AIM:To explore the effects of platelet count(PLT)and11 platelet-based indices on postoperative recurrence of hepatocellular carcinoma(HCC).METHODS:We retrospectively analyzed 172 HCC patients who were treated by parti...AIM:To explore the effects of platelet count(PLT)and11 platelet-based indices on postoperative recurrence of hepatocellular carcinoma(HCC).METHODS:We retrospectively analyzed 172 HCC patients who were treated by partial hepatectomy.Preoperative data,including laboratory biochemical results,were used to calculate the 11 indices included in the analysis.We performed receiver operating characteristic curve analysis to determine the optimal cut-off values for predicting recurrence.Cumulative rates of HCC recurrence were calculated using KaplanMeier survival curves and differences were analyzed by log-rank tests.Multivariate analyses were performed to identify independent predictors of recurrence,early recurrence(within one year after surgery),and late recurrence in HCC.To obtain better prognostic models,PLT-based indices were analyzed separately after being expressed as binary and continuous variables.Two platelet-unrelated,validated HCC prognostic models were included in the analyses as reference indices.Additional analyses were performed after patients were stratified based on hepatitis B virus infection status,cirrhosis,and tumor size to investigate the significance of platelets in different subgroups.RESULTS:In the study cohort,44.2%(76/172)of patients experienced HCC recurrence,and 50.6%(87/172)died during a median follow-up time of 46mo.PLT and five of the 11 platelet-related models were significant predisposing factors for recurrence(P<0.05).Multivariate analysis indicated that,among the clinical parameters,presence of ascites,PLT≥148×109/L,alkaline phosphatase≥116 U/L,and tumor size≥5 cm were independently associated with ahigher risk of HCC recurrence(P<0.05).Independent and significant models included the aspartate aminotransferase/PLT index,fibrosis index based on the four factors,fibro-quotient,aspartate aminotransferase/PLT/γ-glutamyl transpeptidase/alpha-fetoprotein index,and the PLT/age/alkaline phosphatase/alphafetoprotein/aspartate aminotransferase index.There were different risk factors between early and late recurrences,and PLT and these indices were more inclined to influence late recurrence.PLT was only predictive of recurrence in non-cirrhotic HCC patients,and was not influenced by tumor size,which was a critical confounder in our study.CONCLUSION:PLT and PLT-basednoninvasive models are effective tools for predicting postoperative recurrence,especially late recurrence.Larger cohorts are needed to validate our findings.展开更多
BACKGROUND Liver organoids have recently been applied as models for liver disease and drug screening,especially when combined with liver-on-a-chip technologies.Compared to hepatocyte-like cells,primary hepatocytes hav...BACKGROUND Liver organoids have recently been applied as models for liver disease and drug screening,especially when combined with liver-on-a-chip technologies.Compared to hepatocyte-like cells,primary hepatocytes have high functionality but cannot maintain their function when cultured in vitro.Mesenchymal stem cells(MSCs)enhance hepatocyte function and maintain hepatocyte metabolism when co-cultured with hepatocytes.MSCs can help induced pluripotent stem cells to generate an organoid structure via the MSC-based traction force triggered by extracellular matrix(ECM)proteins.In this study,primary hepatocytes were cocultured with MSCs on a liver-derived ECM to generate liver organoids within a short duration.AIM To create hepatocyte organoids by co-culturing primary hepatocytes with MSCs on a porcine liver extracellular matrix(PLECM)gel.METHODS Perfusion and enzymatic hydrolysis were used to form the PLECM gel.Rat hepatocytes and human MSCs were mixed and plated on pre-solidified PLECM gel in a 48-well plate for 48 h to generate organoids.Generated organoids were evaluated through hematoxylin and eosin,periodic acid-Schiff,immunohistological,and immunofluorescence staining,and quantitative PCR for alb,CYP450 gene markers,and urea cycle genes.Culture medium was collected to detect albumin(ALB)and urea production on days 2,4,6,8,14,and 20.RESULTS The whole porcine liver was perfused and enzymatically hydrolyzed to form a PLECM gel.The structural components and basement membrane composition of the ECM,such as collagen type I,collagen type IV,fibronectin,and laminin,were demonstrated to be retained.Through interaction of human MSCs with the liverderived ECM,primary hepatocytes and human MSCs assembled together into a 3D construction and generated primary hepatocyte organoids for 48 h.The mRNAs of the gene alb,the CYP450 gene markers cyp1a1,cyp1a2,and cyp3a2 as well as urea cycle genes arg-1,asl,ass-1,cps-1,nags were highly expressed in hepatocyte organoids.Long-term survival of the primary hepatocyte organoids,as well as stable functionality,was demonstrated via ALB and urea production in vitro.CONCLUSION Our new method of creating primary hepatocyte organoids by co-culturing hepatocytes with MSCs on liver-derived ECM hydrogels could be used to develop models for liver disease and for drug screening.展开更多
