Astrocytes regulate glial scar formation in cerebral ischemic stroke / 中国组织工程研究

BACKGROUND:Cerebral ischemic stroke is one of the main fatal and disabling diseases in the clinic,but only a few patients benefit from vascular recanalization in time,so it is urgent to explore new and effective therapy.As one of the critical pathological changes of ischemic stroke,the glial scar formed mainly by astrocytes is one major cause that hinders axonal regeneration and neurological recovery at the late stage of stroke. OBJECTIVE:To elucidate the pathological process and crucial signal regulatory mechanism of astrocytes in the formation of glial scar after ischemic stroke,as well as the potential therapeutic targets,to provide a theoretical reference for intervening astrocytic scar formation against ischemic stroke effectively,and novel strategies for promoting post-stroke rehabilitation. METHODS:The relevant articles published in CNKI,PubMed and Web of Science databases from 2010 to 2022 were retrieved.The search terms were"Ischemic stroke,Brain ischemi*,Cerebral ischemi*,Astrocyt*,Astroglia*,Glial scar,Gliosis,Astrogliosis"in Chinese and English.Finally,78 articles were included after screening and summarized. RESULTS AND CONCLUSION:(1)Astrocytes play an important role in the maintenance of central nervous system homeostasis.After ischemic stroke,astrocytes change from a resting state to an active state.According to the different severities of cerebral ischemic injury,astrocyte activation changes dynamically from swelling and proliferation to glial scar formation.(2)Mature astrocytes are stimulated to restart the cell cycle,then proliferate and migrate to lesions,which is the main source of the glial scar.Neural stem cells in the subventricular zone,neuron-glial antigen 2 precursor cells and ependymal precursor cells in the brain parenchyma can also differentiate into astrocytes.Endothelin-1,aquaporin 4,ciliary neurotrophic factor and connexins are involved in this process.In addition,chondroitin sulfate proteoglycan,as the main component of the extracellular matrix,forms the dense glial scar barrier with proliferated astrocytes,which hinders the polarization and extension of axons.(3)Activation or inhibition of crucial signal molecules involved in astrocyte activation,proliferation,migration and pro-inflammation functions regulate the glial scar formation.Transforming growth factor beta 1/Smad and Janus kinase/signal transducer and activator of transcription 3 are classical pathways related to astrogliosis,while receptor-interacting protein 1 kinase and glycogen synthase kinase 3β are significant molecules regulating the inflammatory response.However,there are relatively few studies on Smad ubiquitination regulatory factor 2 and Interleukin-17 and their downstream signaling pathways in glial scar formation,which are worthy of further exploration.(4)Drugs targeting astrogliosis-related signaling pathways,cell proliferation regulatory proteins and inflammatory factors effectively inhibit the formation of glial scar after cerebral ischemic stroke.Among them,the role of commonly used clinical drugs such as melatonin and valproic acid in regulating glial scar formation has been verified,which makes it possible to use drugs that inhibit glial scar formation to promote the recovery of neurological function in patients with stroke.(5)Considering the protective effects of glial scar in the acute phase,how to choose the appropriate intervention chance of drugs to maintain the protective effect of the glial scar while promoting nerve regeneration and repair in the local microenvironment is the direction of future efforts.

Immunomodulatory effect of astragaloside IV on T cells of experimental autoimmune encephalomyelitis mice / 中国组织工程研究

BACKGROUND:In the initial stage of multiple sclerosis,central immune cells activate and release a large number of inflammatory factors,causing white matter demyelination and even involving gray matter neurons.The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis.The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice,and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE:To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS:Female C57BL/6 mice were divided into the normal control group,experimental autoimmune encephalomyelitis disease model group,and astragaloside IV treatment group(n=8 per group).Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups.On day 10 to 28 after immunization,the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically.Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day.On the 28th day after immunization,the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord.Percentage of splenic T cell subsets was detected using flow cytometry.Western blot assay was used to determine the protein expression of interferon-γ,interleukin-17 and interleukin-6 in the spinal cord.Levels of interferon-γ,interleukin-17,interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION:(1)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice(P<0.05),ameliorate clinical symptoms(P<0.05),inhibit the infiltration of inflammatory cells and alleviate myelin loss(P<0.01,P<0.05).(2)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could inhibit the proportion of CD4+T cell subsets expressing interferon-γ(P<0.001)and interleukin-17(P<0.001),but increase percentages of CD4+ interleukin-10+(P<0.001)and CD4+ transforming growth factor-β+(P<0.01)T cell subsets.(3)Astragaloside IV could inhibit the expression of interferon-γ(P<0.05,P<0.01),interleukin-17(P<0.05,P<0.05),and interleukin-6(P<0.05,P<0.05)in the spinal cord and spleen,and up-regulate the expression of interleukin-4(P<0.01)in spleen.(4)These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice,which may be related to regulating the splenic T cell subsets,therefore,inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination.

