1.Mechanism of action and research progress of vaccine adjuvants
Li ZHANG ; Chang LU ; Minghui AN ; Mengmeng WANG ; Xiaoyu ZONG ; Lin YU ; Zhuo-Ling RAN ; Jing SONG ; Huijie LI ; Jian GONG
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(7):785-791
Vaccines are among the most effec-tive measures for preventing infectious diseases and play a crucial role in controlling the spread of these diseases.Adjuvants,serving as auxiliary com-ponents in vaccines,are indispensable in the vac-cine development process.Ideal adjuvants not only enhance the immune response,enabling the body to achieve optimal protective immunity but also play important roles in reducing the dosage of im-munogens and lowering vaccine production costs.To meet the demands of novel vaccines,many new types of adjuvants have been developed.However,there is still a lack of adjuvants that are safe,effec-tive,easy to prepare,highly pure,and suitable for a variety of vaccines in clinical settings.This article categorizes adjuvants and summarizes their mecha-nisms of action and characteristics,focusing on tra-ditional aluminum salt adjuvants and more modern lipid-based and nucleic acid-based adjuvants.The summary is based on a computer search of data-bases including PubMed,Embase,The Cochrane Li-brary,CNKI(China National Knowledge Infrastruc-ture),VIP Database,and Wanfang Database,using English search keywords such as Adjuvants,Vac-cine,Vaccine Adjuvant,aluminum salts,MF59,AS03,Toll-like receptor agonist,etc.,and corre-sponding Chinese search terms.The aim is to pro-vide references for the development and applica-tion of adjuvants.
2.Construction of nutrition management plan for chronic kidney disease patients based on nutritional care procedure and model
Xueqi TIAN ; Zhenxiang LI ; Yan KONG ; Kejing ZONG ; Yanzheng LIU ; Jing ZHANG
Chinese Journal of Modern Nursing 2024;30(15):2008-2014
Objective:To build a systematic and standardized nutrition management plan for patients with chronic kidney disease.Methods:Based on the nutrition care procedure and model, a preliminary draft of a nutrition management plan for chronic kidney disease patients was developed through a literature search, quality evaluation, and group discussions. After two rounds of expert consultation and revision of the preliminary draft of the nutrition management plan, the final plan was formed.Results:A total of 32 experts were invited to complete two rounds of consultation. In two rounds of expert consultation, 32 questionnaires were distributed, and 32 and 31 valid questionnaires were collected, with valid response rates of 100.0% and 96.9%, respectively. The expert authority coefficients were 0.853 and 0.871, respectively. The final nutrition management plan for chronic kidney disease patients included six first-level items of nutrition management personnel: nutrition risk screening, nutrition assessment, nutrition treatment, nutrition monitoring, and nutrition health education, with 23 second-level and 52 third-level items.Conclusions:The constructed nutrition management plan for chronic kidney disease patients is scientific and can provide a reference for nutrition guidance.
3.Advances in lipopolysaccharide structural variations and immune escape in Yersinia pestis
Wen-Jing FENG ; Yuan ZHANG ; Zong-Min DU
Chinese Journal of Zoonoses 2024;40(9):860-866
Plague,caused by Yersinia pestis,is a zoonotic disease that infects both humans and animals.Y.pestis not only encodes various virulence factors that can disrupt host immune signaling but also can modify its lipopolysaccharide(LPS)struc-ture,thereby evading host immune surveillance and potently suppressing the host's immune response,in an important molecu-lar mechanism underlying its high pathogenicity.The LPS of Y.pestis lacks an O antigen,and its lipid A structure possesses a unique temperature transition regulatory mechanism.At different temperatures,Y.pestis forms lipid A with different numbers of acyl side chains,which plays a pivotal role in the evasion of host innate immune recognition and clearance.Here,we present a comprehensive review of research progress in the biosynthetic regulation,structural variation,and immune escape mechanism of Y.pestis LPS,to provide a reference for the study of the molecular mechanisms of pathogens using LPS structural modifica-tions to elude host innate immune defenses.
