BACKGROUND Patients with stroke frequently experience pulmonary dysfunction.AIM To explore the effects of information-motivation-behavioral(IMB)skills modelbased nursing care on pulmonary function,blood gas indices,co...BACKGROUND Patients with stroke frequently experience pulmonary dysfunction.AIM To explore the effects of information-motivation-behavioral(IMB)skills modelbased nursing care on pulmonary function,blood gas indices,complication rates,and quality of life(QoL)in stroke patients with pulmonary dysfunction.METHODS We conducted a controlled study involving 120 stroke patients with pulmonary dysfunction.The control group received routine care,whereas the intervention group received IMB-model-based nursing care.Various parameters including pulmonary function,blood gas indices,complication rates,and QoL were assessed before and after the intervention.RESULTS Baseline data of the control and intervention groups were comparable.Post-intervention,the IMB model-based care group showed significant improvements in pulmonary function indicators,forced expiratory volume in 1 sec,forced vital capacity,and peak expiratory flow compared with the control group.Blood gas indices,such as arterial oxygen pressure and arterial oxygen saturation,increased significantly,and arterial carbon dioxide partial.pressure decreased significantly in the IMB model-based care group compared with the control group.The intervention group also had a lower complication rate(6.67%vs 23.33%)and higher QoL scores across all domains than the control group.CONCLUSION IMB model-based nursing care significantly enhanced pulmonary function,improved blood gas indices,reduced complication rates,and improved the QoL of stroke patients with pulmonary dysfunction.Further research is needed to validate these results and to assess the long-term efficacy and broader applicability of the model.展开更多
Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that partici...Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway,is an independent prognostic marker for pancreatic cancer(PC).First,overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen.Second,the high expression of kynurenine induces and activates the aryl hydrocarbon receptor,resulting in upregulated programmed cell death protein 1 expression.Third,the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance,mediated by the proximal tryptophan catabolite from IDO metabolism.In our study,we found that overexpression of IDO1 upregulated CD8+T cells and reduced natural killer T cells in pancreatic carcinoma in mice.Hence,it may be essential to pay more attention to tryptophan metabolism in patients,especially those who are tolerant to immunotherapy for PC.展开更多
BACKGROUND Hepatic stellate cells(HSCs)are the key effector cells mediating the occurrence and development of liver fibrosis,while aerobic glycolysis is an important metabolic characteristic of HSC activation.Transfor...BACKGROUND Hepatic stellate cells(HSCs)are the key effector cells mediating the occurrence and development of liver fibrosis,while aerobic glycolysis is an important metabolic characteristic of HSC activation.Transforming growth factor-β1(TGF-β1)induces aerobic glycolysis and is a driving factor for metabolic reprogramming.The occurrence of glycolysis depends on a high glucose uptake level.Glucose transporter 1(GLUT1)is the most widely distributed glucose transporter in the body and mainly participates in the regulation of carbohydrate metabolism,thus affecting cell proliferation and growth.However,little is known about the relationship between TGF-β1 and GLUT1 in the process of liver fibrosis and the molecular mechanism underlying the promotion of aerobic glycolysis in HSCs.AIM To investigate the mechanisms of action of GLUT1,TGF-β1 and aerobic glycolysis in the process of HSC activation during liver fibrosis.METHODS Immunohistochemical staining and immunofluorescence assays were used to examine GLUT1 expression in fibrotic liver tissue.A Seahorse extracellular flux(XF)analyzer was used to examine changes in aerobic glycolytic flux,lactate production levels and glucose consumption levels in HSCs upon TGF-β1 stimulation.The mechanism by which TGF-β1 induces GLUT1 protein expression in HSCs was further explored by inhibiting/promoting the TGF-β1/mothersagainst-decapentaplegic-homolog 2/3(Smad2/3)signaling pathway and inhibiting the p38 and phosphoinositide 3-kinase(PI3K)/AKT signaling pathways.In addition,GLUT1 expression was silenced to observe changes in the growth and proliferation of HSCs.Finally,a GLUT1 inhibitor was used to verify the in vivo