycemic (C), normoglycemic supplemented with 40 mg/day quercetin (Q), diabetic (D) and diabetic supplemented with 40 mg/day quercetin (DQ). After 120 days, the jejunum was collected and fixated in Zamboni's solution for 18 h. After obtaining cryosections, immunohistochemistry was performed to label 5-HT and caspase-3. Quantification of 5-HT and caspase-3 immunoreactive (IR) cells in the lamina propria, villi and crypts were performed. RESULTS: The diabetic condition displayed an increase of the number of 5-HT-IR cells in villi and crypts, while decreased number of these cells was observed in lamina propria in the jejunum of STZ-rats. In the diabetic animals, an increased density of apoptotic cells in epithelial villi and crypts of the jejunum was observed, whereas a decreased number of caspase-3-IR cells was observed in lamina propria. Possibly, quercetin supplementation slightly suppressed the apoptosis phenomena in the epithelial villi and crypts of the STZ-rats, however the opposite effect was observed on the 5-HT-IR cells of the lamina propria. Quercetin supplementation on healthy animals promoted few changes of serotoninergic function and apoptotic stimuli. CONCLUSION: These results suggest that quercetin supplementation mostly improved the serotonergic function affected by diabetes maybe due to antioxidant and anti-inflammatory properties of quercetin.

RESUMO CONTEXTO: A serotonina (5-HT) está presente nas células epiteliais enterocromafins (CE), nos mastócitos da lâmina própria e nos neurônios entéricos. A 5-HT está envolvida na regulação da motilidade, secreção, nocepção intestinal, sistema imunológico e inflamação. Objetivo: Avaliar os efeitos do diabetes e da suplementação de quercetina sobre a função serotoninérgica e a perda celular por apoptose na mucosa jejunal de ratos diabéticos induzidos por estreptozotocina (ratos STZ). MÉTODOS: Vinte e quatro ratos Wistar machos foram divididos em quatro grupos: normoglicêmico (C), normoglicêmico suplementado com quercetina 40 mg/dia (Q), diabético (D) e diabético suplementado com quercetina 40 mg/dia (DQ). Após 120 dias, o jejuno foi coletado e fixado na solução de Zamboni por 18 horas. Após a obtenção de cortes em criostato, a imuno-histoquímica foi realizada para marcar 5-HT e caspase-3. A quantificação de células imunorreativas (IR) à 5-HT e caspase-3 foram realizadas na lâmina própria, vilosidades e criptas. RESULTADOS: A condição diabética ocasionou um aumento do número de células 5-HT-IR nas vilosidades e criptas, enquanto que na lâmina própria houve uma redução dessas células, no jejuno de ratos STZ. Nos animais diabéticos, foi observada uma densidade aumentada de células apoptóticas no epitélio do jejuno, tanto nas vilosidades quanto nas criptas, por outro lado um número reduzido de células caspase-3-IR foi observado na lâmina própria. Possivelmente, a suplementação de quercetina suprimiu ligeiramente os fenômenos de apoptose no epitélio de vilosidades e criptas do jejuno de ratos STZ, no entanto, o efeito oposto foi observado nas células 5-HT-IR da lâmina própria. A suplementação com quercetina em animais saudáveis promoveu poucas alterações na função serotoninérgica e nos estímulos apoptóticos. CONCLUSÃO: Estes resultados sugerem que a suplementação de quercetina melhorou principalmente a função serotoninérgica afetada pelo diabetes, talvez devido às propriedades antioxidantes e anti-inflamatórias da quercetina.

