Objective To observe the efficacy of deep learning(DL)model based on PET/CT and its combination with Cox proportional hazard model for predicting progressive disease(PD)of lung invasive adenocarcinoma within 5 years a...Objective To observe the efficacy of deep learning(DL)model based on PET/CT and its combination with Cox proportional hazard model for predicting progressive disease(PD)of lung invasive adenocarcinoma within 5 years after surgery.Methods The clinical,PET/CT and 5-year follow-up data of 250 patients with lung invasive adenocarcinoma were retrospectively analyzed.According to PD or not,the patients were divided into the PD group(n=71)and non-PD group(n=179).The basic data and PET/CT findings were compared between groups,among which the quantitative variables being significant different between groups were transformed to categorical variables using receiver operating characteristic(ROC)curve and corresponding cut-off value.Multivariant Cox proportional hazard model was used to select independent predicting factors of PD of lung invasive adenocarcinoma within 5 years after surgery.The patients were divided into training,validation and test sets at the ratio of 6∶2∶2,and PET/CT data in training set and validation set were used to train model and tuning parameters to build the PET/CT DL model,and the combination model was built in serial connection of DL model and the predictive factors.In test set,the efficacy of each model for predicting PD of lung invasive adenocarcinoma within 5 years after surgery was assessed and compared using the area under the curve(AUC).Results Patients'gender and smoking status,as well as the long diameter,SUV max and SUV mean of lesions measured on PET images,the long diameter,short diameter and type of lesions showed on CT were statistically different between groups(all P<0.05).Smoking(HR=1.787[1.053,3.031],P=0.031)and lesion SUV max>4.15(HR=5.249[1.062,25.945],P=0.042)were both predictors of PD of lung invasive adenocarcinoma within 5 years after surgery.In test set,the AUC of PET/CT DL model for predicting PD was 0.847,of the combination model was 0.890,of the latter was higher than of the former(P=0.036).Conclusion DL model based on PET/CT had high efficacy for predicting PD of lung invasive adenocarcinoma within 5 years after surgery.Combining with Cox proportional hazard model could further improve its predicting efficacy.展开更多
Preliminary experiments are carried out to characterize the droplets generated in two aerosol-generating health care procedures,i.e.taking nasopharyngeal aspirates(NPA)and nebulizer therapy.Glass slides and water-se...Preliminary experiments are carried out to characterize the droplets generated in two aerosol-generating health care procedures,i.e.taking nasopharyngeal aspirates(NPA)and nebulizer therapy.Glass slides and water-sensitive paper(WSP)are used to collect large droplets when taking NPA.Droplet stain-marks on glass slides are counted under a microscope,and then a size analysis is performed.During nebulizer therapy dust monitors are used to detect small droplets and droplet nuclei at different positions around the nebulizer and in the room.From the preliminary results it is found that taking NPA can stimulate coughing and generate large droplets.Nebulizers can generate more than tens of millions fine droplets ranging from 0.3 to 20 μm per minute,a large volume of which can escape from the holes on the nebulizer's facemask and disperse in the whole room.Droplets coagulate on the inner surface of the mask and the volunteer's face,suggesting a great possibility of drug solution contamination by patients' secretion during nebulizer therapy.展开更多
AIM: To compare the cleansing quality of polyethylene glycol electrolyte solution and sodium phosphate with different schedules of administration, and to evaluate whether the timing of the administration of bowel pre...AIM: To compare the cleansing quality of polyethylene glycol electrolyte solution and sodium phosphate with different schedules of administration, and to evaluate whether the timing of the administration of bowel preparation affects the detection of polyps. METHODS: One hundred and seventy-seven consecutive outpatients scheduled for colonoscopy were randomized in one of four groups to receive polyethylene glycol electrolyte solution or oral sodium phosphate with two different timing schedules. Quality of cleansing, polyp detection, and tolerance were evaluated. RESULTS: Patients receiving polyethylene glycol or sodium phosphate on the same day as the colonoscopy, obtained good to excellent global cleansing scores more frequently than patients who received polyethylene glycol or sodium phosphate on the day prior to the procedure (P 〈 0.001). Flat lesions, but not fiat adenomas, were more frequent in patients prepared on the same day (P = 0.02). CONCLUSION: The quality of colonic cleansing and the detection of fiat lesions are significantly improved when the preparation is taken on the day of the colonoscopy.展开更多
Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with...Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal mac- rophages play an important role in the mucosal im- mune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major con- tributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of the inflammatory process in IBD. Therefore, several cyto- kine therapies have been developed and tested for the treatment of IBD patients.展开更多
Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some...Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some is systemic. The full story is yet to be discovered. Probiotics have a definite positive effect on rotavirus diarrhea, post antibiotic diarrhea and pouchitis. Their exact role in inflammatory bowel disease, irritable bowel syndrome, other forms of infectious diarrhea, and prevention of cancer is yet to be determined. This review summarizes the data about probiotics in these conditions.展开更多
AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples we...AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 ug/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori(Hpylon) culture. IL-17 and IL-8 protein levels in culture supematants were assayed by ELISA. IL- 17 mRNA expression was analyzed by reverse transcriptasepolymerase chain reaction (RT-PCR). Hpylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (UPA). IL-8 levels in culture supematants were assayed after AGS cells were co-cultured with Hpylori strain 26 695 or recombinant human (rh) IL-17. RESULTS: All 36 GU patients and 15 of 29 NU patients were found to be Hpy/or/-positive, while 14 NU patients were Hpylori-nogative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAsl/ml-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2 499; Hpylori negative NU patients: median 104 pg/mg/protein, range 16-312, P〈0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1 356 pcj/mg/protein, range 121-1 3730; antrum: median 761 pg/mg/protein, range 24-7 620, P〈0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the Hpylori-negativecontrols showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r = 0.62,P〈0.0001; antrum: r = 0.61, P〈0.0001) in GU patients. RhIL-17 and Hpylori strain 26 695 each stimulated IL-8 production from AGS cells. CONCLUSION: IL-17 may play an important role in the inflammatory response to Hpyloricolonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.展开更多
AIM: To investigate Kupffer cell dynamics and phagocytic activity,using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defin...AIM: To investigate Kupffer cell dynamics and phagocytic activity,using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet,followed by contrast enhanced ultrasonography (CEUS) using Levovist. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy. The status of the Kupffer cells was compared between the two groups,using the immunohistochemical staining technique. RESULTS: After 4 or more wk of the CDAA diet,CEUS examination revealed a decrease in the signal intensity,20 min after intravenous Levovist. Fluorescent microscopic examination showed that the uptake of latex beads by the Kupffer cells was reduced at week 1 and 2 in the study group,compared with the controls,with no further reduction after 3 wk. Immunohistochemical staining revealed no significant difference in the Kupffer cell counts between the control group and the CDAA group. CONCLUSION: CEUS examination using Levovist demonstrated reduced contrast effect and phagocytic activity in the liver parenchymal phase,although the Kupffer cell numbers were unchanged,indicating reduced phagocytic function of the Kupffer cells in the rat NASH model. We believe that CEUS examination using Levovist is a useful screening modality,which can detect NASH in fatty liver patients.展开更多
Obstructed defecation (OD) and fecal incontinence (FI) are challenging clinical problems, which are commonly encountered in the practice of colorectal surgeons and gastroenterologists. These disorders sodally and ...Obstructed defecation (OD) and fecal incontinence (FI) are challenging clinical problems, which are commonly encountered in the practice of colorectal surgeons and gastroenterologists. These disorders sodally and psychologically distress patients and greatly impair their quality of life. The underlying anatomical and pathophysiological changes are complex, often incompletely understood and cannot always be determined. As a consequence, many medical, surgical, and behavioral approaches have been described, with no panacea. Over the past decade, advances in an understanding of these disorders together with rational and similar methods of evaluation in anorectal physiology laboratories (ARP), radiology studies, and new surgical techniques have led to promising results. In this brief review, we discuss treatment strategies and recent updates on clinical and therapeutic aspects of obstructed defecation and fecal incontinence.展开更多
Many advances have been made in the understanding of Crohn’s disease (CD) pathogenesis during the last decade. CD is currently seen as a predominantly T-lym-phocyte-driven disease characterized by the presence of a c...Many advances have been made in the understanding of Crohn’s disease (CD) pathogenesis during the last decade. CD is currently seen as a predominantly T-lym-phocyte-driven disease characterized by the presence of a complex cocktail of interacting cytokines, chemokines and other mediators produced by a variety of cell types. Prevailing theories of CD pathogenesis suggest that patients’ T-lymphocytes are inappropriately activated in the setting of an immune imbalance, which is itself caused by an unfortunate confluence of genetic and en- vironmental factors. The T-cell response then leads to the chronic inflammation characteristic for the disease. Various environmental factors may play a role in the development of CD, but microbes are most consistently implied. This theory is based on epidemiological, clinico- pathological, genetic and experimental evidence. Despite the abundance of arguments for the implication of bac-teria in the aetiopathogenesis of CD, the precise role of bacteria in this disease still remains elusive. Three not necessarily mutually exclusive theories have been pro- posed: (1) an unidentified persistent pathogen; (2) an abnormally permeable mucosal barrier leading to exces-sive bacterial translocation; and (3) a breakdown in the balance between putative "protective" versus "harmful" intestinal bacteria ("dysbiosis"). At present, one cannot exclude with certainty any of these three proposed hy-potheses; they may all apply to CD to a certain extent.展开更多