effects of GLUT1 on a mouse model of liver fibrosis.RESULTS GLUT1 protein expression was increased in both mouse and human fibrotic liver tissues.In addition,immunofluorescence staining revealed colocalization of GLUT1 and alpha-smooth muscle actin proteins,indicating that GLUT1 expression was related to the development of liver fibrosis.TGF-β1 caused an increase in aerobic glycolysis in HSCs and induced GLUT1 expression in HSCs by activating the Smad,p38 MAPK and P13K/AKT signaling pathways.The p38 MAPK and Smad pathways synergistically affected the induction of GLUT1 expression.GLUT1 inhibition eliminated the effect of TGF-β1 on HSC proliferation and migration.A GLUT1 inhibitor was administered in a mouse model of liver fibrosis,and GLUT1 inhibition reduced the degree of liver inflammation and liver fibrosis.CONCLUSION TGF-β1 induces GLUT1 expression in HSCs,a process related to liver fibrosis progression.In vitro experiments revealed that TGF-β1-induced GLUT1 expression might be one of the mechanisms mediating the metabolic reprogramming of HSCs.In addition,in vivo experiments also indicated that the GLUT1 protein promotes the occurrence and development of liver fibrosis.展开更多
BACKGROUND Hepatic stellate cell(HSC)hyperactivation is a central link in liver fibrosis development.HSCs perform aerobic glycolysis to provide energy for their activation.Focal adhesion kinase(FAK)promotes aerobic gl...BACKGROUND Hepatic stellate cell(HSC)hyperactivation is a central link in liver fibrosis development.HSCs perform aerobic glycolysis to provide energy for their activation.Focal adhesion kinase(FAK)promotes aerobic glycolysis in cancer cells or fibroblasts,while FAK-related non-kinase(FRNK)inhibits FAK phosphorylation and biological functions.AIM To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs.METHODS Mouse liver fibrosis models were established by administering CCl4,and the effect of FRNK on the degree of liver fibrosis in the model was evaluated.Transforming growth factor-β1 was used to activate LX-2 cells.Tyrosine phosphorylation at position 397(pY397-FAK)was detected to identify activated FAK,and the expression of the glycolysis-related proteins monocarboxylate transporter 1(MCT-1)and enolase1(ENO1)was assessed.Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region,which were validated with chromatin immunoprecipitation(ChIP)and dual luciferase reporter assays.RESULTS The pY397-FAK level was increased in human fibrotic liver tissue.FRNK knockout promoted liver fibrosis in mouse models.It also increased the activation,migration,proliferation and aerobic glycolysis of primary hepatic stellate cells(pHSCs)but inhibited pHSC apoptosis.Nevertheless,opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells.Mechanistically,the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis,which was inhibited by exogenous FRNK.CONCLUSION FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway,thereby improving liver fibrosis.FRNK might be a potential target for liver fibrosis treatment.展开更多
BACKGROUND Lung squamous cell cancer(LSCC)rarely harbors epidermal growth factor receptor(EGFR)mutations,even much rarer for acquired T790M mutation.Although clinical trials of AURA series illustrated that non-small c...BACKGROUND Lung squamous cell cancer(LSCC)rarely harbors epidermal growth factor receptor(EGFR)mutations,even much rarer for acquired T790M mutation.Although clinical trials of AURA series illustrated that non-small cell lung cancer(NSCLC)with EGFR T790M mutation can benefit from osimertinib,only five LSCC patients were enrolled in total;moreover,the efficacy for LSCC was not shown in the results.Therefore,the response of LSCC to osimertinib is still unclear to date.CASE SUMMARY We report an LSCC case with T790M-related acquired resistance after treatments with first-generation EGFR-tyrosine kinase inhibitors(EGFR-TKIs)and benefited from osimertinib significantly.A 63-year-old Chinese man was diagnosed with stage IV(cT2N2M1b)LSCC harboring an EGFR exon 19-deletion mutation.Following disease progression after gefitinib and multi-line chemotherapy,rebiopsy was conducted.Molecular testing of EGFR by amplification refractory mutation system-polymerase chain reaction detected the exon 19-deletion without T790M mutation.Therefore,the patient was given erlotinib,but progression developed only 3 mo later.Then the frozen re-biopsy tissue was tested by next-generation sequencing(NGS),which detected an EGFR T790M mutation.However,he was very weak with symptoms of dysphagia and cachexia.Fortunately,osimertinib was started,leading to alleviation from the symptoms.Four months later,normal deglutition was restored and partial response was achieved.Finally,the patient achieved an overall survival time period of 29 mo.CONCLUSION Our findings highlight that EGFR T790M mutation may also be an important acquired drug resistance mechanism for LSCC and offer direct evidence of the efficacy of osimertinib in LSCC with T790M mutation.NGS and better preservation conditions may contribute to higher sensitivity of EGFR T790M detection.展开更多
