Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and op...Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and optimal volumes of LPA associated with the risks of mortality and disease incidence(i.e.,cardiovascular diseases and cancer).Methods:Data were derived from the population-based UK Biobank cohort study,including 69,492 adults aged 43-78 years.Accelerometermeasured LPA was defined using a validated,published machine learning-based Random Forest activity method,which was categorized into 4 quartile groups.All-cause and cause-specific mortality(cardiovascular disease-and cancer-specific)were determined according to the International Classification of Diseases,10th version codes.Disease incidence was defined based on primary care,hospitalization,or death records.Results:During a median follow-up period of 8.04 years,2024 adults died from all causes,539 from cardiovascular disease,and 1175 from cancer.For all-cause mortality,compared with participants in the lowest quartile of LPA(<3.9 h/day),the hazard ratios(HRs)and 95%confidence intervals(95%CIs)were 0.82(95%CI:0.73-0.93)for those with 3.9 to<5.0 h/day,0.75(95%CI:0.66-0.85)for those with 5.0 to<6.1 h/day,and 0.77(95%CI:0.68-0.88)for those with≥6.1 h/day,respectively.There was an inverse non-linear dose-response association between LPA and all-cause mortality,with an optimal dose of 5.72 h/day(95%CI:5.45-6.41;HR=0.63,95%CI:0.56-0.71)and a minimal dose of 3.59 h/day(95%CI:3.53-8.56;HR=0.81,95%CI:0.78-0.86),with the 5th percentile as the reference.Similar patterns were observed for cause-specific mortality and disease incidence(cardiovascular disease and cancer).Conclusion:Engaging in LPA for~3.5 h/day was conservatively associated with lower risk of mortality and disease incidence,with further risk reductions observed up to an optimal dose of~6.0 h/day.These findings suggest that sufficient LPA offers important health benefits,which can inform the development of future PA guidelines.展开更多
AIM： To assess whether the effectiveness of a combination of transarterial chemoembolization （TACE） and percutaneous ethanol injection （PEI） in the treatment of unresectable hepatocellular carcinoma （HCC） is su...AIM： To assess whether the effectiveness of a combination of transarterial chemoembolization （TACE） and percutaneous ethanol injection （PEI） in the treatment of unresectable hepatocellular carcinoma （HCC） is superior to TACE alone a randomized controlled trial was performed. METHODS： The effect of combination therapy on longterm survival rates and duration of hospitalization was evaluated in 52 previously untreated HCCs, randomly allocated to TACE-PEI （27 pts） or TACE alone （25 pts）. RESULTS： The cumulative survival rate of the TACE group was 75.8% at 6 mo, 62.9% at 12 mo, and 18.0% at 24 mo and of the TACE-PEI group 76.9%, 61.5%, and 38.7%, respectively. Comparison of overall survival in both groups showed no statistically significant difference. Regarding the patients with HCCs Okuda stage I （n = 26）, the median survival of the TACE-PEI group was significantly longer （〉24 mo, median not yet reached in the study period） compared to the TACE group （18.4 mo [range 11.6-21.7 mo]; P = 0.04）. TACE-PEI reduced the relative risk for mortality to 0.4 （95% CI 0.15-0.96） compared to patients who received TACE alone. Median survival in patients with HCCs Okuda stage Ⅱ or Ⅲ was 5.0 mo in the TACE group （1.7 rno-not defined） compared to 10.4 mo in the TACE-PEI group. CONCLUSION： The combination TACE-PEI improved survival time compared to TACE alone. Our study revealed a statistically significant improved survival in HCCs Okuda stage I. Side effects were minor and the combination therapy did not prolong duration of hospitalization considerably.展开更多
AIM： To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal （UGI） bleeding under today＇s therapeutic regimen. METHODS： From 1998 to 2001, 121 patients with the diagnosis ...AIM： To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal （UGI） bleeding under today＇s therapeutic regimen. METHODS： From 1998 to 2001, 121 patients with the diagnosis of UGI bleeding were treated in our hospital. Based on the patients＇ data, a retrospective multivariate data analysis with initially more than 270 single factors was performed. Subsequently, the following potential risk factors underwent a logistic regression analysis： age, gender, initial hemoglobin, coumarines, liver cirrhosis, prothrombin time （PT）, gastric ulcer （small curvature）, duodenal ulcer （bulbus back wall）, Forrest classification, vascular stump, variceal bleeding, MalloryWeiss syndrome, RBC substitution, recurrent bleeding, conservative and surgical therapy. RESULTS： Seventy male （58%） and 51 female （42%） patients with a median age of 70 （range： 21-96） years were treated. Their in-hospital mortality was 14%. While 12% （11/91） of the patients died after conservative therapy, 20% （6/30） died after undergoing surgical therapy. UGI bleeding occurred due to duodenal ulcer （n = 36; 30%）, gastric ulcer （n = 35; 29%）, esophageal varicosis （n = 12; 10%）, Mallory-Weiss syndrome （n = 8, 7%）, erosive lesions of the mucosa （n = 20; 17%）, cancer （n = 5; 4%）, coagulopathy （n = 4; 3%）, lymphoma （n = 2; 2%）, benign tumor （n = 2; 2%） and unknown reason （n = 1, 1%）. A logistic regression analysis of all aforementioned factors revealed that liver cirrhosis and duodenal ulcer （bulbus back wall） were associated risk factors for a fatal course after UGI bleeding. Prior to endoscopy, only liver cirrhosis was an assessable risk factor. Thereafter, liver cirrhosis, the location of a bleeding ulcer （bulbus back wall） andpatients＇ gender （male） were of prognostic importance for the clinical outcome （mortality） of patients with a bleeding ulcer.CONCLUSION： Most prognostic parameters used in clinical routine today are not reliable enough in predicting a patient＇s vital threat posed by an UGI bleeding.Liver cirrhosis, on the other hand, is significantly more frequently associated with an increased risk to die after bleeding of an ulcer located at the posterior duodenal wall.展开更多