AIM: To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use.METHODS: Using a structured pro forma, we conducted a two-month survey of the electronic pre...AIM: To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use.METHODS: Using a structured pro forma, we conducted a two-month survey of the electronic prescriptions containing immediate-release (IR) or sustained-release (SR) product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS: One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori (H pylori) therapy, triple therapy take the dominant position (91.8%), followed by quadruple therapy (4.3%) and dual therapy (3.9%). Amoxicillin was the most frequently co-prescribed antibiotic.Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR, and 6.4% of prescriptions of clarithromycin IR, were prescribed at inappropriate dosing intervals. Surprisingly, disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating Hpy/ori infection although off-label use for this purpose was reported in literature. On the contrary, only one prescription (0.9%) of clarithromycin IR was prescribed for unapproved indication (i.e. gastro-oesophageal reflux disease). 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION: There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease, especially with regard to administration schedule, concordance between indications and diagnoses and management of drug interactions.展开更多
Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors an...Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic in-flammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina pro-pria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-α clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the bio-logical activities of recently-reported cytokines [Inter-leukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-α in the pathophysiology of IBD.展开更多
Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by ...Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay.Results The cell line bore a missense mutation in the 6th coding exon (c.676 C〉T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.展开更多
Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Recent data suggest thromboembolism as a disease-specific extraintestinal manifestation of IBD, wh...Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Recent data suggest thromboembolism as a disease-specific extraintestinal manifestation of IBD, which is developed as the result of multiple interactions between acquired and genetic risk factors. There is evidence indicating an imbalance of procoagulant, anticoagulant and fibrinolitic factors predisposing in thrombosis in patients with IBD. The genetic factors that have been suggested to interfere in the thrombotic manifestations of IBD include factor V Leiden, factor Ⅱ (prothrombin, G20210A), methylenetetrahydrofolate reductase gene mutation (MTHFR, 6777T, plasminogen activator inhibitor type 1 (PAI-1) gene mutation and factor X Ⅲ (val34leu). In this article we review the current data and future prospects on the role of genetic risk factors in the development of thromboembolism in TBD.展开更多
文摘Objective To observe the efficacy of deep learning(DL)model based on PET/CT and its combination with Cox proportional hazard model for predicting progressive disease(PD)of lung invasive adenocarcinoma within 5 years after surgery.Methods The clinical,PET/CT and 5-year follow-up data of 250 patients with lung invasive adenocarcinoma were retrospectively analyzed.According to PD or not,the patients were divided into the PD group(n=71)and non-PD group(n=179).The basic data and PET/CT findings were compared between groups,among which the quantitative variables being significant different between groups were transformed to categorical variables using receiver operating characteristic(ROC)curve and corresponding cut-off value.Multivariant Cox proportional hazard model was used to select independent predicting factors of PD of lung invasive adenocarcinoma within 5 years after surgery.The patients were divided into training,validation and test sets at the ratio of 6∶2∶2,and PET/CT data in training set and validation set were used to train model and tuning parameters to build the PET/CT DL model,and the combination model was built in serial connection of DL model and the predictive factors.In test set,the efficacy of each model for predicting PD of lung invasive adenocarcinoma within 5 years after surgery was assessed and compared using the area under the curve(AUC).Results Patients'gender and smoking status,as well as the long diameter,SUV max and SUV mean of lesions measured on PET images,the long diameter,short diameter and type of lesions showed on CT were statistically different between groups(all P<0.05).Smoking(HR=1.787[1.053,3.031],P=0.031)and lesion SUV max>4.15(HR=5.249[1.062,25.945],P=0.042)were both predictors of PD of lung invasive adenocarcinoma within 5 years after surgery.In test set,the AUC of PET/CT DL model for predicting PD was 0.847,of the combination model was 0.890,of the latter was higher than of the former(P=0.036).Conclusion DL model based on PET/CT had high efficacy for predicting PD of lung invasive adenocarcinoma within 5 years after surgery.Combining with Cox proportional hazard model could further improve its predicting efficacy.