Hydroxysafflor yellow A intervenes astrocyte lipocalin 2 expression after cerebral ischemia/reperfusion injury / 中国组织工程研究

BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.

Visualization analysis of stem cell therapy for myocardial infarction based on Web of Science in recent ten years / 中国组织工程研究

BACKGROUND:Although traditional therapies,including drugs and surgery,cannot repair the damaged myocardial tissue,the mortality rate of myocardial infarction remains high.Stem cells provide the possibility to solve this problem due to their self-renewal and multi-directional differentiation potential. OBJECTIVE:To analyze the research progress of stem cell therapy for myocardial infarction in recent ten years by bibliometric analysis. METHODS:The related articles on stem cells and myocardial infarction published in SCI-E and SSCI from January 1,2012 to December 1,2022 in the Web of Science database were searched.EXCEL,CiteSpace and VOSviewer software were used to make statistical and visualization analyses of the data such as the number of publications,authors,institutions,journals,countries and keywords. RESULTS AND CONCLUSION:A total of 3 210 core articles were published,and the total number increased year by year.hausenloy,derek j.is the author with the largest number of publications,China is the country with the largest number of publications,and the Fourth Military Medical University is the institution with the largest number of publications.The research hotspots in this field are changing from cell experiments and animal experiments to clinical trials.In the past ten years,research in this field has been highly popular and still has great development prospects.It is necessary to promote international and inter-agency exchange and learning,and further explore the role of stem cells in the treatment of myocardial infarction.

Frontier hot trends in ischemic stroke and vascular regeneration based on bibliometric analysis / 中国组织工程研究

BACKGROUND:Vascular regeneration,as one of the crucial repair processes after its onset,necessitates visual analysis between the two. OBJECTIVE:To analyze the literature on ischemic stroke and vascular regeneration in the past decade using bibliometrics and sort out the current status,hotspots,and future research trends in this field. METHODS:We used a bibliometric approach to search the Web of Science database for literature on ischemic stroke and vascular regeneration published between January 2011 and May 2023.The obtained data were systematically analyzed using the VOSviewer visualization software to identify the number of articles,countries,keywords,institutions,authors,citations,and trends. RESULTS AND CONCLUSION:We searched and selected 1 484 articles and found that the relationship between ischemic stroke and vascular regeneration has emerged as a research hotspot in the cerebrovascular field,with the number of published articles continuing to rise.Most of these articles were authored by institutions from China and the United States.Shanghai Jiao Tong University was the most cited institution.The most influential author was Hermann DM,whose article had been cited 1 003 times.The current hot research topics in the field include extracellular vesicles,microRNAs and mesenchymal stem cells,which are being studied for their correlations with relevant diseases.To conclude,the bibliometric analysis provides a visual analysis of ischemic stroke and vascular regeneration,which is found to be an emerging focus as well as a valuable reference for future trends and highlights in ischemic stroke and vascular regeneration.

Visual analysis of the effect of apoptosis on ischemic stroke / 中国组织工程研究

BACKGROUND:Ischemic stroke is a highly prevalent disease associated with apoptosis.Neuronal death occurs after cerebral ischemia,including necrosis and apoptosis.The ischemic core region is dominated by necrosis,while delayed neuronal death in the penumbra is dominated by apoptosis.The penumbra has become a target for the treatment of ischemic stroke.This bibliometric analysis was used to identify the characteristics,hotspots,and frontiers of global scientific output related to apoptosis in ischemic stroke over the past 5 years. OBJECTIVE:To analyze the role of apoptosis and its mechanisms in the pathological process of ischemic stroke through a bibliometric approach. METHODS:A total of 927 relevant literature records from 2018 to 2022 were retrieved from Science Citation Index Expanded(SCI-Expanded)and Social Science Citation Index Expanded(SSCI-Expanded)of the Web of Science Core Collection.Research trends and hotspots of apoptosis in ischemic stroke were visualized using Citespace,VOSviewer and Bibliometrix. RESULTS AND CONCLUSION:From 2018 to 2020,the number of papers on the role of apoptosis in ischemic stroke showed an upward trend,but in 2020,the number of papers began to reduce.China had the largest number of publications,and the United States ranked the second.Capital Medical University and BRAIN RESEARCH BULLETIN were the institutions and journals with the most articles,respectively.In recent years,the two keywords"expression"and"oxidative stress"have appeared more frequently.The bibliometric study showed that in the past 5 years,most of the studies focused on basic research,in which research on the role of apoptosis in ischemic stroke has gradually decreased in the last 3 years,showing a downward trend.On the contrary,nerve regeneration has gradually become a research hotspot,especially the regulation of neurotrophic factors under the influence of different mechanisms,and the research on angiogenesis and glial cell repair is on the rise.At the same time,apoptosis in nerve regeneration is a potential point of discovery.

