BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clini...BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma(LUSC).METHODS Lung KLF5 mRNA data were extracted from bioinformatics databases.Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry,Western blot,Enzyme Linked Immunosorbent Assay or quantitative polymerase chain reaction.Furthermore,KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo,respectively.RESULTS A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC(P<0.001)but lower KLF5 mRNA expression in lung adenocarcinoma.Upregulated KLF5 in the lung or sera of patients with lung cancer(P<0.001)were confirmed that related to poor differentiation,lymph node or distant metastasis.Furthermore,the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%,which was significantly greater(P<0.001)than that in cases with benign lung diseases(13.3%)or healthy controls.Functionally,silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation,decreased cell migration,increased the ratio of G2 phase cells in vitro,and inhibited the growth of nude mouse xenografts in vivo.CONCLUSION KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC.展开更多
Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to ...Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to establish a novel geneticallyengineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system.Methods : A single- guide ribonucleic acid targeting exon 1 of SHARPIN gene was designedand constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatalmutants were identified by genotyping. SHARPIN protein expression was detectedusing Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymicweights were measured, and organ coefficients were calculated. Histopathologicalexamination of the spleen, liver, lung, small intestine, and esophagus was performedindependently by a pathologist. The expression of lymphocytic markers and cytokineswas evaluated using reverse transcriptase- quantitative polymerase chain reaction.Results : All the offspring harbored germline- transmitted SHARPIN mutations.Compared with wild- type hamsters, SHARPIN protein was undetectable in SHARPIN −/−hamsters. Spleen enlargement and splenic coefficient elevation were spotted inSHARPIN −/− hamsters, with the descent of MLNs and thymuses. Further, eosinophilinfiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagiwere obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless,the expression of CCR3, CCL11, Il4 , and Il13 was upregulated in the esophagi. Theexpression of NF- κB and phosphorylation of NF- κB and IκB protein significantly diminishedin SHARPIN −/− animals.Conclusions : A novel SHARPIN KO hamster was successfully established using theCRISPR/Cas9 system. Abnormal development of secondary lymphoid organs andeosinophil infiltration in multiple organs reveal its potential in delineating SHARPINfunction and chronic inflammation.展开更多
Quantum dynamics of many-body systems is a fascinating and significant subject for both theory and experiment.The question of how an isolated many-body system evolves to its steady state after a sudden perturbation or...Quantum dynamics of many-body systems is a fascinating and significant subject for both theory and experiment.The question of how an isolated many-body system evolves to its steady state after a sudden perturbation or quench still remains challenging.In this paper,using the Bethe ansatz wave function,we study the quantum dynamics of an inhomogeneous Gaudin magnet.We derive explicit analytical expressions for various local dynamic quantities with an arbitrary number of flipped bath spins,such as:the spin distribution function,the spin-spin correlation function,and the Loschmidt echo.We also numerically study the relaxation behavior of these dynamic properties,gaining considerable insight into coherence and entanglement between the central spin and the bath.In particular,we find that the spin-spin correlations relax to their steady value via a nearly logarithmic scaling,whereas the Loschmidt echo shows an exponential relaxation to its steady value.Our results advance the understanding of relaxation dynamics and quantum correlations of long-range interacting models of the Gaudin type.展开更多
To systematically evaluate the clinical efficacy and safety of acupuncture in treating cancer-related insomnia.Methods:Randomized controlled trials(RCTs)and quasi-randomized controlled trials of acupuncture in the tre...To systematically evaluate the clinical efficacy and safety of acupuncture in treating cancer-related insomnia.Methods:Randomized controlled trials(RCTs)and quasi-randomized controlled trials of acupuncture in the treatment of cancer-related insomnia were searched by computer in a Pubmed database,and the retrieved literature was screened according to inclusion and exclusion criteria.After the literature screening was completed,two reviewers read the literature titles independently and extracted effective information.The migration risk assessment was performed by Cochrane.All statistical calculation requirements for this study were fully completed by RevMan5.3 software.Results:Among the 68 selected works of literature,3 RCTs were finally included,with a total of 133 patients.The risk of research bias is generally very low.In 3 RCTs,the sleep score of the experimental group was decreased by 0.48 more than that of the control group in 3 RCTs,with a 95%confidence interval of-0.82 and-0.13,and the degree of decrease was statistically significant(Z=2.70,P<0.05).Conclusion:Higher levels may indicate that acupuncture-related therapies are more effective in improving cancer-related insomnia.Although the included literatures feature low bias and no heterogeneity,the number may have reduced its clinical significance.Therefore,more studies on high-quality randomized controlled trials should be conducted in the future to better clarify the therapeutic effect of acupuncture and moxibustion on cancer-related insomnia.展开更多
