AIM: To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 controls.METHODS: Constipation was diagnosed by Rome Ⅱ criteria.Coping ability and anxiety/depre...AIM: To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 controls.METHODS: Constipation was diagnosed by Rome Ⅱ criteria.Coping ability and anxiety/depression were assessed by validated questionnaires. Transit time and balloon distension test were performed.RESULTS: 34.5% patients were classified as slow transit type of constipation. The total colonic transit time (56 h vs 10 h, P＜0.0001) and rectal sensation including urge sensation (79 mL vs 63 mL, P = 0.019) and maximum tolerable volume (110 mL vs95 mL, P = 0.03) differed in patients and controls. Constipated subjects had significantly higher anxiety and depression scores and lower SF-36 scores in all categories. They also demonstrated higher scores of'monitoring' coping strategy (14+6 vs9+3, P = 0.001),which correlated with the rectal distension sensation (P = 0.005), urge sensation (P=0.002), and maximum tolerable volume (P = 0.035). The less use of blunting strategy predicted slow transit constipation in both univariate (P = 0.01) and multivariate analysis (P = 0.03).CONCLUSION: Defective or ineffective use of coping strategies may be an important etiology in functional constipation and subsequently reflected in abnormal anorectal physiology.展开更多
Previously, mouse bone marrow-derived stem cells （MSC） treated with the unspecific DNA methyltransferase inhibitor 5-azacytidine were reported to differentiate into cardiomyocytes. The aim of the present study was t...Previously, mouse bone marrow-derived stem cells （MSC） treated with the unspecific DNA methyltransferase inhibitor 5-azacytidine were reported to differentiate into cardiomyocytes. The aim of the present study was to investigate the efficiency of a similar differentiation strategy in human mononuclear cells obtained from healthy bone marrow donors. After 1-3 passages, cultures were exposed for 24 h to 5-azacytidine （3 μM） followed by 6 weeks of further culture. Drug treatment did not induce expression of myogenic marker MyoD or cardiac markers Nkx2.5 and GATA-4 and did not yield beating cells during follow-up. In patch clamp experiments, approximately 10-15% of treated and untreated cells exhibited L-type Ca^2＋ currents. Almost all cells showed outwardly rectifying K^＋ currents of rapid or slow activation kinetics. Mean current amplitude at ＋60 mV doubled after 6 weeks of treatment compared with time-matched controls. Membrane capacitance of treated cells was significantly larger than in controls 2 weeks after treatment and remained high after 6 weeks, Expression levels of mRNAs for the K^＋ channels Kv 1,1, Kv 1,5, Kv2,1, Kv4,3 and KCNMA 1 and for the Ca^2＋ channel Cav 1.2 were not affected by 5-azacytidine. Treatment with potassium channel blockers tetraethylammonium and clofilium at concentrations shown previously to inhibit rapid or slowly activating K^＋ currents of hMSC inhibited proliferation of these cells. Our results suggest that despite the absence of differentiation ofhMSC into cardiomyocytes, treatme.nt with 5-azacytidine caused profound changes in current density.展开更多
AIM: To evaluate acute cholecystitis, complicated by peritonitis, acute phase response and immunological status in patients treated by laparoscopic or open approach. METHODS: From January 2002 to May 2012, we conducte...AIM: To evaluate acute cholecystitis, complicated by peritonitis, acute phase response and immunological status in patients treated by laparoscopic or open approach. METHODS: From January 2002 to May 2012, we conducted a prospective randomized study on 45 consecutive patients (27 women, 18 men; mean age 58 years). These subjects were taken from a total of 681 patients who were hospitalised presenting similar preoperative findings: acute upper abdominal pain with tenderness, involuntary guarding under the right hypochondrium and/or in the flank; fever higher than 38 ℃, leukocytosis greater than 10 × 10 9 /L or both, and ultrasonographic evidence of calculous cholecystitis possibly complicated by peritonitis. These patients had undergone cholecystectomy for acute calculous cholecystitis,complicated by bile peritonitis. Randomly, 23 patients were assigned to laparoscopic cholecystectomy (LC), and 22 patients to open cholecystectomy (OC). Blood samples were collected from all patients before operation and at days 1, 3 and 6 after surgery. Serum bacteraemia, endotoxaemia, white blood cells (WBCs), WBC subpopulations, human leukocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin-1 (IL-1) and IL-6, and C-reactive protein (CRP) were measured at 0, 30, 60, 90, 120 and 180 min, at 4, 6, 12, 24 h, and then daily (8 A.M.) until post-operative day 6.RESULTS: The two groups were comparable in the severity of peritoneal contamination as indicated by the viable bacterial count (open group = 90% of positive cultures vs laparoscopic group = 87%) and endotoxin level (open group = 33.21 ± 6.32 pg/mL vs laparoscopic group = 35.02 ± 7.23 pg/mL). Four subjects in the OC group (18.1%) and 1 subject (4.3%) in the LC group (P < 0.05) developed intra-abdominal abscess. Severe leukocytosis (range 15.8-19.6/mL) was observed only after OC but not after LC, mostly due to an increase in neutrophils (days 1 and 3, P < 0.05). This value returned to the normal range within 3-4 d after LC and 5-7 d after OC. Other WBC types and lymphoc展开更多
Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative path...Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer(CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of Cp G islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy.展开更多
A prerequisite of a successful statistical downscaling is that large-scale predictors simulated by the General Circulation Model (GCM) must be realistic. It is assumed here that features smaller than the GCM resolutio...A prerequisite of a successful statistical downscaling is that large-scale predictors simulated by the General Circulation Model (GCM) must be realistic. It is assumed here that features smaller than the GCM resolution are important in determining the realism of the large-scale predictors. It is tested whether a three-step method can improve conventional one-step statistical downscaling. The method uses predictors that are upscaled from a dynamical downscaling instead of predictors taken directly from a GCM simulation. The method is applied to downscaling of monthly precipitation in Sweden. The statistical model used is a multiple regression model that uses indices of large-scale atmospheric circulation and 850-hPa specific humidity as predictors. Data from two GCMs (HadCM2 and ECHAM4) and two RCM experiments of the Rossby Centre model (RCA1) driven by the GCMs are used. It is found that upscaled RCA1 predictors capture the seasonal cycle better than those from the GCMs, and hence increase the reliability of the downscaled precipitation. However, there are only slight improvements in the simulation of the seasonal cycle of downscaled precipitation. Due to the cost of the method and the limited improvements in the downscaling results, the three-step method is not justified to replace the one-step method for downscaling of Swedish precipitation.展开更多
AIM： To examine the presence of human papillomavirus （HPV） in esophageal squamous cell carcinoma （ESCC） specimens collected from Colombia and Chile located in the northern and southern ends of the continent, resp...AIM： To examine the presence of human papillomavirus （HPV） in esophageal squamous cell carcinoma （ESCC） specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.METHODS： We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5＋/GP6＋ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16^INK4A protein immunostaining of all the specimens was conducted.RESULTS： HPV was detected in 21 ESCC specimens （29%）. Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases （13%） and in 5 Chilean cases （19%）. HPV-18 was detected in i0 cases （21%） in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 （without statistical significance）, but a significantly lower prevalence of HPV-18 than in Colombian cases （P = 0.011） even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country.CONCLUSION： HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.展开更多
Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent year...Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent years,there are still points of conflict concerning the pathogenesis,immune response,development of new and more effective vaccines,therapies,and treatment.This review focuses on the most important research topics that deal with issues that are currently being solved,those that remain to be solved,and future research directions.For hepatitis A virus we will address epidemiology,molecular surveillance,new susceptible populations as well as environmental and food detections.In the case of hepatitis B virus,we will discuss host factors related to disease,diagnosis,therapy,and vaccine improvement.On hepatitis C virus,we will focus on pathogenesis,immune response,direct action antivirals treatment in the context of solid organ transplantation,issues related to hepatocellular carcinoma development,direct action antivirals resistance due to selection of resistanceassociated variants,and vaccination.Regarding hepatitis D virus,we describe diagnostic methodology,pathogenesis,and therapy.Finally,for hepatitis E virus,we will address epidemiology(including new emerging species),diagnosis,clinical aspects,treatment,the development of a vaccine,and environmental surveillance.展开更多
Quality of life and functional recovery after burn injury is the final goal of burn care,especially as most of burn patients survive the injury due to advanced medical science.However,dysfunction,disfigurement,contrac...Quality of life and functional recovery after burn injury is the final goal of burn care,especially as most of burn patients survive the injury due to advanced medical science.However,dysfunction,disfigurement,contractures,psychological problems and other discomforts due to burns and the consequent scars are common,and physical therapy and occupational therapy provide alternative treatments for these problems of burn patients.This guideline,organized by the Chinese Burn Association and Chinese Association of Burn Surgeons aims to emphasize the importance of team work in burn care and provide a brief introduction of the outlines of physical and occupational therapies during burn treatment,which is suitable for the current medical circumstances of China.It can be used as the start of the tools for burn rehabilitation.展开更多
AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human co...AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control. RESULTS Our results showed that 20 mu mol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3 beta, and beta-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of beta-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice. CONCLUSION TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.展开更多
In recent years,high-entropy alloys(HEAs)have become prominent metallic materials due to their unique design strategies and excellent mechanical properties.The HEAs-inherent high-entropy,lattice-distortion,sluggish-di...In recent years,high-entropy alloys(HEAs)have become prominent metallic materials due to their unique design strategies and excellent mechanical properties.The HEAs-inherent high-entropy,lattice-distortion,sluggish-diffusion,and cocktail effects make HEAs maintain high strength,oxidation resistance,corrosion resistance,wear resistance,and other excellent comprehensive properties,showing stronger competitiveness relative to traditional alloys.Refractory high-entropy alloys(RHEAs)are considered as a new kind of high-temperature materials with great application prospects due to their excellent mechanical properties and have the potential to replace nickel-based superalloy as the next generation of high-temperature materials.We reviewed the research status and preparation methods of RHEAs in recent years,including the metallurgical smelting,powder metallurgy,magnetron sputtering,and additive manufacturing technologies.The microstructure and phase-transformation process of RHEAs were analyzed.The mechan-ical properties and main strengthening and toughening mechanisms of RHEAs,such as solid-solution strengthening,precipitation strengthening,and the transformation-induced plasticity(TRIP),were discussed,and the deformation mechanism of RHEAs was revealed.The properties of RHEAs,including high strength,oxidation resistance,corrosion and wear resistance were reviewed.RHEAs will meet the huge market demand in the engineering materials field,but there are still many challenges,such as the tradeoff between high strength and high ductility,structural design,and performance optimization of RHEAs with brittle BCC structures.We believe that this combination of knowledge may shape the future of RHEAs and break through the mutually exclusive conundrum of high strength and high toughness for RHEAs.展开更多
Myeloid cells in tumor tissues constitute a dynamic immune population characterized by a non-uniform phenotype and diverse functional activities.Both tumor-associated macrophages(TAMs),which are more abundantly repres...Myeloid cells in tumor tissues constitute a dynamic immune population characterized by a non-uniform phenotype and diverse functional activities.Both tumor-associated macrophages(TAMs),which are more abundantly represented,and tumor-associated neutrophils(TANs)are known to sustain tumor cell growth and invasion,support neoangiogenesis and suppress anticancer adaptive immune responses.In recent decades,several therapeutic approaches have been implemented in preclinical cancer models to neutralize the tumor-promoting roles of both TAMs and TANs.Some of the most successful strategies have now reached the clinic and are being investigated in clinical trials.In this review,we provide an overview of the recent literature on the evergrowing complexity of the biology of TAMs and TANs and the development of the most promising approaches to target these populations therapeutically in cancer patients.展开更多
In citrus,lignin overaccumulation in the juice sac results in granulation and an unpleasant fruit texture and taste.By integrating metabolic phenotyping and transcriptomic analyses,we found 702 differentially expresse...In citrus,lignin overaccumulation in the juice sac results in granulation and an unpleasant fruit texture and taste.By integrating metabolic phenotyping and transcriptomic analyses,we found 702 differentially expressed genes(DEGs),including 24 transcription factors(TFs),to be significantly correlated with lignin content.CgMYB58 was further identified as a critical R2R3 MYB TF involved in lignin overaccumulation owing to its high transcript levels in Huanong Red-fleshed pummelo(HR,Citrus grandis)fruits.Transient expression of CgMYB58 led to an increase in the lignin content in the pummelo fruit mesocarp,whereas its stable overexpression significantly promoted lignin accumulation and upregulated 19 lignin biosynthetic genes.Among these genes,CgPAL1,CgPAL2,Cg4CL1,and CgC3H were directly modulated by CgMYB58 through interaction with their promoter regions.Moreover,we showed that juice sac granulation in pummelo fruits could be affected by indole-3-acetic acid(IAA)and abscisic acid(ABA)treatments.In HR pummelo,ABA significantly accelerated this granulation,whereas IAA effectively inhibited this process.Taken together,these results provide novel insight into the lignin accumulation mechanism in citrus fruits.We also revealed the theoretical basis via exogenous IAA application,which repressed the expression of CgMYB58 and its target genes,thus alleviating juice sac granulation in orchards.展开更多
