BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extend...BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extended period to address hypertension,with the syndrome known as Yin deficiency and Yang hyperactivity syndrome(YDYHS)frequently observed in individuals with elevated blood pressure.This syndrome is characterized by symptoms including dizziness,tinnitus,irritability,and insomnia,which are thought to result from an imbalance between Yin,representing the cooling and nourishing aspects,and Yang,denoting the active and warming aspects of the body.Despite the prevalent application of TCM in clinical settings,the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.AIM To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry(GC-MS)to elucidate the distinctive blood metabolite pattern in this patient population.METHODS GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls.Chemometric methods,including principal component analysis and partial least squares discriminant analysis,were employed to identify potential biochemical patterns.Simultaneously,the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways.Using variable importance in projection and receiver operating characteristic curve analyses,potential biomarkers were extracted to assess their clinical utility.RESULTS Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers(4-hydroxybenzoic acid,pectin,1,2,3-trihydroxybenzene,D-ribose,3-hydroxybutyric acid,quinic acid,L-lysine,oleic acid,2-hydroxybutyric acid,linoleic acid,citric acid,alpha-tocopherol,D-glucuronic acid,glycerol,N-acetyl-L-aspartic acid,betamannosylglycerate,indolelactic acid,L-glutamic acid,D-maltose,L-aspartic acid)and four metabolic pathways(linoleic acid metabolism;alanine,aspartate and glutamate metabolism;D-glutamine and D-glutamate metabolism;arginine biosynthesis).The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls.The area under the curve values ranged from 0.750 to 0.866.Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.CONCLUSION The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group,highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients.These findings may serve as an important material basis for understanding the occurrence and development of the disease,providing a scientific foundation for future clinical diagnosis.展开更多
Objective:This study explores the mechanism and clinical efficacy of combined external therapies of traditional Chinese medicine(such as moxibustion,acupoint application,etc.)in intervening renal Yang deficiency hyper...Objective:This study explores the mechanism and clinical efficacy of combined external therapies of traditional Chinese medicine(such as moxibustion,acupoint application,etc.)in intervening renal Yang deficiency hypertension through regulating the renin-angiotensin-aldosterone system(RASS).Methods:Sixty-one patients with renal Yang deficiency hypertension admitted to the hospital were selected as the study subjects.They were divided into a Western medicine combined with external therapies of traditional Chinese medicine group(n=30)and a conventional Western medicine treatment group(n=31)based on a random number table method.The enrollment information,blood pressure changes,and differences in aldosterone,angiotensin II,and renin activity during follow-up were compared between the two groups.Results:There were no statistically significant differences in gender,past history,pre-study medication,hypertension grading,aldosterone,angiotensin II,renin activity levels,and blood pressure between the two groups at baseline(P>0.05).Aldosterone,angiotensin II,and renin activity levels were significantly reduced in both groups after treatment compared to pre-treatment levels.Moreover,the aldosterone,angiotensin II,and renin activity levels in the Western medicine combined with external therapies of traditional Chinese medicine group were significantly lower than those in the conventional Western medicine treatment group,with statistically significant differences(P<0.05).Conclusion:Western medicine combined with external therapies of traditional Chinese medicine may regulate the RASS system through multiple targets,restoring renal Yang Qi transformation function and providing a new strategy for the integrated treatment of renal Yang deficiency hypertension with Chinese and Western medicine.展开更多