The role and mechanism of TLRs/MyD88/NF-κB signaling pathway in multiple sclerosis / 中国组织工程研究

BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.

Astragaloside inhibits astrocyte activation and inflammatory response induced by inflammation / 中国组织工程研究

BACKGROUND:Astrocytes play an important role in the pathology of central nervous system diseases.The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases.Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response.Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE:To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS:Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro.CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT.The astrocytes were divided into five groups:PBS group,lipopolysaccharide group,lipopolysaccharide + astragaloside group,lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group.The secretion level of inflammatory factors was detected by ELISA,and the level of nitric oxide was detected by Griess method.The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells.The expression of astrocyte activation marker GFAP,A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining.The expressions of CFB,C3,S100A10,PTX3,Notch-1,Jag-1,and Hes were detected by western blot assay. RESULTS AND CONCLUSION:(1)According to the results of CCK8 assay,the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments.(2)Compared with PBS group,interleukin-6,interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased(P<0.05,P<0.05,P<0.01).Compared with the lipopolysaccharide group,interleukin-6(all P<0.05),interleukin-12(P>0.05,P<0.05,P<0.05)and nitric oxide(P<0.05,P<0.01,P<0.01)secretion significantly reduced in the lipopolysaccharide + astragaloside group,lipopolysaccharide +DAPT group,lipopolysaccharide + DAPT + astragaloside group.(3)Compared with the PBS group,the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group(P<0.01).Compared with the lipopolysaccharide group,astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group(P<0.05,P<0.05,P<0.01).(4)Compared with the PBS group,the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased(P<0.01,P<0.05),and the expressions of A2 markers S100A10 and PTX3 were decreased(P<0.01,P<0.05).Compared with the lipopolysaccharide group,C3(all P<0.01)and CFB(both P<0.05)were significantly reduced and S100A10(all P<0.01)and PTX3(P<0.05,P<0.05 and P>0.05)were increased in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(5)Compared with the PBS group,the expressions of Jag-1,Notch-1 and Hes in the lipopolysaccharide group were significantly increased(all P<0.01).Compared with the lipopolysaccharide group,the expressions of Jag-1(all P<0.01),Notch-1(all P<0.01)and Hes(P<0.05,P<0.01 and P<0.01)were significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(6)The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway,reduce the secretion of inflammatory factors and the migration of CD4 T cells,and thus inhibit astrocyte activation and inflammatory response.

Study on epidemiological prevalence and serological marker characteristics of hepatitis E infection / 中华检验医学杂志

Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.

Prescription Rule of Traditional Chinese Medicine in the Treatment of Diabetic Nephropathy via Data Analysis and Biofilm Interference / 医药导报

Objective To analyze the medication rule of Traditional Chinese Medicine(TCM)in treating diabetes nephropathy(DN)and to explore the interaction between core components and key targets.Methods Based on the ancient and modern medical case cloud platform,the medication rules of TCMs and the drug pairs with the highest frequency in treating DN were summarized.Then the network pharmacology approach was utilized to analyze the pharmacodynamic material basis and mechanisms of the highest frequency-drug pairs.The potential targets were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)databases.TTD,DISGENET,and GENECARD databases were used to obtain the related targets of DN and screen out the potential targets for DN.In order to clarify the relationships between the active ingredients,the core targets,and pathways,STRING and Cytoscape 3.7.1 software were used to construct the protein-protein interaction(PPI)network and core drugs-ingredients-targets-disease interaction network,DAVID database was screened for Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis of core targets.Sybyl 2.1 software and biofilm interference verify the combined capacity between the core ingredients and key targets.Results Among 183 prescriptions,Astragali Radix had the highest use frequency and average dose,43 times and 37 g,respectively,followed by Salviae miltiorrhizae Radix and Poria cocos.To find the core combined with the highest confidence in association analysis was astragalus,salvia miltiorrhiza,and tuckahoe.Correlation analysis indicates that the core combination with the highest confidence was Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos.Network pharmacologic showed 89 potential targets and 15 key signaling pathways for the treatment of DN by the drug pair.TNF signaling pathway,Nod-like receptor signaling pathway,and MAPK signaling pathway were disease-related pathways,and IL-6,TNF,and vascular endothelial growth factor A(VEGFA)were core targets.Isorhamnetin and quercetin of the drug pair had high binding ability with IL6,the scores were 8.2 and 7.4,respectively,and the dissociation constants(KD)were 5.6×10-5 mol·L-1 and 6.8×10-5 mol·L-1,respectively.Conclusion This study preliminarily finds the prescription rule of treating DN with Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos as the core drug pair,isorhamnetin,and quercetin are probably the main active compounds of this drug pair in DN treatment,which provides a basis for clinical treatment and drug discovery of DN.

