Objective:To explore the role of the gut microbiota in the effect of orlistat on pancreatic exocrine function in mice.Methods:Sixty male C57BL/6J mice were divided into normal drinking water group and antibiotic group by using random number table method. In antibiotic group, vancomycin hydrochloride 0.5 g/L, ampicillin sodium 1 g/L, neomycin sulfate 1 g/L and metronidazole 1 g/L were added to the drinking water, which were administrated in combination for 2 weeks. The normal drinking water group and the antibiotic group were fed by normal diet (ND group, AND group), high-starch diet (HSD group, AHSD group), and high-fat diet (HFD group, AHFD group), respectively. The six groups were then gavaged with orlistat (O, 50 mg/kg) twice a day on the basis of the same diet, and were designated as ND+O group, AND+O group, HSD+O group, AHSD+O group, HFD+O group and AHFD+O group. The corresponding control groups were gavaged with the same amount of sterilized water, and the antibiotic group continued to drink antibiotic water. The intervention lasted for 12 weeks. Body weight and pancreatic weight were measured and recorded, and the pancreatic-to-body weight ratio was calculated. Blood samples were collected for the detection of inflammatory factor IL-6 and TNF α by ELISA. Pancreatic tissues were harvested for hematoxylin-eosin staining and subsequent pathological evaluation. Proteins were extracted from pancreatic tissues, and Western blot analysis was performed to detect the expression levels of pancreatic lipase and amylase.Results:In condition of normal diet and high fat diet, the body weights in the HFD group, HFD+O group, AHFD group [(37.22±4.49), (32.36±1.12), (33.64±2.52)g], were higher than that of ND group, ND+O group and AND group [(29.46±2.48), (27.48±1.98), (24.78±1.50)g], respectively; while the body weight of HFD+O group and AHFD+O group[(32.36±1.12), (27.82±0.61)g] were greatly lower than that of HFD group and AHFD group [(37.22±4.49), (33.64±2.52)g], respectively and body weight of ANFD+O group decreased to the level of normal diet group. In condition of normal diet, high fat diet and high starch diet, the pancreatic weight/body weight ratio was significantly higher in ND+O group (7.51±1.51)mg/g than ND group (5.19±1.06)mg/g, in HSD+O group and AHSD+O group [(6.68±0.34), (6.80±0.72)mg/g] higher than HSD group (4.37±0.91), in HFD+O group and AHFD+O group [(6.43±0.20), (6.67±0.53)mg/g] higher than HFD group (4.58±0.42)mg/g. The pancreatic acinar cells in mice from the ND+O, AND, AND+O, HSD+O, AHSD, AHSD+O, HFD+O, AHFD, and AHFD+O groups had significantly higher density of zymogen granules and exhibited larger eosinophilic stained area. The expression of pancreatic lipase was higher in AND+O group (1.96±0.39) than ND group and ND+O group [(1.00±0.28), (1.16±0.49)], in AHSD+O group (1.70±0.36) than HSD group (0.83±0.15), in AHFD+O group (1.71±0.45) than HFD group and HFD+O group [(0.89±0.23), (0.98±0.17)]. All the differences above were statistically significant (all P values <0.05). Conclusions:The gut microbiota can reduce the damage of orlistat to exocrine function of the pancreas and has a protective effect on the exocrine function of the pancreas.

