Alkali and alkaline‐earth metals from fly ash have a significant deactivation effect on catalysts used for selective catalytic reduction of NOx by NH3(NH3‐SCR).Bromides are considered effective additives to improve ...Alkali and alkaline‐earth metals from fly ash have a significant deactivation effect on catalysts used for selective catalytic reduction of NOx by NH3(NH3‐SCR).Bromides are considered effective additives to improve Hg0 oxidation on SCR catalysts.In this work,the effects of different bromides(NH4Br,NaBr,KBr,and CaBr2)on a commercial V2O5‐WO3/TiO2 catalyst were studied.NOx conversion decreased significantly over the KBr‐poisoned catalyst(denoted as L‐KBr),while that over NaBr‐and CaBr2‐poisoned catalysts(denoted as L‐NaBr and L‐CaBr,respectivity)decreased to a lesser extent compared with the fresh sample.Poor N2 selectivity was observed over L‐NaBr,L‐KBr and L‐CaBr catalysts.The decrease in the ratio of chemisorbed oxygen to total surface oxygen(Oα/(Oα+Oβ+Ow)),reducibility and surface acidity might contribute to the poor activity and N2 selectivity over L‐KBr catalyst.The increased Oαratio was conducive to the enhanced reducibility of L‐CaBr.Combined with enhanced surface acidity,this might offset the negative effect of the loss of active sites by CaBr2 covering.The overoxidation of NH3 and poor N2 selectivity in NH3 oxidation should retard the SCR activity at high temperatures over L‐CaBr catalyst.The increased basicity might contribute to increased NOx adsorption on L‐KBr and L‐CaBr catalysts.A correlation between the acid‐basic and redox properties of bromide‐poisoned catalysts and their catalytic properties is established.展开更多
The urea-catalyzed aziridination of 1,2-vicinal haloamines derived from aminohalogenation of olefins has been developed. This rapid and simple method was carried out by simply grinding the solid mixture of the substra...The urea-catalyzed aziridination of 1,2-vicinal haloamines derived from aminohalogenation of olefins has been developed. This rapid and simple method was carried out by simply grinding the solid mixture of the substrate, K2CO3 and catalytic amount of urea at room temperature in air. The reaction provides a protocol for quantitative preparation of aziridines in a large scope of aminohalogenated derivatives of olefins including α,β-unsaturated ketones, α,β-unsaturated esters and simple olefins. The possible mechanism involving an H-bond promoting deprotonation has been suggested for this reaction.展开更多
Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic s...Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However,increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes,and endothelial cells within the brain parenchyma and the neurovascular unit.展开更多
Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuropr...Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a 展开更多
There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessar...There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.展开更多
AIM: To determine the NF-kB activity in peripheral blood mononuclear cells (PBMC) in patients with acute cholangitis of severe type (ACST) and correlate the degree of NF-kB activation with severity of biliary tract in...AIM: To determine the NF-kB activity in peripheral blood mononuclear cells (PBMC) in patients with acute cholangitis of severe type (ACST) and correlate the degree of NF-kB activation with severity of biliary tract infection and clinical outcome. METHODS: Twenty patients with ACST were divided into survivor group (13 cases) and nonsurvivor group (7 cases). Other ten patients undergoing elective gastrectomy or inguinal hernia repair were selected as control group. Peripheral blood samples were taken 24 hours postoperatively. PBMC were separated by density gradient centrifugation, then nuclear proteins were isolated from PBMC, and Electrophoretic Mobility Shift Assay (EMSA) used determined. The results were quantified by scanning densitometer of a Bio-Image Analysis System and expressed as relative optical density (ROD). The levels of TNF-alpha, IL-6, and IL-10 in the plasma of patients with ACST and healthy control subjects were determined by using an enzyme-linked immunoassay (ELISA). RESULTS: The NF-kB activity was 5.02 +/- 1.03 in nonsurvivor group, 2.98 +/- 0.51 in survivor group and 1.06 +/- 0.34 in control group. There were statistical differences in three groups (P【0.05). The levels of TNF-alpha and IL-6 in plasma were (498 +/- 53)ng.L(-1)and (587 +/- 64)ng.L(-1)in nonsurvivor group, (284 +/- 32)ng.L(-1) and (318 +/- 49)ng.L(-1)in survivor group and (89 +/- 11)ng.L(-1) and (102 +/-13)ng.L(-1)in control group. All patients with ACST had increased levels of TNF-alpha and IL-6, which were many-fold greater than those of control group, and there was an evidence of significantly higher levels in those of nonsurvivor group than that in survivor group (P【0.05). The levels of IL-10 in plasma were (378+/-32)ng.L(-1), (384+/-37)ng.L(-1) and (68+/-11)ng.L(-1) in three groups, respectively. All patients had also increased levels of IL-10 when compared with control group (P【0.05), but the IL-10 levels were not significantly higher in nonsurvivors than in survivors (P】0.05). CONCLUSION: NF-kB activity in PBMC展开更多
