OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patient...Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patients on LT waiting lists is increasing,and the organ shortage crisis is obvious,various efforts have been made to increase the pool of available liver grafts[1].In addition to living donor liver transplantation(LDLT),improving the utilization rate of extended criteria donor(ECD)livers is an important way.However,under traditional cold storage,ECD livers are usually associated with a higher risk of ischemic biliary disease,early allograft dysfunction(EAD)or even primary nonfunction(PNF).The frequently described definition in the literature for ECD grafts generally includes elderly,steatotic,long cold ischemia time(CIT),grafts obtained from donation after circulatory death(DCD),split liver grafts,donors with increased risk of infectious disease transmission and prolonged donor intensive care unit stay[2].展开更多
Background:The benefit of adjuvant chemotherapy for stage I ovarian endometrioid carcinoma(OEC)remains controversial.Hence,the study sought to explore its value in stage I OEC patients.Methods:Stage I OEC patients(198...Background:The benefit of adjuvant chemotherapy for stage I ovarian endometrioid carcinoma(OEC)remains controversial.Hence,the study sought to explore its value in stage I OEC patients.Methods:Stage I OEC patients(1988–2018)were identified from the Surveillance,Epidemiology,and End Results(SEER)database.Multivariate Cox analysis was used to control confounders.Logistic regression was used to explore factors associated with adjuvant chemotherapy.Cox regression analysis and Kaplan-Meier curves were used to assess the survival benefits.Single-center clinical data and meta-analysis following PRISMA guidelines provided external validation.Result:Adjuvant chemotherapy correlated with improved survival(Hazard Ratio(HR):0.860,p=0.011),as did lymphadenectomy(HR:0.842,p<0.001).Higher age,pathological stage,and tumor grade negatively affected survival.Chemotherapy administration associated with higher pathological stage(IB:Odds Ratio(OR)1.565,p<0.001;IC:OR 4.091,p<0.001),higher grade(G2:OR 2.336,p<0.001;G3:OR 4.563,p<0.001),and lymphadenectomy(OR 1.148,p=0.040).Stratification analysis showed adjuvant chemotherapy failed to improve prognosis in stage IA/IB patients regardless of grade or lymphadenectomy.For stage IC patients,chemotherapy benefited grade 1-2 or grade 3 patients without lymphadenectomy,and grade 3 patients with lymphadenectomy.Meta-analysis revealed reduced recurrence in stage IC patients(OR=0.50,p=0.035).Conclusion:Adjuvant chemotherapy confers survival benefits for stage IC patients,particularly those without lymphadenectomy.展开更多
BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram ...BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary adenocarcinoma.METHODS Data were sourced from the surveillance,epidemiology,and end results stat database.The patients in the database were randomized in a 7:3 ratio into training and validation groups.Using Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the nomogram.The nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical University.RESULTS For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the nomogram.The area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific survival.The internal and external validation cohorts indicated good consistency of the nomogram.CONCLUSION The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.展开更多
Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-gro...Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-group py-razolinones have the advantages of simple synthesis steps,low cost and environmental friendliness,compared to the classical end-group dicyanomethyleneindianone.The properties of the synthesized A-D-A type molecules with non-fused azacyclic end groups were characterized by theoretical calculation,UV-vis absorption,cyclic voltammetry,X-ray diffraction and space charge limited current.It is shown that the strong UV-vis absorptions of the synthesized A-D-A type molecules are located in the wavelength range of 500~700 nm,with a moderate band gap of nearly 1.7 eV.At the same time,the influence of end-group chlorination on the properties of A-D-A type molecules was compared and explored.It is proven that this kind of A-D-A type molecule with non-fused azacyclic end groups has the potential to be applied as interfacial modified layer of the active layer in perovskite solar cell devices.展开更多
BACKGROUND Lung ultrasonography is being increasingly used in mechanically ventilated patients to evaluate the lung aeration during incremental positive end expiratory pressure(PEEP)adjustments and to evaluate the wea...BACKGROUND Lung ultrasonography is being increasingly used in mechanically ventilated patients to evaluate the lung aeration during incremental positive end expiratory pressure(PEEP)adjustments and to evaluate the weaning process from mechanical ventilation.The effects of PEEP may vary across different lung pathologies and may not consistently correlate with changes in lung aeration as assessed by lung ultrasound scores(LUSs).AIM To assess the role of lung ultrasonography in evaluating lung aeration during the application of PEEP in mechanically ventilated patients with various lung