Based on the foundation laid by the h-index we introduce and study the R- and AR-indices. These new indices eliminate some of the disadvantages of the h-index, especially when they are used in combina-tion with the h-...Based on the foundation laid by the h-index we introduce and study the R- and AR-indices. These new indices eliminate some of the disadvantages of the h-index, especially when they are used in combina-tion with the h-index. The R-index measures the h-core’s citation intensity, while AR goes one step further and takes the age of publications into account. This allows for an index that can actually in-crease and decrease over time. We propose the pair (h, AR) as a meaningful indicator for research evaluation. We further prove a relation characterizing the h-index in the power law model.展开更多
D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucos...D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials(RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council(MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recur-rence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.展开更多
Pancreatic cancer is associated with a poor prognosis,and surgical resection remains the only chance for curative therapy.In the absence of metastatic disease,which would preclude resection,assessment of vascular inva...Pancreatic cancer is associated with a poor prognosis,and surgical resection remains the only chance for curative therapy.In the absence of metastatic disease,which would preclude resection,assessment of vascular invasion is an important parameter for determining resectability of pancreatic cancer.A frequent error is to misdiagnose an involved major vessel.Obviously,surgical exploration with pathological examination remains the"gold standard"in terms of evaluation of resectability,especially from the point of view of vascular involvement.However,current imaging modalities have improved and allow detection of vascular invasion with more accuracy.A venous resection in pancreatic cancer is a feasible technique and relatively reliable.Nevertheless,a survival benefit is not achieved by curative resection in patients with pancreatic cancer and vascular invasion.Although the discovery of an arterial invasion during the operation might require an aggressive management,discovery before the operation should be considered as a contraindication.Detection of vascular invasion remains one of the most important challenges in pancreatic surgery.The aim of this article is to provide a complete review of the different imaging modalities in the detection of vascular invasion in pancreatic cancer.展开更多
Transarterial chemoembolization(TACE) is the current standard of care for patients with large or multinodular hepatocellular carcinoma(HCC), preserved liver function, absence of cancer-related symptoms and no evidence...Transarterial chemoembolization(TACE) is the current standard of care for patients with large or multinodular hepatocellular carcinoma(HCC), preserved liver function, absence of cancer-related symptoms and no evidence of vascular invasion or extrahepatic spread(i.e., those classified as intermediate stage according to the Barcelona Clinic Liver Cancer staging system). The rationale for TACE is that the intra-arterial injection of a chemotherapeutic drug such as doxorubicin or cisplatin followed by embolization of the blood vessel will result in a strong cytotoxic effect enhanced by ischemia. However, TACE is a very heterogeneous operative technique and varies in terms of chemotherapeutic agents, treatment devices and schedule. In order to overcome the major drawbacks of conventional TACE(c TACE), non-resorbable drug-eluting beads(DEBs) loaded with cytotoxic drugs have been developed. DEBs are able to slowly release the drug upon injection and increase the intensity and duration of ischemia while enhancing the drug delivery to the tumor. Unfortunately, despite the theoretical advantages of this new device and the promising results of the pivotal studies, definitive data in favor of its superiority over c TACE are still lacking. The recommendation for TACE as the standard-of-care for intermediate-stage HCC is based on the demonstration of improved survival compared with best supportive care or suboptimal therapies in a meta-analysis of six randomized controlled trials, but other therapeutic options(namely, surgery and radioembolization) proved competitive in selected subsets of intermediate HCC patients. Other potential fields of application of TACE in hepato-oncology are the pre-transplant setting(as downstaging/bridging treatment) and the early stage(in patients unsuitable to curative therapy). The potential of TACE in selectedadvanced patients with segmental portal vein thrombosis and preserved liver function deserves further reports.展开更多