OBJECTIVE:To explore the effect of Traditional Chinese Medicine(TCM)constitution on cognitive impairment(CI)in patients with cerebral small vessel disease(CSVD)and its underlying neuroimaging mechanism and to provide ...OBJECTIVE:To explore the effect of Traditional Chinese Medicine(TCM)constitution on cognitive impairment(CI)in patients with cerebral small vessel disease(CSVD)and its underlying neuroimaging mechanism and to provide countermeasures for health management of CSVD patients.METHODS:A total of 241 CSVD patients were recruited from the Department of Neurology.All subjects underwent head magnetic resonance imaging(MRI),Chinese Medicine Questionnaire(CCMQ)and cognitive function examination.The CSVD patients were divided according to the Montreal Cognitive Assessment(MoCA)score into a normal cognitive group(73 cases)and a CI group(168 cases).Logistic regression was used to analyse the risk constitution of CSVD-CI and to construct a risk prediction model.3DT1 MRI images and FreeSurfer 6.0 software(Athinoula A.Martinos,Boston,MA,USA)were used to further explore the involvement of hippocampal subregion volume in patients with at-risk constitution and its correlation with cognitive function.RESULTS:Logistic regression analysis showed that Yang-deficiency constitution(YADC)(P=0.020),older age(P=0.008)and hypertension(P=0.011)were risk factors for CSVD-CI but that balanced constitution(P=0.003)and education(P<0.001)were protective factors.A receiver operating characteristic curve(ROC)was drawn,and the area under the curve was 0.820.Further comparison of overall hippocampal and 12 hippocampal subregion volumes between YADC and non-YADC patients revealed decreased total volume of the left and right hippocampus,bilateral subiculum,presubiculum,molecular layer and right fimbria in the YADC group(P<0.05/13,13 is the number of hypothesis tests).Moreover,in the YADC group,the cognitive function of CSVD patients correlated positively with the overall volume of the left hippocampus(r=0.304,P<0.05)and the molecular layer volume of the left hippocampus(r=0.288,P<0.05).CONCLUSION:CSVD patients with YADC are more prone towards developing CI,and asymmetric atrophy of the hippocampus might be the underlying neuroimaging mechanism.In particular,the volume of the left whole hippocampus and the left hippocampal molecular layer correlated significantly with general cognitive function.展开更多
OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which...OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which serve as key references for disease prevention and management.METHODS:The dataset containing the data of Yin and Yang deficiency constitution was identified through the Gene Expression Omnibus database.This database was used for differential expression genes(DEGs)analysis and weighted gene co-expression network analysis(WGCNA),and the characteristic genes were then obtained in the dataset using a machine learning method.The hub genes of Yin and Yang deficiency constitution were obtained after analysis using the above three methods,and the hub genes were enriched and analyzed.Subsequently,the hub genes of Yin and Yang deficiency constitution were validated using external datasets.Receiver operating characteristic(ROC)analysis was used on each hub genes of the two groups to further understand their diagnostic performance.The mi RNA–lnc RNA-gene network was used to further analyze the hub genes.Immunoinfiltration and gene set enrichment analysis were performed on the shared hub genes.RESULTS:The GSE87474 dataset was used for DEGs analysis and WGCNA.Using machine learning analyses,we identified 15 and 14 hub genes for Yin and Yang deficiency constitutions,respectively.The results of enrichment analyses showed that Yin deficiency constitution was associated with interleukin-17 signaling pathway,whereas Yang deficiency constitution was associated with glycosaminoglycan biosynthesis–keratan sulfate.The validation dataset GSE56116 showed statistically significant data for s-adenosylmethionine sensor upstream of MTORC1(SAMTOR,also named C7orf60),cofilin 2(CFL2),cytohesin 1 interacting protein(CYTIP),G protein-coupled receptor 183(GPR183),hippocampus abundant transcript 1(HIAT1),kelch like family member 15(KLHL15),mitogen-activated protein kinase 6(MAPK6),and prostaglandin-endoperoxide synthase 2(PTGS2)in Yin deficiency and fucosyltransferase 8(FUT8),TATA-box binding protein associated factor,RNA polymerase I subunit D(TAF1D),zinc finger protein 24(ZNF24),MAPK6,and leptin receptor overlapping transcript like 1(LEPROTL1)in Yang deficiency.The ROC results indicated that these genes have diagnostic value.MAPK6 is a shared hub gene for Yin and Yang deficiencies.CONCLUSIONS:This study identified C7orf60,CFL2,CYTIP,GPR183,HIAT1,KLHL15,MAPK6,and PTGS2 in Yin deficiency and FUT8,TAF1D,ZNF24,MAPK6,and LEPROTL1 in Yang deficiency as potential biomarkers,providing insights into their pathogenesis.This theory not only guides the diagnostic approach in TCM but also extends its influence to various scientific research fields.展开更多
BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on ...BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on the traditional Chinese medicine theory of“Yin tumor”,we believe that“Yang does not transform Yin,and it is blocked in the intestines”is the core pathogenesis of mCRC.Based on the basic treatment principle of“warming Yang and dredging intestines”,we developed the Quxie Capsule.Previous randomized controlled clinical trials demonstrated that the Quxie Capsule can significantly prolong the overall survival of patients with mCRC,but it remains to be verified whether the combination of the“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong the efficacy and safety of the mCRC during the period of maintenance therapy.AIM To confirm and clinically validate that the combination of“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong progression-free survival(PFS)during maintenance treatment of mCRC.The safety of“warming Yang and dredging intestines method”prescription is also assessed.METHODS The study has a prospective,open-label,randomized,controlled study design.Patients have been recruited beginning November 2023 from Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang’anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital of Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The study period is from March 2024 to March 2026.After screening in outpatient clinics or wards,subjects who met the inclusion criteria are randomized into the treatment or control group in a 2:1 ratio.The treatment group receives the“warming Yang and dredging intestines method”formula combined with Western standard maintenance therapy.The control group receives Western standard maintenance therapy formulated by the investigators based on the Chinese Society of Clinical Oncology guidelines for colorectal cancer.All participants receive treatment until the occurrence of disease progression,death,or unmanageable adverse effects,with post-treatment monitoring continued until mortality.An independent panel of chief physicians with extensive clinical experience evaluates the progression of the disease.RESULTS This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.The goal is to provide a combined Chinese and Western medicine treatment option for clinical physicians and mCRC patients.Notably,with the actual sample size,this study has an 80%probability of detecting a significant difference if a true difference exists.Small sample sizes may lead to increased instability of the results of subgroup analyses,and may also result in findings that are only applicable to patients with characteristics highly similar to those of the present study population(e.g.,specific genotypes,therapeutic backgrounds,etc.),making it difficult to generalize to the broader mCRC population.In the future,it may be possible to expand the sample size based on this study to further validate the efficacy and safety of combining Chinese and Western medicine in the treatment of mCRC.Basic research on the therapeutic combination of warming Yang and dredging intestines method formula and standard Western regimen will be performed in parallel.CONCLUSION This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is widely considered to be a major risk factor for gastric cancer,contributing to its development through the Correa cascade.Yin Yang 1(YY1)is a transcription factor t...BACKGROUND Helicobacter pylori(H.pylori)infection is widely considered to be a major risk factor for gastric cancer,contributing to its development through the Correa cascade.Yin Yang 1(YY1)is a transcription factor that acts as a promoter or suppressor of cancer progression.However,the role of YY1 in the inflammatory transformation associated with H.pylori-induced gastric cancer remains unclear.AIM To explore the expression of YY1 in gastric cancer and its impact on cancer progression with H.pylori infection.METHODS H.pylori bacteria were cocultured with GSE1 cells,AGS cells,and SGC7901 cells,as well as in infected and xenograft mouse models.Expression of YY1,members of the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway,and epithelial-mesenchymal transition(EMT)-related proteins in gastric cancer was examined using Western blotting,quantitative realtime polymerase