Background Diabetic wound is one of the most serious complications of diabetes mellitus. There are no significantly effective therapies for chronic non-healing diabetes ulcer so far. This study aimed to explore the fe...Background Diabetic wound is one of the most serious complications of diabetes mellitus. There are no significantly effective therapies for chronic non-healing diabetes ulcer so far. This study aimed to explore the feasibility of healing impaired wound using artificial dermis constructed with human adipose derived stem cells (ASCs) and poly(L-glutamic acid)/chitosan (PLGA/CS) scaffold in streptozotocin-induced diabetic mice. Methods ASCs were isolated from fresh human lipoaspirates and expanded ex vivo for three passages, and then cells were seeded onto PLGNCS scaffold to form artificial dermis. Expression of VEGF and TGFI31 by ASCs presented in artificial dermis was determined. The artificial dermis was transplanted to treat the 20 mm ~ 20 mm full-thickness cutaneous wound created on the back of diabetic mice. Wound treated with scaffold alone and without treatment, and wound in normal non-diabetic mice served as control. Results Cells growing within scaffold showed great proliferation potential, depositing abundant collagen matrix. Meanwhile, expression of VEGF and TGF-131 by seeded ASCs maintained at a consistent high level. After treated with ASC based artificial dermis, diabetic wounds exhibited significantly higher healing rate compared with wounds treated with scaffold alone or without treatment. Histological examination also demonstrated an improvement in cutaneous restoration with matrix deposition and organization. Further quantitative analysis showed that there was a significant increase in dermis thickness and collagen content on artificial dermis treated wounds. Conclusion ASC/PLGA artificial dermis can effectively accelerate diabetic wound healing by promoting angiogenic growth factors and dermal collagen synthesis.展开更多
基金Supported by Jiangsu Commission of Health of China,No.M2020096.
文摘BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma(LUSC).METHODS Lung KLF5 mRNA data were extracted from bioinformatics databases.Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry,Western blot,Enzyme Linked Immunosorbent Assay or quantitative polymerase chain reaction.Furthermore,KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo,respectively.RESULTS A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC(P<0.001)but lower KLF5 mRNA expression in lung adenocarcinoma.Upregulated KLF5 in the lung or sera of patients with lung cancer(P<0.001)were confirmed that related to poor differentiation,lymph node or distant metastasis.Furthermore,the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%,which was significantly greater(P<0.001)than that in cases with benign lung diseases(13.3%)or healthy controls.Functionally,silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation,decreased cell migration,increased the ratio of G2 phase cells in vitro,and inhibited the growth of nude mouse xenografts in vivo.CONCLUSION KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC.
基金Natural Science Foundation of Henan Province,Grant/Award Number:202300410259Henan Postdoctoral Science Foundation,Grant/Award Number:202001043China Postdoctoral Science Foundation,Grant/Award Number:2021T140184。
文摘Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to establish a novel geneticallyengineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system.Methods : A single- guide ribonucleic acid targeting exon 1 of SHARPIN gene was designedand constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatalmutants were identified by genotyping. SHARPIN protein expression was detectedusing Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymicweights were measured, and organ coefficients were calculated. Histopathologicalexamination of the spleen, liver, lung, small intestine, and esophagus was performedindependently by a pathologist. The expression of lymphocytic markers and cytokineswas evaluated using reverse transcriptase- quantitative polymerase chain reaction.Results : All the offspring harbored germline- transmitted SHARPIN mutations.Compared with wild- type hamsters, SHARPIN protein was undetectable in SHARPIN −/−hamsters. Spleen enlargement and splenic coefficient elevation were spotted inSHARPIN −/− hamsters, with the descent of MLNs and thymuses. Further, eosinophilinfiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagiwere obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless,the expression of CCR3, CCL11, Il4 , and Il13 was upregulated in the esophagi. Theexpression of NF- κB and phosphorylation of NF- κB and IκB protein significantly diminishedin SHARPIN −/− animals.Conclusions : A novel SHARPIN KO hamster was successfully established using theCRISPR/Cas9 system. Abnormal development of secondary lymphoid organs andeosinophil infiltration in multiple organs reveal its potential in delineating SHARPINfunction and chronic inflammation.