pathologies.METHODS An observational study was conducted over 18 months in a tertiary care hospital.Patients of both genders,aged between 18-75 years,who had been admitted to the intensive care unit,and required mechanical ventilation,were studied.A standard ventilatory strategy was used and incremental levels of PEEP[5,10,and 15 cm water(H_(2)O)]were applied.Baseline characteristics,including oxygen saturation(SpO2),LUS,mean arterial pressure(MAP),heart rate(HR),and their changes with incremental PEEP levels,were recorded and analyzed.RESULTS In this study,45.9%of patients required a PEEP of 5 cm H_(2)O to achieve the endpoint of lung aeration(LUS of 0).In addition,86.5% and 13.5% of patients reached the endpoint of lung aeration at PEEP levels of 10 and 15 cm H_(2)O,respectively.The proportion of patients with higher lung scores decreased significantly with increasing PEEP levels(P<0.001 for 5 and 10 cm H_(2)O and P=0.032 for 15 cm H_(2)O).SpO2 increased significantly with higher PEEP levels(P<0.001),confirming the effectiveness of PEEP in improving oxygenation.The results also revealed a significant increase in HR and a decrease in MAP following the application of higher PEEP levels.CONCLUSION Increasing PEEP levels in mechanically ventilated patients improves lung aeration,which can be effectively assessed using bedside lung ultrasonography.展开更多
Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidativ...Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidative damage remains unclear.Therefore,this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans.The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology.First,CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential,reducing ROS production and apoptosis,and promoting the expression of NRF2 translocation and downstream genes,which were consistent with the results of molecular docking,molecular dynamics,and covariance matrix simulations.Second,treatment with ML385(Nrf2 inhibitor)eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA.Third,CA exhibited stronger capacities in extending lifespan,inhibiting ROS production,and increasing SKN-1 proportion than CGA in C.elegans.Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA,which might be related to the alteration of the proteinα-helix.Therefore,considering the higher antioxidant effects of CA,it can be used as a promising antioxidant natural drug resource.展开更多
Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and hom...Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and homologous recombination(HR)being the two most prominent.Although two major pathways have been extensively studied in Arabidopsis,rice and other mammals,the exact functions and differences between the two DSB repair pathways in maize still remain less well understood.Here,we characterized mre11a and rad50,mutants of HR pathway patterns,which showed drastic degradation of the typically persistent embryo and endosperm during kernel development.Loss of MRE11 or RAD50 function led to chromosomal fragments and chromosomal bridges in anaphase.While we also reported that the NHEJ pathway patterns,KU70 and KU80 are associated with developmental growth and genome stability.ku70 and ku80 both displayed an obvious dwarf phenotype.Cytological analysis of the mutants revealed extensive chromosome fragmentation in metaphase and subsequent stages.Loss of KU70/80 function upregulated the expression of genes involved in cell cycle progression and nuclear division.These results provide insights into how NHEJ and HR are mechanistically executed during different plant developmental periods and highlight a competitive and complementary relationship between the NHEJ and HR pathways for DNA double-strand break repair in maize.展开更多
To improve the accuracy of thermal response estimation and overcome the limitations of the linear regression model and Artificial Neural Network(ANN)model,this study introduces a deep learning estimation method specif...To improve the accuracy of thermal response estimation and overcome the limitations of the linear regression model and Artificial Neural Network(ANN)model,this study introduces a deep learning estimation method specifically based on the Long Short-Term Memory(LSTM)network,to predict temperature-induced girder end displacements of the Dasha Waterway Bridge,a suspension bridge in China.First,to enhance data quality and select target sensors,preprocessing based on the sigma rule and nearest neighbor interpolation is applied to the raw data.Furthermore,to eliminate the high-frequency components from the displacement signal,the wavelet transform is conducted.Subsequently,the linear regression model and ANN model are established,whose results do not meet the requirements and fail to address the time lag effect between temperature and displacements.The study proceeds to develop the LSTM network model and determine the optimal parameters through hyperparameter sensitivity analysis.Finally,the results of the LSTM network model are discussed by a comparative analysis against the linear regression model and ANN model,which indicates a higher accuracy in predicting temperatureinduced girder end displacements and the ability to mitigate the time-lag effect.To be more specific,in comparison between the linear regression model and LSTM network,the mean square error decreases from 6.5937 to 1.6808 and R^(2) increases from 0.683 to 0.930,which corresponds to a 74.51%decrease in MSE and a 36.14%improvement in R^(2).Compared to ANN,with an MSE of 4.6371 and an R^(2) of 0.807,LSTM shows a decrease in MSE of 63.75%and an increase in R^(2) of 13.23%,demonstrating a significant enhancement in predictive performance.展开更多