BACKGROUND Postpolypectomy syndrome(PPS)is a rare postoperative complication of colonic polypectomy.It presents with abdominal pain and fever accompanied by coagulopathy and elevated inflammatory markers.Its prognosis...BACKGROUND Postpolypectomy syndrome(PPS)is a rare postoperative complication of colonic polypectomy.It presents with abdominal pain and fever accompanied by coagulopathy and elevated inflammatory markers.Its prognosis is usually good,and it only requires outpatient treatment or observation in a general ward.How-ever,it can be life-threatening.CASE SUMMARY The patient was a 58-year-old man who underwent two colonic polypectomies,each resulting in life-threatening sepsis,septic shock,and coagulopathy.Each of the notable manifestations was a rapid drop in blood pressure,an increase in heart rate,loss of consciousness,and heavy sweating,accompanied by shortness of breath and decreased oxygen in the finger pulse.Based on the criteria of organ dysfunction due to infection,we diagnosed him with sepsis.The patient also experienced severe gastrointestinal bleeding after the second operation.Curiously,he did not complain of any abdominal pain throughout the course of the illness.He had significantly elevated concentrations of inflammatory markers and coagulopathy.Except for the absence of abdominal pain,his fever,significant coagulopathy,and elevated inflammatory marker concentrations were all consistent with PPS.Abdominal computed tomography and superior mesenteric artery computed tomography angiography showed no free air or vascular damage.Thus,the diagnosis of colon perforation was not considered.The final blood culture results indicated Moraxella osloensis.The patient was transferred to the intensive care unit and quickly improved after fluid resuscitation,antibiotic treatment,oxygen therapy,and blood transfusion.CONCLUSION PPS may induce dysregulation of the systemic inflammatory response,which can lead to sepsis or septic shock,even in the absence of abdominal pain.展开更多
Objective: This study aims to elucidate and quantify the composition of Jiangtang Qingre formula(JQF), delineate the absorbed components in the bloodstream, predict the major biologically active components, and identi...Objective: This study aims to elucidate and quantify the composition of Jiangtang Qingre formula(JQF), delineate the absorbed components in the bloodstream, predict the major biologically active components, and identify potential targets for the treatment of diabetes mellitus(DM). Materials and Methods: The chemical composition and metabolites of JQF were elucidated using ultra-high-performance liquid chromatography(UHPLC)-linear ion trap quadrupole-orbitrap high-resolution mass spectrometry(MS). The various components of JQF were concurrently determined using UHPLC-triple–quadrupole MS. Network pharmacological analysis was employed to explore the bioactive components and potential therapeutic targets in DM. Results: A total of 63 compounds were identified and provisionally characterized, with fiavones, organic acids, and alkaloids emerging as the major chemical constituents. A robust analytical method that enables the simultaneous quantification of 24 representative components was successfully developed. The contents of 11 batches of samples were assessed. Ten prototype components were identified in rat plasma. The pathways associated with the efficacy of JQF in DM treatment were linked to signal transduction, endocrine and immune systems, lipid metabolism, and amino acid metabolism. Conclusion: This study systematically and comprehensively characterized the major chemical components and patterns in JQF, laying the groundwork for understanding its pharmacodynamic mechanisms and clinical applications.展开更多