4.Effects of PIM1 Gene on Proliferation,Apoptosis and JAK2/STAT3 Signaling Pathway of Acute Myeloid Leukemia U937 Cells
Xin GAO ; Li-Jing CHU ; Zong-Hai YAN
Journal of Experimental Hematology 2024;32(3):663-669
Objective:To investigate the effects of the serine/threonine kinase family member 1(PIM1)gene on the proliferation and apoptosis of acute myeloid leukemia(AML)U937 cells,and the regulation effect on Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods:Bone marrow mononuclear cells from newly diagnosed adult AML patients and patients with iron deficiency anemia were collected and PIM1 mRNA expression was detected by RT-qPCR.AML cell line U937 cells were divided into U937 group(U937 cells were cultured normally),Si-PIM1 group(U937 cells were transfected with low expression adenovirus vector containing PIM1 mRNA),Si-NC group(U937 cells were transfected with low expression adenovirus vector without PIM1 mRNA),coumermycin A1(CoA1)group(JAK2 activator CoA1 was added to U937 cells at a concentration of 20 μ mol/L),and Si-PIM1+CoA1 group(U937 cells were transfected with adenoviral vector containing low expression of PIM1 mRNA and added with CoA1 at a concentration of 20 μ mol/L).After culture for 24 h,the expressions of PIM1 mRNA and protein,JAK2/STAT3 pathway,cell cycle and apoptosis-related proteins in U937 cells were detected by RT-qPCR and Western blot,the cell proliferation activity was detected by MTT assay,and flow cytometry was used to detect cell cycle changes and apoptosis rate.Results:The PIM1 mRNA expression level in bone marrow mononuclear cells in AML patients was higher than that in patients with iron deficiency anemia(P<0.05).Compared with U937 group,PIM1 mRNA and protein,phosphorylated JAK2(p-JAK2)/JAK2,phosphorylated STAT3(p-STAT3)/STAT3,Cyclin D1,cyclin-dependent kinase 2(CDK2)protein,cell proliferation activity,S phase and G2/M phase proportions were decreased in Si-PIM1 group(all P<0.05),while p27,Caspase-3 protein,G0/G,phase proportion and apoptosis rate were increased(all P<0.05).However,the changes of above indicators in CoA1 group were just opposite to those in Si-PIM1 group,indicating that CoA1 could reverse the effect of Si-PIM1 on U937 cells.There were no significant differences in above indexes of U937 cells between U937 group,Si-PIM1+CoA1 group and Si-NC group(P>0.05).Conclusion:Knockdown of PIM1 gene expression can inhibit U937 cell proliferation and promote apoptosis,in order to alleviate ALM process,which may be related to the inhibition of JAK2/STAT3 pathway activation.
5.Effect of frailty on elderly patients suffering from heart failure with reduced ejection fraction
Min ZONG ; Xiaonan GUAN ; Jing CHANG ; Jianjun ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(5):523-526
Objective To investigate the long-term effect of frailty on heart failure with reduced ejection fraction(HFrEF)in elderly patients.Methods A retrospective analysis was conducted on 245 HFrEF patients aged ≥75 years admitted to our hospital from October 2017 to October 2020 due to acute exacerbation of chronic heart failure(HF).Based on their clinical frailty scale(CFS)score,they were divided into frailty group(1-4,135 cases)and non-frailty group(5-9,110 cases).Their general clinical data,clinical medication,and prognosis were compared between the two groups,and the influencing factors for frailty and death were analyzed.Results Faster heart rate,higher NT-proBNP level,and larger proportions of male,diabetes,coronary heart disease,≥5 chronic diseases,LVEF ≤35%,anemia and increased troponin I level,while lower BMI,eGFR and score of activity of daily living scale were observed in the frailty group than the non-frailty group(P<0.05,P<0.01).The frail group had significantly lower utilization rates of angiotensin converting enzyme inhibitors(ACEI),angiotensin receptor blockers(ARB),angiotensin receptor enkephalin inhibitors(ARNI)β receptor blockers,and sodium-glucose cotransporter 2 inhibitors than the non-frailty group(P<0.01).Additionally,the frailty group exhibited a higher incidence of emergency room visits/readmissions within 3 months and 2-year mortality than the non-frailty group(P<0.05,P<0.01).Binary logistic regression analysis revealed that ≥5 chronic diseases,LVEF ≤ 35%,BMI,and GFR were independent risk factors for frailty(OR=0.167,95%CI:0.064-0.453,P=0.000;OR=0.306,95%CI:0.160-0.586,P=0.000;OR=0.868,95%CI:0.786-0.958,P=0.005;OR=0.966,95%CI:0.943-0.991,P=0.007),while ≥5 chronic disea-ses and frailty were independent risk factors for death in HF patients(P<0.05).Conclusion The incidence of frailty is high in elderly HF patients with HFrEF.They have poor compliance to guideline directed drug therapy(GDMT).Frailty is an independent risk factor for long-term mor-tality in the patients.
