Cutaneous squamous cell carcinoma(cSCC),a type of non-melanoma skin cancer(NMSC),is the most common malignancy worldwide.Thioredoxin(TXN)domain-containing protein 9(TXNDC9)is a member of the TXN family that is importa...Cutaneous squamous cell carcinoma(cSCC),a type of non-melanoma skin cancer(NMSC),is the most common malignancy worldwide.Thioredoxin(TXN)domain-containing protein 9(TXNDC9)is a member of the TXN family that is important in cell differentiation.However,the biological function of this protein in cancer,particularly cSCC,is still unknown.In the present study,our experiments revealed the protective effects of TXNDC9 on UV-B-irritated cSCC cells.The initial findings showed that TXNDC9 is significantly upregulated in cSCC tissue and cells compared to normal skin tissue and keratinocytes.UV-B radiation robustly induces the expression of TXNDC9,and UV-B-induced cSCC cell death is boosted by TXNDC9 deficiency.Moreover,cSCC cells lacking TXNDC9 displayed attenuated activation of the NF-κB pathway.Additional studies by inhibiting TXNDC9 confirmed this finding,as TXNDC9 deficiency attenuated UV-B radiation-induced translocation of NF-κB p65 from the cytoplasm to the nucleus of cSCC.In conclusion,our work demonstrates the biological roles of TXNDC9 in cSCC progression and may provide a novel therapeutic target to treat cSCC in the future.展开更多
To achieve accurate classification and recognition of ship target types,it is necessary to establish a sample library of ship targets to be identified.On the basis of exploring the principles of building a ship target...To achieve accurate classification and recognition of ship target types,it is necessary to establish a sample library of ship targets to be identified.On the basis of exploring the principles of building a ship target image library,the paper determines the sample set.Using 3DS MAX software as the platform,combined with the accurate 3D model of the ship in an offline state,the software fully utilizes its own rendering and animation functions to achieve the automatic generation of multi-view and multi-scale views of ship targets.To reduce the storage capacity of the image database,a construction method of the ship target image database based on the AP algorithm is presented.The algorithm can obtain the optimal cluster number,reduce the data storage capacity of the image database,and save the calculation amount for the subsequent matching calculation.展开更多
Lactulose is known to improve cognitive function in patients with early hepatic encephalopa- thy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and n...Lactulose is known to improve cognitive function in patients with early hepatic encephalopa- thy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cog- nitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.展开更多
Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity ...Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-l,2,3,6 tetrahydropyridine (MPTP)-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson's disease. Oral administration of octacosanol (100 mg/kg) significantly improved behavioral impairments Jn mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signa transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson's disease.展开更多
BACKGROUND: There is controversy regarding whether saddle main pulmonary artery(MPA) embolism represents a high risk of deterioration in non-high-risk acute pulmonary embolism(PE) patients. This study aims to address ...BACKGROUND: There is controversy regarding whether saddle main pulmonary artery(MPA) embolism represents a high risk of deterioration in non-high-risk acute pulmonary embolism(PE) patients. This study aims to address this issue by conducting a propensity score matching(PSM) study.METHODS: A total of 727 non-high-risk acute PE patients were retrospectively evaluated. We evaluated the Bova score and risk stratification to examine the risk of deterioration. Deterioration defined as any adverse event within 30 days after admission. Computed tomographic pulmonary angiography was used to identify the embolism type. All patients were matched into four subgroups by PSM according to age, sex, Bova score, and risk stratification:(1) MPA and non-MPA embolism;(2) non-saddle MPA and non-MPA embolism;(3) saddle MPA and non-saddle MPA embolism;(4) saddle MPA and non-MPA embolism. Correlations were analyzed using Cox regression analysis, and deterioration risk was compared between subgroups using Kaplan-Meier analysis.RESULTS: Cox regression analysis revealed that MPA embolism was correlated with deterioration, regardless of whether saddle MPA embolism was included or excluded. Saddle MPA embolism was not correlated with deterioration, regardless of comparison with non-saddle MPA embolism or non-MPA embolism. Patients with MPA and non-saddle MPA embolism presented a high risk for deterioration(logrank test=5.23 and 4.70, P=0.022 and 0.030, respetively), while patients with saddle MPA embolism were not at a high risk of deterioration(log-rank test=1.20 and 3.17, P=0.729 and 0.077, respetively).CONCLUSIONS: Saddle MPA embolism is not indicative of a high risk of deterioration in nonhigh-risk acute PE patients.展开更多
Dynamic linearization based model free adaptive control(MFAC) algorithm has been widely used in practical systems, in which some parameters should be tuned before it is successfully applied to process industries. Cons...Dynamic linearization based model free adaptive control(MFAC) algorithm has been widely used in practical systems, in which some parameters should be tuned before it is successfully applied to process industries. Considering the random noise existing in real processes, a parameter tuning method based on minimum entropy optimization is proposed,and the feature of entropy is used to accurately describe the system uncertainty. For cases of Gaussian stochastic noise and non-Gaussian stochastic noise, an entropy recursive optimization algorithm is derived based on approximate model or identified model. The extensive simulation results show the effectiveness of the minimum entropy optimization for the partial form dynamic linearization based MFAC. The parameters tuned by the minimum entropy optimization index shows stronger stability and more robustness than these tuned by other traditional index,such as integral of the squared error(ISE) or integral of timeweighted absolute error(ITAE), when the system stochastic noise exists.展开更多