AIM: To study the safety of epidural anesthesia(EA),its effect on pancreatic perfusion and the outcome of patients with acute pancreatitis(AP).METHODS: From 2005 to August 2010,patients with predicted severe AP [Ranso...AIM: To study the safety of epidural anesthesia(EA),its effect on pancreatic perfusion and the outcome of patients with acute pancreatitis(AP).METHODS: From 2005 to August 2010,patients with predicted severe AP [Ranson score ≥ 2,C-reactive protein > 100 or necrosis on computed tomography(CT)] were prospectively randomized to either a group receiving EA or a control group treated by patientcontrolled intravenous analgesia. Pain management was evaluated in the two groups every eight hours using the visual analog pain scale(VAS). Parameters for clinical severity such as length of hospital stay,use of antibiotics,admission to the intensive care unit,radiological/clinical complications and the need for surgical necrosectomy including biochemical data were recorded. A CT scan using a perfusion protocol was performed on admission and at 72 h to evaluate pancreatic blood flow. A significant variation in blood flow was defined as a 20% difference in pancreatic perfusion between admission and 72 h and was measured in the head,body and tail of the pancreas.RESULTS: We enrolled 35 patients. Thirteen were randomized to the EA group and 22 to the control group. There were no differences in demographic characteristics between the two groups. The Balthazar radiological severity score on admission was higher in the EA group than in the control group(mean score 4.15 ± 2.54 vs 3.38 ± 1.75,respectively,P = 0.347) and the median Ranson scores were 3.4 and 2.7 respectively(P = NS). The median duration of EA was 5.7 d,and no complications of the epidural procedure were reported. An improvement in perfusion of the pancreas was observed in 13/30(43%) of measurements in the EA group vs 2/27(7%) in the control group(P = 0.0025). Necrosectomy was performed in 1/13 patients in the EA group vs 4/22 patients in the control group(P = 0.63). The VAS improved during the first ten days in the EA group compared to the control group(0.2 vs 2.33,P = 0.034 at 10 d). Length of stay and mortality were not statistically different between the 2 groups展开更多
Therapeutic management of Helicobacter pylori(H.pylori)remains an unsolved issue.Indeed,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the admin...Therapeutic management of Helicobacter pylori(H.pylori)remains an unsolved issue.Indeed,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the administration of several consecutive standard therapies.Although antibiotic resistance reports describe alarming results,the outcome of therapeutic regimens does not seem to parallel this scenario in most cases,since a successful performance is often reached in more than 80%of cases.However,the phenomenon of increasing antibiotic resistance is being closely studied,and the results show controversial aspects even in the same geographic area.For the continents of Europe,America,Asia,Africa,and Oceania,minimal and maximal values of resistance to the main antibiotics(clarithromycin,amoxicillin,metronidazole,and levofloxacin)feature wide ranges in different countries.The real enigma is therefore linked to the several different therapeutic regimens,which show results that often do not parallel the in vitro findings even in the same areas.A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts.Moreover,not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome.The additional use of probiotics may help to reduce adverse events,but their therapeutic impact is doubtful.In conclusion,the"ideal therapy",paradoxically,appears to be a"utopia",despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H.pylori.The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide.On these bases,one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances.In this context,geography must be considered a relevant matter.展开更多
AIM To define probiotic monotherapy effect on Helicobacter pylori(H. pylori) status by performing a systematic review.METHODS Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant p...AIM To define probiotic monotherapy effect on Helicobacter pylori(H. pylori) status by performing a systematic review.METHODS Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching Pub Med, MEDLINE, Science Direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios(ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and placebo.RESULTS Eleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14%(95%CI: 2%-25%, P =0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16%(95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12%(95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14%(95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics(95%CI: 2.97-21.05, P < 0.001). Probiotics induced a mean reduction in delta values higher than placebo(8.61% with a 95%CI: 5.88-11.34, vs 0.19% for placebo, P < 0.001). Finally, no significant difference in adverse events was found between probiotics and placebo(OR = 1, 95%CI: 0.06-18.08).CONCLUSION Probiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role.展开更多