AIM:To determine an optimal cutoff value for abnormal splenic artery diameter/proper hepatic artery diameter(S/P) ratio in cirrhosis-induced portal hypertension.METHODS:Patients with cirrhosis and portal hypertension(...AIM:To determine an optimal cutoff value for abnormal splenic artery diameter/proper hepatic artery diameter(S/P) ratio in cirrhosis-induced portal hypertension.METHODS:Patients with cirrhosis and portal hypertension(n = 770) and healthy volunteers(n = 31) underwent volumetric computed tomography threedimensional vascular reconstruction to measure the internal diameters of the splenic artery and proper hepatic artery to calculate the S/P ratio.The cutoff value for abnormal S/P ratio was determined using receiver operating characteristic curve analysis,and the prevalence of abnormal S/P ratio and associations between abnormal S/P ratio and major complications of portal hypertension were studied using logistic regression.RESULTS:The receiver operating characteristic analysis showed that the cutoff points for abnormal splenic artery internal diameter and S/P ratio were > 5.19 mm and > 1.40,respectively.The sensitivity,specificity,positive predictive value,and negative predictive value were 74.2%,45.2%,97.1%,and 6.6%,respectively.The prevalence of an abnormal S/P ratio in the patients with cirrhosis and portal hypertension was 83.4%.Patients with a higher S/P ratio had a lower risk of developing ascites [odds ratio(OR) = 0.708,95%CI:0.508-0.986,P = 0.041] and a higher risk of developing esophageal and gastric varices(OR = 1.483,95%CI:1.010-2.175,P = 0.044) and forming collateral circulation(OR = 1.518,95%CI:1.033-2.230,P = 0.034).After splenectomy,the portal venous pressure and maximum and mean portal venous flow velocities were reduced,while the flow rate and maximum and minimum flow velocities of the hepatic artery were increased(P < 0.05).CONCLUSION:The prevalence of an abnormal S/P ratio is high in patients with cirrhosis and portal hypertension,and it can be used as an important marker of splanchnic hemodynamic disturbances.展开更多
Ischemic stroke is caused primarily by an interruption in cerebral blood flow,which induces severe neural injuries,and is one of the leading causes of death and disability worldwide.Thus,it is of great necessity to fu...Ischemic stroke is caused primarily by an interruption in cerebral blood flow,which induces severe neural injuries,and is one of the leading causes of death and disability worldwide.Thus,it is of great necessity to further detailly elucidate the mechanisms of ischemic stroke and find out new therapies against the disease.In recent years,efforts have been made to understand the pathophysiology of ischemic stroke,including cellular excitotoxicity,oxidative stress,cell death processes,and neuroinflammation.In the meantime,a plethora of signaling pathways,either detrimental or neuroprotective,are also highly involved in the forementioned pathophysiology.These pathways are closely intertwined and form a complex signaling network.Also,these signaling pathways reveal therapeutic potential,as targeting these signaling pathways could possibly serve as therapeutic approaches against ischemic stroke.In this review,we describe the signaling pathways involved in ischemic stroke and categorize them based on the pathophysiological processes they participate in.Therapeutic approaches targeting these signaling pathways,which are associated with the pathophysiology mentioned above,are also discussed.Meanwhile,clinical trials regarding ischemic stroke,which potentially target the pathophysiology and the signaling pathways involved,are summarized in details.Conclusively,this review elucidated potential molecular mechanisms and related signaling pathways underlying ischemic stroke,and summarize the therapeutic approaches targeted various pathophysiology,with particular reference to clinical trials and future prospects for treating ischemic stroke.展开更多
The integration QTL map for gray leaf spot resistance in maize was constructed by compiling a total of 57 QTLs available with genetic map IBM2 2005 neighbors as reference. Twenty-six ＂real QTLs＂ and seven consensus ...The integration QTL map for gray leaf spot resistance in maize was constructed by compiling a total of 57 QTLs available with genetic map IBM2 2005 neighbors as reference. Twenty-six ＂real QTLs＂ and seven consensus QTLs were identified by refining these 57 QTLs using overview and meta-analysis approaches. Seven consensus QTLs were found on chromosomes 1.06, 2.06, 3.04, 4.06, 4.08, 5.03, and 8.06, and the map coordinates were 552.53,425.72, 279.20, 368.97, 583.21, 308.68 and 446.14 cM, respectively. Using a synteny conservation approach based on comparative mapping between the maize genetic map and rice physical map, a total of 69 rice and maize resistance genes collected from websites Gramene and MaizeGDB were projected onto the maize genetic map IBM2 2005 neighbors, and 2 （Rgene32, htl）, 4 （RgeneS, rp3, scmv2, wsm2）, and 4 （ht2, Rgene6, Rgene8 and Rgene7） positional candidate genes were found in three consensus QTLs on chromosomes 2.06, 3.04, and 8.06, respectively. The results suggested that the combination of meta-analysis of gray leaf spot in maize and sequence homologous comparison between maize and rice could be an efficient strategy for identifying major QTLs and corresponding candidate genes for the gray leaf spot.展开更多
Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations....Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn’s disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn’s disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.展开更多
Background Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and ...Background Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats. Methods Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity. Results Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection （P 〈 0.05）. The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge. Conclusions Septic challenge induced myocardial apoptosis and mito展开更多
We applied the reflectivity method and the constrained sparse spike inverse modeling(CSSI) method to the interpretation of coal field lithologic seismic data.After introducing the principles of these two methods we di...We applied the reflectivity method and the constrained sparse spike inverse modeling(CSSI) method to the interpretation of coal field lithologic seismic data.After introducing the principles of these two methods we discuss some parameters of a geological model involving possible gas enriched areas or intruded igneous rock.The geological model was constructed and a 60 Hz seismic response profile was obtained looking for igneous rock intrusion and coked areas of the coal seam using the reflectivity method.Starting from synthesized logging data from two wells and a synthesized seismic wavelet we calibrated the model to show accurate strata.Finally,we predicted the lithology within a 10 m igneous rock area,a 3 m coal seam area,and a coked area using the CSSI technique.The results show that the CSSI technique can identify hard to recognize lithologic features that normal profil-ing methods might miss.It can quantitatively analyze and evaluate the intrusive area,the coked area,and the gas-enriched area.展开更多
BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatiti...BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatitis B virus decompensated cirrhosis(HBV-DC)remains to be investigated.AIM To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF.METHODS This retrospective study included patients with HBV-DC admitted to two tertiary centers in China.In-hospital overall survival,90-d transplant-free survival,5-year post-discharge survival,and cumulative incidence of ACLF were evaluated.Risk factors for death were analyzed considering liver transplantation as a competing event.RESULTS A total of 1281 hospitalized HBV-DC patients were included;284 had ACLF at admission.The overall prevalence of BI was 28.1%.The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without,in both the patients admitted with and without ACLF.The presence of BI significantly increased the risk of developing ACLF[subdistribution hazard ratio(sHR)=2.52,95%CI:1.75-3.61,P<0.001]in the patients without ACLF.In the patients discharged alive,those who had an episode of BI had a significantly lower 5-year transplant-free survival.BI was an independent risk factor for death in the patients admitted without ACLF(sHR=3.28,95%CI:1.93-5.57),while in ACLF admissions,the presence of pneumonia,but not other type of BI,independently increased the risk of death(sHR=1.87,95%CI:1.24-2.82).CONCLUSION BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival.HBV-DC patients should be monitored carefully for the development of BI,especially pneumonia,to avoid an adverse outcome.展开更多
In airborne tracking,the blind Doppler makes the target undetectable,resulting in tracking difficulties. In this paper,we studied most possible blind-Doppler cases and summed them up into two types:targets' intent...In airborne tracking,the blind Doppler makes the target undetectable,resulting in tracking difficulties. In this paper,we studied most possible blind-Doppler cases and summed them up into two types:targets' intentional tangential flying to radar and unintentional flying with large tangential speed. We proposed an interacting multiple model(IMM) particle filter which combines a constant velocity model and an acceleration model to handle maneuvering motions. We compared the IMM particle filter with a previous particle filter solution. Simulation results showed that the IMM particle filter outperforms the method in previous works in terms of tracking accuracy and continuity.展开更多