We investigate the effect of torsion on DNA condensation with the covalently closed circular DNA as the torsionconstrained system, using an atomic force microscope. It is found that there are two stages in the DNA con...We investigate the effect of torsion on DNA condensation with the covalently closed circular DNA as the torsionconstrained system, using an atomic force microscope. It is found that there are two stages in the DNA condensation process under torsional constraint. At the early stage, the low torsion will accelerate DNA condensation by promoting the formation of micro-loops or intersection structures; while at the later stage, the increasing torsion will slow it down by preventing the crosslinking of cisplatin and DNA since the DNA molecule becomes more rigid. Our results show the important role of torsion in DNA condensation and sheds new light on the mechanism for DNA condensation.展开更多
Information is a key factor in emergency management, which helps decision makers to make effective decisions. In this paper, aiming at clarifying the information aggregation laws, and according to the characteristic o...Information is a key factor in emergency management, which helps decision makers to make effective decisions. In this paper, aiming at clarifying the information aggregation laws, and according to the characteristic of emergency information, information relative entropy is applied in the information aggregation to establish the information aggregation model of emergency group decision-making. The analysis shows that support and credibility of decision rule are the two factors in information aggregation. The results of four emergency decision-making groups in case study support the analysis in the paper.展开更多
Psoriasis is a chronic,recurrent,inflammatory systemic disease that is not only characterized by skin manifestations but may also be accompanied by various comorbidities,imposing a heavy burden on patients’physical a...Psoriasis is a chronic,recurrent,inflammatory systemic disease that is not only characterized by skin manifestations but may also be accompanied by various comorbidities,imposing a heavy burden on patients’physical and mental health and affecting their quality of life.Although the continuous approval of various biological agents for clinical use has provided more effective treatment options to patients with psoriasis,no consensus on the evaluation of comprehensive treatment goals has yet been established.The treat-to-target(T2T)strategy requires consideration of multiple dimensions of treatment outcomes,the development of long-term management goals,and regular assessments of treatment conditions,which are often used in the management of chronic diseases.Therefore,based on the latest consensuses and guidelines,research data,and clinical experience as well as the combination of survey results and expert group discussions,the present consensus focuses on 4 dimensions of short-and long-term integrated management goals for biological agents:alleviating skin lesions,improving quality of life,screening and managing psoriasis comorbidities,and ensuring drug safety.The implementation methods,evaluation time,treatment monitoring,and program adjustments are also herein described to achieve comprehensive management of psoriasis to the maximum extent.This consensus provides a reference for clinical practice.展开更多
The response to endoplasmic reticulum(ER)stress has been noted in both human depression cases and depression models in rodents.Wuling powder,derived from the mycelium of the esteemed fungus Xylaria Nigripes(Kl.)Sacc,h...The response to endoplasmic reticulum(ER)stress has been noted in both human depression cases and depression models in rodents.Wuling powder,derived from the mycelium of the esteemed fungus Xylaria Nigripes(Kl.)Sacc,has demonstrated efficacy in alleviating depressive symptoms.The purpose of this research was to explore the antidepressant properties of Wuling powder and its basic molecular effects,particularly regarding alterations in ER stress.A model of social defeat stress was created by introducing a mouse to the cage of an unfamiliar,hostile mouse for intervals of 5–10 min daily over a span of 10 d.Subsequently,the mice received oral doses of Wuling powder for 2 weeks.The social approach-avoidance assay was employed to evaluate signs of depression-like behaviors.Moreover,protein and gene expressions linked to ER stress triggered by social defeat were analyzed through Western blotting analysis and quantitative real-time PCR.The behavioral tests indicated that Wuling powder ameliorated behaviors associated with depression due to social defeat stress.Treatment with Wuling powder markedly reduced the increased levels of the 78-k Da glucose-regulated protein and protein disulfide isomerase caused by social defeat stress.It also diminished the expression of inositol-requiring enzyme 1α(IRE1α)and spliced X box-binding protein-1(s XBP1)at the protein and m RNA levels.Furthermore,Wuling treatment notably decreased the levels of phosphorylated eukaryotic initiation factor 2 alpha kinase(P-e IF2α),activating transcription factor 4(ATF4)and C/EBP homologous protein(CHOP),simultaneously enhancing the ratio of B-cell lymphoma 2(Bcl-2)to Bcl-2-associated X protein(Bax).These results suggested that Wuling powder could alleviate ER stress and inhibit cell apoptosis in the hippocampus by inhibiting protein translation and synthesis,thereby attenuating depressive-like behavior.展开更多
