Advances in the research of intestinal fungi in Crohn's disease

This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology,delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease(CD).Insights were gained from fecal microbiota transplantation(FMT)in mouse models,revealing the intricate interplay between the gut microbiota,mesenteric adipose tissue(MAT),and creeping fat.The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD;moreover,through the FMT mouse model,it observed the impact of samples from healthy patients and those with CD on symptoms.The pathogenesis of CD is complex,and its etiology remains unclear;however,it is widely believed that gut microbiota dysbiosis plays a significant role.Recently,with the development and application of next-generation sequen-cing technology,research on the role of fungi in the pathogenesis and chronicity of CD has deepened.This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.

What is the optimal dialysis method for diabetic patients with end stage kidney disease?

Diabetes is one of the most catastrophic diseases ruling every corner of the world,and this has led to elevated incidents of end-stage kidney disease(ESKD).The standard treatment for ESKD is kidney transplantation/replacement,which is limited due to a deficiency of donors.Hence,dialysis has become the second-best option for treating patients with ESKD.Patients with ESKD with underlying diabetes have an additional risk of complications and infections over non-diabetic ESKD patients.Furthermore,these patients also experience variations in blood glucose levels and are more liable to develop malnutrition.This article elaborates on the different dialysis methods for ESKD patients.This editorial highlights the evidence-based studies that include randomized clinical trials,cohort studies,retrospective studies and case-control studies and suggests the most suitable type of dialysis under the following components.

Neural stem cell transplantation in a double-layer collagen membrane with unequal pore sizes for spinal cord injury repair

A novel double-layer collagen membrane with unequal pore sizes in each layer was designed and tested in this study. The inner, loose layer has about 100-μm-diameter pores, while the outer, compact layer has about 10-μm-diameter pores. In a rat model of incomplete spinal cord injury, a large number of neural stem cells were seeded into the loose layer, which was then adhered to the injured side, and the compact layer was placed against the lateral side. The results showed that the transplantation of neural stem cells in a double-layer collagen membrane with unequal pore sizes promoted the differentiation of neural stem cells, attenuated the pathological lesion, and signiifcantly improved the motor function of the rats with incomplete spinal cord injuries. These experimental ifndings suggest that the transplantation of neural stem cells in a double-lay-er collagen membrane with unequal pore sizes is an effective therapeutic strategy to repair an injured spinal cord.

Zinc finger protein A20 protects rats against chronic liver allograft dysfunction

AIM： To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats. METHODS： AIIogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day （POD） 5. Hepatic overexpression of A20 was achieved by recom- binant adenovirus （rAd.）-mediated gene transfer ad- ministered intravenously every 10 d starting from POD 10. The recipient rats were injected with physiologi- cal saline, rAdEasy-A20 （1 × 109 pfu/30 g weight） or rAdEasy （1 × 109 pfu/30 g weight） every 10 d through the tail vein for 3 mo starting from POD 10. Liver tissue samples were harvested on POD 30 and POD 60. RESULTS： Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis. A20 overexpression ameliorated the effects on liver function, attenuated liver allograft fibrosis and prolonged the survival of the recipient rats. Treatment with A20 suppressed hepatic protein pro- duction of tumor growth factor （TGF）-β1, interleukin- 113, caspase-8, CD40, CD40L, intercellular adhesion molecule-i, vascular cell adhesion molecule-1 and E-selectin. A20 treatment suppressed liver cell apopto- sis and inhibited nuclear factor-KB activation of Kupffer cells （KCs）, liver sinusoidal endothelial cells （LSECs） and hepatic stellate cells （HSCs）, and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs. CONCLUSION： A20 might prevent chronic liver allogra- ft dysfunction by re-establishing functional homeostasis of KCs, LSECs and HSCs.