chain reaction,and immunohistochemistry.Survival analysis was performed using the Kaplan-Meier method with the log-rank test.The role of YY1 in gastric cancer cell proliferation was further evaluated through in vitro and in vivo assays.RESULTS YY1 was highly expressed in gastric cancer tissues and cells.Kaplan-Meier survival curves indicated that high YY1 expression correlated with a poor prognosis.YY1 expression showed a gradually increasing trend in H.pyloriinduced gastritis and gastric tumors.In vivo and in vitro experiments demonstrated that H.pylori infection promoted phosphorylation of JAK2 and STAT3,thereby activating the EMT pathway,in which YY1 played a key role.YY1 and JAK2 interaction was validated by chromatin immunoprecipitation.YY1 knockdown or pharmacological inhibition reversed EMT and suppressed gastric cancer cell proliferation and metastasis.CONCLUSION These results suggest that YY1 plays an important role in progression of H.pylori-induced gastric cancer by activating EMT.展开更多
The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV c...The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies.In this study,we investigated the role of RNA binding motif protein 25(RBM25)in HBV replication,focusing on its interaction with cccDNA and its regulation of host transcription factors.The results demonstrated that RBM25 knockdown markedly inhibited HBV replication,reducing levels of HBV DNA,hepatitis B e antigen(HBeAg),hepatitis B surface antigen(HBsAg),HBV RNA,and L-HBs in HBV-replicating and infected cell models.Consistent results were observed in a mouse model hydrodynamically injected with 1.2HBV plasmid.Conversely,RBM25 overexpression significantly enhanced HBV replication.Mechanistically,RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains.This effect was mediated by increased Yin Yang 1(YY1)expression,which enhanced acetylation of cccDNA-bound histones,promoting HBV transcription.Furthermore,RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation,while overexpression of RBM25 promoted core protein degradation.In conclusion,this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA.It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25,which helps sustain HBV replication.展开更多
In this paper, in Section 1, we have described some equations and theorems concerning the Lebesgue integral and the Lebesgue measure. In Section 2, we have described the possible mathematical applications, of Lebesgue...In this paper, in Section 1, we have described some equations and theorems concerning the Lebesgue integral and the Lebesgue measure. In Section 2, we have described the possible mathematical applications, of Lebesgue integration, in some equations concerning various sectors of Chern-Simons theory and Yang-Mills gauge theory, precisely the two dimensional quantum Yang-Mills theory. In conclusion, in Section 3, we have described also the possible mathematical connections with some sectors of String Theory and Number Theory, principally with some equations concerning the Ramanujan’s modular equations that are related to the physical vibrations of the bosonic strings and of the superstrings, some Ramanujan’s identities concerning π and the zeta strings.展开更多
由于SNMP(S imp le Network M anagem ent Protocol)管理系统在配置管理方面具有一定弱点。Net-conf协议被认为是解决网络配置管理问题较为有效的方法。文中采用XML Schem a描述网络管理系统的数据模型,并且为了保证Netconf配置操作的...由于SNMP(S imp le Network M anagem ent Protocol)管理系统在配置管理方面具有一定弱点。Net-conf协议被认为是解决网络配置管理问题较为有效的方法。文中采用XML Schem a描述网络管理系统的数据模型,并且为了保证Netconf配置操作的事务可靠性,在Netconf的概念模型基础之上定义了网络管理应用操作层。同时也描述了基于Netconf的网络管理系统的系统结构和实现模型,提出了用于建立网络管理应用系统的设计模式,最后介绍了开发基于XML网络管理系统的经验。展开更多
Through exploring and studying the rebuilding and protection planning of the Temple of YANG Shengan and Guihu Lake,the design principles and experience of rebuilding and protecting gardens of antiquity were summarized...Through exploring and studying the rebuilding and protection planning of the Temple of YANG Shengan and Guihu Lake,the design principles and experience of rebuilding and protecting gardens of antiquity were summarized,the effective approaches to integrate the rebuilding design and the protection of relics were explored and the suggestions for the protection and development of antiquity gardens were put forward.展开更多
基金Supported by the Projects of Design and Statistics of Clinical Trials in Traditional Chinese Medicine,No.A YXC2022-01-0110Exploring the Mechanism by which Pingyang Yuyin Granules Improve Hypertensive Kidney Injury Based on the'Balance'Theory of PPARγ/HGF and TGF-β1/Smads Signaling Pathways,No.Y2022ZR09.