Background:Concurrent chemoradiotherapy is the preferred treatment for stage IVB cervical cancer;however,some patients experience a poor prognosis.The prognostic significance of body composition indicators,including v...Background:Concurrent chemoradiotherapy is the preferred treatment for stage IVB cervical cancer;however,some patients experience a poor prognosis.The prognostic significance of body composition indicators,including visceral obesity,has been extensively investigated in patients with cancer.This study aimed to assess the impact of body composition indicators,specifically pretreatment fat content,on the survival outcomes of patients with stage IVB cervical cancer.Methods:We retrospectively analyzed clinical information from patients diagnosed with stage IVB cervical cancer between 2010 and 2018.We measured visceral obesity(visceral-to-subcutaneous adipose tissue area ratio[VSR])and skeletal muscle index(SMI)on pretreatment computed tomography(CT)images.We evaluated the impact of these body composition parameters on the prognosis of patients with cervical cancer.Results:Overall,116 patients were included,81 of whom had complete clinical and imaging information.Based on the cut-off values from X-tile analysis,we categorized patients into high and low VSR and SMI groups.The overall survival(OS)rate of patients with a high VSR was significantly higher than that of patients with a low VSR(P=0.022).Multivariate Cox regression analysis showed that a low VSR was an independent risk factor for the prognosis of patients with stage IVB cervical cancer.Conclusion:Visceral obesity before radiotherapy and chemotherapy has a protective effect on the prognosis of patients with stage IVB cervical cancer,while low muscle index and VSR are associated with poor prognosis.展开更多
Background:Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy.Transforming growth factor-β(TGF-β)signaling pathway-related genes are asso...Background:Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy.Transforming growth factor-β(TGF-β)signaling pathway-related genes are associated with multiple tumors,but their role in prognosis prediction and tumor microenvironment(TME)regulation in colon cancer is poorly understood.Using bioinformatics,this study aimed to construct a risk prediction signature for colon cancer,which may provide a means for developing new effective treatment strategies.Methods:Using consensus clustering,patients in The Cancer Genome Atlas(TCGA)with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-βsignaling pathway-related genes,and differences in survival,molecular,and immunological TME characteristics and drug sensitivity were examined in each subtype.Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation(LASSO)regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus(GEO)dataset.A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy.Results:Two TGF-βsubtypes were identified,with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy.Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype.After completing signature construction,patients with colon cancer were categorized into high-and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature.The risk score exhibited superior predictive performance relative to age,gender,and stage,as evidenced by its AUC of 0.686.Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME,suggesting that these patients had better responses to immunotherapy.Conclusions:Patients with colon cancer were divided into two subtypes with different survival and immune characteristics using consensus clustering analysis based on TGF-βsignaling pathway-related genes.The constructed risk prediction signature may show promise as a biomarker for evaluating the prognosis of colon cancer,with potential utility for screening individuals for immunotherapy。展开更多
有机-无机杂化卤化物钙钛矿太阳能电池(perovskite solar cells, PSCs)由于其成本低廉、制备工艺简单、光电转换率高等优点引起了越来越多的关注,在下一代半导体光伏技术中显示出巨大的发展潜力。然而PSCs器件在商业化生产应用之前,必...有机-无机杂化卤化物钙钛矿太阳能电池(perovskite solar cells, PSCs)由于其成本低廉、制备工艺简单、光电转换率高等优点引起了越来越多的关注,在下一代半导体光伏技术中显示出巨大的发展潜力。然而PSCs器件在商业化生产应用之前,必须解决某些关键问题,例如器件在湿度、光照和过热条件下缺乏稳定性,性能会急剧衰退。层状二维(two-dimensional, 2D)钙钛矿由于其优异的环境稳定性而受到研究人员的广泛关注。通过引入不同种类的疏水性大体积有机铵阳离子可以在钙钛矿体内形成稳定的2D结构。然而,由于绝缘有机间隔阳离子的存在,使其电荷输运能力受阻并影响光电转换性能。本文根据不同种类2D钙钛矿光伏器件的发展进程,总结了影响2D钙钛矿结构和性能的关键问题,如晶体垂直取向设计、量子阱调控和有机层间隔阳离子替换工程等。最后对2D PSCs的未来发展进行展望。展开更多
In this special topic "Herbal small RNAs, novel precision medicine from Mother Nature", we present four original articles that study the entry of small RNAs derived from herbs used in traditional Chinese med...In this special topic "Herbal small RNAs, novel precision medicine from Mother Nature", we present four original articles that study the entry of small RNAs derived from herbs used in traditional Chinese medicine into mammalian cells and their function within human and mouse cells, and one review paper focusing on current trends in herb genomics (Du et al., 2017;Huang et al., 2018;Zhang et al., 2018;Li et al., 2019;Xin et al., 2018).展开更多
Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin hav...Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin have already been investigated.However,the conformation transitions induced by cisplatin are not clear.In the present letter,we have studied the effect of low-concentration cisplatin on DNA conformation by using AFM imaging.We observed formations of micro-rod structures of linear DNA induced by cisplatin.A method is presented to quantitatively analyze the occurrence of micro-rod structures.We found that the formation of micro-rod structures depends on the DNA sequence.Based on the results,we proposed a physical mechanism to explain the local conformation transitions of DNA molecules under the influence of cisplatin.展开更多