The effect of ileocecal valve removal in a model of short bowel syndrome / Efeito da remoção da válvula ileocecal em modelo de síndrome do intestino curto

ABSTRACT Background : Short bowel syndrome is a harmful condition that needs experimental research. Aim: To assess the impact of the ileocecal valve removal in a model of short bowel syndrome, in order to investigate the evolution of the colon under this circumstance. Method: Fifteen Wistar rats were equitable divided into: Control (Sham), Group I (70% enterectomy preserving ileocecal valve) and Group II (70% enterectomy excluding ileocecal valve). After enterectomy was performed jejunoileal or jejunocecal anastomosis and sacrificed the animals on 30th postoperative day for histomorphometric study of the colon. During this period, was observed the clinical evolution of the animals weekly including body weight measurement. Results: Group I and II presented progressive loss of weight. In Group I was observed diarrhea, perineal hyperemia and purple color of the colon during autopsy. Histomorphometry assay showed hypertrophy and hyperplasia of colon mucosa in Group I. In Group II the colon wall was thicker due to hypertrophy and muscular hyperplasia, and in mucosa vascular proliferation and inflammatory infiltrate were intense. Conclusion : This short bowel syndrome model is relevant and achieve 100% of survival. Animal's weight loss was not altered by the presence or exclusion of the ileocecal valve. Animals with 70% of small bowel removal and presence of the ileocecal valve attained a better clinical evolution and histological colon adaptation than those without ileocecal valve.

RESUMO Racional: Síndrome do intestino curto é condição clínica crítica e que precisa de pesquisa experimental. Objetivo: Avaliar o impacto da remoção da válvula ileocecal em um modelo de síndrome do intestino curto para investigar o comportamento do cólon nesta circunstância. Método: Quinze ratos Wistar foram divididos em três grupos de cinco: Controle (Sham), grupo I (enterectomia de 70% com preservação da válvula ileocecal), e grupo II (70% enterectomia de 70% excluindo a válvula ileocecal). Após a enterectomia foi restabelecido o trânsito com anastomose jejunoileal no grupo I e jejunocecal no grupo II. Os animais foram sacrificados no 30º dia do pós-operatório para histomorfometria do cólon. Durante este período, observou-se a evolução clínica semanal, incluindo a medição do peso corporal. Resultados: Grupos I e II apresentaram perda progressiva de peso. No grupo I houve diarreia, períneo hiperemiado e cor violácea do cólon durante a autópsia. A histomorfometria mostrou hipertrofia e hiperplasia da mucosa do cólon no grupo I. No grupo II a parede do cólon estava mais espessa devido à hipertrofia e hiperplasia das camadas muscular e mucosa onde a proliferação vascular e infiltração inflamatória foi intensa. Conclusão: Este modelo é factível e atingiu 100% de sobrevida. A perda de peso não foi alterada pela presença ou exclusão da válvula ileocecal. Animais com remoção de 70% do intestino delgado e presença da válvula ileocecal apresentaram melhor evolução clínica e adaptação histológica do cólon que os sem válvula ileocecal.

Resolvin D1 mitigates inflammatory response in DSS-induced colitis mice by inhibiting NLRP3 inflammasome activation / 中国药理学通报

Aim: To investigate the effect of resolvin Dl (RvDl) on DSS-induced mice colitis model and the possible mechanism. Methods: C57BL/6 mice were divided into four groups: normal group, control group, dextran sodium sulfate (DSS) model group, and RvDl group. RvDl was dissolved in physiological saline and intraperitoneally injected into experimental mice on 2nd day, 4th day and 6th day. The disease activity index (DAI), histological index (HI), myeloperoxidase (MPO) were detected using Evans blue test, electron microscopy and cytokine level test. The expression differences of NLRP3, ASC, caspase-1, pro-IL-1 β and other related genes were analyzed. Results: The DAI score, HI score, MPO activity level, and pro-inflammatory cytokine in colon tissue homogenate were significantly raised in DSS group compared with those of the normal group (P < 0. 05). The above indexes of RvDl experimental group were significantly reduced(P < 0. 05). At the same time, the expressions of NPRP3 pathway-related proteins, such as NLRP3, ASC, caspase-1 and pro-IL-1 (3, increased in DSS group(F < 0. 05); the expression of the above proteins decreased after RvDl treatment(P < 0. 05). Conclusions: RvDl can mitigate inflammatory response in DSS-induced colitis mice, which may involve the inhibition of RvDl of the NLRP3 inflammasome signaling pathway.