Gaseous molecules, such as hydrogen sulfide(H_2S)and nitric oxide(NO), are crucial players in cellular and(patho)physiological processes in biological systems. The biological functions of these gaseous molecules, whic...Gaseous molecules, such as hydrogen sulfide(H_2S)and nitric oxide(NO), are crucial players in cellular and(patho)physiological processes in biological systems. The biological functions of these gaseous molecules, which were first discovered and identified as gasotransmitters in animals, have received unprecedented attention from plant scientists in recent decades. Researchers have arrived at the consensus that H_2S is synthesized endogenously and serves as a signaling molecule throughout the plant life cycle.However, the mechanisms of H_2S action in redox biology is still largely unexplored. This review highlights what we currently know about the characteristics and biosynthesis of H_2S in plants. Additionally,we summarize the role of H_2S in plant resistance to abiotic stress. Moreover, we propose and discuss possible redox-dependent mechanisms by which H_2S regulates plant physiology.展开更多
There are a number of sources of uncertainty in regional climate change scenarios. When statistical downscaling is used to obtain regional climate change scenarios, the uncertainty may originate from the uncertainties...There are a number of sources of uncertainty in regional climate change scenarios. When statistical downscaling is used to obtain regional climate change scenarios, the uncertainty may originate from the uncertainties in the global climate models used, the skill of the statistical model, and the forcing scenarios applied to the global climate model. The uncertainty associated with global climate models can be evaluated by examining the differences in the predictors and in the downscaled climate change scenarios based on a set of different global climate models. When standardized global climate model simulations such as the second phase of the Coupled Model Intercomparison Project （CMIP2） are used, the difference in the downscaled variables mainly reflects differences in the climate models and the natural variability in the simulated climates. It is proposed that the spread of the estimates can be taken as a measure of the uncertainty associated with global climate models. The proposed method is applied to the estimation of global-climate-model-related uncertainty in regional precipitation change scenarios in Sweden. Results from statistical downscaling based on 17 global climate models show that there is an overall increase in annual precipitation all over Sweden although a considerable spread of the changes in the precipitation exists. The general increase can be attributed to the increased large-scale precipitation and the enhanced westerly wind. The estimated uncertainty is nearly independent of region. However, there is a seasonal dependence. The estimates for winter show the highest level of confidence, while the estimates for summer show the least.展开更多
Hydrogen sulfide(H2S)is a signaling molecule that regulates plant hormone and stress responses.The phytohormone abscisic acid(ABA)plays an important role in plant adaptation to unfavorable environmental conditions and...Hydrogen sulfide(H2S)is a signaling molecule that regulates plant hormone and stress responses.The phytohormone abscisic acid(ABA)plays an important role in plant adaptation to unfavorable environmental conditions and induces the persulfidation of L-CYSTEINE DESULFHYDRASE1(DES1)and the production of H2S in guard cells.However,it remains largely unclear how H2S and protein persulfidation participate in the relay of ABA signals.In this study,we discovered that ABSCISIC ACID INSENSITIVE 4(ABI4)acts downstream of DES1 in the control of ABA responses in Arabidopsis.ABI4 undergoes persulfidation at Cys250 that is triggered in a time-dependent manner by ABA,and loss of DES1 function impairs this process.Cys250 and its persulfidation are essential for ABI4 function in the regulation of plant responses to ABA and the H2S donor NaHS during germination,seedling establishment,and stomatal closure,which are abolished in the ABI4Cys250Ala mutated variant.Introduction of the ABI4Cys250Ala variant into the abi4 des1 mutant did not rescue its hyposensitivity to ABA.Cys250 is critical for the binding of ABI4 to its cognate motif in the promoter of Mitogen-Activated Protein Kinase Kinase Kinase 18(MAPKKK18),which propagates the MAPK signaling cascade induced by ABA.Furthermore,the DES1-mediated persulfidation of ABI4 enhances the transactivation activity of ABI4 toward MAPKKK18,and ABI4 can bind the DES1 promoter,forming a regulatory loop.Taken together,these findings advance our understanding of a post-translational regulatory mechanism and suggest that ABI4 functions as an integrator of ABA and MAPK signals through a process in which DES1-produced H2S persulfidates ABI4 at Cys250.展开更多