AIM： To evaluate whether contrast enhanced ultra- sound （CEUS） might also be used for response predic- tion and early response evaluation in patients receiving bevacizumab based chemotherapy for metastasized colore...AIM： To evaluate whether contrast enhanced ultra- sound （CEUS） might also be used for response predic- tion and early response evaluation in patients receiving bevacizumab based chemotherapy for metastasized colorectal cancer.METHODS： Thirty consecutive patients with non prima- ry resectable liver metastases from colorectal cancer underwent CEUS before treatment （CEUS date 1） and before the second （CEUS date 2） and fourth （CEU5 date 3） cycle of bevacizumab based chemotherapy. Three parameters [PEAK, Time to peak （l-I-P） and RISE RATE]were correlated with radiological response.RESULTS： For neoadjuvant purpose a reduction of tu- mour mass was required to assume clinical response. Based on these response criteria there was a significant （P 〈 0.001） correlation in TTP between metastases of responders （9.08 s） and non-responders （14.76 s） ar- chived on CEUS date 1. By calculating a standardized quotient （metastases divided by normal liver tissue） we were able to define a cut off, predicting response with a sensitivity of 92.3 % and a specificity of 100 %. To reflect a palliative intention only those patients with progressive disease were classified as non-responders. In this stetting -FI-P was also significantly （P 〈 0.01） dif- ferent between responders and non-responders. In con- trast, Peak and Rise rate did not show any significant difference between responder and non-responder. CONCLUSION： CEUS might serve as a surrogate mark- er to predict treatment response in patients with me- tastasized colorectal cancer who receive antiangiogenic therapy.展开更多
Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) is a novel approach in liver surgery that allows for extensive resection of liver parenchyma by inducing a rapid hypertrophy of the fu...Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) is a novel approach in liver surgery that allows for extensive resection of liver parenchyma by inducing a rapid hypertrophy of the future remnant liver. However,recent reports indicate that not all patients eligible for ALPPS will benefit from this procedure. Therefore,careful patient selection will be necessary to fully exploit possible benefits of ALPPS. Here,we provide a comprehensive overview of the technical evolution of ALPPS with a special emphasis on safety and oncologic efficacy. Furthermore,we review the contemporary literature regarding indication and benefits,but also limitations of ALPPS.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is common in the German population,with an even higher prevalence in inflammatory bowel disease patients.AIM To investigate the risk factors for NAFLD in inflammatory ...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is common in the German population,with an even higher prevalence in inflammatory bowel disease patients.AIM To investigate the risk factors for NAFLD in inflammatory bowel disease patients.METHODS This monocentric retrospective study with a cross-sectional and a longitudinal part included 694 patients.Inclusion criteria were diagnosed inflammatory bowel disease,age≥18 years,availability of at least one abdominal ultrasound.Patients with infectious or suspected alcoholic fatty liver disease were excluded.NAFLD was defined by increased echogenicity at liver ultrasound.Demographic characteristics,disease activity and medications were analyzed as potential risk factors.Parameters influencing the course of NAFLD were identified by a generalized linear mixed model.RESULTS Forty-eight percent of Crohn’s disease(CD)patients and 44%of ulcerative colitis patients suffered from NAFLD.Its occurrence was associated with greater age,hypertension and body mass index(BMI)in both groups,and with higher disease activity and dyslipidemia in CD.2467 ultrasound results were included in the longitudinal analysis.Risk factors for NAFLD were age,BMI,higher disease activity,bowel resection(s),endoscopic activity and azathioprine use in CD;and BMI and endoscopic activity in ulcerative colitis.CONCLUSION NAFLD was highly prevalent in this cohort of German inflammatory bowel disease patients.Its risk increased mainly with rising age and BMI.This analysis provides a rationale for non-invasive liver screening in inflammatory bowel disease patients.展开更多
AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcin...AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma. METHODS: In 70 patients with historically proven non neoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion. RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years. A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected. Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P= 0.0004). CONCLUSION: The long-term relapse rate of non neoplastic BE following complete ablation with high-power APC is low (3% per year).展开更多