Clinical significance of hepatitis B virus DNA detection in screening patients with hepatitis B / 中华检验医学杂志

Objective:To explore the clinical significance of hepatitis B virus (HBV) DNA detection in screening patients with hepatitis B.Methods:Clinical data of 682 331 hepatitis B patients were retrospectively analyzed. The HBV DNA of these patients was detected in the Fifth Medical Center of the PLA General Hospital from January 2017 to December 2021, there were 481 159 males and 201 172 females in this cohort, the average age was (41.34±16.13) years. Patients were divided into HBV DNA positive group (219 879 cases) and HBV DNA negative group (462 452 cases). Clinical characteristics, data of five serologic markers of hepatitis B and hepatitis B surface antigen quantification (HBsAg-QN), liver function, alpha fetoprotein (AFP) and prothrombin time (PT) results were collected and analyzed and compared between the two groups.Results:The positive rate of HBV DNA was 32.22% (219 879/682 331) in this cohort. Among the different age groups, the positive rate of HBV DNA was the highest (40.34%, 128 038/317 380) in young people aged 18-44 years. The proportion of patients was lower among aged <1, 45-59 and ≥60 years patients in HBV DNA positive group than that in HBV DNA negative group, while the proportion of patients was higher among aged 1-17 and 18-44 years patients in HBV DNA positive group than that in HBV DNA negative group (all P<0.001). Among 2 291 <1-year-old infants tested for HBV DNA, 71 infants were HBV DNA positive. The positive rates of HBV DNA from 2017 to 2021 were 4.86% (27/556), 3.68% (14/380), 3.47% (17/490), 1.55% (6/386) and 1.46% (7/479) respectively, showing a downward trend year by year. The positive rate of HBV DNA in acute hepatitis B (AHB) patients was the highest (49.88%, 208/417) among 680 040 patients with hepatitis B. The proportion of AHB patients (0.09%, 208/219 808) and chronic hepatitis B (80.44%, 176 806/219 808) in HBV DNA positive group was higher than that in HBV DNA negative group [0.05% (209/460 232) and 65.45% (301, 216/460 232)], while the proportion of patients with HBV-related liver cirrhosis (11.28%, 24 793/219 808), HBV-related liver cancer (6.72%, 14 775/219 808), liver cancer surgery (1.39%, 3 055/219 808) and liver transplantation (0.08%, 171/219 808) were lower than that in HBV DNA negative group [22.99% (105 813/460 232), 7.25% (33 385/460 232), 3.50% (16 129/460 232) and 0.76% (3 480/460 232)] (all P<0.001). At the same time, positive rate of hepatitis B surface antigen (HbsAg), HBsAg-QN, hepatitis B e antigen (HbeAg), level of total bilirubin, total bilirubin, AFP and PT were higher in HBV DNA positive group than those in HBV DNA negative group, while the age, male ratio and albumin results in HBV DNA positive group were lower than those in HBV DNA negative group (all P<0.01). The HBV DNA loads were higher in HBsAg positive group, hepatitis B surface antibody positive group and HBeAg positive group than those in respective negative groups, while the HBV DNA loads were lower in hepatitis B e antibody positive group and hepatitis B core antibody positive group than those in respective negative groups (all P<0.001). Conclusions:The mother to child transmission rate of<1-year-old infants decreases year by year. HBV DNA is an important factor for the progression of hepatitis B disease. HBV DNA positive hepatitis B patients with higher HBsAg-QN values are more likely to have abnormal serum markers such as liver dysfunction. HBV DNA detection is therefore of clinical importance in screening patients with hepatitis B.