文摘BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extended period to address hypertension,with the syndrome known as Yin deficiency and Yang hyperactivity syndrome(YDYHS)frequently observed in individuals with elevated blood pressure.This syndrome is characterized by symptoms including dizziness,tinnitus,irritability,and insomnia,which are thought to result from an imbalance between Yin,representing the cooling and nourishing aspects,and Yang,denoting the active and warming aspects of the body.Despite the prevalent application of TCM in clinical settings,the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.AIM To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry(GC-MS)to elucidate the distinctive blood metabolite pattern in this patient population.METHODS GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls.Chemometric methods,including principal component analysis and partial least squares discriminant analysis,were employed to identify potential biochemical patterns.Simultaneously,the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways.Using variable importance in projection and receiver operating characteristic curve analyses,potential biomarkers were extracted to assess their clinical utility.RESULTS Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers(4-hydroxybenzoic acid,pectin,1,2,3-trihydroxybenzene,D-ribose,3-hydroxybutyric acid,quinic acid,L-lysine,oleic acid,2-hydroxybutyric acid,linoleic acid,citric acid,alpha-tocopherol,D-glucuronic acid,glycerol,N-acetyl-L-aspartic acid,betamannosylglycerate,indolelactic acid,L-glutamic acid,D-maltose,L-aspartic acid)and four metabolic pathways(linoleic acid metabolism;alanine,aspartate and glutamate metabolism;D-glutamine and D-glutamate metabolism;arginine biosynthesis).The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls.The area under the curve values ranged from 0.750 to 0.866.Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.CONCLUSION The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group,highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients.These findings may serve as an important material basis for understanding the occurrence and development of the disease,providing a scientific foundation for future clinical diagnosis.
文摘Objective:This study explores the mechanism and clinical efficacy of combined external therapies of traditional Chinese medicine(such as moxibustion,acupoint application,etc.)in intervening renal Yang deficiency hypertension through regulating the renin-angiotensin-aldosterone system(RASS).Methods:Sixty-one patients with renal Yang deficiency hypertension admitted to the hospital were selected as the study subjects.They were divided into a Western medicine combined with external therapies of traditional Chinese medicine group(n=30)and a conventional Western medicine treatment group(n=31)based on a random number table method.The enrollment information,blood pressure changes,and differences in aldosterone,angiotensin II,and renin activity during follow-up were compared between the two groups.Results:There were no statistically significant differences in gender,past history,pre-study medication,hypertension grading,aldosterone,angiotensin II,renin activity levels,and blood pressure between the two groups at baseline(P>0.05).Aldosterone,angiotensin II,and renin activity levels were significantly reduced in both groups after treatment compared to pre-treatment levels.Moreover,the aldosterone,angiotensin II,and renin activity levels in the Western medicine combined with external therapies of traditional Chinese medicine group were significantly lower than those in the conventional Western medicine treatment group,with statistically significant differences(P<0.05).Conclusion:Western medicine combined with external therapies of traditional Chinese medicine may regulate the RASS system through multiple targets,restoring renal Yang Qi transformation function and providing a new strategy for the integrated treatment of renal Yang deficiency hypertension with Chinese and Western medicine.