BACKGROUND: Local ablative procedures such as cryo-surgery and thermo-ablation are increasingly employed as a supplement to liver resection for the therapy of primary and secondary liver tumors. It is still unclear if...BACKGROUND: Local ablative procedures such as cryo-surgery and thermo-ablation are increasingly employed as a supplement to liver resection for the therapy of primary and secondary liver tumors. It is still unclear if the survival time can be extended through local ablative procedures. This prospective study shows operative actions, complications and long-term follow-up of 19 patients undergoing cryotherapy. METHODS: Between 1997 and 1998, 19 patients underwent cryotherapy due to a non-resectable malignant liver tumor (17 patients with metastases of a colon carcinoma, 2 patients with a hepatocellular carcinoma). Twelve patients (63.2%) received cryotherapy only and seven patients (36.8%) received a combination of resection and cryotherapy. The median follow-up period was 23 months. RESULTS: In a total of 59 liver tumors (18 were resected and 41 received cryotherapy), 12 had cryotherapy only, and 7 had a combination of cryotherapy and resection. The 30-day lethality was 0%, and the rate of major complications was 21%. After one year, 27.3% of the patients were still recurrence- free. The recurrence rate for all tumors treated was 58.8%. The median survival time for all patients was 21 months. The one- and three-year survival rates were 62. 5% and 15.8%, respectively. CONCLUSIONS: The mortality for cryotherapy is low, but there is a high rate of complications and long-term tumor control is not sufficient. If local ablative procedures of hepatic lesions are to be performed, not laparotomy but percutaneous, percutaneous thermoablation should be discussed as an alternative therapeutic measure.展开更多
AIM： To evaluate the efficacy of water supplementation treatment in patients with functional dyspepsia or irritable bowe syndrome （IBS） accompanying predominant constipation. METHODS： A total of 3872 patients with...AIM： To evaluate the efficacy of water supplementation treatment in patients with functional dyspepsia or irritable bowe syndrome （IBS） accompanying predominant constipation. METHODS： A total of 3872 patients with functional dyspepsia and 3609 patients with irritable bowel syndrome were enrolled in the study by 18 Italina thermal centres. Patients underwent a first cycle of thermal therapy for 21 d. A year later patients were re-evaluated at the same centre and received another cycle of thermal therapy. A questionnare to collect personal data on social and occupational status, family and pathological case history, life style, clinical records, utilisation of welfare and health structure and devices was administered to each patient at basal time and one year after each thermal treatment. Sixty patients with functional dyspepsia and 20 with IBS and 80 healthy controls received an evaluation of gastric output and oro-cecal transit time by breath test analysis. Breath test was performed at basal time and after water supplementaton therapies. Gastrointestinal symptoms were evaluated at the same time points. Breath samples were analyzed with a mass spectometer and a gascromatograph. Results were expressed as T1/2 and T-lag for octanoic add breath test and as oro-cecal transit time for lactulose breath test. RESULTS： A significant reduction of prevalence of symptoms was observed at the end of the first and second cycles of thermal therapy in dyspeptic and IBS patients, The analysis of variance showed a real and persistant improvement of symptoms in all patients. After water supplementation for 3 wk a reduction of gastric output was observed in 49 （87.5%） of 56 dyspepUc patients. Both T1/2 and T-lag were significantly reduced after the therapy compared to basal values [91 ± 12 （T1/2） and 53± 11 （T-lag）, Tables 1 and 2] with results of octanoic acid breath test similar to healthy subjects. After water supplementation for 3 wk oro-cecal transit time was shorter than that at the beginning of the study. CONCLUSION： Mineral water supplementation treatment for functional dyspepsia or conspipation accompanying IBS can improve gastric add output and intestinal transit time.展开更多
AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS...AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.展开更多
AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS...AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS： The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS： HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant （P=0.49 at 12 too）. In addition, recurrent hepatitis as determined by serum transarninases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo （P= 0.34）.CONCLUSION： Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV- infected patients after liver transplantation.展开更多
Gastric cancer still represents one of the major causes of cancer mortality worldwide.Patients survival is mainly related to stage,with a high proportion of patients with metastatic disease at presentation.Thus,the cu...Gastric cancer still represents one of the major causes of cancer mortality worldwide.Patients survival is mainly related to stage,with a high proportion of patients with metastatic disease at presentation.Thus,the cure rate largely depend upon surgical resection.Despite the additional,albeit small,benefit of adjuvant chemotherapy has been clearly demonstrated,no general consensus has been reached on the best treatment option.Moreover,the narrow therapeutic index of adjuvant chemotherapy(i.e.,limited survival benefit with considerable toxicity)requires a careful assessment of expected risks and benefits for individual patients.Treatment choices vary widely based on the different geographic areas,with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States.In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses.The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery;the same Authors also showed that disease free survival may be used as a surrogate end-point for overall survival.We finally discuss future research issues such as the need of economic evaluations,development of prognostic or predictive biomarkers,and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.展开更多
BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening medical condition requiring hospitalization and often colectomy.Despite the increasing choice of medical thera...BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening medical condition requiring hospitalization and often colectomy.Despite the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases(IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently elucidated.AIM To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.METHODS We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018, and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side effects.RESULTSIn the majority of the 22 included patients(68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d(mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4%were discharged from the hospital under continued oral tacrolimus therapy. In36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 194 d after the initiation of tacrolimus treatment(mean: 97.4 ± 20.8 d). Colectomy-free survival rates at 1, 3, 6 and 12 mo after the initiation of tacrolimus therapy were 90.9%, 86.4%, 77.3% and 68.2%,respectively. The safety profile of tacrolimus was overall favorable. Only two patients discontinued the treatment due to side effects.CONCLUSION The short-term outcome of tacrolimus in steroid-refractory acute severe ulcerative colitis was beneficial, and side effects were rare. In all, tacrolimus therapy appears to be a viable option for short-term treatment of steroidrefractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.展开更多
Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalici...Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalicine and ajmaline are powerful antihypertensive,tranquilizing agents used in hypertension.Yohimbine is an aphrodisiac used in dietary supplements.As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species,we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry(LC–MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using highperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(HPLC–ESI–QTOF–MS/MS) in positive ion mode.We identified and established diagnostic fragment ions and fragmentation pathways using reserpine,ajmalicine,ajmaline,serpentine and yohimbine.The MS/MS spectra of reserpine,ajmalicine,and ajmaline showed C-ring-cleavage whereas E-ring cleavage was observed in serpentine via Retro Diels Alder(RDA).A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula,exact mass measurements and MS/MS analysis.Reserpine,ajmalicine,ajmaline,serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri,Rauwolfia micrantha,Rauwolfia serpentina,Rauwolfia verticillata,Rauwolfia tetraphylla and Rauwolfia vomitoria.Application of LC–MS followed by principal component analysis(PCA) has been successfully used to discriminate among six Rauwolfia species.展开更多
Background: The importance of structurally diverse forests for the conservation of biodiversity and provision of a wide range of ecosystem services has been widely recognised. However, tools to quantify structural div...Background: The importance of structurally diverse forests for the conservation of biodiversity and provision of a wide range of ecosystem services has been widely recognised. However, tools to quantify structural diversity of forests in an objective and quantitative way across many forest types and sites are still needed, for example to support biodiversity monitoring. The existing approaches to quantify forest structural diversity are based on small geographical regions or single forest types, typically using only small data sets.Results: Here we developed an index of structural diversity based on National Forest Inventory(NFI) data of BadenWurttemberg, Germany, a state with 1.3 million ha of diverse forest types in different ownerships. Based on a literature review, 11 aspects of structural diversity were identified a priori as crucially important to describe structural diversity. An initial comprehensive list of 52 variables derived from National Forest Inventory(NFI) data related to structural diversity was reduced by applying five selection criteria to arrive at one variable for each aspect of structural diversity. These variables comprise 1) quadratic mean diameter at breast height(DBH), 2) standard deviation of DBH, 3) standard deviation of stand height, 4) number of decay classes, 5) bark-diversity index, 6) trees with DBH ≥ 40 cm, 7) diversity of flowering and fructification, 8) average mean diameter of downed deadwood, 9) mean DBH of standing deadwood, 10) tree species richness and 11) tree species richness in the regeneration layer. These variables were combined into a simple,additive index to quantify the level of structural diversity, which assumes values between 0 and 1. We applied this index in an exemplary way to broad forest categories and ownerships to assess its feasibility to analyse structural diversity in large-scale forest inventories.Conclusions: The forest structure index presented here can be derived in a similar way from standard inventory variables for most other large-scale forest inventories to provide important information about biodiversity relevant forest conditions and thus provide an evidence-base for forest management and planning as well as reporting.展开更多
AIM： To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model. METHODS： To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine （...AIM： To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model. METHODS： To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine （5-FC）, we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase （YCD） and the yeast uracil phosphoribosyltransferase （YUPRT） gene. RESULTS： In vitro stably transduced Morris rat hepatoma cells （MH） expressing the bifunctional SuperCD suicide gene （MH SuperCD） showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH cells stably expressing YCD solely （MH YCD） or the cytosine deaminase gene of bacterial origin （MH BCD）, respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions （P〈0.01） under both high dose as well as low dose systemic 5-FC application, whereas MH tumors without transgene expression （MH naive） showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness （SuperCD〉〉 YCD〉〉BCD〉〉〉negative control） was defined as a result of a direct in vivo comparison of all three suicide genes. CONCLUSION： Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model, thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.展开更多
