Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer

BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through its inhibitory effect on butyric acid,via the AMPK signaling pathway.

Preparation method of an ideal model of multiple organ injury of rat with severe acute pancreatitis

AIM: To establish an ideal model of multiple organ injury of rats with severe acute pancreatitis (SAP). METHODS: SAP models were induced by retrograde injection of 0.1 mL/100 g 3.5% sodium taurocholate into the biliopancreatic duct of Sprague-Dawley rats. The plasma and samples of multiple organ tissues of rats were collected at 3, 6 and 12 h after modeling. The ascites volume, ascites/body weight ratio, and contents of amylase, endotoxin, endothelin-1 (ET-1), nitrogen monoxidum (NO), phospholipase A2 (PLA2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in plasma were determined. The histological changes of multiple organs were observed under light microscope. RESULTS: The ascites volume, ascites/body weight ratio, and contents of various inflammatory mediators in blood were higher in the model group than in the sham operation group at all time points [2.38 (1.10), 2.58 (0.70), 2.54 (0.71) vs 0.20 (0.04), 0.30 (0.30), 0.22 (0.10)at 3, 6 and 12 h in ascites/body weight ratio; 1582 (284), 1769 (362), 1618 (302) (U/L) vs 5303 (1373), 6276 (1029), 7538 (2934) (U/L) at 3, 6 and 12 h in Amylase; 0.016 (0.005), 0.016 (0.010), 0.014 (0.015) (EU/mL) vs 0.053 (0.029), 0.059 (0.037), 0.060 (0.022) (EU/mL) at 3, 6 and 12 h in Endotoxin; 3.900 (3.200), 4.000 (1.700), 5.300 (3.000) (ng/L) vs 41.438 (37.721), 92.151 (23.119), 65.016 (26.806) (ng/L) at 3, 6 and 12 h in TNF-α, all P < 0.01]. Visible congestion, edema and lamellar necrosis and massive leukocytic infiltration were found in the pancreas of rats of model group. There were also pathological changes of lung, liver, kidney, ileum, lymphonode, thymus, myocardium and brain. CONCLUSION: This rat model features reliability, convenience and a high achievement ratio. Complicated with multiple organ injury, it is an ideal animal model of SAP.

Intestinal obstruction in pregnancy with reverse rotation of the midgut:A case report

BACKGROUND Reverse rotation of the midgut is a rare type of intestinal malrotation.Volvulus of the right colon or entire midgut,stenosis of the transverse colon and obstruction of the duodenojejunal junction are common complications of reverse rotation.In this study,we report the first case of intestinal obstruction associated with reverse rotation in pregnancy.CASE SUMMARY A 31-year-old woman at 362+wk gestation presented to the emergency department with progressive abdominal cramping,nausea and bilious vomiting.Abdominal ultrasound scanning showed dilatation of the bowel.Computed tomography scanning revealed features of reverse rotation of the midgut with intestinal volvulus.After consultation with the obstetrician,the pregnancy was terminated and exploratory abdominal surgery was performed.Intra-operatively,it was found that the mesentery of the colon and small intestine was insufficiently attached.The right colon and the small intestinal mesentery was twisted,and intestinal necrosis was observed.The duodenum and duodenojejunal junction were curved in front of the transverse colon,and the transverse colon passed through the tunnel behind the mesenteric root.Intestinal reverse rotation with volvulus was confirmed.The necrotic intestine was resected and small intestine mesenteric reconstruction was performed.The patient recovered after surgery.After leaving the hospital,the patient and her daughter remained well during an 8-month follow-up period.CONCLUSION We report the diagnosis,treatment and etiology of a pregnant patient with intestinal obstruction due to reverse rotation of the midgut.For similar cases,appropriate diagnosis and treatment should be carried out according to the condition of the fetus and pregnant woman.