基金Supported by National Natural Science Foundation of China:Role and Mechanism of Microglial Environmental Sensing Element P2RY13 in Ischemic Brain Injury (No.81920108017)Key Research and Development Program of Jiangsu Province of China:Research on the Early Diagnosis, Treatment and Evaluation System and Early Warning Model of Ischemic Cerebrovascular Disease (No.BE2020620)
文摘OBJECTIVE:To explore the effect of Traditional Chinese Medicine(TCM)constitution on cognitive impairment(CI)in patients with cerebral small vessel disease(CSVD)and its underlying neuroimaging mechanism and to provide countermeasures for health management of CSVD patients.METHODS:A total of 241 CSVD patients were recruited from the Department of Neurology.All subjects underwent head magnetic resonance imaging(MRI),Chinese Medicine Questionnaire(CCMQ)and cognitive function examination.The CSVD patients were divided according to the Montreal Cognitive Assessment(MoCA)score into a normal cognitive group(73 cases)and a CI group(168 cases).Logistic regression was used to analyse the risk constitution of CSVD-CI and to construct a risk prediction model.3DT1 MRI images and FreeSurfer 6.0 software(Athinoula A.Martinos,Boston,MA,USA)were used to further explore the involvement of hippocampal subregion volume in patients with at-risk constitution and its correlation with cognitive function.RESULTS:Logistic regression analysis showed that Yang-deficiency constitution(YADC)(P=0.020),older age(P=0.008)and hypertension(P=0.011)were risk factors for CSVD-CI but that balanced constitution(P=0.003)and education(P<0.001)were protective factors.A receiver operating characteristic curve(ROC)was drawn,and the area under the curve was 0.820.Further comparison of overall hippocampal and 12 hippocampal subregion volumes between YADC and non-YADC patients revealed decreased total volume of the left and right hippocampus,bilateral subiculum,presubiculum,molecular layer and right fimbria in the YADC group(P<0.05/13,13 is the number of hypothesis tests).Moreover,in the YADC group,the cognitive function of CSVD patients correlated positively with the overall volume of the left hippocampus(r=0.304,P<0.05)and the molecular layer volume of the left hippocampus(r=0.288,P<0.05).CONCLUSION:CSVD patients with YADC are more prone towards developing CI,and asymmetric atrophy of the hippocampus might be the underlying neuroimaging mechanism.In particular,the volume of the left whole hippocampus and the left hippocampal molecular layer correlated significantly with general cognitive function.
基金Supported by National Natural Science Foundation of China:Establishment and Validation of a High-throughput Screening System for Traditional Chinese Medicine Against Dry Eye Disease based on transforming growth factor-βand B-cell lymphoma-2(No.81574031)2023 Hunan Provincial Department of Education Scientific Research Project:Yiguanjian Decoction Regulates Th17/Treg Cell Balance and Its Intervention Mechanism in Dry Eye with Liver Yin Deficiency Syndrome(No.23A0300)。
文摘OBJECTIVE:To utilize the Traditional Chinese Medicine constitution(TCMC)as a complementary and alternative approach for early disease detection and treatment,with a focus on Yin and Yang deficiency constitutions,which serve as key references for disease prevention and management.METHODS:The dataset containing the data of Yin and Yang deficiency constitution was identified through the Gene Expression Omnibus database.This database was used for differential expression genes(DEGs)analysis and weighted gene co-expression network analysis(WGCNA),and the characteristic genes were then obtained in the dataset using a machine learning method.The hub genes of Yin and Yang deficiency constitution were obtained after analysis using the above three methods,and the hub genes were enriched and analyzed.Subsequently,the hub genes of Yin and Yang deficiency constitution were validated using external datasets.Receiver operating characteristic(ROC)analysis was used on each hub genes of the two groups to further understand their diagnostic performance.The mi RNA–lnc RNA-gene network was used to further analyze the hub genes.Immunoinfiltration and gene set enrichment analysis were performed on the shared hub genes.RESULTS:The GSE87474 dataset was used for DEGs analysis and WGCNA.Using machine learning analyses,we identified 15 and 14 hub genes for Yin and Yang deficiency constitutions,respectively.The results of enrichment analyses showed that Yin deficiency constitution was associated with interleukin-17 signaling pathway,whereas Yang deficiency constitution was associated with glycosaminoglycan biosynthesis–keratan sulfate.The validation dataset GSE56116 showed statistically significant data for s-adenosylmethionine sensor upstream of MTORC1(SAMTOR,also named C7orf60),cofilin 2(CFL2),cytohesin 1 interacting protein(CYTIP),G protein-coupled receptor 183(GPR183),hippocampus abundant transcript 1(HIAT1),kelch like family member 15(KLHL15),mitogen-activated protein kinase 6(MAPK6),and prostaglandin-endoperoxide synthase 2(PTGS2)in Yin deficiency and fucosyltransferase 8(FUT8),TATA-box binding protein associated factor,RNA polymerase I subunit D(TAF1D),zinc finger protein 24(ZNF24),MAPK6,and leptin receptor overlapping transcript like 1(LEPROTL1)in Yang deficiency.The ROC results indicated that these genes have diagnostic value.MAPK6 is a shared hub gene for Yin and Yang deficiencies.CONCLUSIONS:This study identified C7orf60,CFL2,CYTIP,GPR183,HIAT1,KLHL15,MAPK6,and PTGS2 in Yin deficiency and FUT8,TAF1D,ZNF24,MAPK6,and LEPROTL1 in Yang deficiency as potential biomarkers,providing insights into their pathogenesis.This theory not only guides the diagnostic approach in TCM but also extends its influence to various scientific research fields.
