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Pneumonia caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection poses a threat to human life and health,resulting in great socio-economic losses.The structural protein spike protein(S protein)of viruses has always been considered to primarily mediate virus invasion into host cells.S protein can act independently of viruses and cause inflammatory reactions on a variety of cells,therefore,understanding the impact of S protein on the respiratory tract can provide a new perspective for the prevention and treatment of COVID-19.This article reviews the advances in the possible mechanisms and clinical manifestations of SARS-CoV-2 structural protein S protein-induced inflammatory response in respiratory epithelial cells,aiming to provide reference for the prevention and treatment of diseases.
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Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for＞48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06％,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.
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Objective To explore the expression of serum miR-410-3p in patients with rheumatoid arthritis(RA)and its relationship with knee soft tissue lesions.Methods A total of 89 RA patients admitted to our hospital were selected and divided into the active group(42 cases)and the remission group(47 cases)according to disease activity score in 28 joints(DAS28).In addition,52 healthy volunteers underwent physical examination during the same period in our hospital were selected as the healthy group.The expression level of serum miR-410-3p was detected by RT-PCR,the lesions of knee soft tissue was examined by ultrasound,and the relationship between the expression of serum miR-410-3p and knee soft tissue lesions was analyzed by Pearson.Results The expression levels of serum miR-410-3p of patients in the active group and the remission group were lower than that in the healthy group(P<0.05),and the expression level of serum miR-410-3p of patients in the active group was lower than that in the remission group(P<0.05).The cartilage thicknesses of medial and lateral ankle of patients in the active group and the remission group were smaller than those in the healthy group(P<0.05),and the above indexes in the active group were smaller than those in the remission group(P<0.05).The depths of suprapatellar bursa fluid and synovial thicknesses of patients in the active group and the remission group were greater than those in the healthy group(P<0.05),and the depth of suprapatellar bursa fluid and synovial thickness of patients in the active group were greater than those in the remission group(P<0.05).The level of serum miR-410-3p in RA patients was positively correlated with the depth of suprapatellar bursa fluid and synovial thickness(P<0.05),and negatively correlated with the cartilage thicknesses of medial and lateral ankle(P<0.05).Conclusion Serum miR-410-3p expression level in RA patients is decreased,which was closely related to knee soft tissue lesions,detecting the changes of serum miR-410-3p level may provide a reference for the evaluation of knee soft tissue lesions.
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Objective To investigate the application of intravenous iron in patients with abnormal uterine bleeding(AUD)and iron deficiency anemia(IDA)in gynecology,to establish the drug utilization evaluation(DUE)standard,and to comprehensively evaluate the rationality of the clinical application of intravenous iron by analytic hierarchy process(AHP),so as to provide reference for the rational use of intravenous iron in clinical practice.Methods The medical records of patients with AUD and IDA from January to December 2022 in the First Affiliated Hospital of Anhui University of Science and Technology were collected,and the special rationality of the drug was evaluated from the aspects of indications,route and frequency of administration,daily dosage,solvent,combination medication,and contraindications of iron sucrose injection,and the DUE standard of the drug was formulated.AHP was used to analyze and evaluate 113 archived cases of intravenous iron in gynecology from January to December 2022.Results A total of 113 patients were treated with iron sucrose injection,and the indications,route of administration,solvent,contraindications,and allergic reactions were reasonable.The main unreasonableness was that the frequency of administration was inappropriate,the daily dose was inappropriate,the combination was not appropriate,the total iron supplement was not up to standard,and there was no continuous drug monitoring after medication.The case scores 90～100,70～<90 and 60～<70 were 6(5.31%),106(93.81%)and 1(0.88%),respectively.Conclusion Patients with AUD and IDA should pay attention to the dosage,total amount of iron supplementation,combined application of drugs and continuous medication monitoring after intravenous iron supplementation,so as to improve the rationality of their use.