文摘AIM: To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 controls.METHODS: Constipation was diagnosed by Rome Ⅱ criteria.Coping ability and anxiety/depression were assessed by validated questionnaires. Transit time and balloon distension test were performed.RESULTS: 34.5% patients were classified as slow transit type of constipation. The total colonic transit time (56 h vs 10 h, P＜0.0001) and rectal sensation including urge sensation (79 mL vs 63 mL, P = 0.019) and maximum tolerable volume (110 mL vs95 mL, P = 0.03) differed in patients and controls. Constipated subjects had significantly higher anxiety and depression scores and lower SF-36 scores in all categories. They also demonstrated higher scores of'monitoring' coping strategy (14+6 vs9+3, P = 0.001),which correlated with the rectal distension sensation (P = 0.005), urge sensation (P=0.002), and maximum tolerable volume (P = 0.035). The less use of blunting strategy predicted slow transit constipation in both univariate (P = 0.01) and multivariate analysis (P = 0.03).CONCLUSION: Defective or ineffective use of coping strategies may be an important etiology in functional constipation and subsequently reflected in abnormal anorectal physiology.
文摘Previously, mouse bone marrow-derived stem cells （MSC） treated with the unspecific DNA methyltransferase inhibitor 5-azacytidine were reported to differentiate into cardiomyocytes. The aim of the present study was to investigate the efficiency of a similar differentiation strategy in human mononuclear cells obtained from healthy bone marrow donors. After 1-3 passages, cultures were exposed for 24 h to 5-azacytidine （3 μM） followed by 6 weeks of further culture. Drug treatment did not induce expression of myogenic marker MyoD or cardiac markers Nkx2.5 and GATA-4 and did not yield beating cells during follow-up. In patch clamp experiments, approximately 10-15% of treated and untreated cells exhibited L-type Ca^2＋ currents. Almost all cells showed outwardly rectifying K^＋ currents of rapid or slow activation kinetics. Mean current amplitude at ＋60 mV doubled after 6 weeks of treatment compared with time-matched controls. Membrane capacitance of treated cells was significantly larger than in controls 2 weeks after treatment and remained high after 6 weeks, Expression levels of mRNAs for the K^＋ channels Kv 1,1, Kv 1,5, Kv2,1, Kv4,3 and KCNMA 1 and for the Ca^2＋ channel Cav 1.2 were not affected by 5-azacytidine. Treatment with potassium channel blockers tetraethylammonium and clofilium at concentrations shown previously to inhibit rapid or slowly activating K^＋ currents of hMSC inhibited proliferation of these cells. Our results suggest that despite the absence of differentiation ofhMSC into cardiomyocytes, treatme.nt with 5-azacytidine caused profound changes in current density.
文摘AIM: To evaluate acute cholecystitis, complicated by peritonitis, acute phase response and immunological status in patients treated by laparoscopic or open approach. METHODS: From January 2002 to May 2012, we conducted a prospective randomized study on 45 consecutive patients (27 women, 18 men; mean age 58 years). These subjects were taken from a total of 681 patients who were hospitalised presenting similar preoperative findings: acute upper abdominal pain with tenderness, involuntary guarding under the right hypochondrium and/or in the flank; fever higher than 38 ℃, leukocytosis greater than 10 × 10 9 /L or both, and ultrasonographic evidence of calculous cholecystitis possibly complicated by peritonitis. These patients had undergone cholecystectomy for acute calculous cholecystitis,complicated by bile peritonitis. Randomly, 23 patients were assigned to laparoscopic cholecystectomy (LC), and 22 patients to open cholecystectomy (OC). Blood samples were collected from all patients before operation and at days 1, 3 and 6 after surgery. Serum bacteraemia, endotoxaemia, white blood cells (WBCs), WBC subpopulations, human leukocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin-1 (IL-1) and IL-6, and C-reactive protein (CRP) were measured at 0, 30, 60, 90, 120 and 180 min, at 4, 6, 12, 24 h, and then daily (8 A.M.) until post-operative day 6.RESULTS: The two groups were comparable in the severity of peritoneal contamination as indicated by the viable bacterial count (open group = 90% of positive cultures vs laparoscopic group = 87%) and endotoxin level (open group = 33.21 ± 6.32 pg/mL vs laparoscopic group = 35.02 ± 7.23 pg/mL). Four subjects in the OC group (18.1%) and 1 subject (4.3%) in the LC group (P < 0.05) developed intra-abdominal abscess. Severe leukocytosis (range 15.8-19.6/mL) was observed only after OC but not after LC, mostly due to an increase in neutrophils (days 1 and 3, P < 0.05). This value returned to the normal range within 3-4 d after LC and 5-7 d after OC. Other WBC types and lymphoc
文摘Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer(CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of Cp G islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy.