5-Methylcytosine （m^5C） is a well-characterized DNA modification, and is also predominantly reported in abundant non-coding RNAs in both prokaryotes and eukaryotes. However, the distribution and biological functions...5-Methylcytosine （m^5C） is a well-characterized DNA modification, and is also predominantly reported in abundant non-coding RNAs in both prokaryotes and eukaryotes. However, the distribution and biological functions of m^5C in plant mRNAs remain largely unknown. Here, we report transcriptome-wide profiling of RNA m^5C in Arabidopsis thaliana by applying m^5C RNA immunoprecipitation followed by a deep- sequencing approach （m^5C-RIP-seq）. LC-MS/MS and dot blot analyses reveal a dynamic pattern of m^5C mRNA modification in various tissues and at different developmental stages, m^5C-RIP-seq analysis identified 6045 m^5C peaks in 4465 expressed genes in young seedlings. We found that m^5C is enriched in coding sequences with two peaks located immediately after start codons and before stop codons, and is associated with mRNAs with low translation activity. We further demonstrated that an RNA （cytosine-5）-methyl- transferase, tRNA-specific methyltransferase 4B （TRM4B）, exhibits m^5C RNA methyltransferase activity. Mutations in TRM4B display defects in root development and decreased m^5C peaks. TRM4B affects the transcript levels of the genes involved in root development, which is positively correlated with their mRNA stability and m^5C levels. Our results suggest that m^5C in mRNA is a new epitranscriptome marker inArabidopsis, and that regulation of this modification is an integral part of gene regulatory networks underlying plant development.展开更多
Inflammatory bowel diseases(IBDs), namely Crohn's disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origi...Inflammatory bowel diseases(IBDs), namely Crohn's disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origin of IBDs is closely linked to immune response alterations, which governs most medical decision-making, recent findings suggest that gut microbiota may be involved in IBD pathogenesis. Epidemiologic evidence and several studies have shown that a dysregulation of gut microbiota(i.e., dysbiosis) may trigger the onset of intestinal disorders such as IBDs. Animal and human investigations focusing on the microbiota-IBD relationship have suggested an altered balance of the intestinal microbial population in the active phase of IBD. Rigorous microbiota typing could, therefore, soon become part of a complete phenotypic analysis of IBD patients. Moreover, individual susceptibility and environmental triggers such as nutrition, medications, age or smoking could modify bacterial strains in the bowel habitat. Pharmacological manipulation of bowel microbiota is somewhat controversial. The employment of antibiotics, probiotics, prebiotics and synbiotics has been widely addressed in theliterature worldwide, with the aim of obtaining positive results in a number of IBD patient settings, and determining the appropriate timing and modality of this intervention. Recently, novel treatments for IBDs, such as fecal microbiota transplantation, when accepted by patients, have shown promising results. Controlled studies are being designed. In the near future, new therapeutic strategies can be expected, with non-pathogenic or modified food organisms that can be genetically modified to exert anti-inflammatory properties.展开更多
The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its c...The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to antibiotics.On these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be administered.Therefore,several tricks need to be used to optimize eradication rate of different regimens.The administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is discouraged.However,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic variables.Finally,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic effect.However current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.展开更多
The inflammatory process plays a central role in the development and progression of numerous pathological situations,such as inflammatory bowel disease(IBD),autoimmune and neurodegenerative diseases,metabolic syndrome...The inflammatory process plays a central role in the development and progression of numerous pathological situations,such as inflammatory bowel disease(IBD),autoimmune and neurodegenerative diseases,metabolic syndrome,and cardiovascular disorders. IBDs involve inflammation of the gastrointestinal area and mainly comprise Crohn's disease(CD) and ulcerative colitis(UC). Both pathological situations usually involve recurring or bloody diarrhea,pain,fatigue and weight loss. There is at present no pharmacological cure for CD or UC. However,surgery may be curative for UC patients. The prescribed treatment aims to ameliorate the symptoms and prevent and/or delay new painful episodes. Flavonoid compounds are a large family of hydroxylated polyphenolic molecules abundant in plants,including vegetables and fruits which are the major dietary sources of these compounds for humans,together with wine and tea. Flavonoids are becoming very popular because they have many health-promoting and disease-preventive effects. Most interest has been directed towards the antioxidant activity of flavonoids,evidencing a remarkable free-radical scavenging capacity. However,accumulating evidence suggests that flavonoids have many other biological properties,including anti-inflammatory,antiviral,anticancer,and neuroprotective activities through different mechanisms of action. The present review analyzes the available data about the different types of flavonoids and their potential effectiveness as adjuvant therapy of IBDs.展开更多