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Objective To provide pharmaceutical monitoring using the Pharmaceutical Care Network Europe(PCNE)for patients with respiratory diseases,to explore effective pharmaceutical monitoring models in the department of respiratory,and to promote clinical rational drug use.Methods Inpatients diagnosed with chronic obstructive pulmonary disease(COPD)and lung infections in 2022 at the First Affiliated Hospital of Anhui University of Science and Technology were selected and divided into a simple group and an intervention group.According to the PCNE classification system,the types,causes,interventions,acceptance of interventions,and resolution status of drug-related problems(DRPs)were analyzed.Results A total of 120 cases were included,60 cases in the simple group and 60 cases in the intervention group.Regarding the number of DRPs,there were 15 cases in the simple group and 45 cases in the intervention group,and there was a significant difference between the two groups(P<0.05).There were a total of 82 DRPs,which were mainly related to therapeutic efficacy(51.22%)and safety(46.34%),and the reasons for this were that patients'incorrect medication usage method,inappropriate usage and dosage,and unscheduled safety monitoring,etc.The pharmacist interventions were 75(91.46%)at the drug level,38(46.34%)at the physician level,and 43(52.44%)at the patient level;after the pharmacist interventions,the acceptance rate was in the range of 97.56%,and 74.39%of the DRPs were resolved.Conclusion PCNE classification system helps clinical pharmacists to enhance their ability to find and deal with DRPs,reduce the risk of clinical adverse events and promote reasonable and safe drug use.Meanwhile,it is conducive to the standardization of pharmaceutical care records for patients with respiratory diseases and provides reference for pharmaceutical service models for patients in the department of respiratory.
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Objective To explore the tripartite dynamic game strategy involving the interest relationship between government,hospital and patients in the tiered diagnosis and treatment system,which is conducive to improving the theoretical paradigm and policy logic of tiered diagnosis and treatment system.Methods It built a tripartite evolu-tionary game model to analyse their strategy choices and evolutionary paths,and to solve for stable strategies in the three-way evolutionary game.MATLAB R2018b was used to simulate the model,and the evolution paths and the in-fluence of different strategy choices on the promotion of the tiered diagnosis and treatment system were further ana-lyzed.Results Government,hospitals,and patients will influence each other and eventually evolve to the ideal stable state(1,1,1).Increasing government subsidies will accelerate the convergence of the initial participation probability of hospitals and patients to 1,while excessive subsidies will gradually cause the government to deviate from the strategy of encouraging.Conclusions The government should restrict subsidies for high-quality medical resources to a reasonable range,attract hospital experts,and strengthen regulations.It is important for large hospitals and basic medical institutions to realize the free flow and rational distribution of the resources available to doctors.Patients need to change their inherent concept of medical treatment to achieve orderly medical treatment.
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Objective:To study the effects of different doses of X-ray irradiation on the immune microenvironment and cGAS-STING signaling pathway of hepatocellular carcinoma cells.Methods:C57BL/C mice were subcutaneously injected with Hepa 1-6 hepatocellular carcinoma cells in the right axilla to establish a subcutaneous tumor-forming hepatocellular carcinoma model. The mice were randomly divided into 0, 4, 8, 12 Gy irradiation groups, with 10 mice in each group. The body weights and tumor volumes were monitored. Specimens were collected 28 d after irradiation. The ELLSA and Flow Cytometry method was used to compare the macrophage-associated cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), chemokine ligand 5 (CCL5), IL-10, IL-13, transforming growth factor-β (TGF-β), IL-4 and macrophage M1, M2 phenotype ratio (M1/M2). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and immunoblotting assay were used to detect the expression of genes and proteins related to the cGAS-STING signaling pathway in hepatoma cells.Results:With the increase of irradiation dose, the tumor volume was significantly reduced ( F=8.42, P<0.05), the proportion of cell necrosis increased ( F=3.89, P<0.05), the content of macrophage-associated cytokines other than IL-4 increased ( F=6.32-15.50, P<0.05), and the proportion of M1 and M2 types of macrophage in the immune microenvironment of hepatocellular carcinoma tumors was elevated ( F= 5.46, 5.14, P < 0.05).The gene expression and protein expression levels of cGAS-STING signaling pathway were elevated in hepatocellular carcinoma cells (mRNA expression of cGAS and STING: F=6.35, 16.10, P<0.05; protein expression of cGAS and STING: F=71.31, 37.15, P<0.05). Conclusions:X-ray irradiation activates the cGAS-STING signaling pathway in hepatocellular carcinoma cells and contributes to the remodeling of the tumor immune microenvironment.