This article is a part of a larger study called The Abstract Truth of Media focused on the topic of the fictional media content opinions presented and perceived as truth.It will explore the abstract nature of truth in...This article is a part of a larger study called The Abstract Truth of Media focused on the topic of the fictional media content opinions presented and perceived as truth.It will explore the abstract nature of truth in online media and its different forms.These media truths are types of fictional stories with certain effects on the public rather than a truthful presentation of the facts.Thus,the end goal of mass media today is not to tell the truth,but to create moral communities based on common experience and beliefs.Articles,opinions,and news in media are seen as a narrative strategy that can be understood only through storytelling analysis.Here the focus is on the understanding of Truth and Untruth in online media as well as the connection of Internet media technology with the increase of disinformation online.The new media model creates hostile groups instead of generating consent for the nation-state,the new online media model within through,Pseudo-communication,manipulation,delusion,lies,propaganda,and deliberate causing of moral anger.“The end of the truth”means that the truth on the Internet is lost among the vast amount of information and the lack of regulation regarding the correctness of the published data.Instead of truth,media researchers formally talk about post-truth,fake news,and“alternative facts”.Truth on the Internet is more like“Truthiness”or a belief that a statement is true based on the intuition or understanding of individuals,regardless of evidence,logic or facts.The subject of research is the connection between every new technology in mass media and the truth of the information and the effects on the consensus in society.Since the beginning of the 21st century,misinformation on the Internet has increased with the development of online media and social networks,and it is a problem of social peace and consent in every country.展开更多
Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China li...Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China limit patient admissions,leading to overcrowding in the emergency departments(EDs)with critically ill patients.[3]This highlights the urgent need for enhanced risk stratification and optimized sepsis management in emergency settings.展开更多
Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progress...Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progression of diseases,especially the accumulated effect after long-term intake.Thus,the study was proposed to evaluate the effect of dietary ALEs on health after long-term ingestion,specifically through simulating the intake of dietary ALE in mice within 9 months to investigate the intervention effect and underlying mechanism.The unexpected observation of renal insufficiency or impairment after long-term intake of dietary ALEs indicated the negative impact on renal health,which has been verified by the pathological analysis.Further studies revealed that a high-ALEs diet disrupted the intestinal barrier,with enhanced impact after disturbing the gut microbiota to potentially lower the abundance of beneficial microbiome through producing nephrotoxic metabolites.Correlation analysis showed that the proliferation of harmful bacteria and the reduction of beneficial bacteria were strongly correlated with intestinal barrier damage and the development of renal insufficiency.Furthermore,the underlying mechanism was unveiled as that ALEs could inhibit AMPK/SIRT1 signaling to fundamentally induce renal inflammation and oxidative stress.Thus,it was revealed that long-term intake of dietary ALE could result in renal impairment,and the results emphasized the control or intervention on dietary ALE to decrease to accumulated impairment on systemic health.展开更多
A triple-band miniaturized end-fire antenna based on the odd modes of spoof surface plasmonic polariton(SSPP)waveguide resonator is proposed in this paper.To meet the ever increasing demand for more communication chan...A triple-band miniaturized end-fire antenna based on the odd modes of spoof surface plasmonic polariton(SSPP)waveguide resonator is proposed in this paper.To meet the ever increasing demand for more communication channels and less antenna sizes,multi-band antennas are currently under intensive investigation.By a novel feeding method,three odd modes are excited on an SSPP waveguide resonator,which performs as an end-fire antenna operating at three bands,7.15-7.26 GHz,11.6-12.2 GHz and 13.5-13.64 GHz.It exhibits reasonably high and stable maximum gains of 5.26 dBi,7.97 dBi and 10.1 dBi and maximum efficiencies of 64%,92%and 98%at the three bands,respectively.Moreover,in the second band,the main beam angle shows a frequency dependence with a total scanning angle of 19°.The miniaturized triple-band antenna has a great potential in wireless communication systems,satellite communication and radar systems.展开更多
BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between ...BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between chronic inflammation,gut microbiome dysbiosis,and CRC progression.Proinflammatory cytokines[e.g.,interleukin(IL)-6,tumor necrosis factor-alpha(TNF-α)]and mediators like S100 calcium-binding protein A12(S100A12)/soluble receptor for advanced glycation end products(sRAGE)are implicated in tumorigenesis,while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to che-motherapy resistance.However,the triad relationship between S100A12/sRAGE,gut microbiota profiles,and chemotherapy efficacy in elderly patients with CRC remains unexplored,limiting biomarker-driven therapeutic strategies.AIM To analyze the correlation between serum levels of S100A12,sRAGE,gut microbiome dysbiosis,and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.METHODS A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024.These patients were enrolled in the study group.Additionally,120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group.Serum S100A12,sRAGE,IL-6,and TNF-αlevels were measured by ELISA,and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group.Follow-up observations were conducted after chemotherapy.Pearson correlation analysis was used to explore the relationship between serum S100A12,sRAGE levels,and gut microbiome dysbiosis in patients with CRC.The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.RESULTS Pre-chemotherapy serum S100A12,sRAGE,IL-6,and TNF-αlevels were significantly elevated in patients with CRC vs controls(all P<0.05).These biomarkers progressively increased with microbiota dysbiosis severity(severe vs mild dysbiosis:S100A12:340.26±52.39μg/L vs 302.53±56.97μg/L;sRAGE:525.64±37.32 ng/L vs 441.38±48.73 ng/L,P<0.05)and correlated strongly with IL-6(r=0.712)and TNF-α(r=0.698).Post-chemotherapy,biomarker levels decreased(P<0.05),coinciding with beneficial microbiota recovery(Bifidobacterium 176%,Lactobacillus 153%)and pathogenic taxa reduction(Escherichia coli 62%).The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914(sensitivity=86.07%,specificity=88.89%),outper-forming individual biomarkers.CONCLUSION Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation,driven by IL-6/TNF-αsignaling.Their post-chemotherapy decline parallels microbiota restoration,supporting a microbiome-inflammation-biomarker axis.The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.展开更多
In this editorial,we delve into the article and offer valuable insights into a crucial aspect of gastric cancer aetiology.Gastric cancer is a malignancy emanating from the epithelial lining of the gastric mucosa and o...In this editorial,we delve into the article and offer valuable insights into a crucial aspect of gastric cancer aetiology.Gastric cancer is a malignancy emanating from the epithelial lining of the gastric mucosa and one of the most prevalent forms of cancer worldwide.The development of gastric cancer is associated with multiple risk factors,including Helicobacter pylori infection,advanced age,a diet rich in salt,and suboptimal eating patterns.Despite notable reductions in morbidity and mortality rates,gastric cancer remains a formidable public health concern,impacting patients’lives.Advanced glycation end products(AGEs)are complex compounds arising from nonenzymatic reactions within living organisms,the accumulation of which is implicated in cellular and tissue damage;thus,the levels are AGEs are correlated with the risk of diverse diseases.The investigation of AGEs is of paramount importance for the treatment of gastric cancer and can provide pivotal insights into disease pathogenesis and preventive and therapeutic strategies.The reduction of AGEs levels and suppression of their accumulation are promising avenues for mitigating the risk of gastric cancer.This approach underscores the need for further research aimed at identifying innovative interventions that can effectively lower the incidence and mortality rates of this malignancy.展开更多
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
文摘Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patients on LT waiting lists is increasing,and the organ shortage crisis is obvious,various efforts have been made to increase the pool of available liver grafts[1].In addition to living donor liver transplantation(LDLT),improving the utilization rate of extended criteria donor(ECD)livers is an important way.However,under traditional cold storage,ECD livers are usually associated with a higher risk of ischemic biliary disease,early allograft dysfunction(EAD)or even primary nonfunction(PNF).The frequently described definition in the literature for ECD grafts generally includes elderly,steatotic,long cold ischemia time(CIT),grafts obtained from donation after circulatory death(DCD),split liver grafts,donors with increased risk of infectious disease transmission and prolonged donor intensive care unit stay[2].
基金supported by the scientific research project of Jiangsu Province’s“333 Project”(BRA2019097)Jiangsu Provincial Key Medical Discipline of the 14th Five-Year Plan(ZDXK202210)Jiangsu Province Medicine Science and Technology Development Project(No.ZD202014).