Embryonic hepatocyte transplantation for hepatic cirrhosis:Efficacy and mechanism of action

AIM： To investigate the efficacy and mechanism of action of allogeneic embryonic hepatocyte transplantation for the treatment of hepatic cirrhosis. METHODS： Rat embryonic hepatocytes were characterized by examining cell markers. Wistar rats with CCl4-induced cirrhosis were randomly divided into two groups： a model group receiving continuous CCl4, and a cell transplantation group receiving continuous CCh and transplanted with embryonic fluorescent-labeled hepatocytes. In addition, a normal control group was composed of healthy rats. All rats were sacrificed after 2 wk following the initiation of the cell transplant. Ul- trasound, pathological analyses and serum biochemical tests were used to evaluate the efficacy of embryonic hepatocyte transplantation. To analyze the recovery status of cirrhotic hepatocytes and the signaling pathways influenced by embryonic hepatocyte transplantation, real-time polymerase chain reaction was performed to examine the mRNA expression of stellate activation-associated protein （STAP）, c-myb, ~ smooth muscle actin （^-SMA） and endothelin-1 （ET-1）. West- ern blotting and immunohistochemistry were employed to detect ^-SMA and ET-1 protein expression in hepatic tissues. RESULTS： Gross morphological, ultrasound and his- topathological examinations, serum biochemical tests and radioimmunoassays demonstrated that hepatic cir- rhosis was successfully established in the Wistar rats. Stem cell factor receptor （c-kit）, hepatocyte growth factor receptor （c-Met）, Nestin, ~ fetal protein, albu- min and cytokeratin19 markers were observed in the rat embryonic hepatocytes. Following embryonic hepa- tocyte transplantation, there was a significant reversal in the gross appearance, ultrasound findings, histo- pathological properties, and serum biochemical param- eters of the rat liver. In addition, after the activation of hepatic stellate cells and STAP signaling, ^-SMA, c-myb and ET-1 mRNA levels became significantly lower than in the untreated cirrhotic group （P 〈 0.05）. These levels, however, were not statistically different from those of the normal healthy group. Immunohisto- chemical staining and Western blot analyses revealed that ^-SMA and ET-1 protein expression levels in the transplantation group were significantly lower than in the untreated cirrhotic group, but being not statistically different from the normal group. CONCLUSION： Transplantation of embryonic hepatocytes in rats has therapeutic effects on cirrhosis. The described treatment may significantly reduce the expression of STAP and ET-1.

Combined transplantation of GDAs^(BMP) and hr-decorin in spinal cord contusion repair

Following spinal cord injury, astrocyte proliferation and scar formation are the main factors inhibiting the regeneration and growth of spinal cord axons. Recombinant decorin suppresses inflammatory reactions, inhibits glial scar formation, and promotes axonal growth. Rat models of T8 spinal cord contusion were created with the NYU impactor and these models were subjected to combined transplantation of bone morphogenetic protein-4-induced glial-restricted precursor-derived astro- cytes and human recombinant decorin transplantation. At 28 days after spinal cord contusion, dou- ble-immunofluorescent histochemistry revealed that combined transplantation inhibited the early in- flammatory response in injured rats. Furthermore, brain-derived neurotrophic factor, which was se- creted by transplanted cells, protected injured axons. The combined transplantation promoted ax- onal regeneration and growth of injured motor and sensory neurons by inhibiting astrocyte prolif- eration and glial scar formation, with astrocytes forming a linear arrangement in the contused spinal cord, thus providing axonal regeneration channels.

Effect of Yiguanjian decoction on cell differentiation and proliferation in CCl_4-treated mice

AIM： To investigate the cellular mechanisms of action of Yiguanjian （YGJ） decoction in treatment of chronic hepatic injury. METHODS： One group of mice was irradiated, and received enhanced green fluorescent protein （EGFP）- positive bone marrow transplants followed by 13 wk of CCh injection and 6 wk of oral YGJ administration. A second group of Institute for Cancer Research mice was treated with 13 wk of CCI4 injection and 6 wk of oral YGJadministration. Liver function, histological changes in the liver, and Hyp content were analyzed. The expres- sion of m-smooth muscle actin （α-SMA）, F4/80, albumin （AIb）, EGFP, mitogen-activated protein kinase-2 （PKM2）, Ki-67, fetoprotein （AFP）, monocyte chemotaxis pro- tein-1 and CC chemokine receptor 2 were assayed. RESULTS： As hepatic damage progressed, EGFP-po- sitive marrow cells migrated into the liver and were mainly distributed along the fibrous septa. They showed a conspicuous coexpression of EGFP with ^-SMA and F4/80 but no coexpression with AIb. Moreover, the expression of PKM2, AFP and Ki-67 was enhanced dy- namically and steadily over the course of liver injury. YGJ abrogated the increases in the number of bone marrow-derived fibrogenic cells in the liver, inhibited expression of both progenitor and mature hepatocyte markers, and reduced fibrogenesis. CONCLUSION： YGJ decoction improves liver fibrosis by inhibiting the migration of bone marrow cells into the liver as well as inhibiting their differentiation and suppressing the proliferation of both progenitors and hepatocytes in the injured liver.