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Objective:To evaluate the value of 18F-FDG PET metabolic parameters in predicting histopathological grade of soft tissue sarcoma (STS). Methods:From December 2012 to December 2021, 51 patients (26 males, 25 females, age range: 32-84 years) who underwent 18F-FDG PET/CT imaging before treatment and confirmed STS pathologically in the First Affiliated Hospital of Dalian Medical University were retrospectively collected. 18F-FDG PET metabolic parameters SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and intertumoral FDG uptake heterogeneity (IFH) were measured. Kruskal-Wallis rank sum test was used to analyze the differences in metabolic parameters among different groups and Spearman rank correlation analysis was used to analyze the correlation of each metabolic parameter and histological grade. Logistic regression was used to screen and construct the prediction model for high-grade STS. ROC curve was plotted and Delong test was used to analyze the differences among AUCs. Results:The metabolic parameters SUV max, MTV, TLG and IFH were significantly different among French Federation of Cancer Centers Sarcoma Group (FNCLCC)Ⅰ( n=8), Ⅱ( n=10) and Ⅲ ( n=33) grade groups ( H values: 16.24, 10.52, 19.29 and 16.99, all P<0.05), and each metabolic parameter was positively correlated with histological grade ( rs values: 0.58, 0.45, 0.52, and 0.62, all P<0.05). Multivariate logistic regression analysis showed that SUV max(odds ratio ( OR)=1.27, 95% CI: 1.06-1.51, P=0.009) and IFH ( OR=6.83, 95% CI: 1.44-32.27, P=0.015) were independent risk indicators for high-grade STS. The prediction model constructed by combining SUV max and IFH had better diagnostic efficacy for differentiating high-grade STS with the AUC of 0.93, and the sensitivity of 93.9%(31/33) and the specificity of 16/18, respectively. The AUC of prediction model was significant different from SUV max, MTV, TLG and IFH (AUCs: 0.81, 0.78, 0.86 and 0.85; z values: 2.69, 2.53, 1.94 and 1.97, all P<0.05). Conclusions:The metabolic parameters SUV max, MTV, TLG and IFH are valuable predictors for histological grade of STS. The combination of SUV max and IFH may be a more meaningful method than using each of the above metabolic parameters alone.
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Objective:To construct an evaluation indicator system for the efficiency of nursing human resources in integrated medical and elderly care institutions using Data Envelopment Analysis (DEA) and subsequently evaluate its effectiveness.Methods:This cross-sectional survey utilized literature review and investigative methods to initially establish a library of evaluation indicators for nursing human resource efficiency. The Delphi method was employed in two rounds of consultations with 17 experts from various fields, including nursing management, elderly care institution management, integrated medical and elderly care institution management, health economics management, and public health. The reliability of the indicator system was assessed based on factors such as expert enthusiasm, authority, concentration of opinions, and coordination. Adjustments, modifications, and improvements were made to the indicators based on expert opinions to establish the final indicator system. From August to December 2022, the DEA model was applied to evaluate the efficiency of 12 integrated medical and elderly care institutions in Haikou city based on this indicator system.Results:The constructed evaluation indicator system comprised 68 items divided into three levels: 9 primary indicators, 19 secondary indicators, and 40 tertiary indicators. The positive coefficients of the two rounds of expert consultations were 100% and 94.1%, with authority coefficients of 0.88 and 0.92, Kendall harmony coefficients of 0.471 and 0.348, and mean coefficients of variation of 0.16 and 0.12 ( P<0.001). DEA evaluation results for the 12 integrated medical and elderly care institutions showed that 5 were DEA effective institutions with comprehensive efficiency (OE), technical efficiency (TE), and scale efficiency (SE) values all equal to 1.000, while 7 were non-DEA effective institutions, including 4 with SE <1.000 but TE=1.000 and 3 with both SE and TE<1.000. Conclusions:The constructed evaluation indicator system demonstrates high enthusiasm, authority coefficients, and coordination in expert consultations, indicating high acceptability and comprehensive content with distinct levels and strong specialty characteristics. The DEA model′s evaluation results objectively and effectively reflect the efficiency of nursing human resources in integrated medical and elderly care institutions, demonstrating practical utility.