6.Predictive value of cystatin C and antithrombin Ⅲ for contrast-induced acute kidney injury in elderly hypertensive patients
Linsheng WANG ; Xudong ZHANG ; Yuan LU ; Jing ZONG ; Fangfang LI ; Luhong XU ; Wenhua LI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(8):862-866
Objective To investigate the predictive value of Cys C and AT Ⅲ for CIAKI in elderly hypertensive patients with AMI after PCI.Methods A total of 911 elderly hypertensive patients with AMI undergoing emergency PCI in the Affiliated Hospital of Xuzhou Medical University from January 2019 to May 2023 were consecutively enrolled,and then randomly divided into a training group(731 cases)and a validation group(180 cases)in a ratio of 8∶2.According to the diagnostic criteria of CIAKI defined by the European Society of Urogenital Radiology,the patients of the training group were further divided into CIAKI subgroup(n=91)and non-CIAKI sub-group(n=640).The basic clinical data were compared between the CIAKI and non-CIAKI sub-groups and between the training and validation groups.Multivariate logistic regression analysis was used.ROC curve was drawn to analyze the predictive value of Cys C,ATⅢ and their combina-tion for CIAKI.Results Fasting blood glucose,TG,Cys C,and diuretics were independent risk factors(OR=1.116,95%CI:1.009-1.235;OR=1.786,95%CI:1.363-2.339;OR=13.360,95%CI:4.462-39.999;OR=10.606,95%CI:4.110-27.370),while LVEF and AT Ⅲ were protective factors(OR=0.932,95%CI:0.897-0.968;OR=0.949,95%CI:0.929-0.969)for CIAKI in eld-erly hypertensive patients after emergency PCI.The AUC value of Cys C and AT Ⅲ combined to-gether in predicting CIAKI after emergency PCI was 0.818(95%CI:0.773-0.863,P<0.01),which was better than either of them alone.When Cys C level ≥1.10 mg/L,the risk of CIAKI was increased with the increment of the level;when AT Ⅲ ≥69%,the risk of CIAKI was decreased with the increase of AT Ⅲ level.Conclusion High Cys C level and low AT Ⅲ level are independ-ent risk factors for CIAKI,and their combination can improve the accuracy of predicting CIAKI after emergency PCI in elderly patients with hypertensive AMI.
7.Analysis of related factors of frailty in very elderly patients with multimorbidity
Tingwen WENG ; Min ZONG ; Liyan SHEN ; Yaping WANG ; Cheng QIAN ; Yajian LI ; Xinkai QU ; Songbai ZHENG ; Jing YAO
Chinese Journal of Geriatrics 2024;43(7):857-862
Objective:To investigate the factors contributing to frailty in very elderly patients with multimorbidity.Methods:This cross-sectional study enrolled 119 very elderly patients with multimorbidity who were hospitalized in the Department of Geriatrics of Huadong Hospital Affiliated to Fudan University from August 2022 to March 2023.The study aimed to understand the basic status of multimorbidity by collecting general information, the number and types of diseases, and frailty status.The subjects were divided into frail and non-frail groups through comprehensive geriatric assessment.Various factors including gender, age, Tinetti balance gait score, risk of sarcopenia, dementia, depression, risk of deep vein thrombosis, dysphagia, comorbidity index, medication count, Basic Activities of Daily Living(BADL)score, Instrumental Activities of Daily Living(IADL)score, Nutritional Risk Screening 2002(NRS-2002)score, Norton pressure injury risk assessment score, and Social Support Rating Scale(SSRS)score were compared.The correlation between each factor and the occurrence of frailty was analyzed using univariate analysis and multivariate Logistic regression analysis.Results:A total of 119 elderly inpatients with multimorbidity, with an average age of 90.8±5.9 years old, were included in the study.The incidence of frailty was 68.9%(82 cases).Univariate analysis revealed significant statistical differences between the frail group and the non-frail group in various factors including age( t=-3.131, P=0.002), Tinetti score( Z=-5.544, P<0.001), risk of sarcopenia( χ2=39.205, P<0.001), dysphagia( χ2=5.937, P=0.015), Charlson comorbidity index( Z=-2.565, P=0.010), medication count( Z=-3.325, P<0.001), BADL( Z=-5.871, P<0.001), IADL( Z=-5.062, P<0.001), Norton score( Z=-5.922, P<0.001), and SSRS social support( Z=-2.637, P=0.008).Multivariate logistic regression analysis showed that the Tinetti score( OR=0.843, 95% CI: 0.737-0.966, P=0.014), decreased muscle strength( OR=11.226, 95% CI: 2.157-58.432, P=0.004), sarcopenia( OR=18.084, 95% CI: 2.041-106.211, P=0.009), Norton score( OR=0.462, 95% CI: 0.254-0.838, P=0.011), and medication count( OR=1.153, 95% CI: 1.000-1.329, P=0.049)were independently associated with frailty. Conclusions:In very elderly patients with multimorbidities, the occurrence of frailty is notably increased.Frailty is linked to multiple risks including falls, muscle weakness/sarcopenia, pressure ulcer risk, and polypharmacy, and these risks are independent of other factors.