基金The Project of Research Grants Council of the HongKong Special Administrative Region(No.HKU7150/06)
文摘Preliminary experiments are carried out to characterize the droplets generated in two aerosol-generating health care procedures,i.e.taking nasopharyngeal aspirates(NPA)and nebulizer therapy.Glass slides and water-sensitive paper(WSP)are used to collect large droplets when taking NPA.Droplet stain-marks on glass slides are counted under a microscope,and then a size analysis is performed.During nebulizer therapy dust monitors are used to detect small droplets and droplet nuclei at different positions around the nebulizer and in the room.From the preliminary results it is found that taking NPA can stimulate coughing and generate large droplets.Nebulizers can generate more than tens of millions fine droplets ranging from 0.3 to 20 μm per minute,a large volume of which can escape from the holes on the nebulizer's facemask and disperse in the whole room.Droplets coagulate on the inner surface of the mask and the volunteer's face,suggesting a great possibility of drug solution contamination by patients' secretion during nebulizer therapy.
基金Supported by Grants from the Instituto de Salud Carlos III (C03/02), and from the Consejería de Educación, Cultura y Deportes, Gobierno de Canarias, No.PI2002/138
文摘AIM: To compare the cleansing quality of polyethylene glycol electrolyte solution and sodium phosphate with different schedules of administration, and to evaluate whether the timing of the administration of bowel preparation affects the detection of polyps. METHODS: One hundred and seventy-seven consecutive outpatients scheduled for colonoscopy were randomized in one of four groups to receive polyethylene glycol electrolyte solution or oral sodium phosphate with two different timing schedules. Quality of cleansing, polyp detection, and tolerance were evaluated. RESULTS: Patients receiving polyethylene glycol or sodium phosphate on the same day as the colonoscopy, obtained good to excellent global cleansing scores more frequently than patients who received polyethylene glycol or sodium phosphate on the day prior to the procedure (P 〈 0.001). Flat lesions, but not fiat adenomas, were more frequent in patients prepared on the same day (P = 0.02). CONCLUSION: The quality of colonic cleansing and the detection of fiat lesions are significantly improved when the preparation is taken on the day of the colonoscopy.
文摘Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal mac- rophages play an important role in the mucosal im- mune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major con- tributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of the inflammatory process in IBD. Therefore, several cyto- kine therapies have been developed and tested for the treatment of IBD patients.
文摘Probiotic agents are live microbes or components of microbes that have a positive effect on the host. They exert their action through interplay with the immune system of the host. Some of this effect is local and some is systemic. The full story is yet to be discovered. Probiotics have a definite positive effect on rotavirus diarrhea, post antibiotic diarrhea and pouchitis. Their exact role in inflammatory bowel disease, irritable bowel syndrome, other forms of infectious diarrhea, and prevention of cancer is yet to be determined. This review summarizes the data about probiotics in these conditions.
文摘AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis. METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 ug/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori(Hpylon) culture. IL-17 and IL-8 protein levels in culture supematants were assayed by ELISA. IL- 17 mRNA expression was analyzed by reverse transcriptasepolymerase chain reaction (RT-PCR). Hpylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (UPA). IL-8 levels in culture supematants were assayed after AGS cells were co-cultured with Hpylori strain 26 695 or recombinant human (rh) IL-17. RESULTS: All 36 GU patients and 15 of 29 NU patients were found to be Hpy/or/-positive, while 14 NU patients were Hpylori-nogative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAsl/ml-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2 499; Hpylori negative NU patients: median 104 pg/mg/protein, range 16-312, P〈0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1 356 pcj/mg/protein, range 121-1 3730; antrum: median 761 pg/mg/protein, range 24-7 620, P〈0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the Hpylori-negativecontrols showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r = 0.62,P〈0.0001; antrum: r = 0.61, P〈0.0001) in GU patients. RhIL-17 and Hpylori strain 26 695 each stimulated IL-8 production from AGS cells. CONCLUSION: IL-17 may play an important role in the inflammatory response to Hpyloricolonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.
基金Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science,and Technology of Japan,No.19590784
文摘AIM: To investigate Kupffer cell dynamics and phagocytic activity,using a rat nonalcoholic steatohepatitis (NASH) model. METHODS: Male F344 rats were fed either a control diet or a choline-deficient L-amino acid-defined (CDAA) diet,followed by contrast enhanced ultrasonography (CEUS) using Levovist. The uptake of latex beads by the Kupffer cells was determined by fluorescent microscopy. The status of the Kupffer cells was compared between the two groups,using the immunohistochemical staining technique. RESULTS: After 4 or more wk of the CDAA diet,CEUS examination revealed a decrease in the signal intensity,20 min after intravenous Levovist. Fluorescent microscopic examination showed that the uptake of latex beads by the Kupffer cells was reduced at week 1 and 2 in the study group,compared with the controls,with no further reduction after 3 wk. Immunohistochemical staining revealed no significant difference in the Kupffer cell counts between the control group and the CDAA group. CONCLUSION: CEUS examination using Levovist demonstrated reduced contrast effect and phagocytic activity in the liver parenchymal phase,although the Kupffer cell numbers were unchanged,indicating reduced phagocytic function of the Kupffer cells in the rat NASH model. We believe that CEUS examination using Levovist is a useful screening modality,which can detect NASH in fatty liver patients.