基金Supported by the National Natural Science Foundation of China,No.82174461Capacity Enhancement Program of Xiyuan Hospital,China Academy of Traditional Chinese Medicine,No.XYZX0201-22Science and Technology Innovation Project of China Academy of Traditional Chinese Medicine,No.CI2021A01811.
文摘BACKGROUND There is a lack of integrated Chinese and Western medicine treatment regimens supported by high-level evidence-based medicine in the maintenance therapy phase of metastatic colorectal cancer(mCRC).Based on the traditional Chinese medicine theory of“Yin tumor”,we believe that“Yang does not transform Yin,and it is blocked in the intestines”is the core pathogenesis of mCRC.Based on the basic treatment principle of“warming Yang and dredging intestines”,we developed the Quxie Capsule.Previous randomized controlled clinical trials demonstrated that the Quxie Capsule can significantly prolong the overall survival of patients with mCRC,but it remains to be verified whether the combination of the“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong the efficacy and safety of the mCRC during the period of maintenance therapy.AIM To confirm and clinically validate that the combination of“warming Yang and dredging intestines method”prescription with Western medicine standard regimen can prolong progression-free survival(PFS)during maintenance treatment of mCRC.The safety of“warming Yang and dredging intestines method”prescription is also assessed.METHODS The study has a prospective,open-label,randomized,controlled study design.Patients have been recruited beginning November 2023 from Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang’anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital of Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The study period is from March 2024 to March 2026.After screening in outpatient clinics or wards,subjects who met the inclusion criteria are randomized into the treatment or control group in a 2:1 ratio.The treatment group receives the“warming Yang and dredging intestines method”formula combined with Western standard maintenance therapy.The control group receives Western standard maintenance therapy formulated by the investigators based on the Chinese Society of Clinical Oncology guidelines for colorectal cancer.All participants receive treatment until the occurrence of disease progression,death,or unmanageable adverse effects,with post-treatment monitoring continued until mortality.An independent panel of chief physicians with extensive clinical experience evaluates the progression of the disease.RESULTS This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.The goal is to provide a combined Chinese and Western medicine treatment option for clinical physicians and mCRC patients.Notably,with the actual sample size,this study has an 80%probability of detecting a significant difference if a true difference exists.Small sample sizes may lead to increased instability of the results of subgroup analyses,and may also result in findings that are only applicable to patients with characteristics highly similar to those of the present study population(e.g.,specific genotypes,therapeutic backgrounds,etc.),making it difficult to generalize to the broader mCRC population.In the future,it may be possible to expand the sample size based on this study to further validate the efficacy and safety of combining Chinese and Western medicine in the treatment of mCRC.Basic research on the therapeutic combination of warming Yang and dredging intestines method formula and standard Western regimen will be performed in parallel.CONCLUSION This study aims to clarify whether the combination of warming Yang and dredging intestines method formula with standard Western medicine regimens can prolong PFS during maintenance therapy for mCRC and whether the treatment has a favorable safety profile.