Objective:To explore the role of the gut microbiota in the effect of orlistat on pancreatic exocrine function in mice.Methods:Sixty male C57BL/6J mice were divided into normal drinking water group and antibiotic group by using random number table method. In antibiotic group, vancomycin hydrochloride 0.5 g/L, ampicillin sodium 1 g/L, neomycin sulfate 1 g/L and metronidazole 1 g/L were added to the drinking water, which were administrated in combination for 2 weeks. The normal drinking water group and the antibiotic group were fed by normal diet (ND group, AND group), high-starch diet (HSD group, AHSD group), and high-fat diet (HFD group, AHFD group), respectively. The six groups were then gavaged with orlistat (O, 50 mg/kg) twice a day on the basis of the same diet, and were designated as ND+O group, AND+O group, HSD+O group, AHSD+O group, HFD+O group and AHFD+O group. The corresponding control groups were gavaged with the same amount of sterilized water, and the antibiotic group continued to drink antibiotic water. The intervention lasted for 12 weeks. Body weight and pancreatic weight were measured and recorded, and the pancreatic-to-body weight ratio was calculated. Blood samples were collected for the detection of inflammatory factor IL-6 and TNF α by ELISA. Pancreatic tissues were harvested for hematoxylin-eosin staining and subsequent pathological evaluation. Proteins were extracted from pancreatic tissues, and Western blot analysis was performed to detect the expression levels of pancreatic lipase and amylase.Results:In condition of normal diet and high fat diet, the body weights in the HFD group, HFD+O group, AHFD group [(37.22±4.49), (32.36±1.12), (33.64±2.52)g], were higher than that of ND group, ND+O group and AND group [(29.46±2.48), (27.48±1.98), (24.78±1.50)g], respectively; while the body weight of HFD+O group and AHFD+O group[(32.36±1.12), (27.82±0.61)g] were greatly lower than that of HFD group and AHFD group [(37.22±4.49), (33.64±2.52)g], respectively and body weight of ANFD+O group decreased to the level of normal diet group. In condition of normal diet, high fat diet and high starch diet, the pancreatic weight/body weight ratio was significantly higher in ND+O group (7.51±1.51)mg/g than ND group (5.19±1.06)mg/g, in HSD+O group and AHSD+O group [(6.68±0.34), (6.80±0.72)mg/g] higher than HSD group (4.37±0.91), in HFD+O group and AHFD+O group [(6.43±0.20), (6.67±0.53)mg/g] higher than HFD group (4.58±0.42)mg/g. The pancreatic acinar cells in mice from the ND+O, AND, AND+O, HSD+O, AHSD, AHSD+O, HFD+O, AHFD, and AHFD+O groups had significantly higher density of zymogen granules and exhibited larger eosinophilic stained area. The expression of pancreatic lipase was higher in AND+O group (1.96±0.39) than ND group and ND+O group [(1.00±0.28), (1.16±0.49)], in AHSD+O group (1.70±0.36) than HSD group (0.83±0.15), in AHFD+O group (1.71±0.45) than HFD group and HFD+O group [(0.89±0.23), (0.98±0.17)]. All the differences above were statistically significant (all P values <0.05). Conclusions:The gut microbiota can reduce the damage of orlistat to exocrine function of the pancreas and has a protective effect on the exocrine function of the pancreas.

Over the years of exploration and development, the surgical techniques and prognosis of liver transplantation in China have been significantly improved, resulting in a notable decrease in the prevalence of postoperative complications. However, ischemic-type biliary lesion remain a non-negligible issue. The Third Affiliated Hospital of Sun Yat-sen University formulated and published the "Expert Consensus on the Diagnosis and Treatment of Ischemic-Type Biliary Lesions after Liver Transplantation in Mainland China" in 2015, which has now been updated into a guideline based on current conditions and literature reports. This guideline elaborates in detail on the definition, incidence, pathogenesis, diagnosis, prevention of high-risk factors, and treatment of ischemic-type biliary lesion, aiming to provide standardized and normative guidance for the diagnosis and treatment of ischemic-type biliary lesion after liver transplantation, thereby reducing the rate of re-transplantation and fatality, and to improve the overall quality of life of liver transplant recipients.

OBJECTIVE: To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union. METHODS: The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union. RESULTS: Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity. CONCLUSION TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.
Humans ; Fracture Healing/physiology* ; Brain Injuries/metabolism* ; Brain Injuries, Traumatic ; Fractures, Bone ; Osteogenesis

BACKGROUND:The remediation and treatment of bone defects present considerable challenges,with a variety of clinical intervention strategies available.One such approach,the Masquelet technique,has demonstrated high rates of success and reliable outcomes and is currently employed in clinical practice.However,the underlying mechanisms of this technique remain incompletely understood,and certain challenges persist in its clinical application,indicating that this technique is not yet fully mature. OBJECTIVE:To compile and categorize the biomaterials currently employed in research aimed at improving the Masquelet technique,in order to provide insights and references for the further development of this technique. METHODS:A literature search of the China National Knowledge Infrastructure and PubMed databases was conducted,spanning publications from January 2013 to November 2022.The search terms used included"Masquelet technique;induced membrane technique;induced membrane;biomaterial;bone defect"in both Chinese and English.A total of 58 articles meeting the inclusion criteria were reviewed. RESULTS AND CONCLUSION:(1)The emergence and continual development of the Masquelet technique provide a therapeutic strategy for treating bone defects.Some researchers are focusing on developing superior spacer materials,autograft substitutes,and membrane materials that mimic the properties of the induced membrane,to simplify the two-stage procedure,shorten treatment duration,and reduce patient distress.(2)Calcium sulfate,silicone,poly(lactic-co-glycolic acid),and polypropylene can replace polymethylmethacrylate bone cement to form induced membranes in animal experiments or clinical applications,each with their advantages.Contrary to expectations,common materials such as titanium and polyvinyl alcohol sponge cannot replace polymethylmethacrylate bone cement.(3)Autograft substitutes are diverse,with allograft bone,β-tricalcium phosphate,absorbable gelatin sponge,α-calcium sulfate hemihydrate,bioactive glass,titanium,and tantalum demonstrating their ability to reduce the quantity of autologous cancellous bone graft required in the second stage of the procedure.Among them,allograft bone,β-tricalcium phosphate,bioactive glass,titanium and tantalum can replace autogenous bone as grafts,and other materials need to be mixed with autogenous bone,in both clinical and fundamental experiments.(4)Biomimetic-induced membranes,human amnion,human decellularized dermis,polytetrafluoroethylene,and even autogenous cortical bone have been shown to possess properties similar to the induced membrane.(5)Most of the application and research of biomaterials in this technology still exist in the stage of basic research and have not been applied in clinical practice or popularized on a large scale,but the above materials can provide more sufficient theoretical basis and new ideas for the exploration of Masquelet technical mechanism,the improvement of surgical methods and clinical application.