The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression,and participates in cytokine secretion in many diseases.However,the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid ...The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression,and participates in cytokine secretion in many diseases.However,the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied.A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool.Some rats were first treated with JAK2/STAT3 small interfering RNA(Si-JAK2/Si-STAT3)or overexpression plasmids of JAK2/STAT3.In the brains of subarachnoid hemorrhage model rats,the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated,reaching a peak at 48 hours after injury.Simultaneously,the interactions between JAK2 and SOCS1 were reduced.In contrast,the interactions between JAK2 and STAT3 were markedly enhanced.Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis,destruction of the blood-brain barrier,brain edema,and cognitive functional impairment after subarachnoid hemorrhage.This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein,decreased total levels of JAK2 and STAT3 protein,and increased SOCS1 protein expression.However,overexpression of JAK2 and STAT3 exerted opposite effects,aggravating subarachnoid hemorrhage-induced early brain injury.Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors(inducible nitric oxide synthase,interleukin-1β,and tumor necrosis factor-α)and increased the release of anti-inflammatory factors(arginase-1,interleukin-10,and interleukin-4).Furthermore,primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro,and the JAK2 inhibitor AG490 was used as an intervention.The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression.Together,our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in v展开更多
Background： For Chinese patients with hepatocellular carcinoma （HCC）, surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor, and yet the prognosis a...Background： For Chinese patients with hepatocellular carcinoma （HCC）, surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor, and yet the prognosis after surgery is diverse. We aimed to construct a scoring system （Shanghai Score） for individualized prognosis estimation and adjuvant treatment evaluation. Methods： A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital. Age, hepatitis B surface antigen, hepatitis B e antigen, partial thromboplastin time, total bilirubin, alkaline phosphatase, y-glutamyltransferase, a-fetoprotein, tumor size, cirrhosis, vascular invasion, differentiation, encapsulation, and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion. The Harrell＇s concordance index （C-index） was used to measure model performance. Shanghai Score is calculated by summing the products of the 14 variable values times each variable＇s corresponding regression coefficient. Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012, 808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010, and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts. Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis.Results： Shanghai Score showed good calibration and discrimination in postsurgical HCC patients. The bootstrap-corrected C-index （confidence interval [CI]） was 0.74 for overall survival （OS） and 0.68 for recurrence-free survival （RFS） in derivation cohort （4166 patients）, and in the three independent validation cohorts, the CIs for OS ranged 0.70 0.72 and that for RFS ranged 0.63 0.68. Furthermore, Shanghai Score provided evaluation for adjuvant treatment choices （transcatheter arterial chemo展开更多
Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected pa...Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.展开更多
基金supported by the National Key R&D Program of China(2016YFC0203900,2016YFC0203901)National Natural Science Foundation of China(51778619,21577173)~~
文摘Alkali and alkaline‐earth metals from fly ash have a significant deactivation effect on catalysts used for selective catalytic reduction of NOx by NH3(NH3‐SCR).Bromides are considered effective additives to improve Hg0 oxidation on SCR catalysts.In this work,the effects of different bromides(NH4Br,NaBr,KBr,and CaBr2)on a commercial V2O5‐WO3/TiO2 catalyst were studied.NOx conversion decreased significantly over the KBr‐poisoned catalyst(denoted as L‐KBr),while that over NaBr‐and CaBr2‐poisoned catalysts(denoted as L‐NaBr and L‐CaBr,respectivity)decreased to a lesser extent compared with the fresh sample.Poor N2 selectivity was observed over L‐NaBr,L‐KBr and L‐CaBr catalysts.The decrease in the ratio of chemisorbed oxygen to total surface oxygen(Oα/(Oα+Oβ+Ow)),reducibility and surface acidity might contribute to the poor activity and N2 selectivity over L‐KBr catalyst.The increased Oαratio was conducive to the enhanced reducibility of L‐CaBr.Combined with enhanced surface acidity,this might offset the negative effect of the loss of active sites by CaBr2 covering.The overoxidation of NH3 and poor N2 selectivity in NH3 oxidation should retard the SCR activity at high temperatures over L‐CaBr catalyst.The increased basicity might contribute to increased NOx adsorption on L‐KBr and L‐CaBr catalysts.A correlation between the acid‐basic and redox properties of bromide‐poisoned catalysts and their catalytic properties is established.