Cyclic polymers have attracted more and more attentions in recent years because of their unique topological structures and characteristic properties in both solution and bulk state. There are relatively few reports on...Cyclic polymers have attracted more and more attentions in recent years because of their unique topological structures and characteristic properties in both solution and bulk state. There are relatively few reports on cyclic polymers, partly because of the more demanding synthetic procedures. In recent years, 'click' reaction, especially Cu(I)-catalyzed azide-alkyne cycloaddition(CuAAC), has been widely utilized in the synthesis of cyclic polymer materials because of its high efficiency and low susceptibility to side reactions. In this review, we will focus on three aspects:(1) Constructions of monocyclic polymer using CuAAC 'click' chemistry;(2) Formation of complex cyclic polymer topologies through CuAAC reactions;(3) Using CuAAC 'click' reaction in the precise synthesis of molecularly defined macrocycles. We believe that the CuAAC click reaction is playing an important role in the design and synthesis of functional cyclic polymers.展开更多
Objective:To explore the anaphylaxis effect and anaphylaxis substances of honeysuckle.Methods:Rat peritoneal mast cells(PMC)were separated and purified,the cells were incubated with compound 48/80(0.02 g/L),physiologi...Objective:To explore the anaphylaxis effect and anaphylaxis substances of honeysuckle.Methods:Rat peritoneal mast cells(PMC)were separated and purified,the cells were incubated with compound 48/80(0.02 g/L),physiological saline and honeysuckle extract(120 g/L)at 37°C for 0,15,30,45 and 60 min.Degranulation were observed by optical microscope and transmission electron microscope.Annexin V positive cell rate was detected by flow cytometry to reflect the degranulation rate of PMC.SD rats were supplied with honeysuckle extract by intravenous injection at a dose of 2.25 g/L.After administration,different parameters were analyzed,including the symptoms,histamine(HIS)and tryptase(MCT)levels,which were determined to explore the effect of anaphylaxis.Regression analysis was used to calculate the relationships between the peaks and the pharmacological effects to explore potentially anaphylactoid components.Results:The percentage of Annxin V positive cells and the degranulation ratio were markedly elevated in PMC treated with honeysuckle extract for more than 15 min(P<0.05).HIS and MCT level were significantly elevated after injection of honeysuckle extract for more than 15 min.Morphology of PMC and systemic symptoms were also changed compared with the controlled group(P<0.05).Regression analysis was used to calculate the relationship between peaks and pharmacological effects,and to determine peaks 7,10 and 13 as possible anaphylactoid ingredients.Conclusion:This study established a prospective method to clarify the anaphylactoid components of honeysuckle extract,which would provide guidance for screening anaphylactoid components in traditional Chinese medicine injections containing honeysuckle in the prescription.展开更多
Lipocalins exhibit functional diversity,including roles in retinol transport,invertebrate cryptic coloration,and stress response.However,genome-wide identification and characterization of lipocalin in the insect linea...Lipocalins exhibit functional diversity,including roles in retinol transport,invertebrate cryptic coloration,and stress response.However,genome-wide identification and characterization of lipocalin in the insect lineage have not been thoroughly explored.Here,we found that a lineage-specific expansion of the lipocalin genes in Lepidoptera occurred in large part due to tandem duplication events and several lipocalin genes involving insect coloration were expanded more via tandem duplication in butterflies.A comparative analysis of conserved motifs showed both conservation and divergence of lepidopteran lipocalin family protein structures during evolution.We observe dynamic changes in tissue expression preference of paralogs in Bombyx mori,suggesting differential contribution of paralogs to specific organ functions during evolution.Subcellular localization experiments revealed that lipocalins localize to the cytoplasm,nuclear membrane,or nucleus in BmN cells.Moreover,several lipocalin genes exhibited divergent responses to abiotic and biotic stresses,and 1 lipocalin gene was upregulated by 30o fold in B.mori.These results suggest that lipocalins act as signaling components in defense responses by mediating crosstalk between abiotic and biotic stress responses.This study deepens our understanding of the comprehensive characteristics of lipocalins in insects.展开更多
基金Supported by National Natural Science Foundation of China,No.30872482 and No.81072051