Objective　To explore the molecular epidemiological characteristics of local Mycobacterium tuberculosis in Chongqing, China using genotyping methods and establish a suitable genotyping system tuberculosis genotyping in the region. Methods A total of 268 isolates collected from the sputum of tuberculosis patients at two national drug resistance monitoring sites in Chongqing from 2019 to 2021. The DNA of these isolates was extracted, and genotyping of the isolates was performed using VTNR 24 locus typing method. Epidemiological investigations were conducted on clustered isolates, and the clustering rates of isolates from the two surveillance sites were compared to analyze their transmission differences. Results In the two regions, the Hunter-Gaston discriminatory index (HGI) in Fengjie County ranged from 0 to 0.85, with 10 loci having an HGI above 0.6, 11 loci with an HGI between 0.3 and 0.6, and 3 loci with an HGI below 0.3; the highest resolution site was MIRU31, while the lowest resolution site was MIRU24. The HGI index in Fengdu County ranged from 0 to 0.81, with 12 loci having an HGI above 0.6, 9 loci with an HGI between 0.3 and 0.6, and 3 loci with an HGI below 0.3; the highest resolution site was MIRU26, while the lowest resolution site was MIRU23. In the clustering analysis, among the 140 isolates from Fengdu County, 10 samples clustered into 4 clusters, with the largest cluster consisting of 4 samples, resulting in a clustering rate of 4.1%. Among the 128 isolates in Fengjie County, 10 samples clustered into 5 clusters, with a clustering rate of 4.2%. Conclusion In Fengdu County and Fengjie County of Chongqing, the main population of the disease show independent genotypes, indicating a low recent transmission rate. The incidence of patients is mainly endogenous recurrence, that is, latent infection develops into active tuberculosis. While conducting standardized management of tuberculosis patients, prevention and control agencies should also increase the screening of latent infection at two monitoring points and carry out preventive treatment of latent infection, which is the key to reduce the incidence of tuberculosis in the two places.

Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the tricarboxylic acid cycle (TAC). The high mutation frequency of the IDH gene plays a complicated role in gliomas. In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion. In addition, IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells, also affecting their functioning. In this review, we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas. We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas. Finally, we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.
Brain Neoplasms/therapy* ; Glioma/therapy* ; Humans ; Immunotherapy ; Isocitrate Dehydrogenase/genetics* ; Mutation/genetics* ; Tumor Microenvironment