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Objective:To investigate the relationship between the age-adjusted Charlson comorbidity index(aCCI)and the risk of in-hospital death for people aged ≥ 90 years with community-acquired pneumonia(CAP), and to construct a novel scoring model for predicting in-hospital mortality.Methods:Basic personal and medical data about sex, age, hospitalization days, hospitalization expenses, in-hospital outcomes and discharge/admitting diagnosis of CAP patients aged ≥ 90 years hospitalized in Peking University Third Hospital between 2010 and 2019 were collected retrospectively.Multivariate Logistic regression analysis was conducted to examine the association between aCCI or other complications and in-hospital death.The receiver operating characteristic curve(ROC)was used to assess the value of aCCI and a new scoring model in predicting in-hospital death of CAP in people aged ≥ 90 years.Results:A total of 274 CAP patients aged ≥ 90 years were included in this study, of whom 85 died in hospital.Multivariate Logistic regression analysis showed that malnutrition( OR=2.21, 95% CI: 1.05-4.67, P<0.05), respiratory failure( OR=18.91, 95% CI: 9.34-38.25, P<0.001)and aCCI( OR=1.51, 95% CI: 1.23-1.85, P<0.001)were prognostic factors for in-hospital death in CAP patients aged ≥ 90 years.Based on the above results, a novel scoring model, MRC(malnutrition, respiratory failure, aCCI)was established.The area under the ROC curve of the aCCI score for predicting the risk of in-hospital death in CAP patients aged ≥ 90 years was 0.743(95% CI: 0.684-0.802). The area under the ROC curve of the MRC score was 0.891(95% CI: 0.848-0.933), indicating a higher predictive value than that of the aCCI score alone( Z=6.337, P<0.001). Conclusions:The MRC score model can be used to evaluate and predict the risk of in-hospital death in long-living CAP patients.
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AIM To explore the effects of Zishui Qinggan Decoction on the mouse model of depression induced by chronic restraint stress(CRS)via ERK/GSK3β/CREB/BDNF signaling pathway.METHODS Except for those of the blank group,the mice of other groups were induced into depression models by CRS,and divided into the model group,the fluoxetine hydrochloride group(10 mg/kg)and the low,medium and high dose Zishui Qinggan Decoction groups(8.835,17.670 and 35.340 g/kg)for the corresponding drug intervention and simultanous CRS treatment.The mice had their sugar water preference experiment and behavior experiment on the 7th and 14th day after administration;the observation of the hippocampal morphological changes by HE staining,the detection of the superoxide dismutase(SOD)activity and malondialdehyde(MDA)level in serum by kits,the detection of levels of serum 5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)by ELISA,the detection of the hippocampal mRNA expressions of BDNF,TNF-α and IL-1β by RT-qPCR method,and the detection of the hippocampal protein expressions of ERK1/2,p-ERK1/2,GSK3β,p-GSK3β,CREB and BDNF by Western blot method 14 days after administration.RESULTS Compared with the model group,after 14 days of administration,both fluoxetine hydrochloride group and medium-dose Zishui Qinggan Decoction group displayed increased preference rate of sugar water(P<0.01),shortened immobility time of tail suspension and forced swimming(P<0.01),improved hippocampal damage of nerve cells,decreased levels of serum MDA,TNF-α and IL-1β(P<0.05,P<0.01),increased SOD activity and 5-HT level(P<0.05,P<0.01),decreased hippocampal mRNA expressions of TNF-α and IL-1β(P<0.01),and decreased expressions of BDNF mRNA and p-ERK1/2,p-GSK3β,CREB and BDNF proteins(P<0.05,P<0.01).CONCLUSION Zishui Qinggan Decoction can improve the depression-like behaviors in mice exposed to CRS,and its mechanism may be related to the regulation of hippocampal ERK/GSK3β/CREB/BDNF signaling pathway.