基金The authors are grateful to the National Natural Science Foundation of China （No. 20572066）, the Natural Science Foundation of Shaanxi Province （No. 2009JM2011）, and the Innovation Foundation of Postgraduate Cultivation of Shaanxi Normal University （No. 2008CXB009）.
文摘The urea-catalyzed aziridination of 1,2-vicinal haloamines derived from aminohalogenation of olefins has been developed. This rapid and simple method was carried out by simply grinding the solid mixture of the substrate, K2CO3 and catalytic amount of urea at room temperature in air. The reaction provides a protocol for quantitative preparation of aziridines in a large scope of aminohalogenated derivatives of olefins including α,β-unsaturated ketones, α,β-unsaturated esters and simple olefins. The possible mechanism involving an H-bond promoting deprotonation has been suggested for this reaction.
基金the National Natural Science Foundation of China (81571132, 81873743, and 81801223)Fundamental Research Funds for the Central Universities, China (2017KFYXJJ107 and 2017KFYXJJ124)the National Institutes of Health, USA (R01NS088627)
文摘Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However,increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes,and endothelial cells within the brain parenchyma and the neurovascular unit.
文摘Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a
基金The study was supported by National Key Research and Development Program(2018YFA0704100,2018YFA0704104)National Natural Science Foundation of China(81827805,82130060)Jiangsu Provincial Special Program of Medical Science(BE2019750).The funding sources had no role in the writing of the report,or decision to submit the paper for publication.
文摘There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.
基金the National Natural Science Foundation of China,No.39970719,30170919
文摘AIM: To determine the NF-kB activity in peripheral blood mononuclear cells (PBMC) in patients with acute cholangitis of severe type (ACST) and correlate the degree of NF-kB activation with severity of biliary tract infection and clinical outcome. METHODS: Twenty patients with ACST were divided into survivor group (13 cases) and nonsurvivor group (7 cases). Other ten patients undergoing elective gastrectomy or inguinal hernia repair were selected as control group. Peripheral blood samples were taken 24 hours postoperatively. PBMC were separated by density gradient centrifugation, then nuclear proteins were isolated from PBMC, and Electrophoretic Mobility Shift Assay (EMSA) used determined. The results were quantified by scanning densitometer of a Bio-Image Analysis System and expressed as relative optical density (ROD). The levels of TNF-alpha, IL-6, and IL-10 in the plasma of patients with ACST and healthy control subjects were determined by using an enzyme-linked immunoassay (ELISA). RESULTS: The NF-kB activity was 5.02 +/- 1.03 in nonsurvivor group, 2.98 +/- 0.51 in survivor group and 1.06 +/- 0.34 in control group. There were statistical differences in three groups (P【0.05). The levels of TNF-alpha and IL-6 in plasma were (498 +/- 53)ng.L(-1)and (587 +/- 64)ng.L(-1)in nonsurvivor group, (284 +/- 32)ng.L(-1) and (318 +/- 49)ng.L(-1)in survivor group and (89 +/- 11)ng.L(-1) and (102 +/-13)ng.L(-1)in control group. All patients with ACST had increased levels of TNF-alpha and IL-6, which were many-fold greater than those of control group, and there was an evidence of significantly higher levels in those of nonsurvivor group than that in survivor group (P【0.05). The levels of IL-10 in plasma were (378+/-32)ng.L(-1), (384+/-37)ng.L(-1) and (68+/-11)ng.L(-1) in three groups, respectively. All patients had also increased levels of IL-10 when compared with control group (P【0.05), but the IL-10 levels were not significantly higher in nonsurvivors than in survivors (P】0.05). CONCLUSION: NF-kB activity in PBMC
基金Supported by Grants from Beijing Municipal Health Bureau, No.2011-2-18the Capital Health Development Special Funds, No.2011-2018-03