文摘Background:The benefit of adjuvant chemotherapy for stage I ovarian endometrioid carcinoma(OEC)remains controversial.Hence,the study sought to explore its value in stage I OEC patients.Methods:Stage I OEC patients(1988–2018)were identified from the Surveillance,Epidemiology,and End Results(SEER)database.Multivariate Cox analysis was used to control confounders.Logistic regression was used to explore factors associated with adjuvant chemotherapy.Cox regression analysis and Kaplan-Meier curves were used to assess the survival benefits.Single-center clinical data and meta-analysis following PRISMA guidelines provided external validation.Result:Adjuvant chemotherapy correlated with improved survival(Hazard Ratio(HR):0.860,p=0.011),as did lymphadenectomy(HR:0.842,p<0.001).Higher age,pathological stage,and tumor grade negatively affected survival.Chemotherapy administration associated with higher pathological stage(IB:Odds Ratio(OR)1.565,p<0.001;IC:OR 4.091,p<0.001),higher grade(G2:OR 2.336,p<0.001;G3:OR 4.563,p<0.001),and lymphadenectomy(OR 1.148,p=0.040).Stratification analysis showed adjuvant chemotherapy failed to improve prognosis in stage IA/IB patients regardless of grade or lymphadenectomy.For stage IC patients,chemotherapy benefited grade 1-2 or grade 3 patients without lymphadenectomy,and grade 3 patients with lymphadenectomy.Meta-analysis revealed reduced recurrence in stage IC patients(OR=0.50,p=0.035).Conclusion:Adjuvant chemotherapy confers survival benefits for stage IC patients,particularly those without lymphadenectomy.
基金Supported by the Appropriate Technology Promotion Program in Chongqing,No.2023jstg005.
文摘BACKGROUND Ampullary adenocarcinoma is a rare malignant tumor of the gastrointestinal tract.Currently,only a few cases have been reported,resulting in limited information on survival.AIM To develop a dynamic nomogram using internal and external validation to predict survival in patients with ampullary adenocarcinoma.METHODS Data were sourced from the surveillance,epidemiology,and end results stat database.The patients in the database were randomized in a 7:3 ratio into training and validation groups.Using Cox regression univariate and multivariate analyses in the training group,we identified independent risk factors for overall survival and cancer-specific survival to develop the nomogram.The nomogram was validated with a cohort of patients from the First Affiliated Hospital of the Army Medical University.RESULTS For overall and cancer-specific survival,12(sex,age,race,lymph node ratio,tumor size,chemotherapy,surgical modality,T stage,tumor differentiation,brain metastasis,lung metastasis,and extension)and 6(age;surveillance,epidemiology,and end results stage;lymph node ratio;chemotherapy;surgical modality;and tumor differentiation)independent risk factors,respectively,were incorporated into the nomogram.The area under the curve values at 1,3,and 5 years,respectively,were 0.807,0.842,and 0.826 for overall survival and 0.816,0.835,and 0.841 for cancer-specific survival.The internal and external validation cohorts indicated good consistency of the nomogram.CONCLUSION The dynamic nomogram offers robust predictive efficacy for the overall and cancer-specific survival of ampullary adenocarcinoma.
文摘Acceptor-donor-acceptor(A-D-A)type molecules,of which the novel non-fused azacyclic end-group pyrazoli-nones were modified with chlorine substitution on the phenyl ring,were synthesized.The non-fused azacyclic end-group py-razolinones have the advantages of simple synthesis steps,low cost and environmental friendliness,compared to the classical end-group dicyanomethyleneindianone.The properties of the synthesized A-D-A type molecules with non-fused azacyclic end groups were characterized by theoretical calculation,UV-vis absorption,cyclic voltammetry,X-ray diffraction and space charge limited current.It is shown that the strong UV-vis absorptions of the synthesized A-D-A type molecules are located in the wavelength range of 500~700 nm,with a moderate band gap of nearly 1.7 eV.At the same time,the influence of end-group chlorination on the properties of A-D-A type molecules was compared and explored.It is proven that this kind of A-D-A type molecule with non-fused azacyclic end groups has the potential to be applied as interfacial modified layer of the active layer in perovskite solar cell devices.
文摘BACKGROUND Lung ultrasonography is being increasingly used in mechanically ventilated patients to evaluate the lung aeration during incremental positive end expiratory pressure(PEEP)adjustments and to evaluate the weaning process from mechanical ventilation.The effects of PEEP may vary across different lung pathologies and may not consistently correlate with changes in lung aeration as assessed by lung ultrasound scores(LUSs).AIM To assess the role of lung ultrasonography in evaluating lung aeration during the application of PEEP in mechanically ventilated patients with various lung pathologies.METHODS An observational study was conducted over 18 months in a tertiary care hospital.Patients of both genders,aged between 18-75 years,who had been admitted to the intensive care unit,and required mechanical ventilation,were studied.A standard ventilatory strategy was used and incremental levels of PEEP[5,10,and 15 cm water(H_(2)O)]were applied.Baseline characteristics,including oxygen saturation(SpO2),LUS,mean arterial pressure(MAP),heart rate(HR),and their changes with incremental PEEP levels,were recorded and analyzed.RESULTS In this study,45.9%of patients required a PEEP of 5 cm H_(2)O to achieve the endpoint of lung aeration(LUS of 0).In addition,86.5% and 13.5% of patients reached the endpoint of lung aeration at PEEP levels of 10 and 15 cm H_(2)O,respectively.The proportion of patients with higher lung scores decreased significantly with increasing PEEP levels(P<0.001 for 5 and 10 cm H_(2)O and P=0.032 for 15 cm H_(2)O).SpO2 increased significantly with higher PEEP levels(P<0.001),confirming the effectiveness of PEEP in improving oxygenation.The results also revealed a significant increase in HR and a decrease in MAP following the application of higher PEEP levels.CONCLUSION Increasing PEEP levels in mechanically ventilated patients improves lung aeration,which can be effectively assessed using bedside lung ultrasonography.