Liver transplant(LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massi...Liver transplant(LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massive bleeding is common and requires blood transfusion. Allogeneic blood transfusion has an immunosuppressive effect and an impact on recipient survival, in addition to the risk of transmission of viral infections and transfusion errors, among others.Techniques to prevent excessive bleeding or to use autologous blood have been proposed to minimize the negative effects of allogeneic blood transfusion.Intraoperative reinfusion of autologous blood is possible through previous selfdonation or blood collected during the operation. However, LT does not normally allow autologous transfusion by prior self-donation. Hence, using autologous blood collected intraoperatively is the most feasible option. The use of intraoperative blood salvage autotransfusion(IBSA) minimizes the perioperative use of allogeneic blood, preventing negative transfusion effects without negatively impacting other clinical outcomes. The use of IBSA in patients with cancer is still a matter of debate due to the theoretical risk of reinfusion of tumor cells. However, studies have demonstrated the safety of IBSA in several surgical procedures, including LT for hepatocellular carcinoma. Considering the literature available to date, we can state that IBSA should be routinely used in LT, both in patients with cancer and in patients with benign diseases.展开更多
The ubiquitous occurrence of perfluorinated compounds(PFCs) in environmental samples has drawn much attention.Recent human exposure studies found relatively high perfluorooctane sulfonate(PFOS) concentrations in blood...The ubiquitous occurrence of perfluorinated compounds(PFCs) in environmental samples has drawn much attention.Recent human exposure studies found relatively high perfluorooctane sulfonate(PFOS) concentrations in blood samples from several cities in China when compared with other countries.The objectives of the present study were:(1) to measure PFC concentrations and compositions in chicken egg samples from local markets in China;and(2) to conduct a preliminary human health risk assessment of egg consumption.Eight pooled egg samples from eight locations were analyzed for 11 PFCs.The results showed that close to 100% of the PFOS in the egg was distributed in egg yolk and PFOS was not detected in egg white(<0.08 ng/g wet weight,w/w).Of the perfluoroalkylsulfonates,only PFOS was detected in all egg samples,while of the perfluoroalkylcarboxylates,perfluoroundecanoic acid(PFUnDA) was detected in all samples,followed by perfluorooctanoate(PFOA)(75% occurrence) and perfluorodecanoic acid(PFDA)(50% occurrence).PFOS concentrations in egg ranged from 45.0 to 86.9 ng/g w/w.The results suggested that current concentrations of PFOS in domestic chicken eggs are unlikely to cause immediate harm to Chinese populations.展开更多
基金Supported by a Major State Basic Research Special Program China under grant (No. 2004CCC00400)National Natural Science Foundation of China (Grant No. 70376019)
文摘Based on the foundation laid by the h-index we introduce and study the R- and AR-indices. These new indices eliminate some of the disadvantages of the h-index, especially when they are used in combina-tion with the h-index. The R-index measures the h-core’s citation intensity, while AR goes one step further and takes the age of publications into account. This allows for an index that can actually in-crease and decrease over time. We propose the pair (h, AR) as a meaningful indicator for research evaluation. We further prove a relation characterizing the h-index in the power law model.
文摘D2 procedure has been accepted in Far East as the standard treatment for both early(EGC) and advanced gastric cancer(AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials(RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council(MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recur-rence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC.
文摘Pancreatic cancer is associated with a poor prognosis,and surgical resection remains the only chance for curative therapy.In the absence of metastatic disease,which would preclude resection,assessment of vascular invasion is an important parameter for determining resectability of pancreatic cancer.A frequent error is to misdiagnose an involved major vessel.Obviously,surgical exploration with pathological examination remains the"gold standard"in terms of evaluation of resectability,especially from the point of view of vascular involvement.However,current imaging modalities have improved and allow detection of vascular invasion with more accuracy.A venous resection in pancreatic cancer is a feasible technique and relatively reliable.Nevertheless,a survival benefit is not achieved by curative resection in patients with pancreatic cancer and vascular invasion.Although the discovery of an arterial invasion during the operation might require an aggressive management,discovery before the operation should be considered as a contraindication.Detection of vascular invasion remains one of the most important challenges in pancreatic surgery.The aim of this article is to provide a complete review of the different imaging modalities in the detection of vascular invasion in pancreatic cancer.