基金supported by grants from the Chinese Ministry of Science and Technology(2001BA611B-01)the Chinese Academy of Sciences,and SWECLIM which is financed by MISTRA and SMHI.
文摘A prerequisite of a successful statistical downscaling is that large-scale predictors simulated by the General Circulation Model (GCM) must be realistic. It is assumed here that features smaller than the GCM resolution are important in determining the realism of the large-scale predictors. It is tested whether a three-step method can improve conventional one-step statistical downscaling. The method uses predictors that are upscaled from a dynamical downscaling instead of predictors taken directly from a GCM simulation. The method is applied to downscaling of monthly precipitation in Sweden. The statistical model used is a multiple regression model that uses indices of large-scale atmospheric circulation and 850-hPa specific humidity as predictors. Data from two GCMs (HadCM2 and ECHAM4) and two RCM experiments of the Rossby Centre model (RCA1) driven by the GCMs are used. It is found that upscaled RCA1 predictors capture the seasonal cycle better than those from the GCMs, and hence increase the reliability of the downscaled precipitation. However, there are only slight improvements in the simulation of the seasonal cycle of downscaled precipitation. Due to the cost of the method and the limited improvements in the downscaling results, the three-step method is not justified to replace the one-step method for downscaling of Swedish precipitation.
基金Supported by Grants-in-Aid for Scientific Research on Priority Areas of the Ministry of Education, Culture, Sports, Science and Technology, Japan, No. 12218231 and 17015037
文摘AIM： To examine the presence of human papillomavirus （HPV） in esophageal squamous cell carcinoma （ESCC） specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.METHODS： We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5＋/GP6＋ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16^INK4A protein immunostaining of all the specimens was conducted.RESULTS： HPV was detected in 21 ESCC specimens （29%）. Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases （13%） and in 5 Chilean cases （19%）. HPV-18 was detected in i0 cases （21%） in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 （without statistical significance）, but a significantly lower prevalence of HPV-18 than in Colombian cases （P = 0.011） even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country.CONCLUSION： HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.
文摘Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent years,there are still points of conflict concerning the pathogenesis,immune response,development of new and more effective vaccines,therapies,and treatment.This review focuses on the most important research topics that deal with issues that are currently being solved,those that remain to be solved,and future research directions.For hepatitis A virus we will address epidemiology,molecular surveillance,new susceptible populations as well as environmental and food detections.In the case of hepatitis B virus,we will discuss host factors related to disease,diagnosis,therapy,and vaccine improvement.On hepatitis C virus,we will focus on pathogenesis,immune response,direct action antivirals treatment in the context of solid organ transplantation,issues related to hepatocellular carcinoma development,direct action antivirals resistance due to selection of resistanceassociated variants,and vaccination.Regarding hepatitis D virus,we describe diagnostic methodology,pathogenesis,and therapy.Finally,for hepatitis E virus,we will address epidemiology(including new emerging species),diagnosis,clinical aspects,treatment,the development of a vaccine,and environmental surveillance.
文摘Quality of life and functional recovery after burn injury is the final goal of burn care,especially as most of burn patients survive the injury due to advanced medical science.However,dysfunction,disfigurement,contractures,psychological problems and other discomforts due to burns and the consequent scars are common,and physical therapy and occupational therapy provide alternative treatments for these problems of burn patients.This guideline,organized by the Chinese Burn Association and Chinese Association of Burn Surgeons aims to emphasize the importance of team work in burn care and provide a brief introduction of the outlines of physical and occupational therapies during burn treatment,which is suitable for the current medical circumstances of China.It can be used as the start of the tools for burn rehabilitation.