8.Treatment strategy and prognostic analysis of nasopharyngeal necrosis after first radical radiotherapy for nasopharyngeal carcinoma
Dan ZONG ; Wenxuan HUANG ; Yesong GUO ; Jing WEN ; Lijun WANG ; Lanfang ZHANG ; Lirong WU ; Cheng CHEN ; Shengfu HUANG ; Xia HE ; Zhenzhang CHEN
Chinese Journal of Radiation Oncology 2024;33(9):797-803
Objective:To investigate the treatment strategy and prognostic factors of nasopharyngeal necrosis after the first radical radiotherapy for nasopharyngeal carcinoma.Methods:Clinical data of 1020 patients with nasopharyngeal carcinoma undergoing radical intensity-modulated radiotherapy in Jiangsu Cancer Hospital from January 2013 to January 2022 were retrospectively analyzed. Nasopharyngeal necrosis was confirmed by nasopharyngeal MRI, electronic nasopharyngoscopy and biopsy. Patients with nasopharyngeal necrosis were treated with electronic nasopharyngoscope irrigation debridement, combined with systemic anti-infection and nutritional support therapy. Kaplan-Meier method was used to calculate the survival, and Cox regression analysis was used to analyze the relationship between clinical factors and patients' survival.Results:Nasopharyngeal necrosis occurred in 20 cases of 1020 nasopharyngeal carcinoma patients after the first radical intensity-modulated radiotherapy, with an incidence rate of 1.96%. Odd smell and headache were common in nasopharyngeal necrosis patients. All patients had locally advanced nasopharyngeal carcinoma at initial treatment, including 2 (10%) cases of T 3 stage and 18 (90%) cases of T 4 stage. Nasopharyngeal necrosis occurred in the primary nasopharyngeal lesions. According to the stages of nasopharyngeal necrosis, there were 6 (30%) cases of stage I, 14 (70%) cases of stage II and no stage III. The occurrence time of nasopharyngeal necrosis was from 2 to 24 months after radiotherapy, and the median time was 5 months. All 16 cases of nasopharyngeal necrosis were cured clinically after debridement and irrigation under nasopharyngoscope, systemic anti-infection and symptomatic support treatment. Among them, 9 cases had no necrotic cavity and complete healing and 7 cases had residual necrotic cavity. Four patients died of massive nasopharyngeal hemorrhage or due to the inability to nasopharyngeal irrigation. The 5-year survival rates were 37.5% and 85.7% in patients with and without internal carotid artery involvement ( P=0.008), and 25.0% and 77.8% in patients with and without diabetes mellitus ( P=0.016). Univariate Cox regression analysis showed that necrotic lesions involving internal carotid artery ( HR=5.80, 95% CI=1.14-29.38, P=0.034) and diabetes mellitus ( HR=10.24, 95% CI=1.19-88.04, P=0.034) were the influencing factors of overall survival. Conclusions:Nasopharyngoscope irrigation debridement combined with anti-inflammation and nutritional support treatment are effective interventions for nasopharyngeal necrosis after the first radical intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma. The necrosis involving the internal carotid artery and diabetes mellitus are important factors affecting the survival of patients. Vascular invasion caused by vascular rupture is the main cause of death.