We describe herein that the quasi-one-dimensional confinement effect of functionalized nanoporous supports is particularly advantageous for boosting formic acid(FA)dehydrogenation efficiency over palladium nanoparticl...We describe herein that the quasi-one-dimensional confinement effect of functionalized nanoporous supports is particularly advantageous for boosting formic acid(FA)dehydrogenation efficiency over palladium nanoparticles(NPs).Benefiting from their unique structural merits that lead to significant lowering of the entropic barrier for FA activation,the Pd NPs interiorly located on the amino-modified MCM-41 offer the promise of more than an order of magnitude speedup of the initial activity in H2 production from FA over their exterior analogs.Under mild and additive-free conditions,ultrafine Pd NPs confined in aminomodified MCM-41 channels exhibit an initial turnover frequency as high as 46,677 h-1 and a turnover number up to 1,060,000 at 60℃.In conjunction with the enhancement and robust performance for efficient regeneration of FA via CO2 hydrogenation,the presented approach greatly contributes to the development of FA-based hydrogen storage and related technologies as viable means of enabling sustainable future energy prospects.展开更多
Objective:The differences of ovarian morphology,reproductive hormones,glucose and lipid metabolism and intestinal bacteria in rats with polycystic ovary syndrome(PCOS)induced by triazole were compared.Method:Eighteen ...Objective:The differences of ovarian morphology,reproductive hormones,glucose and lipid metabolism and intestinal bacteria in rats with polycystic ovary syndrome(PCOS)induced by triazole were compared.Method:Eighteen 21 SPF female SD rats were randomly divided into group A(3-week group),group B(5-week group)and group D(control group)by random number table.Group A received letrozole+CMC-Na mixture by gavage in the first 3 weeks and CMC-Na solution by gavage in the last 2 weeks,group B received letrozole+CMC-Na mixture by gavage for 5 weeks,and group D received CMC-Na solution by gavage for 5 weeks,and all three groups of rats were fed with normal diet.At the end of gavage,the body weight of rats in each group was observed,the histological changes of ovaries were observed by hematoxylin-eosin(HE)staining,the serum levels of estradiol(E2),follicle stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),total cholesterol(TC),triglyceride(TG),fasting blood glucose(Glu),fasting insulin(FINS)and lipopolysaccharide(LPS)were measured by enzyme-linked immunosorbent assay(ELISA),and the LH/FSH ratio and insulin resistance index(HOMA IR)were calculated;the intestinal bacteria of rats were detected by 16S rRNA technique.Result:1.Comparison of ovary histomorphology:Under light microscope,multiple luteum and oocytes were observed in mature follicles in group D,and granulosa cells were orderly arranged and multilayered,without cystic dilated follicles.There were no mature follicles in the ovarian tissues of group A and GROUP B.The follicles were irregular in structure and more cystic dilated follicles were visible.The number of granular cells in some follicles decreased or even disappeared.2.Comparison of sex hormone levels:compared with group D,T level in group B was significantly increased(P<0.001),and T level in group A had an upward trend(P>0.05);The LH/FSH levels in group A and B were significantly increased(P<0.001;P<0.001).Compared with group A,E2 in group B was significantly decreased(P<0.05)and T was significantly increased(P<0.01).3.Comparison of glucose and lipid metabolism levels:Compared with group D,TC levels in groups A and B were significantly increased(P<0.01;P<0.01).Compared with group A,TG in group B was significantly increased(P<0.05).There were no significant differences in Glu,FINS and HOMA-IR levels among all groups.4.Comparison of LPS levels:Compared with group D,the serum LPS levels of rats in groups A and B were significantly increased(P<0.001;P<0.01).5.Intestinal flora analysis and comparison:At the phylum level,compared with group D,the abundance of Firmicutes in group B increased(P<0.01),Firmicutes