基金Supported by the National Natural Science Foundation of China,No.82372646Research Fund of Anhui Institute of Translational Medicine,No.2023zhyx-C70 and No.2023zhyx-C80.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is widely considered to be a major risk factor for gastric cancer,contributing to its development through the Correa cascade.Yin Yang 1(YY1)is a transcription factor that acts as a promoter or suppressor of cancer progression.However,the role of YY1 in the inflammatory transformation associated with H.pylori-induced gastric cancer remains unclear.AIM To explore the expression of YY1 in gastric cancer and its impact on cancer progression with H.pylori infection.METHODS H.pylori bacteria were cocultured with GSE1 cells,AGS cells,and SGC7901 cells,as well as in infected and xenograft mouse models.Expression of YY1,members of the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway,and epithelial-mesenchymal transition(EMT)-related proteins in gastric cancer was examined using Western blotting,quantitative realtime polymerase chain reaction,and immunohistochemistry.Survival analysis was performed using the Kaplan-Meier method with the log-rank test.The role of YY1 in gastric cancer cell proliferation was further evaluated through in vitro and in vivo assays.RESULTS YY1 was highly expressed in gastric cancer tissues and cells.Kaplan-Meier survival curves indicated that high YY1 expression correlated with a poor prognosis.YY1 expression showed a gradually increasing trend in H.pyloriinduced gastritis and gastric tumors.In vivo and in vitro experiments demonstrated that H.pylori infection promoted phosphorylation of JAK2 and STAT3,thereby activating the EMT pathway,in which YY1 played a key role.YY1 and JAK2 interaction was validated by chromatin immunoprecipitation.YY1 knockdown or pharmacological inhibition reversed EMT and suppressed gastric cancer cell proliferation and metastasis.CONCLUSION These results suggest that YY1 plays an important role in progression of H.pylori-induced gastric cancer by activating EMT.
基金supported by the National Key R&D Program of China(No.2022YFA1303600 and No.2023YFC2306800)the National Natural Science Foundation of China(No.82372235 and No.82272315)the Sanming Project of Medicine in Shenzhen(No.SZSM202311032).
文摘The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies.In this study,we investigated the role of RNA binding motif protein 25(RBM25)in HBV replication,focusing on its interaction with cccDNA and its regulation of host transcription factors.The results demonstrated that RBM25 knockdown markedly inhibited HBV replication,reducing levels of HBV DNA,hepatitis B e antigen(HBeAg),hepatitis B surface antigen(HBsAg),HBV RNA,and L-HBs in HBV-replicating and infected cell models.Consistent results were observed in a mouse model hydrodynamically injected with 1.2HBV plasmid.Conversely,RBM25 overexpression significantly enhanced HBV replication.Mechanistically,RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains.This effect was mediated by increased Yin Yang 1(YY1)expression,which enhanced acetylation of cccDNA-bound histones,promoting HBV transcription.Furthermore,RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation,while overexpression of RBM25 promoted core protein degradation.In conclusion,this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA.It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25,which helps sustain HBV replication.
文摘In this paper, in Section 1, we have described some equations and theorems concerning the Lebesgue integral and the Lebesgue measure. In Section 2, we have described the possible mathematical applications, of Lebesgue integration, in some equations concerning various sectors of Chern-Simons theory and Yang-Mills gauge theory, precisely the two dimensional quantum Yang-Mills theory. In conclusion, in Section 3, we have described also the possible mathematical connections with some sectors of String Theory and Number Theory, principally with some equations concerning the Ramanujan’s modular equations that are related to the physical vibrations of the bosonic strings and of the superstrings, some Ramanujan’s identities concerning π and the zeta strings.
文摘由于SNMP(S imp le Network M anagem ent Protocol)管理系统在配置管理方面具有一定弱点。Net-conf协议被认为是解决网络配置管理问题较为有效的方法。文中采用XML Schem a描述网络管理系统的数据模型,并且为了保证Netconf配置操作的事务可靠性,在Netconf的概念模型基础之上定义了网络管理应用操作层。同时也描述了基于Netconf的网络管理系统的系统结构和实现模型,提出了用于建立网络管理应用系统的设计模式,最后介绍了开发基于XML网络管理系统的经验。
文摘Through exploring and studying the rebuilding and protection planning of the Temple of YANG Shengan and Guihu Lake,the design principles and experience of rebuilding and protecting gardens of antiquity were summarized,the effective approaches to integrate the rebuilding design and the protection of relics were explored and the suggestions for the protection and development of antiquity gardens were put forward.