Knock-down of ROCK2 gene improves cognitive function and reduces neuronal apoptosis in AD mice by promoting mitochondrial fusion and inhibiting its division / 细胞与分子免疫学杂志

Objective To explore the effect of knocking down Rho-associated coiled-coil kinase (ROCK2) gene on the cognitive function of amyloid precursor protein/presenilin-1 (APP/PS1) double transgenic mice and its mechanism. Methods APP/PS1 double transgenic mice were randomly divided into AD model group (AD group), ROCK2 gene knock-down group (shROCK2 group), ROCK2 gene knock-down control group (shNCgroup), and wild-type C57BL/6 mice of the same age served as the wild-type control (WT group). Morris water maze and Y maze were employed to test the cognitive function of mice. Neuron morphology was detected by Nissl staining. Immunofluorescence histochemical staining was used to detect the expression of phosphorylated dynamin-related protein 1 (p-Drp1) and mitochondrial fusion 1 (Mfn1). Western blot analysis was used to detect the expression ROCK2, cleaved-caspase-3 (c-caspase-3), B-cell lymphoma 2 (Bcl2), Bcl2-related protein X (BAX), p-Drp1, mitochondrial fission 1 (Fis1), optic atrophy 1 (OPA1), Mfn1 and Mfn2. Results Compared with AD group mice, the expression of ROCK2 in shROCK2 group mice was significantly reduced; the cognitive function was significantly improved with the number of neurons in the hippocampal CA3 and DG areas increasing, and nissl bodies were deeply stained; the expression of c-caspase-3 and BAX was decreased, while the expression of Bcl2 was increased; the expression of mitochondrial division related proteins p-Drp1 and Fis1 were decreased, while the expression of mitochondrial fusion-related proteins OPA1, Mfn1 and Mfn2 were increased. Conclusion Knock-down of ROCK2 gene can significantly improve the cognitive function and inhibit the apoptosis of nerve cells of APP/PS1 mice. The mechanism may be related to promoting mitochondrial fusion and inhibiting its division.

Comparative analysis of endoscopic resection and laparoscopic surgery in the treatment of gastric gastrointestinal stromal tumor with a maximum diameter of 2 to 5 cm / 中华消化杂志