文摘AIM:To explore the effects of platelet count(PLT)and11 platelet-based indices on postoperative recurrence of hepatocellular carcinoma(HCC).METHODS:We retrospectively analyzed 172 HCC patients who were treated by partial hepatectomy.Preoperative data,including laboratory biochemical results,were used to calculate the 11 indices included in the analysis.We performed receiver operating characteristic curve analysis to determine the optimal cut-off values for predicting recurrence.Cumulative rates of HCC recurrence were calculated using KaplanMeier survival curves and differences were analyzed by log-rank tests.Multivariate analyses were performed to identify independent predictors of recurrence,early recurrence(within one year after surgery),and late recurrence in HCC.To obtain better prognostic models,PLT-based indices were analyzed separately after being expressed as binary and continuous variables.Two platelet-unrelated,validated HCC prognostic models were included in the analyses as reference indices.Additional analyses were performed after patients were stratified based on hepatitis B virus infection status,cirrhosis,and tumor size to investigate the significance of platelets in different subgroups.RESULTS:In the study cohort,44.2%(76/172)of patients experienced HCC recurrence,and 50.6%(87/172)died during a median follow-up time of 46mo.PLT and five of the 11 platelet-related models were significant predisposing factors for recurrence(P<0.05).Multivariate analysis indicated that,among the clinical parameters,presence of ascites,PLT≥148×109/L,alkaline phosphatase≥116 U/L,and tumor size≥5 cm were independently associated with ahigher risk of HCC recurrence(P<0.05).Independent and significant models included the aspartate aminotransferase/PLT index,fibrosis index based on the four factors,fibro-quotient,aspartate aminotransferase/PLT/γ-glutamyl transpeptidase/alpha-fetoprotein index,and the PLT/age/alkaline phosphatase/alphafetoprotein/aspartate aminotransferase index.There were different risk factors between early and late recurrences,and PLT and these indices were more inclined to influence late recurrence.PLT was only predictive of recurrence in non-cirrhotic HCC patients,and was not influenced by tumor size,which was a critical confounder in our study.CONCLUSION:PLT and PLT-basednoninvasive models are effective tools for predicting postoperative recurrence,especially late recurrence.Larger cohorts are needed to validate our findings.
基金National Natural Science Foundation of China,No.81770618Key R&D(Major Science and Technology Project)Project of Sichuan Science and Technology Department,No.2019YFS0138+1 种基金Technological Innovation Project of Chengdu New Industrial Technology Research Institute,No.2018-CY02-00046-GXand the 1.3.5 Project for Disciplines of Excellence,West China Hospital,No.ZYGD18012.
文摘BACKGROUND Liver organoids have recently been applied as models for liver disease and drug screening,especially when combined with liver-on-a-chip technologies.Compared to hepatocyte-like cells,primary hepatocytes have high functionality but cannot maintain their function when cultured in vitro.Mesenchymal stem cells(MSCs)enhance hepatocyte function and maintain hepatocyte metabolism when co-cultured with hepatocytes.MSCs can help induced pluripotent stem cells to generate an organoid structure via the MSC-based traction force triggered by extracellular matrix(ECM)proteins.In this study,primary hepatocytes were cocultured with MSCs on a liver-derived ECM to generate liver organoids within a short duration.AIM To create hepatocyte organoids by co-culturing primary hepatocytes with MSCs on a porcine liver extracellular matrix(PLECM)gel.METHODS Perfusion and enzymatic hydrolysis were used to form the PLECM gel.Rat hepatocytes and human MSCs were mixed and plated on pre-solidified PLECM gel in a 48-well plate for 48 h to generate organoids.Generated organoids were evaluated through hematoxylin and eosin,periodic acid-Schiff,immunohistological,and immunofluorescence staining,and quantitative PCR for alb,CYP450 gene markers,and urea cycle genes.Culture medium was collected to detect albumin(ALB)and urea production on days 2,4,6,8,14,and 20.RESULTS The whole porcine liver was perfused and enzymatically hydrolyzed to form a PLECM gel.The structural components and basement membrane composition of the ECM,such as collagen type I,collagen type IV,fibronectin,and laminin,were demonstrated to be retained.Through interaction of human MSCs with the liverderived ECM,primary hepatocytes and human MSCs assembled together into a 3D construction and generated primary hepatocyte organoids for 48 h.The mRNAs of the gene alb,the CYP450 gene markers cyp1a1,cyp1a2,and cyp3a2 as well as urea cycle genes arg-1,asl,ass-1,cps-1,nags were highly expressed in hepatocyte organoids.Long-term survival of the primary hepatocyte organoids,as well as stable functionality,was demonstrated via ALB and urea production in vitro.CONCLUSION Our new method of creating primary hepatocyte organoids by co-culturing hepatocytes with MSCs on liver-derived ECM hydrogels could be used to develop models for liver disease and for drug screening.