文摘Obstructed defecation (OD) and fecal incontinence (FI) are challenging clinical problems, which are commonly encountered in the practice of colorectal surgeons and gastroenterologists. These disorders sodally and psychologically distress patients and greatly impair their quality of life. The underlying anatomical and pathophysiological changes are complex, often incompletely understood and cannot always be determined. As a consequence, many medical, surgical, and behavioral approaches have been described, with no panacea. Over the past decade, advances in an understanding of these disorders together with rational and similar methods of evaluation in anorectal physiology laboratories (ARP), radiology studies, and new surgical techniques have led to promising results. In this brief review, we discuss treatment strategies and recent updates on clinical and therapeutic aspects of obstructed defecation and fecal incontinence.
文摘Many advances have been made in the understanding of Crohn’s disease (CD) pathogenesis during the last decade. CD is currently seen as a predominantly T-lym-phocyte-driven disease characterized by the presence of a complex cocktail of interacting cytokines, chemokines and other mediators produced by a variety of cell types. Prevailing theories of CD pathogenesis suggest that patients’ T-lymphocytes are inappropriately activated in the setting of an immune imbalance, which is itself caused by an unfortunate confluence of genetic and en- vironmental factors. The T-cell response then leads to the chronic inflammation characteristic for the disease. Various environmental factors may play a role in the development of CD, but microbes are most consistently implied. This theory is based on epidemiological, clinico- pathological, genetic and experimental evidence. Despite the abundance of arguments for the implication of bac-teria in the aetiopathogenesis of CD, the precise role of bacteria in this disease still remains elusive. Three not necessarily mutually exclusive theories have been pro- posed: (1) an unidentified persistent pathogen; (2) an abnormally permeable mucosal barrier leading to exces-sive bacterial translocation; and (3) a breakdown in the balance between putative "protective" versus "harmful" intestinal bacteria ("dysbiosis"). At present, one cannot exclude with certainty any of these three proposed hy-potheses; they may all apply to CD to a certain extent.
基金Zhejiang Provincial Bureau of Education,No.20070227Zhejiang Medical Association,No.2007ZYC18Association of Zhejiang Hospital Administration,No.2007AZHA-KEB312
文摘AIM: To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use.METHODS: Using a structured pro forma, we conducted a two-month survey of the electronic prescriptions containing immediate-release (IR) or sustained-release (SR) product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS: One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori (H pylori) therapy, triple therapy take the dominant position (91.8%), followed by quadruple therapy (4.3%) and dual therapy (3.9%). Amoxicillin was the most frequently co-prescribed antibiotic.Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR, and 6.4% of prescriptions of clarithromycin IR, were prescribed at inappropriate dosing intervals. Surprisingly, disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating Hpy/ori infection although off-label use for this purpose was reported in literature. On the contrary, only one prescription (0.9%) of clarithromycin IR was prescribed for unapproved indication (i.e. gastro-oesophageal reflux disease). 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION: There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease, especially with regard to administration schedule, concordance between indications and diagnoses and management of drug interactions.
文摘Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic in-flammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina pro-pria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-α clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the bio-logical activities of recently-reported cytokines [Inter-leukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-α in the pathophysiology of IBD.
基金Supported by the National Science and Technology Major Project(2011ZX09102-010-04)
文摘Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay.Results The cell line bore a missense mutation in the 6th coding exon (c.676 C〉T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.
文摘Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Recent data suggest thromboembolism as a disease-specific extraintestinal manifestation of IBD, which is developed as the result of multiple interactions between acquired and genetic risk factors. There is evidence indicating an imbalance of procoagulant, anticoagulant and fibrinolitic factors predisposing in thrombosis in patients with IBD. The genetic factors that have been suggested to interfere in the thrombotic manifestations of IBD include factor V Leiden, factor Ⅱ (prothrombin, G20210A), methylenetetrahydrofolate reductase gene mutation (MTHFR, 6777T, plasminogen activator inhibitor type 1 (PAI-1) gene mutation and factor X Ⅲ (val34leu). In this article we review the current data and future prospects on the role of genetic risk factors in the development of thromboembolism in TBD.