Objective:To compare the clinical efficacy of endoscopic resection and laparoscopic surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) with a maximum diameter of 2 to 5 cm, and to analyze the influence of factors such as tumor surface, growth pattern and lesion origin on the choice of resection method, so as to provide a safer and more effective treatment for patients with gastric GIST.Methods:From January 2012 to November 2019, at the First Affiliated Hospital of Zhengzhou University, the clinical data of 301 patients with gastric GIST who underwent endoscopic resection (137 cases in the endoscopic resection group) or laparoscopic surgery (164 cases in the laparoscopic surgery group) were retrospectively analyzed, including age, gender, whether there was depression on the tumor surface (the local subsidence depth of the mucosa on the tumor surface was >5 mm), whether the tumor surface was irregular (non-hemispherical or non-elliptical tumor surface), whether there was combined ulcer, location, shape, origin of the lesion, growth pattern (intralumina growth or combined intraluminal and extraluminal growth), risk classification (very low risk, low risk, medium risk, high risk), whether the tumor was en bloc resection, operation time, whether bleeding or not, fasting time, indwelling time of gastric tube, time of hospitalization, time of postoperative hospital stay, postoperative complications and follow-up. Independent sample t test, chi-square test or Fisher′s exact test and Wilcoxon rank sum test were used for statistical analysis. Results:Among the 137 patients with gastric GIST in the endoscopic resection group, 85 cases (62.0%) underwent endoscopic submucosal dissection, 9 cases (6.6%) underwent endoscopic submucosal excavation, 42 cases (30.7%) underwent endoscopic full-thickness resection, and 1 case (0.7%) underwent submucosal tunnel endoscopic resection. There were no significant differences in gender, age, lesion location, tumor size, and risk classification between the endoscopic resection group and the laparoscopic surgery group (all P>0.05). The tumor surface was depressed, with ulcer or irregular in 1, 49, 26, and 2 cases of patients with gastric GIST of very low risk, low risk, medium risk and high risk, respectively. There was statistically significant difference in the proportion of depression, irregularity and ulcer on the tumor surface at different risk levels ( Z=-2.55, P=0.011). The complete tumor resection rate of the endoscopic resection group was lower than that of the laparoscopic surgery group (86.1%, 118/137 vs. 100.0%, 164/164), and the difference was statistically significant ( χ2=24.28, P<0.001). However the operation time, fasting time, the indwelling time of gastric tube, time of hospitalization, and the time of postoperative hospital stay of the endoscopic resection group were shorter than those of the laparoscopic surgery group, and the total hospitalization cost was lower than that of the laparoscopic surgery group (90.0 min (62.5 min, 150.0 min) vs. 119.5 min, (80.0 min, 154.2 min); 3 d (3 d, 4 d) vs. 5 d (4 d, 7 d); 3 d (2 d, 4 d) vs. 4 d (2 d, 6 d); 11 d (10 d, 14 d) vs. 16 d (12 d, 20 d); 7 d (6 d, 9 d) vs. 9 d (7 d, 11 d); (38 211.6±10 221.0) yuan vs. (59 926.1±17 786.1) yuan), and the differences were statistically significant ( Z=-2.46, -7.12, -4.44, -6.89 and -5.92, t=-13.24; all P<0.05). The incidence of postoperative abdominal pain and other severe postoperative complications (including shock, respiratory failure, pulmonary embolism, gastroparesis, etc.) of the endoscopic resection group were all lower than those of the laparoscopic surgery group (16.8%, 23/137 vs. 27.4%, 45/164; 0.7%, 1/137 vs. 4.9%, 8/164), and the differences were statistically significant ( χ2=4.84, Fisher′s exact test, P=0.028 and 0.043). There were no significant differences in the incidence of intraoperative bleeding, postoperative bleeding, fever and perforation between the two groups (all P>0.05). The incidence of operation-related complications of lesions with intraluminal growth and originating from muscularis propria in the endoscopic resection group were lower than those of the laparoscopic surgery group (19.5%, 25/128 vs. 32.6%, 45/138; 12.6%, 12/95 vs. 31.4%, 37/118), and the differences were statistically significant ( χ2=5.86 and 10.42, P=0.016 and 0.001). There was no significant difference in the postoperative tumor recurrent rate between the endoscopic resection group and the laparoscopic surgery group (0, 0/137 vs. 2.4%, 4/164; Fisher’s exact test, P=0.129). Conclusions:Endoscopic treatment is safe and effective for gastric GIST with a maximum diameter of 2 to 5 cm, which is superior to laparoscopic surgery. However, laparoscopic surgery is recommended for tumor with depressed, ulcerative, or irregular surface and combined intraluminal and extraluminal growth.

Comparison of endoscopic mucosal resection with a cap and endoscopic submucosal dissection in the treatment of smaller gastric neuroendocrine neoplasms / 中华消化内镜杂志

Data of 55 cases of gastric neuroendocrine neoplasms (G-NENS) with diameter ≤12 mm in the First Affiliated Hospital of Zhengzhou University from August 2014 to August 2019 were retrospectively analyzed. According to the methods of endoscopic resection, the patients were divided into two groups: the endoscopic mucosal resection with a cap (EMR-C) group (35 cases) and the endoscopic submucosal dissection (ESD) group (20 cases). The results showed that the success rates of operation, the whole resection rates and the complete resection rates were all 100.0% in the two groups. Compared with the ESD group, the EMR-C group had a shorter median operation time (12.00 min VS 28.35 min, P<0.001), less mean hospitalization costs (21 165.19 yuan VS 28 400.35 yuan, P=0.004), and a similar overall incidence of complications [2.86% (1/35) VS 0, P=1.000]. By March 2020, the recurrence rate of EMR-C group and ESD group were 28.6% (10/35) and 15.0% (3/20), respectively, without significant difference ( P=0.418). It is suggested that for G-NENS with diameter ≤12 mm, without muscular invasion, lymph node metastasis or distant metastasis, EMR-C and ESD are both safe and effective, but EMR-C has more advantages in terms of operation time and hospitalization costs.