In the present study,we aimed to evaluate the anti-inflammatory mechanism of galanthamine,a classic therapeutic drug for Alzheimer s disease(AD).The co-culture system of hippocampal nerve cell line HT-22 and microglia...In the present study,we aimed to evaluate the anti-inflammatory mechanism of galanthamine,a classic therapeutic drug for Alzheimer s disease(AD).The co-culture system of hippocampal nerve cell line HT-22 and microglial cell line BV-2 was established to observe the effect of galanthamine on the expressions of inflammatory factors induced by lipopolysaccharide(LP S).MTT method was used to observe the protective effect of galanthamine on neurons.ELISA and qPCR methods were used to detect the expressions of interleukin-β(IL-1β) and IL-1 receptor antagonist(IL-1 RA) at the protein and mRNA levels,respectively.IL-1β and IL-1 RA were evaluated by the ELISA method after pretreating with galanthamine and α7 nAChR blockerα-bungarotoxin(α-bun),mAChR blocker atropine(Atr),PI3 K inhibitor LY294002,IKKβ inhibitor SC514,or MEK inhibitor PD98059,respectively.The results showed that galanthamine significantly inhibited LPS-induced increased IL-1β and IL-1 RA expressions and maintained the ratio of IL-1β/IL-1 RA.α-Bun could block the regulatory effect of galanthamine on IL-1β and IL-1 RA.As PI3 K and NF-κB pathways were blocked,the regulatory effect of galanthamine on the IL-1β expression was significantly inhibited.Blocking PI3 K and MEK pathways could significantly inhibit the regulation of galanthamine on IL-1 RA expression.In summary,galanthamine regulated the inflammatory activity of the IL-1 subfamily to play an anti-inflammatory role mediated by α7 nAChR and PI3 K/NF-κB/MAPK pathways,which probably provided a new strategy for AD treatment.展开更多
To the Editor:Psoriasis is a chronic autoimmune inflammatory disease that has a significant negative impact on quality of life.Interleukin(IL)-17A,a key molecule in the T helper 17 pathway,is important in the pathogen...To the Editor:Psoriasis is a chronic autoimmune inflammatory disease that has a significant negative impact on quality of life.Interleukin(IL)-17A,a key molecule in the T helper 17 pathway,is important in the pathogenesis of psoriasis.Secukinumab,a fully human immunoglobulin G1 kappa monoclonal antibody that targets IL-17A,was the first anti-IL-17A antibody approved by the US Food and Drug Administration in 2015.In China,it was approved in March 2019 for the treatment of moderate to severe psoriasis vulgaris(PsV),whereas in Japan,it is not only used for PsV but also psoriatic arthritis and generalized pustular psoriasis(GPP).The safety and efficacy of secukinumab have been assessed in four randomized controlled trials(RCTs)(ERASURE,FEATURE,JUNCTURE,and FIXTURE),which showed the superiority of secukinumab compared with placebo,etanercept,and ustekinumab,with long-term persistence of the clearance rate.However,the real-world setting of clinical practice is different from the strictly regulated setting of RCTs,which are conducted in only selected patients that fulfill strict inclusion and exclusion criteria to maximize internal validity.To date,there have been no official English reports of real-world studies published in China.展开更多
It is imperative to carry out research on residual plastic film collection technology to solve the serious problem of farmland pollution.The residual plastic film baler was designed as a package for film strip collect...It is imperative to carry out research on residual plastic film collection technology to solve the serious problem of farmland pollution.The residual plastic film baler was designed as a package for film strip collection,cleaning and baling.The collection device is a core component of the baler.Response surface analysis was used in this study to optimize the structure and working parameters for improving the collection efficiency of residual film and the impurity of film package.The results show that the factors affecting the collection rate of residual film and the impurity of the film package are the speed ratio(k)between the trash removal roller and eccentric collection mechanism,the number(z)and the mounting angle(θ)of spring teeth in the same revolution plane.For the collection rate,the importance of the three factors are in the order,k>z>θ.Meanwhile,for the impurity,the importance of three factors are in the order,z>k>θ.When the speed ratio,the mounting angle and the number of spring teeth was set at 1.6°,45°,and 8°,respectively,the collection rate of residual film was 88.9%and the impurity of residual film package was 14.2%for the baler.展开更多
This article concerns the existence of multi-bump positive solutions for the following logarithmic Schrödinger equation:{−Δu+λV(x)u=ulogu^(2)inRN,u∈H^(1)(R^(N)),where N≥1,⋋>0 is a parameter and the nonnega...This article concerns the existence of multi-bump positive solutions for the following logarithmic Schrödinger equation:{−Δu+λV(x)u=ulogu^(2)inRN,u∈H^(1)(R^(N)),where N≥1,⋋>0 is a parameter and the nonnegative continuous function V:ℝ^(N)→ℝhas potential wellΩ:=int V^(−1)(0)which possesses k disjoint bounded componentsΩ=∪^(k)_(j)=1Ω_(j).Using the variational methods,we prove that if the parameter⋋>0 is large enough,then the equation has at least 2^(k)−1 multi-bump positive solutions.展开更多
基金supported by grants from the National Natural Science Fund Youth Fund of China(No.81901164)the Natural Science Foundation of Fujian Province(No.2020J02053)+2 种基金the Natural Science Foundation of Fujian Province(No.2020J01966)the Talent Introduction Project of the First Affiliated Hospital of Fujian Medical University(No.YJRC3813)the Startup Fund for Scientific Research,Fujian Medical University(2020QH2029).