基金Supported by (in part) the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence,No.MOHW105-TDU-B-212-133019
文摘AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control. RESULTS Our results showed that 20 mu mol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3 beta, and beta-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of beta-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice. CONCLUSION TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.
文摘In recent years,high-entropy alloys(HEAs)have become prominent metallic materials due to their unique design strategies and excellent mechanical properties.The HEAs-inherent high-entropy,lattice-distortion,sluggish-diffusion,and cocktail effects make HEAs maintain high strength,oxidation resistance,corrosion resistance,wear resistance,and other excellent comprehensive properties,showing stronger competitiveness relative to traditional alloys.Refractory high-entropy alloys(RHEAs)are considered as a new kind of high-temperature materials with great application prospects due to their excellent mechanical properties and have the potential to replace nickel-based superalloy as the next generation of high-temperature materials.We reviewed the research status and preparation methods of RHEAs in recent years,including the metallurgical smelting,powder metallurgy,magnetron sputtering,and additive manufacturing technologies.The microstructure and phase-transformation process of RHEAs were analyzed.The mechan-ical properties and main strengthening and toughening mechanisms of RHEAs,such as solid-solution strengthening,precipitation strengthening,and the transformation-induced plasticity(TRIP),were discussed,and the deformation mechanism of RHEAs was revealed.The properties of RHEAs,including high strength,oxidation resistance,corrosion and wear resistance were reviewed.RHEAs will meet the huge market demand in the engineering materials field,but there are still many challenges,such as the tradeoff between high strength and high ductility,structural design,and performance optimization of RHEAs with brittle BCC structures.We believe that this combination of knowledge may shape the future of RHEAs and break through the mutually exclusive conundrum of high strength and high toughness for RHEAs.
基金funding from Associazione Italiana Ricerca Cancro(AIRC):AIRC 5X1000 IG-21147 to A.M.
文摘Myeloid cells in tumor tissues constitute a dynamic immune population characterized by a non-uniform phenotype and diverse functional activities.Both tumor-associated macrophages(TAMs),which are more abundantly represented,and tumor-associated neutrophils(TANs)are known to sustain tumor cell growth and invasion,support neoangiogenesis and suppress anticancer adaptive immune responses.In recent decades,several therapeutic approaches have been implemented in preclinical cancer models to neutralize the tumor-promoting roles of both TAMs and TANs.Some of the most successful strategies have now reached the clinic and are being investigated in clinical trials.In this review,we provide an overview of the recent literature on the evergrowing complexity of the biology of TAMs and TANs and the development of the most promising approaches to target these populations therapeutically in cancer patients.
基金supported by the National Key Research and Development Program of China(2018YFD1000204)the National Natural Science Foundation of China(31672102).
文摘In citrus,lignin overaccumulation in the juice sac results in granulation and an unpleasant fruit texture and taste.By integrating metabolic phenotyping and transcriptomic analyses,we found 702 differentially expressed genes(DEGs),including 24 transcription factors(TFs),to be significantly correlated with lignin content.CgMYB58 was further identified as a critical R2R3 MYB TF involved in lignin overaccumulation owing to its high transcript levels in Huanong Red-fleshed pummelo(HR,Citrus grandis)fruits.Transient expression of CgMYB58 led to an increase in the lignin content in the pummelo fruit mesocarp,whereas its stable overexpression significantly promoted lignin accumulation and upregulated 19 lignin biosynthetic genes.Among these genes,CgPAL1,CgPAL2,Cg4CL1,and CgC3H were directly modulated by CgMYB58 through interaction with their promoter regions.Moreover,we showed that juice sac granulation in pummelo fruits could be affected by indole-3-acetic acid(IAA)and abscisic acid(ABA)treatments.In HR pummelo,ABA significantly accelerated this granulation,whereas IAA effectively inhibited this process.Taken together,these results provide novel insight into the lignin accumulation mechanism in citrus fruits.We also revealed the theoretical basis via exogenous IAA application,which repressed the expression of CgMYB58 and its target genes,thus alleviating juice sac granulation in orchards.