Investigation of preoperative anemia and perioperative blood transfusion in patients with duodenal papillarycarcinoma in a tertiary hospital / 中国输血杂志

【Objective】 To investigate the preoperative anemia and perioperative blood transfusion in patients with duodenal papillary carcinoma who underwent Whipple surgery. 【Methods】 The clinical data of 1 959 cases with duodenal papillary carcinoma, subjected to Whipple surgery, were retrospectively analyzed. 【Results】 The rate of anemia in preoperative patients with duodenal papillary carcinoma was 54.87%(1 075/1 959). The incidence rate of anemia in the three age groups from low to high was 44.92% (≤50 years old, 190/423), 52.82% (51~64 years old, 506/958), and 65.57% (≥65 years old, 379/578) (P<0.05), and the highest rate of anemia occurred in patients aged above 65. There was a significant statistical difference among patients with different body mass index (BMI)(P<0.05). Patients with moderate or severe anemia received more red blood cells than patients with mild anemia during the perioperative period (P<0.05). The average hospitalization time of the blood transfusion patients was 27.25 days, and that of non-transfusion patients was 22.22 days (P<0.05). The amount of blood loss and hospitalization time of patients underwent laparoscopic and robotic surgery were significantly lower than those underwent open surgery patients (P <0.05). There were only 24.09%(186/772) treated with drugs for anemia intervention and the majority of patients (75.91%, 586/772) were treated with blood transfusions to interfere with anemia during hospitalization. 【Conclusion】 There are significant differences in the incidence rate of preoperative anemia among patients with duodenal papillary carcinoma who undergone Whipple surgery. Low BMI, abnormal WBC, and perioperative blood transfusion are high-risk factors for prolonged hospital stay, whereas anemia is not associated with prolonged hospital stay.

Characteristics of high cardiovascular risk in 360 000 adults in Northwest China / 西安交通大学学报(医学版)

【Objective】 To assess the prevalence and treatment of high cardiovascular disease （CVD） risk， and identify individual characteristics related to high CVD risk. 【Methods】 Based on the data of the China Patient-Centered Evaluative Assessment of Cardiac Events （PEACE） Million Persons Project （MPP） from 2016 to 2019， this study enrolled local residents aged 35 to 75 years from 39 counties or districts in Northwest China. Rates of high CVD risk and individual characteristics were assessed in the overall study population. Statin and aspirin use was also evaluated among those at high risk for CVD. Multivariable mixed models were fitted to evaluate the relationship between individual characteristics and high CVD risk. 【Results】 Among 364 537 participants， the average age was （54.6±9.7）years， and 5.8% was at a high risk for CVD. Multivariate mixed models showed that individuals who were currently using alcohol， overweight or obese tended to have a high risk for CVD， while married persons， those with a higher education level or a higher household income were correlated with a lower risk for CVD （all P<0.05）. Among high-risk persons， hypertension was the most prevalent risk factor （98.1%）， and only 1.3% and 3.5% reported their use of statins and aspirin， respectively. 【Conclusion】 Of the 364 537 participants， about 1 in 17 had a high risk for CVD. Among those at a high CVD risk， only less than 4% reported taking statins or aspirin. These findings indicate that there is still much room for risk mitigation in this population in China.

Comparison of anti-reflux mucosectomy and endoscopic cardial constriction ligation on treatment of gastroesophageal reflux disease / 中华消化内镜杂志

Objective:To compare the clinical efficacy of anti-reflux mucosectomy (ARMS) and endoscopic cardial constriction ligation (ECCL) on treatment of gastroesophageal reflux disease.Methods:A retrospective study was conducted on the data of 48 consecutive patients with gastroesophageal reflux disease, who underwent ARMS or ECCL at the First Affiliated Hospital of Zhengzhou University from December 2015 to August 2018. Twenty cases were in the ARMS group and 28 cases in the ECCL group. The short-term and long-term efficacies were compared between the two groups.Results:The success rate of operation was 100.0% in the both groups. The operation time of the ECCL group was significantly shorter than that of the ARMS group (8.43±1.59 min VS 34.05±12.35 min, t=-9.227, P<0.001). After 2 months follow-up, the symptom improvement rate of the ECCL group and the ARMS group was 89.3% (25/28) and 60.0% (12/20), respectively ( χ2=4.128, P=0.042). The GERD Q score of the ECCL group was significantly lower than that of the ARMS group (6.24 ±1.22 VS 7.35±1.79, t=-2.400, P=0.023). One year after operation, there were no significant differences in the symptom improvement rate, GERD Q score, DeMeester score and the time percentage of pH<4 between the two groups ( P>0.05). Conclusion:The long-term clinical effect of ARMS and ECCL is similar, but the short-term clinical effect of ECCL is superior to ARMS.