Effects of Taoren Chengqitang on Intestinal Mucosal Barrier and TLR9 Signaling Pathway in Septic Rats / 中国实验方剂学杂志

Objective: To study the protective effect of Taoren Chengqitang on intestinal mucosal barrier in septic rats and its possible mechanism. Method: Rats were divided into sham operation group, model group (replication of septic rats with cecal ligation and perforation), low, middle and high-dose Taoren Chengqitang groups (2.85,5.70,8.55 g·kg-1), and dexamethasone group (0.01 g·kg-1),with 12 rats in each group. After last administration, rats were put to death, the morphological changes of intestinal mucosa were observed under electron microscope, the bacterial translocation rates in lymphoglandulae mesentericae, liver, kidney and spleen tissues were detected; the levels of serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and diamine oxidase (DAO) and intestinal fatty acid binding protein (i-FABP) levels in small intestine tissues were detected by enzyme-linked immunosorbent assay (ELISA).Expressions of Toll like receptor 9 (TLR9), myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B subunit p65 in small intestine tissues were detected by Western blot and immunohistochemistry. Result: Compared with sham operated group, the bacterial translocation rate, TNF-α and IL-1β levels in model group increased significantly, DAO, i-FABP, mucosal thickness and villus height decreased significantly, and protein expressions of TLR9, MyD88 and nucleus NF-κB p65 increased significantly (PPκB p65 protein decreased significantly. Compared with model group, the bacterial translocation rate, TNF-α and IL-1β levels in organs of low, medium and high-dose Taoren Chengqitang groups and dexamethasone group decreased significantly, DAO, i-FABP, mucosal thickness and villus height increased significantly, while the protein expressions of TLR9, MyD88 and nucleus NF-κB p65 decreased significantly (PκB p65 protein increased significantly. Conclusion: Taoren Chengqitang has a certain protective effect on intestinal mucosal barrier in septic rats, which may be related to the inhibition of TLR9 signaling pathway.

Emodin regulates microRNA expressions of ileum in sepsis mice model / 中华急诊医学杂志

Objective@#To investigate the regulation of emodin on microRNA expressions in mouse model with sepsis by GeneChip microRNA array.@*Methods@#Forty two c57 mice were randomly (random number) divided into 3 groups: sham operation group (sham group, n=14),sepsis group(n=14) and emodin group (n=14). The sepsis model of the mouse was subjected to cecal ligation and puncture (CLP). Mice in emodin group received intraperitoneal injection of emodin (40 mg/kg) half an hour before operation and every 12 hours after CLP. All mice were sacrificed 48 h after surgery and part of the ileum were removed for intestine tissue stained with hematoxylin eosin. The levels of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and intestinal fatty acid binding protein (I-FABP) in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). Total RNA of ileum tissues was extracted from the sepsis group and emodin group, and then subjected to miRNA microarray. The results of microarray were further verified by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs were predicted and subjected to gene ontology (GO) and KEGG pathway enrichment analysis. Data of multi-groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by SNK-q tests. Mann-Whitney U test was used when homogeneity of variance were not met. The value of P<0.05 was considered statistically significant.@*Results@#Compared to the sepsis group, the levels of serum TNF-α, IL-6 and I-FABP in the emodin group were decreased significantly. MiRNA microarray showed that 23 miRNAs were differentially expressed in the emodin group as compared to the sepsis group, among which 17 miRNAs were up-regulated and 6 miRNAs were down-regulated. qRT-PCR results were consistent with miRNA array data. Target genes of 10 selected miRNAs were predicted and subjected to bioinformatic analysis. A total of 3 410 target genes were significantly enriched in 2 072 GO biological process terms, 246 GO cellular component items and 277 GO molecular function terms. Moreover, KEGG pathway analysis showed that these differential miRNAs were involved in the regulation of PI3K-Akt signaling pathway, MAPK signaling pathway, and TNF signaling pathway.@*Conclusions@#Emodin can regulate the expression of multiple microRNAs, and play an important role in protecting the intestinal mucosal barrier via a variety of targets and pathways.