in group A showed an upward trend(P>0.05),and the abundance of Bacteroidetes in groups A and B decreased(P<0.05).At the genus level,compared with group D,Lactobacillus in group B increased(P<0.01).The results of LEfSe analysis showed that there were differences in the composition of various intestinal bacteria among the three groups(LDA>3).Conclusion:The phenotype of PCOS rats was related to the length of modeling,and the phenotypic characteristics of PCOS in rats at 5 weeks of modeling were more typical than those in rats at 3 weeks of modeling;PCOS can cause changes in intestinal flora,and the changes in the structure of intestinal flora between groups are related to different modeling duration.展开更多
Objective: To investigate the effects of methotrexate and hydroxychloroquine sulfate and prednisone on inflammatory response, immune function, liver and renal function in patients with systemic lupus erythematosus (SL...Objective: To investigate the effects of methotrexate and hydroxychloroquine sulfate and prednisone on inflammatory response, immune function, liver and renal function in patients with systemic lupus erythematosus (SLE). Methods: A total of 80 cases of SLE patients according to the random data table were divided into the control group (n=40) and observation group (n=40), the control group were treated with hydroxychloroquine sulfate and prednisone treatment, on the basis of treatment of the control group, patients in the observation group in the control group were treated with methotrexate, the levels of inflammatory factors, immune function, liver and kidney function indexes in the two groups between the before treatment and after treatment were compared. Results: Comparison of the levels before treatment, the difference of the CRP, WBC, ESR, IgA, IgG, complement C3, complement C4, ALT, AST, SCr and BUN levels were not statistically significant. After treatment, the levels of CRP, ESR, IgA, IgG, ALT, AST, SCr and BUN in the observation group were significantly lower than those in the control group, and the difference was statistically significant. The levels of WBC and complement C4 in the observation group [(5.18±1.08)×109 /L, (0.22±0.05) g/L] were significantly higher than those in the control group [(4.51±0.52)×109 /L, (0.18±0.03) g/L], and there was no significant difference in the level of complement C3 between the two groups after treatment. Conclusion: Methotrexate combined with hydroxychloroquine sulfate and prednisone for the treatment of SLE can effectively reduce inflammation, improve immune function, has little effect on kidney function, high safety, which has an important clinical value.展开更多
According to WHO, one of these mass gatherings with critical risk is stampedes. Shanghai “12.31” stampede was a preventable tragedy that the government and event planner hold responsibility for. At the same time, it...According to WHO, one of these mass gatherings with critical risk is stampedes. Shanghai “12.31” stampede was a preventable tragedy that the government and event planner hold responsibility for. At the same time, it can be a legacy for improvement in the future. The government should draw experience on the implementation of an emergency preparedness system, in order to improve the rapid emergency response during mass gatherings in the future.展开更多
Sulfuric acid was used in the pretreatment of corn stover to obtain xylose as a value-added by-product,and the pretreated corn stover(Pre-CS)was hydrolyzed to produce glucose for butanol fermentation.The aim of this w...Sulfuric acid was used in the pretreatment of corn stover to obtain xylose as a value-added by-product,and the pretreated corn stover(Pre-CS)was hydrolyzed to produce glucose for butanol fermentation.The aim of this work is to achieve high xylose accumulation and reduced wastewater by recycling the pretreatment solution.The pretreatment conditions were optimized as follows:180°C,15 min,1:7 solid-liquid ratio(w/w),0.6%H_(2)SO_(4)(w/w,first batch)/0.9%H_(2)SO_(4)(w/w,second and third batches),in which pretreatment solution was recycled for three times.Under above conditions,pretreatment solution containing 56.3 g/L xylose and 4.5 g/L glucose was obtained.Pre-CS residue was further hydrolyzed by cellulase to achieve 35.7-39.9 g/L glucose.The condensed corn stover hydrolysate was subjected to simultaneous detoxification and sterilization using 1%(w/w)activated carbon and then applied in butanol fermentation.The highest butanol titer of 9.5 g/L was obtained in 72 h.The results provide a practical approach for coproducing xylose and biobutanol from corn stover.展开更多