文摘Cutaneous squamous cell carcinoma(cSCC),a type of non-melanoma skin cancer(NMSC),is the most common malignancy worldwide.Thioredoxin(TXN)domain-containing protein 9(TXNDC9)is a member of the TXN family that is important in cell differentiation.However,the biological function of this protein in cancer,particularly cSCC,is still unknown.In the present study,our experiments revealed the protective effects of TXNDC9 on UV-B-irritated cSCC cells.The initial findings showed that TXNDC9 is significantly upregulated in cSCC tissue and cells compared to normal skin tissue and keratinocytes.UV-B radiation robustly induces the expression of TXNDC9,and UV-B-induced cSCC cell death is boosted by TXNDC9 deficiency.Moreover,cSCC cells lacking TXNDC9 displayed attenuated activation of the NF-κB pathway.Additional studies by inhibiting TXNDC9 confirmed this finding,as TXNDC9 deficiency attenuated UV-B radiation-induced translocation of NF-κB p65 from the cytoplasm to the nucleus of cSCC.In conclusion,our work demonstrates the biological roles of TXNDC9 in cSCC progression and may provide a novel therapeutic target to treat cSCC in the future.
文摘To achieve accurate classification and recognition of ship target types,it is necessary to establish a sample library of ship targets to be identified.On the basis of exploring the principles of building a ship target image library,the paper determines the sample set.Using 3DS MAX software as the platform,combined with the accurate 3D model of the ship in an offline state,the software fully utilizes its own rendering and animation functions to achieve the automatic generation of multi-view and multi-scale views of ship targets.To reduce the storage capacity of the image database,a construction method of the ship target image database based on the AP algorithm is presented.The algorithm can obtain the optimal cluster number,reduce the data storage capacity of the image database,and save the calculation amount for the subsequent matching calculation.
基金supported by a grant from the National Natural Science Foundation of China,No.30873390
文摘Lactulose is known to improve cognitive function in patients with early hepatic encephalopa- thy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cog- nitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.
基金supported by the grants from National Basic Research Program of China (973 Program), No.2007B507400, 2010CB934002, 2011CB504101, 2011CBA00408the National Natural Science Foundation of China, No. 81050025the grant from the Ministry of Science and Technology of China Eleventh 5-year Plan-Technical Platform for Drug Development, No. 2009ZX09303-8
文摘Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-l,2,3,6 tetrahydropyridine (MPTP)-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson's disease. Oral administration of octacosanol (100 mg/kg) significantly improved behavioral impairments Jn mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signa transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson's disease.
基金supported by the 345 Talent Project,Shengjing Hospital of China Medical University。
文摘BACKGROUND: There is controversy regarding whether saddle main pulmonary artery(MPA) embolism represents a high risk of deterioration in non-high-risk acute pulmonary embolism(PE) patients. This study aims to address this issue by conducting a propensity score matching(PSM) study.METHODS: A total of 727 non-high-risk acute PE patients were retrospectively evaluated. We evaluated the Bova score and risk stratification to examine the risk of deterioration. Deterioration defined as any adverse event within 30 days after admission. Computed tomographic pulmonary angiography was used to identify the embolism type. All patients were matched into four subgroups by PSM according to age, sex, Bova score, and risk stratification:(1) MPA and non-MPA embolism;(2) non-saddle MPA and non-MPA embolism;(3) saddle MPA and non-saddle MPA embolism;(4) saddle MPA and non-MPA embolism. Correlations were analyzed using Cox regression analysis, and deterioration risk was compared between subgroups using Kaplan-Meier analysis.RESULTS: Cox regression analysis revealed that MPA embolism was correlated with deterioration, regardless of whether saddle MPA embolism was included or excluded. Saddle MPA embolism was not correlated with deterioration, regardless of comparison with non-saddle MPA embolism or non-MPA embolism. Patients with MPA and non-saddle MPA embolism presented a high risk for deterioration(logrank test=5.23 and 4.70, P=0.022 and 0.030, respetively), while patients with saddle MPA embolism were not at a high risk of deterioration(log-rank test=1.20 and 3.17, P=0.729 and 0.077, respetively).CONCLUSIONS: Saddle MPA embolism is not indicative of a high risk of deterioration in nonhigh-risk acute PE patients.