9.Predictive value of systemic immune-inflammation index and NT-proBNP for contrast-induced acute kidney injury in elderly STEMI patients
Guoqi SHEN ; Linsheng WANG ; Xudong ZHANG ; Luhong XU ; Fangfang LI ; Jing ZONG ; Tongda XU ; Wenhua LI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(1):25-29
Objective To investigate the predictive value of systemic immune-inflammation index(SII)and N-terminal pro-brain natriuretic peptide(NT-proBNP)level in elderly patients with acute ST-segment elevation myocardial infarction(STEMI)developing contrast-induced acute kidney injury(CIAKI)after PCI.Methods A total of 1085 elderly STEMI patients undergoing emergency PCI in the Affiliated Hospital of Xuzhou Medical University from January 2018 to March 2023 were consecutively recruited as a training set,and another 287 elderly STEMI pa-tients receiving emergency PCI in the East Branch of the Affiliated Hospital from January 2021 to June 2023 were included as a verification set.According to the diagnostic criteria of CIAKI,they were divided into CIAKI group(n=95)and non-CIAKI group(n=990).Based on the results of restricted cubic spline(RCS)analysis,the patients from the training set were assigned into low-risk subgroup(n=292),moderate-risk group(n=515)and high-risk group(n=278).Multivari-ate logistic regression analysis was used to analyze the independent risk factors of CIAKI in elder-ly STEMI patients after PCI,and ROC curve was plotted to analyze the predictive value of combi-nation of SII and NT-proBNP.The risk of CIAKI was compared among the patients at different risk grades.Results Age,SII,baseline serum creatinine,NT-proBNP,fasting blood glucose and use of diuretics were independent risk factors for CIAKI after primary PCI in elderly STEMI patients(P<0.05,P<0.01).The AUC value of SII combined with NT-proBNP in predicting CIAKI was 0.801(95%CI:0.761-0.842,P<0.01),with a sensitivity of 83.2%and a specificity of 67.5%,both superior to that of SII or NT-proBNP alone.RCS analysis revealed an increased risk of CIAKI at SII ≥1084.97 × 109/L and NT-proBNP ≥296.12 ng/L.The incidence of CIAKI was increased with the increase of risk grades(1.71%vs 6.41%vs 20.50%).Conclusion SII and NT-proBNP are independent risk factors for CIAKI after emergency PCI in elderly STEMI pa-tients.And their combination has better predictive value for CIAKI.
10.Protective effect of quercetin mediated ferroptosis pathway on hypertonic stimulation induced dry eye cell model
Jia-Di WANG ; Bai-Ping AN ; Yue LIU ; Cong-Hong CAO ; Bei-Ting ZONG ; Jing YAO
The Chinese Journal of Clinical Pharmacology 2024;40(4):529-533
Objective To investigate the effect of quercetin on HCE-2 injury of human corneal epithelial cells induced by high osmotic pressure and its mechanism.Methods HCE-2 cells were randomly divided into control group(normal osmotic pressure),model group(high osmotic pressure),experimental-L group(high osmotic pressure+31.25 pg·mL-1 quercetin),experimental-M group(high osmotic pressure+62.50 μg·mL-1 quercetin),experimental-H group(high osmotic pressure+125.00 μg·mL-1 quercetin),erastin group(high osmotic pressure+125.00 μg·mL-1 quercetin+30.00 μmol·L-1 iron death inducer erastin).Cell survival rate was detected by cell counting kit 8;reactive oxygen species(ROS)levels was detected by C11-BODIPY 581/591 probe staining;glutathione(GSH)and malondialdehyde(MDA)levels were determined by kit method;the expression levels of glutathione peroxidase 4(GPX4),dihydrolactate dehydrogenase(DHODH)and ferroptosis suppressor protein 1(FSP1)were detected by real-time quantitative polymerase chain reaction and Western blot.Results The cell survival rates of control group,model group,experimental-H group and erastin group were(100.00±3.97)%,(50.05±5.83)%,(86.35±7.35)%and(58.32±4.66)%,respectively;ROS levels were 1.00±0.09,2.45±0.16,1.19±0.05 and 2.09±0.30,respectively;GPX4 protein levels were 1.09±0.11,0.34±0.03,0.91±0.12 and 0.30±0.04,respectively;FSP1 protein levels were 0.92±0.06,0.25±0.03,0.89±0.07 and 0.39±0.07,respectively;DHODH protein levels were 0.89±0.11,0.31±0.04,0.86±0.11,0.41±0.04,respectively.Compared with model group,the above indexes in control group were statistically significant(all P<0.05);the differences between experimental-H group and model group were statistically significant(all P<0.05);the above indexes in erastin group were significantly different from those in experimental-H group(all P<0.05).Conclusion Quercetin can ameliorate HCE-2 cell damage induced by high osmotic pressure by inhibiting iron death pathway.

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