文摘Transarterial chemoembolization(TACE) is the current standard of care for patients with large or multinodular hepatocellular carcinoma(HCC), preserved liver function, absence of cancer-related symptoms and no evidence of vascular invasion or extrahepatic spread(i.e., those classified as intermediate stage according to the Barcelona Clinic Liver Cancer staging system). The rationale for TACE is that the intra-arterial injection of a chemotherapeutic drug such as doxorubicin or cisplatin followed by embolization of the blood vessel will result in a strong cytotoxic effect enhanced by ischemia. However, TACE is a very heterogeneous operative technique and varies in terms of chemotherapeutic agents, treatment devices and schedule. In order to overcome the major drawbacks of conventional TACE(c TACE), non-resorbable drug-eluting beads(DEBs) loaded with cytotoxic drugs have been developed. DEBs are able to slowly release the drug upon injection and increase the intensity and duration of ischemia while enhancing the drug delivery to the tumor. Unfortunately, despite the theoretical advantages of this new device and the promising results of the pivotal studies, definitive data in favor of its superiority over c TACE are still lacking. The recommendation for TACE as the standard-of-care for intermediate-stage HCC is based on the demonstration of improved survival compared with best supportive care or suboptimal therapies in a meta-analysis of six randomized controlled trials, but other therapeutic options(namely, surgery and radioembolization) proved competitive in selected subsets of intermediate HCC patients. Other potential fields of application of TACE in hepato-oncology are the pre-transplant setting(as downstaging/bridging treatment) and the early stage(in patients unsuitable to curative therapy). The potential of TACE in selectedadvanced patients with segmental portal vein thrombosis and preserved liver function deserves further reports.
基金Supported by a research grant of the University Hospitals of Geneva(to Bühler L)
文摘AIM: To study the safety of epidural anesthesia(EA),its effect on pancreatic perfusion and the outcome of patients with acute pancreatitis(AP).METHODS: From 2005 to August 2010,patients with predicted severe AP [Ranson score ≥ 2,C-reactive protein > 100 or necrosis on computed tomography(CT)] were prospectively randomized to either a group receiving EA or a control group treated by patientcontrolled intravenous analgesia. Pain management was evaluated in the two groups every eight hours using the visual analog pain scale(VAS). Parameters for clinical severity such as length of hospital stay,use of antibiotics,admission to the intensive care unit,radiological/clinical complications and the need for surgical necrosectomy including biochemical data were recorded. A CT scan using a perfusion protocol was performed on admission and at 72 h to evaluate pancreatic blood flow. A significant variation in blood flow was defined as a 20% difference in pancreatic perfusion between admission and 72 h and was measured in the head,body and tail of the pancreas.RESULTS: We enrolled 35 patients. Thirteen were randomized to the EA group and 22 to the control group. There were no differences in demographic characteristics between the two groups. The Balthazar radiological severity score on admission was higher in the EA group than in the control group(mean score 4.15 ± 2.54 vs 3.38 ± 1.75,respectively,P = 0.347) and the median Ranson scores were 3.4 and 2.7 respectively(P = NS). The median duration of EA was 5.7 d,and no complications of the epidural procedure were reported. An improvement in perfusion of the pancreas was observed in 13/30(43%) of measurements in the EA group vs 2/27(7%) in the control group(P = 0.0025). Necrosectomy was performed in 1/13 patients in the EA group vs 4/22 patients in the control group(P = 0.63). The VAS improved during the first ten days in the EA group compared to the control group(0.2 vs 2.33,P = 0.034 at 10 d). Length of stay and mortality were not statistically different between the 2 groups
文摘Therapeutic management of Helicobacter pylori(H.pylori)remains an unsolved issue.Indeed,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the administration of several consecutive standard therapies.Although antibiotic resistance reports describe alarming results,the outcome of therapeutic regimens does not seem to parallel this scenario in most cases,since a successful performance is often reached in more than 80%of cases.However,the phenomenon of increasing antibiotic resistance is being closely studied,and the results show controversial aspects even in the same geographic area.For the continents of Europe,America,Asia,Africa,and Oceania,minimal and maximal values of resistance to the main antibiotics(clarithromycin,amoxicillin,metronidazole,and levofloxacin)feature wide ranges in different countries.The real enigma is therefore linked to the several different therapeutic regimens,which show results that often do not parallel the in vitro findings even in the same areas.A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts.Moreover,not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome.The additional use of probiotics may help to reduce adverse events,but their therapeutic impact is doubtful.In conclusion,the"ideal therapy",paradoxically,appears to be a"utopia",despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H.pylori.The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide.On these bases,one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances.In this context,geography must be considered a relevant matter.