文摘AIM:To determine an optimal cutoff value for abnormal splenic artery diameter/proper hepatic artery diameter(S/P) ratio in cirrhosis-induced portal hypertension.METHODS:Patients with cirrhosis and portal hypertension(n = 770) and healthy volunteers(n = 31) underwent volumetric computed tomography threedimensional vascular reconstruction to measure the internal diameters of the splenic artery and proper hepatic artery to calculate the S/P ratio.The cutoff value for abnormal S/P ratio was determined using receiver operating characteristic curve analysis,and the prevalence of abnormal S/P ratio and associations between abnormal S/P ratio and major complications of portal hypertension were studied using logistic regression.RESULTS:The receiver operating characteristic analysis showed that the cutoff points for abnormal splenic artery internal diameter and S/P ratio were > 5.19 mm and > 1.40,respectively.The sensitivity,specificity,positive predictive value,and negative predictive value were 74.2%,45.2%,97.1%,and 6.6%,respectively.The prevalence of an abnormal S/P ratio in the patients with cirrhosis and portal hypertension was 83.4%.Patients with a higher S/P ratio had a lower risk of developing ascites [odds ratio(OR) = 0.708,95%CI:0.508-0.986,P = 0.041] and a higher risk of developing esophageal and gastric varices(OR = 1.483,95%CI:1.010-2.175,P = 0.044) and forming collateral circulation(OR = 1.518,95%CI:1.033-2.230,P = 0.034).After splenectomy,the portal venous pressure and maximum and mean portal venous flow velocities were reduced,while the flow rate and maximum and minimum flow velocities of the hepatic artery were increased(P < 0.05).CONCLUSION:The prevalence of an abnormal S/P ratio is high in patients with cirrhosis and portal hypertension,and it can be used as an important marker of splanchnic hemodynamic disturbances.
基金funded by National Natural Science Foundation of China(Grants:82071380,81873743,81801223)Tongji Hospital(HUST)Foundation for Excellent Young Scientist(Grant No.2020YQ06).
文摘Ischemic stroke is caused primarily by an interruption in cerebral blood flow,which induces severe neural injuries,and is one of the leading causes of death and disability worldwide.Thus,it is of great necessity to further detailly elucidate the mechanisms of ischemic stroke and find out new therapies against the disease.In recent years,efforts have been made to understand the pathophysiology of ischemic stroke,including cellular excitotoxicity,oxidative stress,cell death processes,and neuroinflammation.In the meantime,a plethora of signaling pathways,either detrimental or neuroprotective,are also highly involved in the forementioned pathophysiology.These pathways are closely intertwined and form a complex signaling network.Also,these signaling pathways reveal therapeutic potential,as targeting these signaling pathways could possibly serve as therapeutic approaches against ischemic stroke.In this review,we describe the signaling pathways involved in ischemic stroke and categorize them based on the pathophysiological processes they participate in.Therapeutic approaches targeting these signaling pathways,which are associated with the pathophysiology mentioned above,are also discussed.Meanwhile,clinical trials regarding ischemic stroke,which potentially target the pathophysiology and the signaling pathways involved,are summarized in details.Conclusively,this review elucidated potential molecular mechanisms and related signaling pathways underlying ischemic stroke,and summarize the therapeutic approaches targeted various pathophysiology,with particular reference to clinical trials and future prospects for treating ischemic stroke.
文摘The integration QTL map for gray leaf spot resistance in maize was constructed by compiling a total of 57 QTLs available with genetic map IBM2 2005 neighbors as reference. Twenty-six ＂real QTLs＂ and seven consensus QTLs were identified by refining these 57 QTLs using overview and meta-analysis approaches. Seven consensus QTLs were found on chromosomes 1.06, 2.06, 3.04, 4.06, 4.08, 5.03, and 8.06, and the map coordinates were 552.53,425.72, 279.20, 368.97, 583.21, 308.68 and 446.14 cM, respectively. Using a synteny conservation approach based on comparative mapping between the maize genetic map and rice physical map, a total of 69 rice and maize resistance genes collected from websites Gramene and MaizeGDB were projected onto the maize genetic map IBM2 2005 neighbors, and 2 （Rgene32, htl）, 4 （RgeneS, rp3, scmv2, wsm2）, and 4 （ht2, Rgene6, Rgene8 and Rgene7） positional candidate genes were found in three consensus QTLs on chromosomes 2.06, 3.04, and 8.06, respectively. The results suggested that the combination of meta-analysis of gray leaf spot in maize and sequence homologous comparison between maize and rice could be an efficient strategy for identifying major QTLs and corresponding candidate genes for the gray leaf spot.