基金supported by the National Key Research and Development Plan:Real-Time Intelligent Active Intervention on Integration of Ten Important Chronic Diseases(2020YFC2003504-2,to BX)。
文摘Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and optimal volumes of LPA associated with the risks of mortality and disease incidence(i.e.,cardiovascular diseases and cancer).Methods:Data were derived from the population-based UK Biobank cohort study,including 69,492 adults aged 43-78 years.Accelerometermeasured LPA was defined using a validated,published machine learning-based Random Forest activity method,which was categorized into 4 quartile groups.All-cause and cause-specific mortality(cardiovascular disease-and cancer-specific)were determined according to the International Classification of Diseases,10th version codes.Disease incidence was defined based on primary care,hospitalization,or death records.Results:During a median follow-up period of 8.04 years,2024 adults died from all causes,539 from cardiovascular disease,and 1175 from cancer.For all-cause mortality,compared with participants in the lowest quartile of LPA(<3.9 h/day),the hazard ratios(HRs)and 95%confidence intervals(95%CIs)were 0.82(95%CI:0.73-0.93)for those with 3.9 to<5.0 h/day,0.75(95%CI:0.66-0.85)for those with 5.0 to<6.1 h/day,and 0.77(95%CI:0.68-0.88)for those with≥6.1 h/day,respectively.There was an inverse non-linear dose-response association between LPA and all-cause mortality,with an optimal dose of 5.72 h/day(95%CI:5.45-6.41;HR=0.63,95%CI:0.56-0.71)and a minimal dose of 3.59 h/day(95%CI:3.53-8.56;HR=0.81,95%CI:0.78-0.86),with the 5th percentile as the reference.Similar patterns were observed for cause-specific mortality and disease incidence(cardiovascular disease and cancer).Conclusion:Engaging in LPA for~3.5 h/day was conservatively associated with lower risk of mortality and disease incidence,with further risk reductions observed up to an optimal dose of~6.0 h/day.These findings suggest that sufficient LPA offers important health benefits,which can inform the development of future PA guidelines.
文摘AIM： To assess whether the effectiveness of a combination of transarterial chemoembolization （TACE） and percutaneous ethanol injection （PEI） in the treatment of unresectable hepatocellular carcinoma （HCC） is superior to TACE alone a randomized controlled trial was performed. METHODS： The effect of combination therapy on longterm survival rates and duration of hospitalization was evaluated in 52 previously untreated HCCs, randomly allocated to TACE-PEI （27 pts） or TACE alone （25 pts）. RESULTS： The cumulative survival rate of the TACE group was 75.8% at 6 mo, 62.9% at 12 mo, and 18.0% at 24 mo and of the TACE-PEI group 76.9%, 61.5%, and 38.7%, respectively. Comparison of overall survival in both groups showed no statistically significant difference. Regarding the patients with HCCs Okuda stage I （n = 26）, the median survival of the TACE-PEI group was significantly longer （〉24 mo, median not yet reached in the study period） compared to the TACE group （18.4 mo [range 11.6-21.7 mo]; P = 0.04）. TACE-PEI reduced the relative risk for mortality to 0.4 （95% CI 0.15-0.96） compared to patients who received TACE alone. Median survival in patients with HCCs Okuda stage Ⅱ or Ⅲ was 5.0 mo in the TACE group （1.7 rno-not defined） compared to 10.4 mo in the TACE-PEI group. CONCLUSION： The combination TACE-PEI improved survival time compared to TACE alone. Our study revealed a statistically significant improved survival in HCCs Okuda stage I. Side effects were minor and the combination therapy did not prolong duration of hospitalization considerably.
文摘AIM： To analyze the importance in predicting patients risk of mortality due to upper gastrointestinal （UGI） bleeding under today＇s therapeutic regimen. METHODS： From 1998 to 2001, 121 patients with the diagnosis of UGI bleeding were treated in our hospital. Based on the patients＇ data, a retrospective multivariate data analysis with initially more than 270 single factors was performed. Subsequently, the following potential risk factors underwent a logistic regression analysis： age, gender, initial hemoglobin, coumarines, liver cirrhosis, prothrombin time （PT）, gastric ulcer （small curvature）, duodenal ulcer （bulbus back wall）, Forrest classification, vascular stump, variceal bleeding, MalloryWeiss syndrome, RBC substitution, recurrent bleeding, conservative and surgical therapy. RESULTS： Seventy male （58%） and 51 female （42%） patients with a median age of 70 （range： 21-96） years were treated. Their in-hospital mortality was 14%. While 12% （11/91） of the patients died after conservative therapy, 20% （6/30） died after undergoing surgical therapy. UGI bleeding occurred due to duodenal ulcer （n = 36; 30%）, gastric ulcer （n = 35; 29%）, esophageal varicosis （n = 12; 10%）, Mallory-Weiss syndrome （n = 8, 7%）, erosive lesions of the mucosa （n = 20; 17%）, cancer （n = 5; 4%）, coagulopathy （n = 4; 3%）, lymphoma （n = 2; 2%）, benign tumor （n = 2; 2%） and unknown reason （n = 1, 1%）. A logistic regression analysis of all aforementioned factors revealed that liver cirrhosis and duodenal ulcer （bulbus back wall） were associated risk factors for a fatal course after UGI bleeding. Prior to endoscopy, only liver cirrhosis was an assessable risk factor. Thereafter, liver cirrhosis, the location of a bleeding ulcer （bulbus back wall） andpatients＇ gender （male） were of prognostic importance for the clinical outcome （mortality） of patients with a bleeding ulcer.CONCLUSION： Most prognostic parameters used in clinical routine today are not reliable enough in predicting a patient＇s vital threat posed by an UGI bleeding.Liver cirrhosis, on the other hand, is significantly more frequently associated with an increased risk to die after bleeding of an ulcer located at the posterior duodenal wall.