文摘BACKGROUND Patients with stroke frequently experience pulmonary dysfunction.AIM To explore the effects of information-motivation-behavioral(IMB)skills modelbased nursing care on pulmonary function,blood gas indices,complication rates,and quality of life(QoL)in stroke patients with pulmonary dysfunction.METHODS We conducted a controlled study involving 120 stroke patients with pulmonary dysfunction.The control group received routine care,whereas the intervention group received IMB-model-based nursing care.Various parameters including pulmonary function,blood gas indices,complication rates,and QoL were assessed before and after the intervention.RESULTS Baseline data of the control and intervention groups were comparable.Post-intervention,the IMB model-based care group showed significant improvements in pulmonary function indicators,forced expiratory volume in 1 sec,forced vital capacity,and peak expiratory flow compared with the control group.Blood gas indices,such as arterial oxygen pressure and arterial oxygen saturation,increased significantly,and arterial carbon dioxide partial.pressure decreased significantly in the IMB model-based care group compared with the control group.The intervention group also had a lower complication rate(6.67%vs 23.33%)and higher QoL scores across all domains than the control group.CONCLUSION IMB model-based nursing care significantly enhanced pulmonary function,improved blood gas indices,reduced complication rates,and improved the QoL of stroke patients with pulmonary dysfunction.Further research is needed to validate these results and to assess the long-term efficacy and broader applicability of the model.
基金National Natural Science Foundation of China,No.82200695。
文摘Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway,is an independent prognostic marker for pancreatic cancer(PC).First,overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen.Second,the high expression of kynurenine induces and activates the aryl hydrocarbon receptor,resulting in upregulated programmed cell death protein 1 expression.Third,the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance,mediated by the proximal tryptophan catabolite from IDO metabolism.In our study,we found that overexpression of IDO1 upregulated CD8+T cells and reduced natural killer T cells in pancreatic carcinoma in mice.Hence,it may be essential to pay more attention to tryptophan metabolism in patients,especially those who are tolerant to immunotherapy for PC.
基金by National Natural Science Foundation of China,No.82060116,No.81860115 and No.81960118Guizhou Science and Technology Support Project Fund,No.[2021]058.
文摘BACKGROUND Hepatic stellate cells(HSCs)are the key effector cells mediating the occurrence and development of liver fibrosis,while aerobic glycolysis is an important metabolic characteristic of HSC activation.Transforming growth factor-β1(TGF-β1)induces aerobic glycolysis and is a driving factor for metabolic reprogramming.The occurrence of glycolysis depends on a high glucose uptake level.Glucose transporter 1(GLUT1)is the most widely distributed glucose transporter in the body and mainly participates in the regulation of carbohydrate metabolism,thus affecting cell proliferation and growth.However,little is known about the relationship between TGF-β1 and GLUT1 in the process of liver fibrosis and the molecular mechanism underlying the promotion of aerobic glycolysis in HSCs.AIM To investigate the mechanisms of action of GLUT1,TGF-β1 and aerobic glycolysis in the process of HSC activation during liver fibrosis.METHODS Immunohistochemical staining and immunofluorescence assays were used to examine GLUT1 expression in fibrotic liver tissue.A Seahorse extracellular flux(XF)analyzer was used to examine changes in aerobic glycolytic flux,lactate production levels and glucose consumption levels in HSCs upon TGF-β1 stimulation.The mechanism by which TGF-β1 induces GLUT1 protein expression in HSCs was further explored by inhibiting/promoting the TGF-β1/mothersagainst-decapentaplegic-homolog 2/3(Smad2/3)signaling pathway and inhibiting the p38 and phosphoinositide 3-kinase(PI3K)/AKT signaling pathways.In addition,GLUT1 expression was silenced to observe changes in the growth and proliferation of HSCs.Finally,a GLUT1 inhibitor was used to verify the in vivo effects of GLUT1 on a mouse model of liver fibrosis.RESULTS GLUT1 protein expression was increased in both mouse and human fibrotic liver tissues.In addition,immunofluorescence staining revealed colocalization of GLUT1 and alpha-smooth muscle actin proteins,indicating that GLUT1 