基金Supported by Partially supported by the grant"Intestine Initiative"
文摘Eosinophilic gastroenteritis is a rare disease of unknown etiology. It is characterized by patchy or diffuse eosinophilic infiltration of the bowel wall to a variable depth and various gastrointestinal manifestations. We describe a case of severe eosinophilic gastroenteritis presenting as frequent bowel obstruction and diarrhea in a 35-year-old man. The patient was misdiagnosed and underwent surgery because of intestinal obstruction when he was first admitted to a local hospital. Then he was misdiagnosed as having Crohn’s disease in another university teaching hospital. Finally, the patient asked for further treatment from our hospital because of the on-going clinical trial for treating refractory Crohn’s disease by fecal microbiota transplantation. Physical examination revealed a slight distended abdomen with diffuse tenderness. Laboratory investigation showed the total number of normal leukocytes with neutrophilia as 90.5%, as well as eosinopenia, monocytopenia and lymphocytopenia. Barium radiography and sigmoidoscopy confirmed inflammatory stenosis of the sigmoid colon. We diagnosed the patient as having eosinophilic gastroenteritis by multi-examinations. The patient was treated by fecal microbiota transplantation combined with oral prednisone, and was free from gastrointestinal symptoms at the time when we reported his disease. This case highlights the importance of awareness of manifestations of a rare disease like eosinophilic gastroenteritis.
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 81171784）, and Zhejiang Province Natural Science Foundation （No. Z2100237 and No. Y2110801）.
文摘Background Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats. Methods Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity. Results Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection （P 〈 0.05）. The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge. Conclusions Septic challenge induced myocardial apoptosis and mito
基金Projects 40874054 and 40804026 supported by the National Natural Science Foundation of Chinathe National Basic Research Program of China (2007CB209400 and 2009CB219603)the National Key Scientific and Technological Project (2008ZX05035)
文摘We applied the reflectivity method and the constrained sparse spike inverse modeling(CSSI) method to the interpretation of coal field lithologic seismic data.After introducing the principles of these two methods we discuss some parameters of a geological model involving possible gas enriched areas or intruded igneous rock.The geological model was constructed and a 60 Hz seismic response profile was obtained looking for igneous rock intrusion and coked areas of the coal seam using the reflectivity method.Starting from synthesized logging data from two wells and a synthesized seismic wavelet we calibrated the model to show accurate strata.Finally,we predicted the lithology within a 10 m igneous rock area,a 3 m coal seam area,and a coked area using the CSSI technique.The results show that the CSSI technique can identify hard to recognize lithologic features that normal profil-ing methods might miss.It can quantitatively analyze and evaluate the intrusive area,the coked area,and the gas-enriched area.
基金Supported by the National Natural Science Foundation of China,No.81570535 and No.81770587Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period,No.2017ZX10203201-008,No.2018ZX09206005-003,and 2017ZX10202202-005-004+4 种基金the Shanghai Three-Year Plan of the Clinical Skills and Innovations,No.16CR1002Athe Shanghai Municipal Key Clinical Specialty,No.shslczdzk01103the Shanghai Three-Year Plan of the Key Subjects Construction in Public Health-Infectious Diseases and Pathogenic Microorganism,No.15GWZK0102the Suzhou Expert Team of Clinical Medicine,No.SZYJTD201717the Joint Research Initiative-Shanghai Jiao Tong University School of Medicine,No.YW20190002
文摘BACKGROUND Reports on bacterial infection(BI)in decompensated cirrhosis(DC)is mainly from alcoholic cirrhosis.The role of BI as a trigger or complication of acute-onchronic liver failure(ACLF)in patients with hepatitis B virus decompensated cirrhosis(HBV-DC)remains to be investigated.AIM To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF.METHODS This retrospective study included patients with HBV-DC admitted to two tertiary centers in China.In-hospital overall survival,90-d transplant-free survival,5-year post-discharge survival,and cumulative incidence of ACLF were evaluated.Risk factors for death were analyzed considering liver transplantation as a competing event.RESULTS A total of 1281 hospitalized HBV-DC patients were included;284 had ACLF at admission.The overall prevalence of BI was 28.1%.The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without,in both the patients admitted with and without ACLF.The presence of BI significantly increased the risk of developing ACLF[subdistribution hazard ratio(sHR)=2.52,95%CI:1.75-3.61,P<0.001]in the patients without ACLF.In the patients discharged alive,those who had an episode of BI had a significantly lower 5-year transplant-free survival.BI was an independent risk factor for death in the patients admitted without ACLF(sHR=3.28,95%CI:1.93-5.57),while in ACLF admissions,the presence of pneumonia,but not other type of BI,independently increased the risk of death(sHR=1.87,95%CI:1.24-2.82).CONCLUSION BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival.HBV-DC patients should be monitored carefully for the development of BI,especially pneumonia,to avoid an adverse outcome.