文摘AIM： To evaluate whether contrast enhanced ultra- sound （CEUS） might also be used for response predic- tion and early response evaluation in patients receiving bevacizumab based chemotherapy for metastasized colorectal cancer.METHODS： Thirty consecutive patients with non prima- ry resectable liver metastases from colorectal cancer underwent CEUS before treatment （CEUS date 1） and before the second （CEUS date 2） and fourth （CEU5 date 3） cycle of bevacizumab based chemotherapy. Three parameters [PEAK, Time to peak （l-I-P） and RISE RATE]were correlated with radiological response.RESULTS： For neoadjuvant purpose a reduction of tu- mour mass was required to assume clinical response. Based on these response criteria there was a significant （P 〈 0.001） correlation in TTP between metastases of responders （9.08 s） and non-responders （14.76 s） ar- chived on CEUS date 1. By calculating a standardized quotient （metastases divided by normal liver tissue） we were able to define a cut off, predicting response with a sensitivity of 92.3 % and a specificity of 100 %. To reflect a palliative intention only those patients with progressive disease were classified as non-responders. In this stetting -FI-P was also significantly （P 〈 0.01） dif- ferent between responders and non-responders. In con- trast, Peak and Rise rate did not show any significant difference between responder and non-responder. CONCLUSION： CEUS might serve as a surrogate mark- er to predict treatment response in patients with me- tastasized colorectal cancer who receive antiangiogenic therapy.
文摘Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) is a novel approach in liver surgery that allows for extensive resection of liver parenchyma by inducing a rapid hypertrophy of the future remnant liver. However,recent reports indicate that not all patients eligible for ALPPS will benefit from this procedure. Therefore,careful patient selection will be necessary to fully exploit possible benefits of ALPPS. Here,we provide a comprehensive overview of the technical evolution of ALPPS with a special emphasis on safety and oncologic efficacy. Furthermore,we review the contemporary literature regarding indication and benefits,but also limitations of ALPPS.
基金the Ethics Committee of the University of Heidelberg(protocol number:S-299/2018).
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is common in the German population,with an even higher prevalence in inflammatory bowel disease patients.AIM To investigate the risk factors for NAFLD in inflammatory bowel disease patients.METHODS This monocentric retrospective study with a cross-sectional and a longitudinal part included 694 patients.Inclusion criteria were diagnosed inflammatory bowel disease,age≥18 years,availability of at least one abdominal ultrasound.Patients with infectious or suspected alcoholic fatty liver disease were excluded.NAFLD was defined by increased echogenicity at liver ultrasound.Demographic characteristics,disease activity and medications were analyzed as potential risk factors.Parameters influencing the course of NAFLD were identified by a generalized linear mixed model.RESULTS Forty-eight percent of Crohn’s disease(CD)patients and 44%of ulcerative colitis patients suffered from NAFLD.Its occurrence was associated with greater age,hypertension and body mass index(BMI)in both groups,and with higher disease activity and dyslipidemia in CD.2467 ultrasound results were included in the longitudinal analysis.Risk factors for NAFLD were age,BMI,higher disease activity,bowel resection(s),endoscopic activity and azathioprine use in CD;and BMI and endoscopic activity in ulcerative colitis.CONCLUSION NAFLD was highly prevalent in this cohort of German inflammatory bowel disease patients.Its risk increased mainly with rising age and BMI.This analysis provides a rationale for non-invasive liver screening in inflammatory bowel disease patients.
文摘AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma. METHODS: In 70 patients with historically proven non neoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion. RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years. A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected. Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P= 0.0004). CONCLUSION: The long-term relapse rate of non neoplastic BE following complete ablation with high-power APC is low (3% per year).
文摘BACKGROUND: Local ablative procedures such as cryo-surgery and thermo-ablation are increasingly employed as a supplement to liver resection for the therapy of primary and secondary liver tumors. It is still unclear if the survival time can be extended through local ablative procedures. This prospective study shows operative actions, complications and long-term follow-up of 19 patients undergoing cryotherapy. METHODS: Between 1997 and 1998, 19 patients underwent cryotherapy due to a non-resectable malignant liver tumor (17 patients with metastases of a colon carcinoma, 2 patients with a hepatocellular carcinoma). Twelve patients (63.2%) received cryotherapy only and seven patients (36.8%) received a combination of resection and cryotherapy. The median follow-up period was 23 months. RESULTS: In a total of 59 liver tumors (18 were resected and 41 received cryotherapy), 12 had cryotherapy only, and 7 had a combination of cryotherapy and resection. The 30-day lethality was 0%, and the rate of major complications was 21%. After one year, 27.3% of the patients were still recurrence- free. The recurrence rate for all tumors treated was 58.8%. The median survival time for all patients was 21 months. The one- and three-year survival rates were 62. 5% and 15.8%, respectively. CONCLUSIONS: The mortality for cryotherapy is low, but there is a high rate of complications and long-term tumor control is not sufficient. If local ablative procedures of hepatic lesions are to be performed, not laparotomy but percutaneous, percutaneous thermoablation should be discussed as an alternative therapeutic measure.