Comments on the evaluation standards of traditional Chinese medicine talents in the new era / 国际中医中药杂志

According to the principles of politics should combine with professional work, business, successful career can’t be isolated with talented people, general conditions should combine with special conditions, and based on different categories and classification, this paper proposes a framework of Talent Evaluation Standards of the traditional Chinese medicine consisting the basic elements such as morality, capability, contribution, and reputation and sub-elements, which could provide reference for perfecting the Talent Evaluation Standard in the new ear. Among them, the moral system consists of factors such as the unwavering self-confidence of the traditional Chinese medicine culture, the patriotism and love of the people, and the benevolence of the great doctors. The contribution system consists of academic theoretical contributions, talent training contributions and medical service contributions. The reputation system consists of patient satisfaction, peer evaluation, and organizational evaluation.

Role of spinal histone acetylation in persistent postoperative pain in rats / 中华麻醉学杂志

Objective To evaluate the role of spinal histone acetylation in persistent postoperative pain in rats. Methods Pathogen?free healthy male Sprague?Dawley rats, weighing 200-250 g, aged 2 months, in which intrathecal catheters were implanted at the lumbar level according to an improved method, were used in the study. Eighty?four rats, in which intrathecal catheters were successfully implanted, were divided intoⅠ-Ⅵgroups(n=14 each)using a random number table. Artificial cerebrospinal fluid 20 μl was intrathecally administered at 1, 2, 3 and 4 days before operation and 1 day after operation inⅠandⅣgroups. At 1, 2, 3 and 4 days before operation and 1 day after operation, dimethyl sulfoxide 10 μl and SAHA(50 μg∕10μl)were intrathecally injected inⅡandⅤgroups and inⅢandⅥgroups, respective?ly, followed by artificial cerebrospinal fluid(10 μl)flush after each injection. Rats underwent sham oper?ation inⅠ?Ⅲ groups. Persistent postoperative pain was evoked by skin∕muscle incision and traction in Ⅳ?Ⅵ groups. The mechanical paw withdrawal threshold(MWT)was measured at 1 day before operation(T0)and 1, 3, 7, 14 and 21 days after operation(T1?5). Four rats were sacrificed in each group after measurement of MWT at T4, and the lumbar segments(L4?6)of the spinal cord were removed for determi?nation of the expression of acetylated histone H3(Ac?H3)and Ac?H4 by Western blot. Results There was no significant difference in each index amongⅠ?Ⅲ groups(P>0.05). Compared with group Ⅰ, the MWT was significantly decreased at T2?5, and the expression of Ac?H3 and Ac?H4 was down?regulated at T4 in group Ⅳ(P<0.05). Compared with group Ⅳ, the MWT was significantly increased at T2?5, and the expression of Ac?H3 and Ac?H4 was up?regulated at T4in group Ⅵ(P<0.05). Conclusion Histone acetylation is involved in the development and maintenance of persistent postoperative pain in rats.

Changes in acetylation of histone in spinal dorsal horn in a rat model of persistent postoperative pain / 中华麻醉学杂志

Objective To investigate the changes in acetylation of histone in the spinal dorsal horn in a rat model of persistent postoperative pain.Methods Ninety-six malc Sprague-Dawley rats,weighing 200-250 g,aged 6-8 weeks,were randomly divided into 2 groups (n=48 each) using a random number table:sham operation group (group S) and persistent postoperative pain group (group PPP).The rat model of persistent postoperative pain evoked by skin/muscle incision and retraction was established according to the method described by Flatters.After the rats were anesthetized with intraperitoneal chloral hydrate,the skin and superficial muscle of the medial thigh were incised and retractors inserted.This tissue was retracted for 1 h.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before operation and 1,3,7,14,and 21 days after operation.Four animals were sacrificed in each group after measurement of MWT at each time point for detection of acetylated histone H3 (Ac-H3) and acetylated histone H4 (Ac-H4) expression (by Western blot analysis) and the number of Ac-H3 and Ac-H4 positive cells in the spinal cord horn (by immunofluorescence histochemistry).Results Compared with group S,the MWT was significantly decreased at 3,7,14 and 21 days after operation,the expression of Ac-H3 and Ac-H4b was significantly down-regulated at 3,7 and 14 days after operation,and the number of Ac-H3 and Ac-H4 positive cells was significantly decreased at 7,14 and 21 days after operation in group PPP (P＜0.05 or 0.01).The MWT,expression of Ac-H3 and Ac-H4b,and the number of Ac-H3 and Ac-H4 positive cells were significantly higher at 21 days after operation than at 14 days after operation in group PPP (P＜0.05).Conclusion Acetylation of histone in the spinal dorsal horn is decreased after operation,which may be involved in the development and maintenance of persistent postoperative pain in rats.