基金Project supported by China Postdoctoral Science Foundation (No.20060400313)partly by Zhejiang Postdoctoral Science Founda-tion of China (No. 2006-bsh-25)
文摘In airborne tracking,the blind Doppler makes the target undetectable,resulting in tracking difficulties. In this paper,we studied most possible blind-Doppler cases and summed them up into two types:targets' intentional tangential flying to radar and unintentional flying with large tangential speed. We proposed an interacting multiple model(IMM) particle filter which combines a constant velocity model and an acceleration model to handle maneuvering motions. We compared the IMM particle filter with a previous particle filter solution. Simulation results showed that the IMM particle filter outperforms the method in previous works in terms of tracking accuracy and continuity.
基金This study was supported by the National Natural Science Foundation of China,No.81500375(to XQK)the Fundamental Research Funds for the Central Universities,No.WK9110000112(to YW)+1 种基金the Anhui Provincial Natural Science Foundation of China,No.1508085QH184(to YW)Shandong Provincial Natural Science Foundation of China,No.ZR2015HQ001(to XQK).
文摘The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression,and participates in cytokine secretion in many diseases.However,the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied.A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool.Some rats were first treated with JAK2/STAT3 small interfering RNA(Si-JAK2/Si-STAT3)or overexpression plasmids of JAK2/STAT3.In the brains of subarachnoid hemorrhage model rats,the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated,reaching a peak at 48 hours after injury.Simultaneously,the interactions between JAK2 and SOCS1 were reduced.In contrast,the interactions between JAK2 and STAT3 were markedly enhanced.Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis,destruction of the blood-brain barrier,brain edema,and cognitive functional impairment after subarachnoid hemorrhage.This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein,decreased total levels of JAK2 and STAT3 protein,and increased SOCS1 protein expression.However,overexpression of JAK2 and STAT3 exerted opposite effects,aggravating subarachnoid hemorrhage-induced early brain injury.Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors(inducible nitric oxide synthase,interleukin-1β,and tumor necrosis factor-α)and increased the release of anti-inflammatory factors(arginase-1,interleukin-10,and interleukin-4).Furthermore,primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro,and the JAK2 inhibitor AG490 was used as an intervention.The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression.Together,our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in v
基金This study was supported by grants from the National High Technology Research and Development Program （863 Program） of China （No. 2015AA020401）, National Key Research and Development Program of China （No. 2016YFC0904101）, State Key Program of National Natural Science Foundation of China （No. 81530077）, National Natural Science Foundation of China （No. 81372317, 81472676, and 81572823）, Projects from the Shanghai Science and Technology Commission （No. 14DZ1940300, 14411970200, 134119a1201, and 14140902301）, and Specialized Research Fund for the Doctoral Program of Higher Education and Research Grants Council Earmarked Research Grants Joint Research Scheme （No. 20130071140008）.
文摘Background： For Chinese patients with hepatocellular carcinoma （HCC）, surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor, and yet the prognosis after surgery is diverse. We aimed to construct a scoring system （Shanghai Score） for individualized prognosis estimation and adjuvant treatment evaluation. Methods： A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital. Age, hepatitis B surface antigen, hepatitis B e antigen, partial thromboplastin time, total bilirubin, alkaline phosphatase, y-glutamyltransferase, a-fetoprotein, tumor size, cirrhosis, vascular invasion, differentiation, encapsulation, and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion. The Harrell＇s concordance index （C-index） was used to measure model performance. Shanghai Score is calculated by summing the products of the 14 variable values times each variable＇s corresponding regression coefficient. Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012, 808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010, and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts. Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis.Results： Shanghai Score showed good calibration and discrimination in postsurgical HCC patients. The bootstrap-corrected C-index （confidence interval [CI]） was 0.74 for overall survival （OS） and 0.68 for recurrence-free survival （RFS） in derivation cohort （4166 patients）, and in the three independent validation cohorts, the CIs for OS ranged 0.70 0.72 and that for RFS ranged 0.63 0.68. Furthermore, Shanghai Score provided evaluation for adjuvant treatment choices （transcatheter arterial chemo
文摘Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.