基金supported by the Open Project of State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science&Technology(SKLFNS-KF-202201)Tianjin Food Processing Control and Safety Engineering Technology Center(GCZX202303)。
文摘Although it is known that the accumulation of methylglyoxal(MGO)and advanced glycosylation end products(AGEs)results in oxidative injury,the comparison between caffeic acid(CA)and chlorogenic acid(CGA)against oxidative damage remains unclear.Therefore,this study was conducted to compare the effects of CA and CGA using PC12 cells and Caenorhabditis elegans.The antioxidant regulatory targets for CA and CGA were primarily detected in the NRF2 pathway as predicted by network pharmacology.First,CA exerted higher effects than CGA in increasing cell viability and mitochondrial membrane potential,reducing ROS production and apoptosis,and promoting the expression of NRF2 translocation and downstream genes,which were consistent with the results of molecular docking,molecular dynamics,and covariance matrix simulations.Second,treatment with ML385(Nrf2 inhibitor)eliminated the anti-cytotoxic effect and ROS accumulation reduction effect of CA and CGA.Third,CA exhibited stronger capacities in extending lifespan,inhibiting ROS production,and increasing SKN-1 proportion than CGA in C.elegans.Multi-spectroscopy analysis also revealed a stronger inhibitory effect of CA on the formation of AGEs than that of CGA,which might be related to the alteration of the proteinα-helix.Therefore,considering the higher antioxidant effects of CA,it can be used as a promising antioxidant natural drug resource.
基金supported by the National Natural Science Foundation of China(32372116)to Yan He.
文摘Chromosomal DNA double-strand breaks(DSBs)are often generated in the genome of all living organisms.To combat DNA damage,organisms have evolved several DSB repair mechanisms,with nonhomologous end-joining(NHEJ)and homologous recombination(HR)being the two most prominent.Although two major pathways have been extensively studied in Arabidopsis,rice and other mammals,the exact functions and differences between the two DSB repair pathways in maize still remain less well understood.Here,we characterized mre11a and rad50,mutants of HR pathway patterns,which showed drastic degradation of the typically persistent embryo and endosperm during kernel development.Loss of MRE11 or RAD50 function led to chromosomal fragments and chromosomal bridges in anaphase.While we also reported that the NHEJ pathway patterns,KU70 and KU80 are associated with developmental growth and genome stability.ku70 and ku80 both displayed an obvious dwarf phenotype.Cytological analysis of the mutants revealed extensive chromosome fragmentation in metaphase and subsequent stages.Loss of KU70/80 function upregulated the expression of genes involved in cell cycle progression and nuclear division.These results provide insights into how NHEJ and HR are mechanistically executed during different plant developmental periods and highlight a competitive and complementary relationship between the NHEJ and HR pathways for DNA double-strand break repair in maize.
基金The National Key Research and Development Program of China grant No.2022YFB3706704 received by Yuan Renthe National Natural and Science Foundation of China grant No.52308150 received by Xiang Xu.
文摘To improve the accuracy of thermal response estimation and overcome the limitations of the linear regression model and Artificial Neural Network(ANN)model,this study introduces a deep learning estimation method specifically based on the Long Short-Term Memory(LSTM)network,to predict temperature-induced girder end displacements of the Dasha Waterway Bridge,a suspension bridge in China.First,to enhance data quality and select target sensors,preprocessing based on the sigma rule and nearest neighbor interpolation is applied to the raw data.Furthermore,to eliminate the high-frequency components from the displacement signal,the wavelet transform is conducted.Subsequently,the linear regression model and ANN model are established,whose results do not meet the requirements and fail to address the time lag effect between temperature and displacements.The study proceeds to develop the LSTM network model and determine the optimal parameters through hyperparameter sensitivity analysis.Finally,the results of the LSTM network model are discussed by a comparative analysis against the linear regression model and ANN model,which indicates a higher accuracy in predicting temperatureinduced girder end displacements and the ability to mitigate the time-lag effect.To be more specific,in comparison between the linear regression model and LSTM network,the mean square error decreases from 6.5937 to 1.6808 and R^(2) increases from 0.683 to 0.930,which corresponds to a 74.51%decrease in MSE and a 36.14%improvement in R^(2).Compared to ANN,with an MSE of 4.6371 and an R^(2) of 0.807,LSTM shows a decrease in MSE of 63.75%and an increase in R^(2) of 13.23%,demonstrating a significant enhancement in predictive performance.