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【Objective】 To dynamically monitor and analyze the changes of platelets and related indicators in infants with cow′s milk protein allergy (CMPA) during clinical treatment, in order to provide clues for further diagnosis and treatment of CMPA. 【Methods】 From August to November in 2022, 59 children aged from 1 month to 3 years old with CMPA in the pediatric outpatient clinic were selected as the CMPA group, and 29 healthy children who took physical examination were selected as the control group. The differences in platelet related indicators from a routine blood test were compared between the two groups, and their diagnostic value for CMPA was analyzed by receiver operating characteristic (ROC) curves. 【Results】 The mean platelet count (PLT) and plateletcrit (PCT) at baseline in the CMPA group were (374.68±113.21)×109/L and 0.37±0.10, significantly higher than those in control group[(271.07±40.32)×109/L, 0.26±0.05] (t=6.27, 6.43, P<0.001). In the CMPA group, after treatment, the mean PLT level was (316.39±94.68)×109/L, and the mean PCT level was 0.31±0.10, indicating a statistically significant decrease in PLT and PCT levels after treatment compared to baseline (t=4.32,4.75,P<0.05). The diagnostic performance, indicated by the area under the curve (AUC), for PLT and PCT in diagnosing CMPA was 0.811 and 0.823, respectively. The cutoff values for PLT and PCT were determined to be 304.5×109/L and 0.305, respectively. 【Conclusion】 The PLT and PCT levels in children with CMPA are found to be higher than those in healthy controls, suggesting their potential diagnostic value in the diagnosis of CMPA.
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Objective@#To compare the relative effectiveness of different exercise modalities on inhibitory control in children with attention deficit hyperactivity disorder (ADHD), so as to provide an evidence based basis for the development of effective exercise prescriptions.@*Methods@#The databases of China National Knowledge Internet (CNKI), Pubmed, Web of Science, Embase, and Cochrane were searched to screen the literature of randomized controlled trials of exercise interventions for inhibitory control in children with ADHD up to December 31, 2022. The Cochrane risk of bias assessment tool was used for methodological quality assessment, and Stata 17.0 software was used for network Meta analysis, standardized mean difference ( SMD ) and 95% CI were used as the effect indicators to compare the difference in effect between interventions and rank the effect.@*Results@#Twenty two papers with a total of 1 134 participants aged 6-14.5 years were finally included. Network Meta analysis showed that the impact effects of physical and mental exercises [ SMD (95% CI )=1.08(0.50-1.66)], cognition+exercise [ SMD (95% CI ) =0.81(0.13-1.48)], and ball games [ SMD (95% CI )= 1.54(0.99-2.09)] were significantly superior to that of control group, and the ball games had a significantly better effect than single aerobic exercise [ SMD (95% CI )=1.02(0.20-1.84)], and combined exercises [ SMD (95% CI )=1.08( 0.28 -1.88)]( P < 0.05 ). The results of surface under the cumulative ranking (SUCRA) showed that ball games might be the best means to improve inhibitory control in children with ADHD(SUCRA=95.3).@*Conclusion@#It is recommended to appropriately increase ball sports in sports activities to more effectively improve the inhibitory control of children with ADHD.
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Gold nanoparticles(AuNPs)present unique physicochemical characteristics,excellent biocom-patibility and ease of surface functionalization,which have become the research hotspots in the field of biosens-ing.This article reviews the synthesis methods,main properties and surface functionalization of AuNPs,as well as the research progress of application in various sensing platforms.