基金the Scientific Research Project of the Natural Science Foundation of Changsha,No.kq2202413.
文摘BACKGROUND Postpolypectomy syndrome(PPS)is a rare postoperative complication of colonic polypectomy.It presents with abdominal pain and fever accompanied by coagulopathy and elevated inflammatory markers.Its prognosis is usually good,and it only requires outpatient treatment or observation in a general ward.How-ever,it can be life-threatening.CASE SUMMARY The patient was a 58-year-old man who underwent two colonic polypectomies,each resulting in life-threatening sepsis,septic shock,and coagulopathy.Each of the notable manifestations was a rapid drop in blood pressure,an increase in heart rate,loss of consciousness,and heavy sweating,accompanied by shortness of breath and decreased oxygen in the finger pulse.Based on the criteria of organ dysfunction due to infection,we diagnosed him with sepsis.The patient also experienced severe gastrointestinal bleeding after the second operation.Curiously,he did not complain of any abdominal pain throughout the course of the illness.He had significantly elevated concentrations of inflammatory markers and coagulopathy.Except for the absence of abdominal pain,his fever,significant coagulopathy,and elevated inflammatory marker concentrations were all consistent with PPS.Abdominal computed tomography and superior mesenteric artery computed tomography angiography showed no free air or vascular damage.Thus,the diagnosis of colon perforation was not considered.The final blood culture results indicated Moraxella osloensis.The patient was transferred to the intensive care unit and quickly improved after fluid resuscitation,antibiotic treatment,oxygen therapy,and blood transfusion.CONCLUSION PPS may induce dysregulation of the systemic inflammatory response,which can lead to sepsis or septic shock,even in the absence of abdominal pain.
基金financially by the Scientific and technological innovation project of China Academy of Chinese Medical Sciences (No. CI2021A01606, CI2021A04507, CI2021A04510, Cl2021A04502, CI2021A04509)National Administration of Traditional Chinese Medicine Young Qihuang Scholar Project,ChinaQianjiang Distinguished Expert Project of Hangzhou (2020), China
文摘Objective: This study aims to elucidate and quantify the composition of Jiangtang Qingre formula(JQF), delineate the absorbed components in the bloodstream, predict the major biologically active components, and identify potential targets for the treatment of diabetes mellitus(DM). Materials and Methods: The chemical composition and metabolites of JQF were elucidated using ultra-high-performance liquid chromatography(UHPLC)-linear ion trap quadrupole-orbitrap high-resolution mass spectrometry(MS). The various components of JQF were concurrently determined using UHPLC-triple–quadrupole MS. Network pharmacological analysis was employed to explore the bioactive components and potential therapeutic targets in DM. Results: A total of 63 compounds were identified and provisionally characterized, with fiavones, organic acids, and alkaloids emerging as the major chemical constituents. A robust analytical method that enables the simultaneous quantification of 24 representative components was successfully developed. The contents of 11 batches of samples were assessed. Ten prototype components were identified in rat plasma. The pathways associated with the efficacy of JQF in DM treatment were linked to signal transduction, endocrine and immune systems, lipid metabolism, and amino acid metabolism. Conclusion: This study systematically and comprehensively characterized the major chemical components and patterns in JQF, laying the groundwork for understanding its pharmacodynamic mechanisms and clinical applications.