文摘This article is a part of a larger study called The Abstract Truth of Media focused on the topic of the fictional media content opinions presented and perceived as truth.It will explore the abstract nature of truth in online media and its different forms.These media truths are types of fictional stories with certain effects on the public rather than a truthful presentation of the facts.Thus,the end goal of mass media today is not to tell the truth,but to create moral communities based on common experience and beliefs.Articles,opinions,and news in media are seen as a narrative strategy that can be understood only through storytelling analysis.Here the focus is on the understanding of Truth and Untruth in online media as well as the connection of Internet media technology with the increase of disinformation online.The new media model creates hostile groups instead of generating consent for the nation-state,the new online media model within through,Pseudo-communication,manipulation,delusion,lies,propaganda,and deliberate causing of moral anger.“The end of the truth”means that the truth on the Internet is lost among the vast amount of information and the lack of regulation regarding the correctness of the published data.Instead of truth,media researchers formally talk about post-truth,fake news,and“alternative facts”.Truth on the Internet is more like“Truthiness”or a belief that a statement is true based on the intuition or understanding of individuals,regardless of evidence,logic or facts.The subject of research is the connection between every new technology in mass media and the truth of the information and the effects on the consensus in society.Since the beginning of the 21st century,misinformation on the Internet has increased with the development of online media and social networks,and it is a problem of social peace and consent in every country.
基金supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-062,to BD).
文摘Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China limit patient admissions,leading to overcrowding in the emergency departments(EDs)with critically ill patients.[3]This highlights the urgent need for enhanced risk stratification and optimized sepsis management in emergency settings.
基金supported by grants from the National Natural Science Foundation of China(32030083)。
文摘Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progression of diseases,especially the accumulated effect after long-term intake.Thus,the study was proposed to evaluate the effect of dietary ALEs on health after long-term ingestion,specifically through simulating the intake of dietary ALE in mice within 9 months to investigate the intervention effect and underlying mechanism.The unexpected observation of renal insufficiency or impairment after long-term intake of dietary ALEs indicated the negative impact on renal health,which has been verified by the pathological analysis.Further studies revealed that a high-ALEs diet disrupted the intestinal barrier,with enhanced impact after disturbing the gut microbiota to potentially lower the abundance of beneficial microbiome through producing nephrotoxic metabolites.Correlation analysis showed that the proliferation of harmful bacteria and the reduction of beneficial bacteria were strongly correlated with intestinal barrier damage and the development of renal insufficiency.Furthermore,the underlying mechanism was unveiled as that ALEs could inhibit AMPK/SIRT1 signaling to fundamentally induce renal inflammation and oxidative stress.Thus,it was revealed that long-term intake of dietary ALE could result in renal impairment,and the results emphasized the control or intervention on dietary ALE to decrease to accumulated impairment on systemic health.
基金supported in part by the Natural Science Foundation of Tianjin(No.19JCYBJC16100)the Tianjin Innovation and Entrepreneurship Training Program(No.202210060027)。
文摘A triple-band miniaturized end-fire antenna based on the odd modes of spoof surface plasmonic polariton(SSPP)waveguide resonator is proposed in this paper.To meet the ever increasing demand for more communication channels and less antenna sizes,multi-band antennas are currently under intensive investigation.By a novel feeding method,three odd modes are excited on an SSPP waveguide resonator,which performs as an end-fire antenna operating at three bands,7.15-7.26 GHz,11.6-12.2 GHz and 13.5-13.64 GHz.It exhibits reasonably high and stable maximum gains of 5.26 dBi,7.97 dBi and 10.1 dBi and maximum efficiencies of 64%,92%and 98%at the three bands,respectively.Moreover,in the second band,the main beam angle shows a frequency dependence with a total scanning angle of 19°.The miniaturized triple-band antenna has a great potential in wireless communication systems,satellite communication and radar systems.