expression was related to the development of liver fibrosis.TGF-β1 caused an increase in aerobic glycolysis in HSCs and induced GLUT1 expression in HSCs by activating the Smad,p38 MAPK and P13K/AKT signaling pathways.The p38 MAPK and Smad pathways synergistically affected the induction of GLUT1 expression.GLUT1 inhibition eliminated the effect of TGF-β1 on HSC proliferation and migration.A GLUT1 inhibitor was administered in a mouse model of liver fibrosis,and GLUT1 inhibition reduced the degree of liver inflammation and liver fibrosis.CONCLUSION TGF-β1 induces GLUT1 expression in HSCs,a process related to liver fibrosis progression.In vitro experiments revealed that TGF-β1-induced GLUT1 expression might be one of the mechanisms mediating the metabolic reprogramming of HSCs.In addition,in vivo experiments also indicated that the GLUT1 protein promotes the occurrence and development of liver fibrosis.
基金the National Natural Science Foundation of China,No.81860115,No.82060116 and No.81960118the Science and Technology Support Project of Guizhou Province,No.[2021]094.
文摘BACKGROUND Hepatic stellate cell(HSC)hyperactivation is a central link in liver fibrosis development.HSCs perform aerobic glycolysis to provide energy for their activation.Focal adhesion kinase(FAK)promotes aerobic glycolysis in cancer cells or fibroblasts,while FAK-related non-kinase(FRNK)inhibits FAK phosphorylation and biological functions.AIM To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs.METHODS Mouse liver fibrosis models were established by administering CCl4,and the effect of FRNK on the degree of liver fibrosis in the model was evaluated.Transforming growth factor-β1 was used to activate LX-2 cells.Tyrosine phosphorylation at position 397(pY397-FAK)was detected to identify activated FAK,and the expression of the glycolysis-related proteins monocarboxylate transporter 1(MCT-1)and enolase1(ENO1)was assessed.Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region,which were validated with chromatin immunoprecipitation(ChIP)and dual luciferase reporter assays.RESULTS The pY397-FAK level was increased in human fibrotic liver tissue.FRNK knockout promoted liver fibrosis in mouse models.It also increased the activation,migration,proliferation and aerobic glycolysis of primary hepatic stellate cells(pHSCs)but inhibited pHSC apoptosis.Nevertheless,opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells.Mechanistically,the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis,which was inhibited by exogenous FRNK.CONCLUSION FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway,thereby improving liver fibrosis.FRNK might be a potential target for liver fibrosis treatment.
基金Supported by the National Natural Science Foundation of China,No.81402561
文摘BACKGROUND Lung squamous cell cancer(LSCC)rarely harbors epidermal growth factor receptor(EGFR)mutations,even much rarer for acquired T790M mutation.Although clinical trials of AURA series illustrated that non-small cell lung cancer(NSCLC)with EGFR T790M mutation can benefit from osimertinib,only five LSCC patients were enrolled in total;moreover,the efficacy for LSCC was not shown in the results.Therefore,the response of LSCC to osimertinib is still unclear to date.CASE SUMMARY We report an LSCC case with T790M-related acquired resistance after treatments with first-generation EGFR-tyrosine kinase inhibitors(EGFR-TKIs)and benefited from osimertinib significantly.A 63-year-old Chinese man was diagnosed with stage IV(cT2N2M1b)LSCC harboring an EGFR exon 19-deletion mutation.Following disease progression after gefitinib and multi-line chemotherapy,rebiopsy was conducted.Molecular testing of EGFR by amplification refractory mutation system-polymerase chain reaction detected the exon 19-deletion without T790M mutation.Therefore,the patient was given erlotinib,but progression developed only 3 mo later.Then the frozen re-biopsy tissue was tested by next-generation sequencing(NGS),which detected an EGFR T790M mutation.However,he was very weak with symptoms of dysphagia and cachexia.Fortunately,osimertinib was started,leading to alleviation from the symptoms.Four months later,normal deglutition was restored and partial response was achieved.Finally,the patient achieved an overall survival time period of 29 mo.CONCLUSION Our findings highlight that EGFR T790M mutation may also be an important acquired drug resistance mechanism for LSCC and offer direct evidence of the efficacy of osimertinib in LSCC with T790M mutation.NGS and better preservation conditions may contribute to higher sensitivity of EGFR T790M detection.