文摘AIM： To evaluate the efficacy of water supplementation treatment in patients with functional dyspepsia or irritable bowe syndrome （IBS） accompanying predominant constipation. METHODS： A total of 3872 patients with functional dyspepsia and 3609 patients with irritable bowel syndrome were enrolled in the study by 18 Italina thermal centres. Patients underwent a first cycle of thermal therapy for 21 d. A year later patients were re-evaluated at the same centre and received another cycle of thermal therapy. A questionnare to collect personal data on social and occupational status, family and pathological case history, life style, clinical records, utilisation of welfare and health structure and devices was administered to each patient at basal time and one year after each thermal treatment. Sixty patients with functional dyspepsia and 20 with IBS and 80 healthy controls received an evaluation of gastric output and oro-cecal transit time by breath test analysis. Breath test was performed at basal time and after water supplementaton therapies. Gastrointestinal symptoms were evaluated at the same time points. Breath samples were analyzed with a mass spectometer and a gascromatograph. Results were expressed as T1/2 and T-lag for octanoic add breath test and as oro-cecal transit time for lactulose breath test. RESULTS： A significant reduction of prevalence of symptoms was observed at the end of the first and second cycles of thermal therapy in dyspeptic and IBS patients, The analysis of variance showed a real and persistant improvement of symptoms in all patients. After water supplementation for 3 wk a reduction of gastric output was observed in 49 （87.5%） of 56 dyspepUc patients. Both T1/2 and T-lag were significantly reduced after the therapy compared to basal values [91 ± 12 （T1/2） and 53± 11 （T-lag）, Tables 1 and 2] with results of octanoic acid breath test similar to healthy subjects. After water supplementation for 3 wk oro-cecal transit time was shorter than that at the beginning of the study. CONCLUSION： Mineral water supplementation treatment for functional dyspepsia or conspipation accompanying IBS can improve gastric add output and intestinal transit time.
基金Supported by The Dietmar Hopp Foundation and the Manfred Lautenschlger Foundation,an Olympia-Morata fellowship of the University of Heidelberg (Millonig G)
文摘AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.
文摘AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS： The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS： HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant （P=0.49 at 12 too）. In addition, recurrent hepatitis as determined by serum transarninases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo （P= 0.34）.CONCLUSION： Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV- infected patients after liver transplantation.
文摘Gastric cancer still represents one of the major causes of cancer mortality worldwide.Patients survival is mainly related to stage,with a high proportion of patients with metastatic disease at presentation.Thus,the cure rate largely depend upon surgical resection.Despite the additional,albeit small,benefit of adjuvant chemotherapy has been clearly demonstrated,no general consensus has been reached on the best treatment option.Moreover,the narrow therapeutic index of adjuvant chemotherapy(i.e.,limited survival benefit with considerable toxicity)requires a careful assessment of expected risks and benefits for individual patients.Treatment choices vary widely based on the different geographic areas,with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States.In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses.The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery;the same Authors also showed that disease free survival may be used as a surrogate end-point for overall survival.We finally discuss future research issues such as the need of economic evaluations,development of prognostic or predictive biomarkers,and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.
文摘BACKGROUND Acute severe ulcerative colitis unresponsive to systemic steroid treatment is a lifethreatening medical condition requiring hospitalization and often colectomy.Despite the increasing choice of medical therapy options for ulcerative colitis, the condition remains a great challenge in the field of inflammatory bowel diseases(IBD). The performance of the calcineurin inhibitor tacrolimus in this clinical setting is insufficiently elucidated.AIM To evaluate the short and long-term outcomes of tacrolimus therapy in adult inpatients with steroid-refractory acute severe ulcerative colitis.METHODS We conducted a retrospective monocentric study enrolling 22 patients at a tertiary care center for the treatment of IBD. All patients who were admitted to one of the wards of the Department of Gastroenterology and Hepatology of the Heidelberg University Hospital with acute severe ulcerative colitis between 2007 and 2018, and who received oral or intravenous tacrolimus for steroid-refractory disease were included. Baseline characteristics and data on the disease courses were retrieved from entirely computerized patient charts. The primary study endpoint was clinical response to tacrolimus therapy, resulting in discharge from the hospital. Secondary study endpoints were colectomy rate and time to colectomy, achievement of clinical remission under tacrolimus therapy, and the occurrence of side effects.RESULTSIn the majority of the 22 included patients(68.2%), tacrolimus therapy was initiated intravenously and subsequently converted to oral administration. The treatment duration was 128 ± 28.5 d(mean ± SEM), and the patients were followed up for 705 ± 110 d after treatment initiation. Among all patients, 86.4%were discharged from the hospital under continued oral tacrolimus therapy. In36.4% of the patients, the administration of tacrolimus resulted in clinical remission at some point during the treatment. Thirty-two percent of the patients underwent colectomy between 5 and 194 d after the initiation of tacrolimus treatment(mean: 97.4 ± 20.8 d). Colectomy-free survival rates at 1, 3, 6 and 12 mo after the initiation of tacrolimus therapy were 90.9%, 86.4%, 77.3% and 68.2%,respectively. The safety profile of tacrolimus was overall favorable. Only two patients discontinued the treatment due to side effects.CONCLUSION The short-term outcome of tacrolimus in steroid-refractory acute severe ulcerative colitis was beneficial, and side effects were rare. In all, tacrolimus therapy appears to be a viable option for short-term treatment of steroidrefractory acute severe ulcerative colitis besides ciclosporin and anti-tumor necrosis factor α treatment.