文摘AIM To define probiotic monotherapy effect on Helicobacter pylori(H. pylori) status by performing a systematic review.METHODS Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching Pub Med, MEDLINE, Science Direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios(ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and placebo.RESULTS Eleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14%(95%CI: 2%-25%, P =0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16%(95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12%(95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14%(95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics(95%CI: 2.97-21.05, P < 0.001). Probiotics induced a mean reduction in delta values higher than placebo(8.61% with a 95%CI: 5.88-11.34, vs 0.19% for placebo, P < 0.001). Finally, no significant difference in adverse events was found between probiotics and placebo(OR = 1, 95%CI: 0.06-18.08).CONCLUSION Probiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role.
文摘5-Methylcytosine （m^5C） is a well-characterized DNA modification, and is also predominantly reported in abundant non-coding RNAs in both prokaryotes and eukaryotes. However, the distribution and biological functions of m^5C in plant mRNAs remain largely unknown. Here, we report transcriptome-wide profiling of RNA m^5C in Arabidopsis thaliana by applying m^5C RNA immunoprecipitation followed by a deep- sequencing approach （m^5C-RIP-seq）. LC-MS/MS and dot blot analyses reveal a dynamic pattern of m^5C mRNA modification in various tissues and at different developmental stages, m^5C-RIP-seq analysis identified 6045 m^5C peaks in 4465 expressed genes in young seedlings. We found that m^5C is enriched in coding sequences with two peaks located immediately after start codons and before stop codons, and is associated with mRNAs with low translation activity. We further demonstrated that an RNA （cytosine-5）-methyl- transferase, tRNA-specific methyltransferase 4B （TRM4B）, exhibits m^5C RNA methyltransferase activity. Mutations in TRM4B display defects in root development and decreased m^5C peaks. TRM4B affects the transcript levels of the genes involved in root development, which is positively correlated with their mRNA stability and m^5C levels. Our results suggest that m^5C in mRNA is a new epitranscriptome marker inArabidopsis, and that regulation of this modification is an integral part of gene regulatory networks underlying plant development.
文摘Inflammatory bowel diseases(IBDs), namely Crohn's disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origin of IBDs is closely linked to immune response alterations, which governs most medical decision-making, recent findings suggest that gut microbiota may be involved in IBD pathogenesis. Epidemiologic evidence and several studies have shown that a dysregulation of gut microbiota(i.e., dysbiosis) may trigger the onset of intestinal disorders such as IBDs. Animal and human investigations focusing on the microbiota-IBD relationship have suggested an altered balance of the intestinal microbial population in the active phase of IBD. Rigorous microbiota typing could, therefore, soon become part of a complete phenotypic analysis of IBD patients. Moreover, individual susceptibility and environmental triggers such as nutrition, medications, age or smoking could modify bacterial strains in the bowel habitat. Pharmacological manipulation of bowel microbiota is somewhat controversial. The employment of antibiotics, probiotics, prebiotics and synbiotics has been widely addressed in theliterature worldwide, with the aim of obtaining positive results in a number of IBD patient settings, and determining the appropriate timing and modality of this intervention. Recently, novel treatments for IBDs, such as fecal microbiota transplantation, when accepted by patients, have shown promising results. Controlled studies are being designed. In the near future, new therapeutic strategies can be expected, with non-pathogenic or modified food organisms that can be genetically modified to exert anti-inflammatory properties.