基金supported by grants from the National Natural Science Foundation of China (31670255)the Natural Science Foundation of Jiangsu Province(BK20161447)+2 种基金the Fundamental Research Funds for the Central Universities (KYZ201859)the China Postdoctoral Science Foundation (2019M661860)the European Regional Development Fund through the Agencia Estatal de Investigación of Spain (grant No.PID2019-109785GB-IOO)。
文摘Gaseous molecules, such as hydrogen sulfide(H_2S)and nitric oxide(NO), are crucial players in cellular and(patho)physiological processes in biological systems. The biological functions of these gaseous molecules, which were first discovered and identified as gasotransmitters in animals, have received unprecedented attention from plant scientists in recent decades. Researchers have arrived at the consensus that H_2S is synthesized endogenously and serves as a signaling molecule throughout the plant life cycle.However, the mechanisms of H_2S action in redox biology is still largely unexplored. This review highlights what we currently know about the characteristics and biosynthesis of H_2S in plants. Additionally,we summarize the role of H_2S in plant resistance to abiotic stress. Moreover, we propose and discuss possible redox-dependent mechanisms by which H_2S regulates plant physiology.
文摘There are a number of sources of uncertainty in regional climate change scenarios. When statistical downscaling is used to obtain regional climate change scenarios, the uncertainty may originate from the uncertainties in the global climate models used, the skill of the statistical model, and the forcing scenarios applied to the global climate model. The uncertainty associated with global climate models can be evaluated by examining the differences in the predictors and in the downscaled climate change scenarios based on a set of different global climate models. When standardized global climate model simulations such as the second phase of the Coupled Model Intercomparison Project （CMIP2） are used, the difference in the downscaled variables mainly reflects differences in the climate models and the natural variability in the simulated climates. It is proposed that the spread of the estimates can be taken as a measure of the uncertainty associated with global climate models. The proposed method is applied to the estimation of global-climate-model-related uncertainty in regional precipitation change scenarios in Sweden. Results from statistical downscaling based on 17 global climate models show that there is an overall increase in annual precipitation all over Sweden although a considerable spread of the changes in the precipitation exists. The general increase can be attributed to the increased large-scale precipitation and the enhanced westerly wind. The estimated uncertainty is nearly independent of region. However, there is a seasonal dependence. The estimates for winter show the highest level of confidence, while the estimates for summer show the least.
基金supported by grants from the National Natural Science Foundation of China(31670255)the National Natural Science Foundation of China of Jiangsu Province(BK20200561,BK20200282,BK20161447)+3 种基金the National Science Fund for Outstanding Young Scholars(21922702)the China Postdoctoral Science Foundation(2019M661860)the Fundamental Research Funds for the Central Universities(KYZ201859)the European Regional Development Fund through the Agenda Estatal de Investigacion(grant no.PID2019-109785GB-IOO).
文摘Hydrogen sulfide(H2S)is a signaling molecule that regulates plant hormone and stress responses.The phytohormone abscisic acid(ABA)plays an important role in plant adaptation to unfavorable environmental conditions and induces the persulfidation of L-CYSTEINE DESULFHYDRASE1(DES1)and the production of H2S in guard cells.However,it remains largely unclear how H2S and protein persulfidation participate in the relay of ABA signals.In this study,we discovered that ABSCISIC ACID INSENSITIVE 4(ABI4)acts downstream of DES1 in the control of ABA responses in Arabidopsis.ABI4 undergoes persulfidation at Cys250 that is triggered in a time-dependent manner by ABA,and loss of DES1 function impairs this process.Cys250 and its persulfidation are essential for ABI4 function in the regulation of plant responses to ABA and the H2S donor NaHS during germination,seedling establishment,and stomatal closure,which are abolished in the ABI4Cys250Ala mutated variant.Introduction of the ABI4Cys250Ala variant into the abi4 des1 mutant did not rescue its hyposensitivity to ABA.Cys250 is critical for the binding of ABI4 to its cognate motif in the promoter of Mitogen-Activated Protein Kinase Kinase Kinase 18(MAPKKK18),which propagates the MAPK signaling cascade induced by ABA.Furthermore,the DES1-mediated persulfidation of ABI4 enhances the transactivation activity of ABI4 toward MAPKKK18,and ABI4 can bind the DES1 promoter,forming a regulatory loop.Taken together,these findings advance our understanding of a post-translational regulatory mechanism and suggest that ABI4 functions as an integrator of ABA and MAPK signals through a process in which DES1-produced H2S persulfidates ABI4 at Cys250.