文摘BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignancies in elderly populations,and chemotherapy resistance remains a critical clinical challenge.Emerging evidence highlights the interplay between chronic inflammation,gut microbiome dysbiosis,and CRC progression.Proinflammatory cytokines[e.g.,interleukin(IL)-6,tumor necrosis factor-alpha(TNF-α)]and mediators like S100 calcium-binding protein A12(S100A12)/soluble receptor for advanced glycation end products(sRAGE)are implicated in tumorigenesis,while gut microbial imbalances may exacerbate inflammatory microenvironments conducive to che-motherapy resistance.However,the triad relationship between S100A12/sRAGE,gut microbiota profiles,and chemotherapy efficacy in elderly patients with CRC remains unexplored,limiting biomarker-driven therapeutic strategies.AIM To analyze the correlation between serum levels of S100A12,sRAGE,gut microbiome dysbiosis,and systemic inflammation in elderly patients with CRC and to assess their predictive value for chemotherapy efficacy.METHODS A retrospective analysis was conducted on the clinical data of 120 elderly patients with advanced-stage CRC who visited our hospital from August 2023 to May 2024.These patients were enrolled in the study group.Additionally,120 healthy individuals undergoing routine health check-ups during the same period were selected as the control group.Serum S100A12,sRAGE,IL-6,and TNF-αlevels were measured by ELISA,and fresh stool samples were collected before chemotherapy to analyze gut microbiome composition in the study group.Follow-up observations were conducted after chemotherapy.Pearson correlation analysis was used to explore the relationship between serum S100A12,sRAGE levels,and gut microbiome dysbiosis in patients with CRC.The predictive diagnostic value of pre-chemotherapy serum S100A12 and sRAGE levels for chemotherapy efficacy was assessed using receiver operating characteristic curves.RESULTS Pre-chemotherapy serum S100A12,sRAGE,IL-6,and TNF-αlevels were significantly elevated in patients with CRC vs controls(all P<0.05).These biomarkers progressively increased with microbiota dysbiosis severity(severe vs mild dysbiosis:S100A12:340.26±52.39μg/L vs 302.53±56.97μg/L;sRAGE:525.64±37.32 ng/L vs 441.38±48.73 ng/L,P<0.05)and correlated strongly with IL-6(r=0.712)and TNF-α(r=0.698).Post-chemotherapy,biomarker levels decreased(P<0.05),coinciding with beneficial microbiota recovery(Bifidobacterium 176%,Lactobacillus 153%)and pathogenic taxa reduction(Escherichia coli 62%).The combined S100A12/sRAGE model predicted chemotherapy resistance with an area under the curve of 0.914(sensitivity=86.07%,specificity=88.89%),outper-forming individual biomarkers.CONCLUSION Elevated serum S100A12 and sRAGE in elderly patients with CRC reflected gut microbiome dysbiosis and systemic inflammation,driven by IL-6/TNF-αsignaling.Their post-chemotherapy decline parallels microbiota restoration,supporting a microbiome-inflammation-biomarker axis.The combined biomarker model offers robust clinical utility for chemotherapy efficacy prediction and personalized therapeutic strategies.
基金Supported by The National Natural Science Foundation of China,No.82100599 and No.81960112The Jiangxi Provincial Department of Science and Technology,No.20212ACB216003+1 种基金The Science and Technology Plan of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2023Z021The Young Talents Project of Jiangxi Provincial Academic and Technical Leaders Training Program for Major Disciplines,No.20204BCJ23022.
文摘In this editorial,we delve into the article and offer valuable insights into a crucial aspect of gastric cancer aetiology.Gastric cancer is a malignancy emanating from the epithelial lining of the gastric mucosa and one of the most prevalent forms of cancer worldwide.The development of gastric cancer is associated with multiple risk factors,including Helicobacter pylori infection,advanced age,a diet rich in salt,and suboptimal eating patterns.Despite notable reductions in morbidity and mortality rates,gastric cancer remains a formidable public health concern,impacting patients’lives.Advanced glycation end products(AGEs)are complex compounds arising from nonenzymatic reactions within living organisms,the accumulation of which is implicated in cellular and tissue damage;thus,the levels are AGEs are correlated with the risk of diverse diseases.The investigation of AGEs is of paramount importance for the treatment of gastric cancer and can provide pivotal insights into disease pathogenesis and preventive and therapeutic strategies.The reduction of AGEs levels and suppression of their accumulation are promising avenues for mitigating the risk of gastric cancer.This approach underscores the need for further research aimed at identifying innovative interventions that can effectively lower the incidence and mortality rates of this malignancy.