文摘Dynamic linearization based model free adaptive control(MFAC) algorithm has been widely used in practical systems, in which some parameters should be tuned before it is successfully applied to process industries. Considering the random noise existing in real processes, a parameter tuning method based on minimum entropy optimization is proposed,and the feature of entropy is used to accurately describe the system uncertainty. For cases of Gaussian stochastic noise and non-Gaussian stochastic noise, an entropy recursive optimization algorithm is derived based on approximate model or identified model. The extensive simulation results show the effectiveness of the minimum entropy optimization for the partial form dynamic linearization based MFAC. The parameters tuned by the minimum entropy optimization index shows stronger stability and more robustness than these tuned by other traditional index,such as integral of the squared error(ISE) or integral of timeweighted absolute error(ITAE), when the system stochastic noise exists.
基金Supported by the National Natural Science Foundation of China under Grant Nos 11674383,11774407 and 11874415the Key Research Program of Frontier Sciences of Chinese Academy of Sciences under Grant No QYZDB-SSW-SLH045+3 种基金the National Key Research and Development Program under Grant No 2016YFA0301500the Higher Educational Science and Technology Program of Shandong Province under Grant No J16LM06the Natural Science Foundation of Shandong Province under Grant No ZR2014AQ025the Program of Shandong Provincial Government International Exchanges
文摘We investigate the effect of torsion on DNA condensation with the covalently closed circular DNA as the torsionconstrained system, using an atomic force microscope. It is found that there are two stages in the DNA condensation process under torsional constraint. At the early stage, the low torsion will accelerate DNA condensation by promoting the formation of micro-loops or intersection structures; while at the later stage, the increasing torsion will slow it down by preventing the crosslinking of cisplatin and DNA since the DNA molecule becomes more rigid. Our results show the important role of torsion in DNA condensation and sheds new light on the mechanism for DNA condensation.
文摘Information is a key factor in emergency management, which helps decision makers to make effective decisions. In this paper, aiming at clarifying the information aggregation laws, and according to the characteristic of emergency information, information relative entropy is applied in the information aggregation to establish the information aggregation model of emergency group decision-making. The analysis shows that support and credibility of decision rule are the two factors in information aggregation. The results of four emergency decision-making groups in case study support the analysis in the paper.
文摘Psoriasis is a chronic,recurrent,inflammatory systemic disease that is not only characterized by skin manifestations but may also be accompanied by various comorbidities,imposing a heavy burden on patients’physical and mental health and affecting their quality of life.Although the continuous approval of various biological agents for clinical use has provided more effective treatment options to patients with psoriasis,no consensus on the evaluation of comprehensive treatment goals has yet been established.The treat-to-target(T2T)strategy requires consideration of multiple dimensions of treatment outcomes,the development of long-term management goals,and regular assessments of treatment conditions,which are often used in the management of chronic diseases.Therefore,based on the latest consensuses and guidelines,research data,and clinical experience as well as the combination of survey results and expert group discussions,the present consensus focuses on 4 dimensions of short-and long-term integrated management goals for biological agents:alleviating skin lesions,improving quality of life,screening and managing psoriasis comorbidities,and ensuring drug safety.The implementation methods,evaluation time,treatment monitoring,and program adjustments are also herein described to achieve comprehensive management of psoriasis to the maximum extent.This consensus provides a reference for clinical practice.
基金National Natural Science Foundation of China(Grant No.81100801 and 81050025)the foundation of Zhejiang Jolly Pharmaceutical Co.,Ltd.
文摘The response to endoplasmic reticulum(ER)stress has been noted in both human depression cases and depression models in rodents.Wuling powder,derived from the mycelium of the esteemed fungus Xylaria Nigripes(Kl.)Sacc,has demonstrated efficacy in alleviating depressive symptoms.The purpose of this research was to explore the antidepressant properties of Wuling powder and its basic molecular effects,particularly regarding alterations in ER stress.A model of social defeat stress was created by introducing a mouse to the cage of an unfamiliar,hostile mouse for intervals of 5–10 min daily over a span of 10 d.Subsequently,the mice received oral doses of Wuling powder for 2 weeks.The social approach-avoidance assay was employed to evaluate signs of depression-like behaviors.Moreover,protein and gene expressions linked to ER stress triggered by social defeat were analyzed through Western blotting analysis and quantitative real-time PCR.The behavioral tests indicated that Wuling powder ameliorated behaviors associated with depression due to social defeat stress.Treatment with Wuling powder markedly reduced the increased levels of the 78-k Da glucose-regulated protein and protein disulfide isomerase caused by social defeat stress.It also diminished the expression of inositol-requiring enzyme 1α(IRE1α)and spliced X box-binding protein-1(s XBP1)at the protein and m RNA levels.Furthermore,Wuling treatment notably decreased the levels of phosphorylated eukaryotic initiation factor 2 alpha kinase(P-e IF2α),activating transcription factor 4(ATF4)and C/EBP homologous protein(CHOP),simultaneously enhancing the ratio of B-cell lymphoma 2(Bcl-2)to Bcl-2-associated X protein(Bax).These results suggested that Wuling powder could alleviate ER stress and inhibit cell apoptosis in the hippocampus by inhibiting protein translation and synthesis,thereby attenuating depressive-like behavior.