基金support from NSAF(Grant No.U1930402)supported by the key NSFC grant No.12134015 and No.11874393+2 种基金the National Key R&D Program of China No.2017YFA0304500,the National Key R&D Program of China No.2016YFA0301200support from NSFC(Grants No.11974040 and No.12150610464),NSFC 11734002financial support from National Science Association Funds U1930402
文摘Quantum dynamics of many-body systems is a fascinating and significant subject for both theory and experiment.The question of how an isolated many-body system evolves to its steady state after a sudden perturbation or quench still remains challenging.In this paper,using the Bethe ansatz wave function,we study the quantum dynamics of an inhomogeneous Gaudin magnet.We derive explicit analytical expressions for various local dynamic quantities with an arbitrary number of flipped bath spins,such as:the spin distribution function,the spin-spin correlation function,and the Loschmidt echo.We also numerically study the relaxation behavior of these dynamic properties,gaining considerable insight into coherence and entanglement between the central spin and the bath.In particular,we find that the spin-spin correlations relax to their steady value via a nearly logarithmic scaling,whereas the Loschmidt echo shows an exponential relaxation to its steady value.Our results advance the understanding of relaxation dynamics and quantum correlations of long-range interacting models of the Gaudin type.
文摘To systematically evaluate the clinical efficacy and safety of acupuncture in treating cancer-related insomnia.Methods:Randomized controlled trials(RCTs)and quasi-randomized controlled trials of acupuncture in the treatment of cancer-related insomnia were searched by computer in a Pubmed database,and the retrieved literature was screened according to inclusion and exclusion criteria.After the literature screening was completed,two reviewers read the literature titles independently and extracted effective information.The migration risk assessment was performed by Cochrane.All statistical calculation requirements for this study were fully completed by RevMan5.3 software.Results:Among the 68 selected works of literature,3 RCTs were finally included,with a total of 133 patients.The risk of research bias is generally very low.In 3 RCTs,the sleep score of the experimental group was decreased by 0.48 more than that of the control group in 3 RCTs,with a 95%confidence interval of-0.82 and-0.13,and the degree of decrease was statistically significant(Z=2.70,P<0.05).Conclusion:Higher levels may indicate that acupuncture-related therapies are more effective in improving cancer-related insomnia.Although the included literatures feature low bias and no heterogeneity,the number may have reduced its clinical significance.Therefore,more studies on high-quality randomized controlled trials should be conducted in the future to better clarify the therapeutic effect of acupuncture and moxibustion on cancer-related insomnia.
文摘Background Diabetic wound is one of the most serious complications of diabetes mellitus. There are no significantly effective therapies for chronic non-healing diabetes ulcer so far. This study aimed to explore the feasibility of healing impaired wound using artificial dermis constructed with human adipose derived stem cells (ASCs) and poly(L-glutamic acid)/chitosan (PLGA/CS) scaffold in streptozotocin-induced diabetic mice. Methods ASCs were isolated from fresh human lipoaspirates and expanded ex vivo for three passages, and then cells were seeded onto PLGNCS scaffold to form artificial dermis. Expression of VEGF and TGFI31 by ASCs presented in artificial dermis was determined. The artificial dermis was transplanted to treat the 20 mm ~ 20 mm full-thickness cutaneous wound created on the back of diabetic mice. Wound treated with scaffold alone and without treatment, and wound in normal non-diabetic mice served as control. Results Cells growing within scaffold showed great proliferation potential, depositing abundant collagen matrix. Meanwhile, expression of VEGF and TGF-131 by seeded ASCs maintained at a consistent high level. After treated with ASC based artificial dermis, diabetic wounds exhibited significantly higher healing rate compared with wounds treated with scaffold alone or without treatment. Histological examination also demonstrated an improvement in cutaneous restoration with matrix deposition and organization. Further quantitative analysis showed that there was a significant increase in dermis thickness and collagen content on artificial dermis treated wounds. Conclusion ASC/PLGA artificial dermis can effectively accelerate diabetic wound healing by promoting angiogenic growth factors and dermal collagen synthesis.