基金Financial support from NSF of China(21773033,21972024,91645201)Science&Technology Commission of Shanghai Municipality(19DZ2270100)SINOPEC(X514005)is acknowledged。
文摘We describe herein that the quasi-one-dimensional confinement effect of functionalized nanoporous supports is particularly advantageous for boosting formic acid(FA)dehydrogenation efficiency over palladium nanoparticles(NPs).Benefiting from their unique structural merits that lead to significant lowering of the entropic barrier for FA activation,the Pd NPs interiorly located on the amino-modified MCM-41 offer the promise of more than an order of magnitude speedup of the initial activity in H2 production from FA over their exterior analogs.Under mild and additive-free conditions,ultrafine Pd NPs confined in aminomodified MCM-41 channels exhibit an initial turnover frequency as high as 46,677 h-1 and a turnover number up to 1,060,000 at 60℃.In conjunction with the enhancement and robust performance for efficient regeneration of FA via CO2 hydrogenation,the presented approach greatly contributes to the development of FA-based hydrogen storage and related technologies as viable means of enabling sustainable future energy prospects.
基金National Natural Science Foundation of China(No.81674011)。
文摘Objective:The differences of ovarian morphology,reproductive hormones,glucose and lipid metabolism and intestinal bacteria in rats with polycystic ovary syndrome(PCOS)induced by triazole were compared.Method:Eighteen 21 SPF female SD rats were randomly divided into group A(3-week group),group B(5-week group)and group D(control group)by random number table.Group A received letrozole+CMC-Na mixture by gavage in the first 3 weeks and CMC-Na solution by gavage in the last 2 weeks,group B received letrozole+CMC-Na mixture by gavage for 5 weeks,and group D received CMC-Na solution by gavage for 5 weeks,and all three groups of rats were fed with normal diet.At the end of gavage,the body weight of rats in each group was observed,the histological changes of ovaries were observed by hematoxylin-eosin(HE)staining,the serum levels of estradiol(E2),follicle stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),total cholesterol(TC),triglyceride(TG),fasting blood glucose(Glu),fasting insulin(FINS)and lipopolysaccharide(LPS)were measured by enzyme-linked immunosorbent assay(ELISA),and the LH/FSH ratio and insulin resistance index(HOMA IR)were calculated;the intestinal bacteria of rats were detected by 16S rRNA technique.Result:1.Comparison of ovary histomorphology:Under light microscope,multiple luteum and oocytes were observed in mature follicles in group D,and granulosa cells were orderly arranged and multilayered,without cystic dilated follicles.There were no mature follicles in the ovarian tissues of group A and GROUP B.The follicles were irregular in structure and more cystic dilated follicles were visible.The number of granular cells in some follicles decreased or even disappeared.2.Comparison of sex hormone levels:compared with group D,T level in group B was significantly increased(P<0.001),and T level in group A had an upward trend(P>0.05);The LH/FSH levels in group A and B were significantly increased(P<0.001;P<0.001).Compared with group A,E2 in group B was significantly decreased(P<0.05)and T was significantly increased(P<0.01).3.Comparison of glucose and lipid metabolism levels:Compared with group D,TC levels in groups A and B were significantly increased(P<0.01;P<0.01).Compared with group A,TG in group B was significantly increased(P<0.05).There were no significant differences in Glu,FINS and HOMA-IR levels among all groups.4.Comparison of LPS levels:Compared with group D,the serum LPS levels of rats in groups A and B were significantly increased(P<0.001;P<0.01).5.Intestinal flora analysis and comparison:At the phylum level,compared with group D,the abundance of Firmicutes in group B increased(P<0.01),Firmicutes in group A showed an upward trend(P>0.05),and the abundance of Bacteroidetes in groups A and B decreased(P<0.05).At the genus level,compared with group D,Lactobacillus in group B increased(P<0.01).The results of LEfSe analysis showed that there were differences in the composition of various intestinal bacteria among the three groups(LDA>3).Conclusion:The phenotype of PCOS rats was related to the length of modeling,and the phenotypic characteristics of PCOS in rats at 5 weeks of modeling were more typical than those in rats at 3 weeks of modeling;PCOS can cause changes in intestinal flora,and the changes in the structure of intestinal flora between groups are related to different modeling duration.