基金supported by the scientific development funding from the First Affiliated Hospital of Xi’an Jiaotong University(No.2020QN07)the Fundamental Research Funds for Central Universities(No.xzy012020044).
文摘Background:Concurrent chemoradiotherapy is the preferred treatment for stage IVB cervical cancer;however,some patients experience a poor prognosis.The prognostic significance of body composition indicators,including visceral obesity,has been extensively investigated in patients with cancer.This study aimed to assess the impact of body composition indicators,specifically pretreatment fat content,on the survival outcomes of patients with stage IVB cervical cancer.Methods:We retrospectively analyzed clinical information from patients diagnosed with stage IVB cervical cancer between 2010 and 2018.We measured visceral obesity(visceral-to-subcutaneous adipose tissue area ratio[VSR])and skeletal muscle index(SMI)on pretreatment computed tomography(CT)images.We evaluated the impact of these body composition parameters on the prognosis of patients with cervical cancer.Results:Overall,116 patients were included,81 of whom had complete clinical and imaging information.Based on the cut-off values from X-tile analysis,we categorized patients into high and low VSR and SMI groups.The overall survival(OS)rate of patients with a high VSR was significantly higher than that of patients with a low VSR(P=0.022).Multivariate Cox regression analysis showed that a low VSR was an independent risk factor for the prognosis of patients with stage IVB cervical cancer.Conclusion:Visceral obesity before radiotherapy and chemotherapy has a protective effect on the prognosis of patients with stage IVB cervical cancer,while low muscle index and VSR are associated with poor prognosis.
基金supported by grants from the Scientific Development Funding of the First Affiliated Hospital of Xi'an Jiaotong University(No.YXJLRH2022039 and No.2020QN-07)the Fundamental Research Funds for the Central Universities(No.xzy012020044)the Open Research Fund of Hubei Key Laboratory of Precision Radiation Oncolog(No.jzfs021).
文摘Background:Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy.Transforming growth factor-β(TGF-β)signaling pathway-related genes are associated with multiple tumors,but their role in prognosis prediction and tumor microenvironment(TME)regulation in colon cancer is poorly understood.Using bioinformatics,this study aimed to construct a risk prediction signature for colon cancer,which may provide a means for developing new effective treatment strategies.Methods:Using consensus clustering,patients in The Cancer Genome Atlas(TCGA)with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-βsignaling pathway-related genes,and differences in survival,molecular,and immunological TME characteristics and drug sensitivity were examined in each subtype.Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation(LASSO)regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus(GEO)dataset.A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy.Results:Two TGF-βsubtypes were identified,with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy.Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype.After completing signature construction,patients with colon cancer were categorized into high-and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature.The risk score exhibited superior predictive performance relative to age,gender,and stage,as evidenced by its AUC of 0.686.Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME,suggesting that these patients had better responses to immunotherapy.Conclusions:Patients with colon cancer were divided into two subtypes with different survival and immune characteristics using consensus clustering analysis based on TGF-βsignaling pathway-related genes.The constructed risk prediction signature may show promise as a biomarker for evaluating the prognosis of colon cancer,with potential utility for screening individuals for immunotherapy。
文摘In this special topic "Herbal small RNAs, novel precision medicine from Mother Nature", we present four original articles that study the entry of small RNAs derived from herbs used in traditional Chinese medicine into mammalian cells and their function within human and mouse cells, and one review paper focusing on current trends in herb genomics (Du et al., 2017;Huang et al., 2018;Zhang et al., 2018;Li et al., 2019;Xin et al., 2018).
基金supported by the National Natural Science Foundation of China(11274374)the National BasicResearch Program of China(2009CB930704)
文摘Cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA molecules.Structural modifications of short DNA induced by cisplatin have already been investigated.However,the conformation transitions induced by cisplatin are not clear.In the present letter,we have studied the effect of low-concentration cisplatin on DNA conformation by using AFM imaging.We observed formations of micro-rod structures of linear DNA induced by cisplatin.A method is presented to quantitatively analyze the occurrence of micro-rod structures.We found that the formation of micro-rod structures depends on the DNA sequence.Based on the results,we proposed a physical mechanism to explain the local conformation transitions of DNA molecules under the influence of cisplatin.