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Objective To observe the effects of amyloid-β(Aβ)receptor PirB on mouse astrocyte proliferation and reactive astrogliosis in vitro.Methods Mouse primary astrocytes were cultured,and divided into control group,Aβ group,Aβ+0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group,Aβ+Fluspirilene group,Aβ+GFP-LV group,and Aβ+mPirB-LV group.The mouse astrocytes were treated with soluble PirB extracellular peptide PEP or PirB inhibitor Fluspirilene,respectively,to inhibit endogenous PirB receptor,or overexpressed PirB gene via lentivirus transfection and then treated with Aβ1-42 oligomers.The proliferation of astrocytes was observed by RTCA and EdU methods,and the mRNA expression levels of S-100 calcium-binding protein B(S-100β),Vimentin,Nestin and amyloid precursor protein(APP)associated with reactive astrogliosis of astrocytes were observed by real-time PCR,and the expression level of glial fibrillary acid protein(GFAP)was detected by Western-blotting.Results The results of RTCA monitoring showed that normalized cell index(NCI)values of each group decreased sharply after treatment,and then increased gradually and tended to be stable.The results of EdU staining showed that the proliferative activity of astrocytes was significantly enhanced in the Aβ group(P<0.05)compared with control group;Compared with Aβ group,cell proliferation activity in Aβ + 0.2 μmol/L PEP group,Aβ+0.4 μmol/L PEP group and Aβ+Fluspirilene group were significantly decreased(P<0.01 or P<0.001).The results of real-time PCR showed that compared with control group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ group were significantly increased(P<0.05);Compared with Aβ group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ+0.4 μmol/L PEP group were significantly decreased(P<0.01);Compared with Aβ+GFP-LV group,mRNA expressions of GFAP,S-100β,Vimentin,Nestin,APP and PirB in Aβ +mPirB-LV group were significantly increased(P<0.05).The results of Western blotting showed that compared with control group,the expression of GFAP in Aβ group was significantly increased(P<0.05);Compared with Aβ group,the expression of GFAP in Aβ+0.4 μmol/L PEP group was significantly decreased(P<0.05).Conclusions PirB is an upstream molecule which could regulate astrocyte proliferation and reactive astrogliosis,and inhibiting PirB receptor in astrocytes may be a potential treatment for Alzheimer's disease.
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Objective:To investigate the levels of interleukin-7 (IL-7), T helper cell 9 (Th9), and cytotoxic T cell 9 (Tc9), and to assess the regulation of exogenous IL-7 to Th9 in septic cardiomypathy patients.Methods:A cross-sectional study was conducted. Septic cardiomypathy patients, septic patients, and controls were enrolled in the 7th People’s Hospital of Zhengzhou between June 2018 and January 2022. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. PBMCs were stimulated with recombinant IL-7. Plasma IL-7, IL-9, and soluble CD127 levels were measured by enzyme-linked immunosorbent assay. CD127 expression on T cells and Th9/Tc9 percentageswere measured by flow cytometry. mRNAexpressions of purine-rich nucleic acid binding protein 1 (PU.1) and forkhead box protein O1 (Foxo1) were semi-quantified by real-time PCR. IL-7-stimulated Th9 cells from septic cardiomypathy patients were co-cultured with autologous CD8 + T cells and human umbilical vein endothelial cells. Target cell death, cytotoxic molecules and cytokines secretions were investigated. Kruskal-Wallis test was used for comparison among groups, while Dunns multiple test was used for comparison between the two groups. Paired t test or Wilcoxon paired test was used for comparison before and after stimulation. Results:A total of 21 septic cardiomypathy patients, 56 septic patients, and 31 controls were enrolled. IL-7 level was lower in septic cardiomypathy patients compared with in septic patients and controls [75.71(42.28, 135.59) pg/mL vs. 118.47(60.18, 171.73) pg/mL vs. 168.42(105.41, 232.30) pg/mL, P<0.05]. Soluble CD127 level was higher in septic cardiomypathy patients and septic patients compared with in controls [96.70(56.76, 147.04) pg/mL vs. 69.75(43.19, 111.28) pg/mL vs. 29.13(19.33, 42.11) pg/mL, P<0.001]. There was no significant difference of CD127 +CD8 + percentage among three groups ( P=0.477). Th9 percentage and Foxo1 mRNA expression was lower in septic cardiomypathy patients compared with in septic patients and controls ( P<0.001). Tc9 percentage, PU.1 mRNA expression and IL-9 level was lower in septic cardiomypathy patients and septic patients compared with in controls ( P<0.001). Th9 percentage, PU.1/Foxo1 mRNA expression, and IL-9 secretion was up-regulated in response to IL-7 stimulation in PBMCs from septic cardiomypathy patients ( P<0.05). IL-7 stimulated Th9 cells from septic cardiomypathy patients promoted CD8 + T cell-mediated target cell death ( P<0.05). Perforin, granzyme B, and interferon-γ levels were also increased in the supernatants ( P<0.05). Conclusion:IL-7 could enhance Th9 cell activity in septic cardiomypathy patients.