LIN28 expression and prognostic value in hepatocellular carcinoma patients who meet the Milan criteria and undergo hepatectomy

Stem cell marker LIN28,related closely with SOX2 and OCT4,has been studied as a biomarker for the maintainance of pluripotent cells in several malignancies.Our previous study showed that SOX2 and OCT4 were negative predictors for hepatocellular carcinoma(HCC).However,the predictive value of LIN28 in HCC outcome is still undetermined.We hypothesized that LIN28 may also play a role as a biomarker for HCC.To test this hypothesis,we examined the expression of LIN28 in 129 radically resected HCC tissues using reverse transcription-polymerase chain reaction and analyzed the association of LIN28 expression with clinicopathologic features and prognosis.Our study showed that LIN28 was expressed at a higher frequency in tumor tissues than in non-HCC tissues(45.0% vs.21.7%,P = 0.020).Moreover,LIN28 expression was significantly increased in cases with large tumor size(P = 0.010).Univariate analysis did not reveal a significant correlation between LIN28 expression and overall survival or recurrence-free survival.For HCC patients who met the Milan criteria,stratified analysis revealed shorter overall survival(P = 0.007) and recurrence-free survival(P < 0.001) in those with detectable LIN28 expression compared to those with no detectable LIN28 expression.Furthermore,multivariate analysis revealed that LIN28 was a negative independent predictor for both overall survival(hazard ratio= 7.093,P = 0.017) and recurrence-free survival(hazard ratio=5.518,P = 0.004) in patients who met the Milan criteria.Taken together,our results suggest that LIN28 identifies low-risk and high-risk subsets of HCC patients meeting the Milan criteria who undergo hepatectomy.

Rongchang and Xifeng capsules suppress pentylenetetrazole-induced seizures and change rest/wake behavior in zebrafish larvae

OBJECTIVE:To evaluate the effects of Rongchang capsule and Xifeng capsule on pentylenetetrazoleinduced epilepsy in zebrafish larvae and to explore the possible mechanisms behind their actions.METHODS:We utilized a trajectory tracking system to monitor seizures in zebrafish larva to confirm that certain concentrations of Rongchang capsule and Xifeng capsule produce antiepileptic effects.c-fos expression was assessed by quantitative reverse transcription-polymerase chain reaction to validate the efficacy of the capsules.Rest/wake behavior and correlation analysis predicted the targets of Rongchang capsule and Xifeng capsule.RESULTS:Larval movement times and total distances traveled by zebrafish larvae experiencing pentylenetetrazole(PTZ)-induced seizures were decreasedbyvalproatetreatment.Rongchang(500μg/m L)and Xifeng(200μg/m L)rescued the epileptic behaviors and down-regulated c-fos expression in the brains of larvae,which indicated antiepileptic effects.The rest/wake behavioral profiles showed that Rongchang and Xifeng differentially decreased rest time at night and increased larval locomotor activities during the day.Based on correlation between the actions of the two capsules and known compounds,we predicted that they might change rest/wake behaviors by affecting serotonin,GABAergic and histamine signaling pathways.CONCLUSION:The efficacy of Rongchang capsule and Xifeng capsule in alleviating epilepsy-like behaviors and molecular responses was confirmed.Our study provides insight into the capsules'effect on epilepsy.

Life-saving therapy for complete traumatic hemipelvectomy:a case report

To the Editor:Traumatic hemipelvectomy(THP),which was first described by Turnbull in 1978,is an unstable ligamentous or osseous hemipelvic injury that involves rupture of the pelvic neurovascular bundle(either open or closed integuments).[1]THP is a rare and catastrophic injury that is usually caused by high-energy trauma,as in a traffic,motorcycle,and machinery-related accident,and is accompanied by pelvic fractures.[2]THP usually leads to other associated injuries.[3]The mortality associated with open pelvic fracture is approximately 40%,while the mortality associated with THP may reach as high as 100%.[4]However,few studies describe a standardized approach for handling this fatal trauma.