基金National Natural Science Foundation of China (Grant No. 81100801)Peking Union Medical College Small-Scale Characteristic School Education Project。
文摘In the present study,we aimed to evaluate the anti-inflammatory mechanism of galanthamine,a classic therapeutic drug for Alzheimer s disease(AD).The co-culture system of hippocampal nerve cell line HT-22 and microglial cell line BV-2 was established to observe the effect of galanthamine on the expressions of inflammatory factors induced by lipopolysaccharide(LP S).MTT method was used to observe the protective effect of galanthamine on neurons.ELISA and qPCR methods were used to detect the expressions of interleukin-β(IL-1β) and IL-1 receptor antagonist(IL-1 RA) at the protein and mRNA levels,respectively.IL-1β and IL-1 RA were evaluated by the ELISA method after pretreating with galanthamine and α7 nAChR blockerα-bungarotoxin(α-bun),mAChR blocker atropine(Atr),PI3 K inhibitor LY294002,IKKβ inhibitor SC514,or MEK inhibitor PD98059,respectively.The results showed that galanthamine significantly inhibited LPS-induced increased IL-1β and IL-1 RA expressions and maintained the ratio of IL-1β/IL-1 RA.α-Bun could block the regulatory effect of galanthamine on IL-1β and IL-1 RA.As PI3 K and NF-κB pathways were blocked,the regulatory effect of galanthamine on the IL-1β expression was significantly inhibited.Blocking PI3 K and MEK pathways could significantly inhibit the regulation of galanthamine on IL-1 RA expression.In summary,galanthamine regulated the inflammatory activity of the IL-1 subfamily to play an anti-inflammatory role mediated by α7 nAChR and PI3 K/NF-κB/MAPK pathways,which probably provided a new strategy for AD treatment.
文摘To the Editor:Psoriasis is a chronic autoimmune inflammatory disease that has a significant negative impact on quality of life.Interleukin(IL)-17A,a key molecule in the T helper 17 pathway,is important in the pathogenesis of psoriasis.Secukinumab,a fully human immunoglobulin G1 kappa monoclonal antibody that targets IL-17A,was the first anti-IL-17A antibody approved by the US Food and Drug Administration in 2015.In China,it was approved in March 2019 for the treatment of moderate to severe psoriasis vulgaris(PsV),whereas in Japan,it is not only used for PsV but also psoriatic arthritis and generalized pustular psoriasis(GPP).The safety and efficacy of secukinumab have been assessed in four randomized controlled trials(RCTs)(ERASURE,FEATURE,JUNCTURE,and FIXTURE),which showed the superiority of secukinumab compared with placebo,etanercept,and ustekinumab,with long-term persistence of the clearance rate.However,the real-world setting of clinical practice is different from the strictly regulated setting of RCTs,which are conducted in only selected patients that fulfill strict inclusion and exclusion criteria to maximize internal validity.To date,there have been no official English reports of real-world studies published in China.
基金This work was supported by Major Scientific and Technological Projects in Xinjiang Production and Construction Corps(2014AA002)the National Natural Science Foundation of China(31560336)the China Postdoctoral Science Foundation founded project(2015M572666XB).
文摘It is imperative to carry out research on residual plastic film collection technology to solve the serious problem of farmland pollution.The residual plastic film baler was designed as a package for film strip collection,cleaning and baling.The collection device is a core component of the baler.Response surface analysis was used in this study to optimize the structure and working parameters for improving the collection efficiency of residual film and the impurity of film package.The results show that the factors affecting the collection rate of residual film and the impurity of the film package are the speed ratio(k)between the trash removal roller and eccentric collection mechanism,the number(z)and the mounting angle(θ)of spring teeth in the same revolution plane.For the collection rate,the importance of the three factors are in the order,k>z>θ.Meanwhile,for the impurity,the importance of three factors are in the order,z>k>θ.When the speed ratio,the mounting angle and the number of spring teeth was set at 1.6°,45°,and 8°,respectively,the collection rate of residual film was 88.9%and the impurity of residual film package was 14.2%for the baler.
基金supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq/Brazil(Grant No.304804/2017-7)supported by Natural Science Foundation of Shanghai(Grant Nos.20ZR1413900 and 18ZR1409100)。
文摘This article concerns the existence of multi-bump positive solutions for the following logarithmic Schrödinger equation:{−Δu+λV(x)u=ulogu^(2)inRN,u∈H^(1)(R^(N)),where N≥1,⋋>0 is a parameter and the nonnegative continuous function V:ℝ^(N)→ℝhas potential wellΩ:=int V^(−1)(0)which possesses k disjoint bounded componentsΩ=∪^(k)_(j)=1Ω_(j).Using the variational methods,we prove that if the parameter⋋>0 is large enough,then the equation has at least 2^(k)−1 multi-bump positive solutions.