基金financially supported by the National Natural Science Foundation of China(No.21234005)the State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Program of Innovative Research Team of Soochow University
文摘Cyclic polymers have attracted more and more attentions in recent years because of their unique topological structures and characteristic properties in both solution and bulk state. There are relatively few reports on cyclic polymers, partly because of the more demanding synthetic procedures. In recent years, 'click' reaction, especially Cu(I)-catalyzed azide-alkyne cycloaddition(CuAAC), has been widely utilized in the synthesis of cyclic polymer materials because of its high efficiency and low susceptibility to side reactions. In this review, we will focus on three aspects:(1) Constructions of monocyclic polymer using CuAAC 'click' chemistry;(2) Formation of complex cyclic polymer topologies through CuAAC reactions;(3) Using CuAAC 'click' reaction in the precise synthesis of molecularly defined macrocycles. We believe that the CuAAC click reaction is playing an important role in the design and synthesis of functional cyclic polymers.
基金project supported by the Heilongjiang University of Chinese Medicine Province and Excellent Youth Project of Natural Science Foundation of Heilongjiang Province(YQ2019H031)Postdoctoral Researchers Settled in Heilongjiang Scientific Research Startup Fund(2020)Outstanding Innovative Talents Project from Heilongjiang University of Chinese Medicine(2018)。
文摘Objective:To explore the anaphylaxis effect and anaphylaxis substances of honeysuckle.Methods:Rat peritoneal mast cells(PMC)were separated and purified,the cells were incubated with compound 48/80(0.02 g/L),physiological saline and honeysuckle extract(120 g/L)at 37°C for 0,15,30,45 and 60 min.Degranulation were observed by optical microscope and transmission electron microscope.Annexin V positive cell rate was detected by flow cytometry to reflect the degranulation rate of PMC.SD rats were supplied with honeysuckle extract by intravenous injection at a dose of 2.25 g/L.After administration,different parameters were analyzed,including the symptoms,histamine(HIS)and tryptase(MCT)levels,which were determined to explore the effect of anaphylaxis.Regression analysis was used to calculate the relationships between the peaks and the pharmacological effects to explore potentially anaphylactoid components.Results:The percentage of Annxin V positive cells and the degranulation ratio were markedly elevated in PMC treated with honeysuckle extract for more than 15 min(P<0.05).HIS and MCT level were significantly elevated after injection of honeysuckle extract for more than 15 min.Morphology of PMC and systemic symptoms were also changed compared with the controlled group(P<0.05).Regression analysis was used to calculate the relationship between peaks and pharmacological effects,and to determine peaks 7,10 and 13 as possible anaphylactoid ingredients.Conclusion:This study established a prospective method to clarify the anaphylactoid components of honeysuckle extract,which would provide guidance for screening anaphylactoid components in traditional Chinese medicine injections containing honeysuckle in the prescription.
基金supported by the National Natural Science Foundation of China(grant no.31970460,32170483)the Natural Science Foundation of Zhejiang Province(grant no.LR22C040001)+1 种基金the Zhejiang Provincial Science and Technology Plans(2021C02072-6)the Zhejiang Provincial Key Laboratory Construction Plans(2020E10025).
文摘Lipocalins exhibit functional diversity,including roles in retinol transport,invertebrate cryptic coloration,and stress response.However,genome-wide identification and characterization of lipocalin in the insect lineage have not been thoroughly explored.Here,we found that a lineage-specific expansion of the lipocalin genes in Lepidoptera occurred in large part due to tandem duplication events and several lipocalin genes involving insect coloration were expanded more via tandem duplication in butterflies.A comparative analysis of conserved motifs showed both conservation and divergence of lepidopteran lipocalin family protein structures during evolution.We observe dynamic changes in tissue expression preference of paralogs in Bombyx mori,suggesting differential contribution of paralogs to specific organ functions during evolution.Subcellular localization experiments revealed that lipocalins localize to the cytoplasm,nuclear membrane,or nucleus in BmN cells.Moreover,several lipocalin genes exhibited divergent responses to abiotic and biotic stresses,and 1 lipocalin gene was upregulated by 30o fold in B.mori.These results suggest that lipocalins act as signaling components in defense responses by mediating crosstalk between abiotic and biotic stress responses.This study deepens our understanding of the comprehensive characteristics of lipocalins in insects.