ObjectiveTo investigate the influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). MethodsClinical data were collected from 240 HBV-ACLF patients without liver transplantation who were admitted To The Second Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2019, and the patients were divided into groups according to survival on days 28 and 90 after admission (28-day survival group with 164 patients and 28-day death group with 76 patients; 90-day survival group with 140 patients and 90-day death group with 100 patients). The data collected included predisposing factors, liver function parameters, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and complications. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC), and a multivariate logistic regression analysis was used to investigate the risk factors for the short-term prognosis of HBV-ACLF. ResultsThe main predisposing factors of HBV-ACLF included spontaneous activation of HBV (55.6%) and HBV activation caused by the withdrawal of or resistance to nucleoside analogues (25.2%). There were significant differences in age, prothrombin time activity (PTA), neutrophil-lymphocyte ratio (NLR), serum sodium, MELD score, MELD-Na score, and total bilirubin (TBil) at baseline between the 28-day survival group and the 28-day death group (Z=-2.400,-6.015, -5.070, -5.103, -5.044, -7.430, and -6.637, all P＜0.05), and there were also significant differences in age, PTA, NLR, serum sodium, MELD score, MELD-Na, TBil, and cholesterol at baseline between the 90-day survival group and the 90-day death group (Z=-2.205, -7.728, -3.335, -4.015, -6.053, -7.908, -6.655, and -3.607, all P＜0.05). The multivariate logistic regression analysis showed that TBil ＞260.20 mmol/L (odds ratio ［OR］=4.572, 95% confidence interval ［CI］: 1.321-15823, P＜0.05), PTA ＜24.8% (OR=8.934, 95%CI: 3.026-26.374, P＜0.05), NLR＞5.63 (OR=2.632, 95%CI: 1.126-6.152, P＜0.05), serum sodium ＜130.8 mmol/L (OR=27.467, 95%CI: 6.113-123.423, P＜0.05), MELD score ＞17.84 (OR=4.303, 95%CI: 1.048-17.663, P＜0.05), and MELD-Na score ＞25.1 (OR=3.453, 95%CI: 1.614-7.387, P＜0.05) were independent risk factors for 28-day survival; TBil＞260.20 mmol/L (OR=5.148, 95%CI: 1.918-13.822, P＜0.05), PTA ＜25.5% (OR=15.718, 95%CI: 5.161-47.866, P＜0.05), serum sodium ＜135.3 mmol/L (OR=10.080, 95%CI: 3.244-31.323, P＜005), MELD score ＞17.84 (OR=11.157, 95%CI: 2.580-48.254, P＜0.05), MELD-Na score ＞25.1 (OR=4.391, 95%CI: 2057-9.372, P＜0.05) were independent risk factors for 90-day survival. Among the 240 patients, 160 (66.7%) experienced infection within 90 days, among whom 140 had bacterial infection, 12 had viral infection, and 8 had fungal infection. The 160 patients with infection had a significantly higher 90-day mortality rate than the patients without infection (46.3% vs 32.5%, χ2=6.720, P=0.010). Of all 240 patients, 176 had ascites, 44 had pleural effusion, 36 had acute renal injury, 60 had hepatic encephalopathy, and 12 had gastrointestinal bleeding within 28 days, and there were significant differences in the proportion of patients with acute renal injury, grade Ⅲ-Ⅳ hepatic encephalopathy, or gastrointestinal bleeding between the 28-day survival group and the 28-day death group (χ2=64.088，29811，7.797，all P＜0.05). ConclusionTBil, PTA, serum sodium, MELD score, and MELD-Na score at baseline are independent risk factors for the 28- and 90-day prognosis of HBV-ACLF. Liver inflammation and necrosis caused by HBV activation may be the initiating factor for ACLF, and infection, acute renal injury, hepatic encephalopathy, and gastrointestinal bleeding are the main complications affecting the prognosis of patients.

Objective To observe the effect of recombinant human granulocyte/macrophage colonystimulating factor (rhGM-CSF) combined with nano-silver as a treatment on deep burn degreen Ⅱ about inflammation .Methods The burn model was built with Wistar rats .They were randomly divided into four groups ,petrolatum treatment (group A ,n= 30) ,nano-silver treatment (group B ,n=30) ,rhGM-CSF treatment(group C ,n=30) ,and rhGM-CSF combined with nano-silver treatment(group D ,n=30) . observation the inflammatory reaction ,and culture bacteria on wound of the four groups at 1st ,4th ,7th ,10th ,14th ,21th day after treatment were made .The level of IL-2 and IL-8 were measured in serums with ELISA .Results The inflammatory reaction:group A>group B>group C>group D ;Bacterias were observed in group A ,group B/C and group D at 4th ,10th ,14th day respectively af-ter treatment .The number of bacterial growed in group D was less than in group A ,group B and group C .The numbers of bacterial growed in group B and group C were less than in group A .And after 10 ,14 ,21 days treatment ,there was significantly statistical difference(P<0 .05) .There was difference among groups in the levele of IL-2 and IL-8 ,which were the lowest in group D and the highest in group A .The level of IL-2 has no significantly statistical difference between every groupat 1st day and between B and C group at 4th day(P>0 .05) .After other days treatment ,there was significantly statistical difference(P<0 .05) .There was signifi-cantly statistical difference in every group at each day of the IL-8 levele except A and B group ,B and C group ,C and D group at 1st day (P<0 .05) .Conclusion rhGM-CSF combined with nano-silver treatment could alleviate inflammatory reaction ,and be better than rhGM-CSF or nano-silver alone .