文摘The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to antibiotics.On these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be administered.Therefore,several tricks need to be used to optimize eradication rate of different regimens.The administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is discouraged.However,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic variables.Finally,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic effect.However current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.
文摘The inflammatory process plays a central role in the development and progression of numerous pathological situations,such as inflammatory bowel disease(IBD),autoimmune and neurodegenerative diseases,metabolic syndrome,and cardiovascular disorders. IBDs involve inflammation of the gastrointestinal area and mainly comprise Crohn's disease(CD) and ulcerative colitis(UC). Both pathological situations usually involve recurring or bloody diarrhea,pain,fatigue and weight loss. There is at present no pharmacological cure for CD or UC. However,surgery may be curative for UC patients. The prescribed treatment aims to ameliorate the symptoms and prevent and/or delay new painful episodes. Flavonoid compounds are a large family of hydroxylated polyphenolic molecules abundant in plants,including vegetables and fruits which are the major dietary sources of these compounds for humans,together with wine and tea. Flavonoids are becoming very popular because they have many health-promoting and disease-preventive effects. Most interest has been directed towards the antioxidant activity of flavonoids,evidencing a remarkable free-radical scavenging capacity. However,accumulating evidence suggests that flavonoids have many other biological properties,including anti-inflammatory,antiviral,anticancer,and neuroprotective activities through different mechanisms of action. The present review analyzes the available data about the different types of flavonoids and their potential effectiveness as adjuvant therapy of IBDs.
文摘Liver transplant(LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massive bleeding is common and requires blood transfusion. Allogeneic blood transfusion has an immunosuppressive effect and an impact on recipient survival, in addition to the risk of transmission of viral infections and transfusion errors, among others.Techniques to prevent excessive bleeding or to use autologous blood have been proposed to minimize the negative effects of allogeneic blood transfusion.Intraoperative reinfusion of autologous blood is possible through previous selfdonation or blood collected during the operation. However, LT does not normally allow autologous transfusion by prior self-donation. Hence, using autologous blood collected intraoperatively is the most feasible option. The use of intraoperative blood salvage autotransfusion(IBSA) minimizes the perioperative use of allogeneic blood, preventing negative transfusion effects without negatively impacting other clinical outcomes. The use of IBSA in patients with cancer is still a matter of debate due to the theoretical risk of reinfusion of tumor cells. However, studies have demonstrated the safety of IBSA in several surgical procedures, including LT for hepatocellular carcinoma. Considering the literature available to date, we can state that IBSA should be routinely used in LT, both in patients with cancer and in patients with benign diseases.
基金Supported by the Strategic Research Grant at City University of Hong Kong (Grant No. 7001990)
文摘The ubiquitous occurrence of perfluorinated compounds(PFCs) in environmental samples has drawn much attention.Recent human exposure studies found relatively high perfluorooctane sulfonate(PFOS) concentrations in blood samples from several cities in China when compared with other countries.The objectives of the present study were:(1) to measure PFC concentrations and compositions in chicken egg samples from local markets in China;and(2) to conduct a preliminary human health risk assessment of egg consumption.Eight pooled egg samples from eight locations were analyzed for 11 PFCs.The results showed that close to 100% of the PFOS in the egg was distributed in egg yolk and PFOS was not detected in egg white(<0.08 ng/g wet weight,w/w).Of the perfluoroalkylsulfonates,only PFOS was detected in all egg samples,while of the perfluoroalkylcarboxylates,perfluoroundecanoic acid(PFUnDA) was detected in all samples,followed by perfluorooctanoate(PFOA)(75% occurrence) and perfluorodecanoic acid(PFDA)(50% occurrence).PFOS concentrations in egg ranged from 45.0 to 86.9 ng/g w/w.The results suggested that current concentrations of PFOS in domestic chicken eggs are unlikely to cause immediate harm to Chinese populations.