文摘Objective: To investigate the effects of methotrexate and hydroxychloroquine sulfate and prednisone on inflammatory response, immune function, liver and renal function in patients with systemic lupus erythematosus (SLE). Methods: A total of 80 cases of SLE patients according to the random data table were divided into the control group (n=40) and observation group (n=40), the control group were treated with hydroxychloroquine sulfate and prednisone treatment, on the basis of treatment of the control group, patients in the observation group in the control group were treated with methotrexate, the levels of inflammatory factors, immune function, liver and kidney function indexes in the two groups between the before treatment and after treatment were compared. Results: Comparison of the levels before treatment, the difference of the CRP, WBC, ESR, IgA, IgG, complement C3, complement C4, ALT, AST, SCr and BUN levels were not statistically significant. After treatment, the levels of CRP, ESR, IgA, IgG, ALT, AST, SCr and BUN in the observation group were significantly lower than those in the control group, and the difference was statistically significant. The levels of WBC and complement C4 in the observation group [(5.18±1.08)×109 /L, (0.22±0.05) g/L] were significantly higher than those in the control group [(4.51±0.52)×109 /L, (0.18±0.03) g/L], and there was no significant difference in the level of complement C3 between the two groups after treatment. Conclusion: Methotrexate combined with hydroxychloroquine sulfate and prednisone for the treatment of SLE can effectively reduce inflammation, improve immune function, has little effect on kidney function, high safety, which has an important clinical value.
文摘According to WHO, one of these mass gatherings with critical risk is stampedes. Shanghai “12.31” stampede was a preventable tragedy that the government and event planner hold responsibility for. At the same time, it can be a legacy for improvement in the future. The government should draw experience on the implementation of an emergency preparedness system, in order to improve the rapid emergency response during mass gatherings in the future.
基金This work was supported by National Natural Science Foundation of China(31601463)National Key R&D Program of China(2018YFA0901700)+2 种基金National First-class Discipline Program of Light Industry Technology and Engineering(LITE2018-07)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX19_1834)Top-notch Academic Programs Project of Jiangsu Higher Education Institutions.
文摘Sulfuric acid was used in the pretreatment of corn stover to obtain xylose as a value-added by-product,and the pretreated corn stover(Pre-CS)was hydrolyzed to produce glucose for butanol fermentation.The aim of this work is to achieve high xylose accumulation and reduced wastewater by recycling the pretreatment solution.The pretreatment conditions were optimized as follows:180°C,15 min,1:7 solid-liquid ratio(w/w),0.6%H_(2)SO_(4)(w/w,first batch)/0.9%H_(2)SO_(4)(w/w,second and third batches),in which pretreatment solution was recycled for three times.Under above conditions,pretreatment solution containing 56.3 g/L xylose and 4.5 g/L glucose was obtained.Pre-CS residue was further hydrolyzed by cellulase to achieve 35.7-39.9 g/L glucose.The condensed corn stover hydrolysate was subjected to simultaneous detoxification and sterilization using 1%(w/w)activated carbon and then applied in butanol fermentation.The highest butanol titer of 9.5 g/L was obtained in 72 h.The results provide a practical approach for coproducing xylose and biobutanol from corn stover.