基金Council of Scientific Industrial Research,India for providing financial support
文摘Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalicine and ajmaline are powerful antihypertensive,tranquilizing agents used in hypertension.Yohimbine is an aphrodisiac used in dietary supplements.As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species,we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry(LC–MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using highperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(HPLC–ESI–QTOF–MS/MS) in positive ion mode.We identified and established diagnostic fragment ions and fragmentation pathways using reserpine,ajmalicine,ajmaline,serpentine and yohimbine.The MS/MS spectra of reserpine,ajmalicine,and ajmaline showed C-ring-cleavage whereas E-ring cleavage was observed in serpentine via Retro Diels Alder(RDA).A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula,exact mass measurements and MS/MS analysis.Reserpine,ajmalicine,ajmaline,serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri,Rauwolfia micrantha,Rauwolfia serpentina,Rauwolfia verticillata,Rauwolfia tetraphylla and Rauwolfia vomitoria.Application of LC–MS followed by principal component analysis(PCA) has been successfully used to discriminate among six Rauwolfia species.
基金supported by a grant from the Ministry of Science,Research and the Arts of Baden-Württemberg(7533-10-5-78)to Jürgen BauhusFelix Storch received additional support through the BBW ForWerts Graduate Program
文摘Background: The importance of structurally diverse forests for the conservation of biodiversity and provision of a wide range of ecosystem services has been widely recognised. However, tools to quantify structural diversity of forests in an objective and quantitative way across many forest types and sites are still needed, for example to support biodiversity monitoring. The existing approaches to quantify forest structural diversity are based on small geographical regions or single forest types, typically using only small data sets.Results: Here we developed an index of structural diversity based on National Forest Inventory(NFI) data of BadenWurttemberg, Germany, a state with 1.3 million ha of diverse forest types in different ownerships. Based on a literature review, 11 aspects of structural diversity were identified a priori as crucially important to describe structural diversity. An initial comprehensive list of 52 variables derived from National Forest Inventory(NFI) data related to structural diversity was reduced by applying five selection criteria to arrive at one variable for each aspect of structural diversity. These variables comprise 1) quadratic mean diameter at breast height(DBH), 2) standard deviation of DBH, 3) standard deviation of stand height, 4) number of decay classes, 5) bark-diversity index, 6) trees with DBH ≥ 40 cm, 7) diversity of flowering and fructification, 8) average mean diameter of downed deadwood, 9) mean DBH of standing deadwood, 10) tree species richness and 11) tree species richness in the regeneration layer. These variables were combined into a simple,additive index to quantify the level of structural diversity, which assumes values between 0 and 1. We applied this index in an exemplary way to broad forest categories and ownerships to assess its feasibility to analyse structural diversity in large-scale forest inventories.Conclusions: The forest structure index presented here can be derived in a similar way from standard inventory variables for most other large-scale forest inventories to provide important information about biodiversity relevant forest conditions and thus provide an evidence-base for forest management and planning as well as reporting.
基金Supported by grants from German Research Foundation (LA649-20-2)Federal Ministry of Education, Science, Research and Technology (Fo. 01KS9602, Fo. 01KV9532)Interdisciplinary Clinical Research Center (IZKF) Tubingen, and the fortune-program of the Medical Faculty of Eberhard-Karls-University Tubingen (F. 1281127)W.A.W. supported by a scholarship from Pinguin Foundation (Henkel KGaA)
文摘AIM： To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model. METHODS： To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine （5-FC）, we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase （YCD） and the yeast uracil phosphoribosyltransferase （YUPRT） gene. RESULTS： In vitro stably transduced Morris rat hepatoma cells （MH） expressing the bifunctional SuperCD suicide gene （MH SuperCD） showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH cells stably expressing YCD solely （MH YCD） or the cytosine deaminase gene of bacterial origin （MH BCD）, respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions （P〈0.01） under both high dose as well as low dose systemic 5-FC application, whereas MH tumors without transgene expression （MH naive） showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness （SuperCD〉〉 YCD〉〉BCD〉〉〉negative control） was defined as a result of a direct in vivo comparison of all three suicide genes. CONCLUSION： Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model, thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.