Comparative study of rendezvous techniques in post-liver transplant biliary stricture

AIM： To investigate the usefulness of a new rendezvous technique for placing stents using the Kumpe （KMP） catheter in angulated or twisted biliary strictures. METHODS： The rendezvous technique was performed in patients with a biliary stricture after living donor liver transplantation （LDLT） who required the exchange of percutaneous transhepatic biliary drainage catheters for inside stents. The rendezvous technique was performed using a guidewire in 19 patients （guidewire group） and using a KMP catheter in another 19 （KMP catheter group）. We compared the two groups retrospectively. RESULTS： The baseline characteristics did not differ between the groups. The success rate for placing insidestents was 100% in both groups. A KMP catheter was easier to manipulate than a guidewire. The mean pro- cedure time in the KMP catheter group （1012 s, range： 301-2006 s） was shorter than that in the guidewire group （2037 s, range： 251-6758 s, P = 0.022）. The cu- mulative probabilities corresponding to the procedure time of the two groups were significantly different （P = 0.008）. The factors related to procedure time were the rendezvous technique method, the number of inside stents, the operator, and balloon dilation of the stric- ture （P 〈 0.05）. In a multivariate analysis, the rendez- vous technique method was the only significant factor related to procedure time （P = 0.010）. The procedural complications observed included one case of mild acute pancreatitis and one case of acute cholangitis in the guidewire group, and two cases of mild acute pancre- atitis in the KMP catheter group. CONCLUSION： The rendezvous technique involving use of the KIVlp catheter was a fast and safe method for placing inside stents in patients with LDLT biliary stric- ture that represents a viable alternative to the guide- wire rendezvous technique,

Biliary obstruction following transjugular intrahepatic portosystemic shunt placement in a patient after liver transplantation:A case report

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)is a method used to decrease portal hypertension.Biliary stricture is the rarest of the complications associated with this procedure with only 12 cases previously reported in the literature.None of these cases have documented the resolution of biliary stenosis induced by a stent graft.The only curative solutions reported are liver transplantation or bypassing the stenosis with an artificial biliary tract using advanced endoscopic techniques.CASE SUMMARY This is the first reported case of biliary obstruction secondary to TIPS placement in a transplanted liver.In our patient,a portosystemic shunt was created to treat severe veno-occlusive liver graft disease manifesting itself primarily by fluid retention.A cholestatic liver lesion and cholangitis with abscesses developed due to a stent graft-induced stricture in the dorsal segment of the right hepatic duct and the stricture diminished following percutaneous drainage.Endoscopic drainage was performed after unsuccessful removal of the percutaneous catheter resulting in a bilio-cutaneous fistula.Although the liver graft now functions well,the stricture remains refractory even after 44 mo of treatment.CONCLUSION Biliary strictures caused by TIPS in both transplanted and native livers seem refractory to endoscopic treatment.

Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis

Background and Aims: To evaluate the effect of intrapar-enchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). Methods: Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation. Results: On clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplanta-tion, consistent with structural improvements in mitochondria and nuclear compartments. Conclusions: Intraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.

Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

The aim of this study is to explore the effective-ness of autologous peripheral hematopoietic stem-cell transplantation in the treatment of refractory pemphigus.A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities.The dia-gnosis of pemphigus was made on the basis of the clinical,histologic and immunofluorescence findings.The patient had shown resistance to conventional therapy with gluco-corticoid and immunosuppressive agents.Two months before admission,he complained of hip joint pain.X-ray and CT scan revealed aseptic necrosis of the femoral head.Stem-cell mobilization was achieved by treatment with cyclophosphamide,granulocyte colony-stimulating factor(G-CSF)and rituximab.Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use.Immunoablation was accomplished by using cyclophospha-mide(200 mg/kg;divided into 50 mg/kg on days-5,-4,-3,and-2),antithymocyte globulin(ATG;10 mg/kg;divided into 2.5 mg/kg on days-6,-5,-4,and-3),and rituximab(1200 mg/d;divided into 600 mg/d on days 0 and 7).Autologous peripheral hematopoietic stem cell transplanta-tion was followed by reconstitution of the immune system which was monitored by flow cytometry.The glucocorti-coid was withdrawn immediately after transplantation.The pemphigus titer turned negative 6 weeks after transplanta-tion and remained negative.The patient was in complete drug-free remission with no evidence of residual clinical or serological activity of pemphigus during 1 year of follow-up.The patient’s response suggests that autologous peri-pheral hematopoietic stem cell transplantation may be a potential“cure”for refractory pemphigus.However,fur-ther studies are needed to evaluate the risk-benefit ratio of this approach in patients with pemphigus showing resist-ance to conventional therapy.

Extensor digitorum brevis and extensor hallusis brevis transplantation for treatment of long-standing facial pa-ralysis

Objective: To evaluate the efficacy of free transplan-tation of denervated muscles and vessels in the treatment of long-standing facial paralysis.Methods: A total of 26 patients with facial paralysis (10 males and 16 females, aged 16-65 years, mean: 47 years) were enrolled in this study to receive transplantation of denervated extensor digitorum brevis (EDB) and extensor hallusis brevis (EHB). The muscle tendon was slung to the ala nasi, the middle point of the nasolabial sulcus, the angu-lus otis and the chin to correct the nasal and oral deformity. The muscle belly was buried around the nerves that inner-vated the masseter muscle. Microsurgery was applied to anastomosing the tarsus lateral vessels to the superficial temporalis vessels.Results: After operation, all the patients immediately obtained satisfied static appearance. The movement of the paralyzed comer of the mouth could be obtained one month later and the smile of the paralyzed side could be restored after 3 months of training. And 88% patients achieved per-fect results, 8% obtained satisfactory results, and 4% got improvement 6 months after operation according to Stennert's paresis scoring system.Conclusions: Free transplantation of denervated muscles and vessels for the treatment of long-standing fa-cial paralysis, which seldom causes atrophy or liquefaction of the transferred muscles, can maintain muscle viability and induce reliable nerve regeneration. Therefore, it is a safe and efficient treatment method for the patients suffer-ing from facial paralysis.

Experimental study on the repair of tibial plateau defect

Objective： To evaluate the effect of autograft bone, allograft bone, calcium sulfate bone cement, and calcium phosphate bone cement on the repair of tibial plateau defect in rabbits. Methods： We used autograft bone, allograft bone, calcium sulfate bone cement, and calcium phosphate bone ce ment to repair tibial plateau defect in rabbits. Gross and histo logic observations, Xray examination, and biomechanical test were conducted at 1, 2, 4, 8 weeks after operation. Results： Xray examination found that the bone den sity was evidently reduced in calcium sulfate group at 8 weeks after operation; there were no marked changes in other groups. The maximal load measurements showed that autograft and allograft groups were greater than calcium sulfate and calcium phosphate groups at 1 and 2 weeks after operation. However at 4 and 8 weeks after operation, no significant difference was found among the four groups. In autograft and allograft groups, there was no significant difference in biomechanical intensity at 2, 4, and 8 weeks,but it was significantly higher than that at 1 week. In cal cium sulfate and calcium phosphate groups, the outcome was ranked in descending order as 1 week〈 2 week〈 4 week =8 week. Histologic examination found a great amount of new bones at 8 week in both autograft and allograft groups. In calcium sulfate group, calcium sulfate was almost absorbed and there were numerous bone trabeculations. There was a large amount of unabsorbed calcium phosphate in calcium phosphate group. Conclusion： At 12 weeks postoperatively, the biome chanical intensity is higher in autograft and allograft groups than calcium sulfate and calcium phosphate groups, but after 48 weeks, there is no significant difference among groups. At 12 weeks, the biomechanical intensity in all groups is increased, but at 48 weeks, there is no significant increase. The rates of absorption and bone formation are quicker in calcium sulfate group than calcium phosphate group.