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ObjectiveA growing body of research suggests a strong link between metabolic imbalance and Alzheimer’s disease (AD). In recent years, the development of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in AD. Serum levels of tryptophan and tyrosine were associated with mild cognitive impairment (MCI) and AD. The purpose of this study is to further characterize tryptophan and tyrosine levels in MCI and AD. MethodsWe stratified 765 participants from the Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) cohort into cognitively normal (CN; n=207), stable mild cognitive impairment (sMCI; n=201), progressive mild cognitive impairment (pMCI; n=171), and dementia due to AD (n=186). Serum tryptophan and tyrosine were analyzed for diagnostic value of MCI and AD. To evaluate the relationships between serum tryptophan and tyrosine and cerebrospinal fluid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism (18F-fluorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. ResultsSerum tryptophan was decreased in patients with AD, pMCI or sMCI compared with CN. Serum tyrosine was decreased in patients with AD or pMCI compared with CN. Serum tryptophan has diagnostic value for pMCI and AD. Serum tyrosine has diagnostic value for AD. ConclusionSerum tryptophan and tyrosine contribute to the early diagnosis of AD. The detection of tryptophan and tyrosine can contribute to the pathogenesis of AD. Serum tryptophan and tyrosine were not significantly associated with core AD markers, cognitive function, brain structure and brain metabolism, so serum tryptophan and tyrosine may not be good peripheral AD biomarkers.
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Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.
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Objective To investigate the relationship between cerebrovascular reserve (CVR) capacity and white matter lesions in elderly people. Methods We included 315 participants aged ≥ 60 years in Jinan area of Shandong Province from May 2018 to July 2019. They underwent transcranial Doppler ultrasonography for assessing CVR, breath holding index (BHI), and arterial pulsatility index (PI). According to CVR capacity, they were divided into normal CVR group (CVR ≥ 20%, n = 206) and impaired CVR group (CVR < 20%, n = 109). Magnetic resonance imaging was performed to evaluate periventricular, subcortical, and total white matter hyperintensity (WMH) volumes and Fazekas scores. Results Compared with the normal CVR group, the impaired CVR group showed significantly higher volumes of periventricular, subcortical, and total WMHs and significantly higher proportions of Fazekas scores ≥ 2 (P < 0.01). Periventricular, subcortical, and total WMH volumes were negatively correlated with CVR (r = −0.70, −0.66, −0.73, P < 0.01) and BHI (r = −0.64, −0.65, −0.68, P < 0.01) and positively correlated with PI (r = 0.60, 0.65, 0.65, P < 0.01). After adjusting for confounding factors, periventricular, subcortical, and total WMH volumes were still negatively correlated with CVR and BHI (P < 0.01) and positively correlated with PI (P < 0.01). The logistic regression analysis showed that the risks of periventricular, subcortical, and total Fazekas score ≥ 2 in the impaired CVR group were 1.96 times (95% confidence interval [CI]: 1.17−3.27, P < 0.01), 1.84 times (95% CI: 1.11−3.05, P < 0.05), and 2.33 times (95% CI: 1.30−4.18, P < 0.01) that of the normal CVR group, respectively. Conclusion Impaired CVR is an independent risk factor for white matter lesions in the elderly.
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Hepatic steatosis can be observed in chronic liver diseases of different etiologies. The main predisposing factors for hepatic steatosis include chronic viral hepatitis， cholestatic liver disease， alcoholic liver disease， and nonalcoholic fatty liver disease. Simple fatty liver disease is the initial manifestation of hepatic steatosis， followed by steatohepatitis， liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. With the development of medical imaging technology， magnetic resonance imaging-proton density fat fraction （MRI-PDFF） has been widely used in the diagnosis of fatty liver disease （FLD） in clinical practice. MRI-PDFF is gradually becoming the gold standard for the noninvasive diagnosis of FLD due to its high accuracy and good repeatability. This article reviews the clinical application of MRI-PDFF in liver fat quantification and related research advances.