1.Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses.
Liping BAI ; Jin YANG ; Siting YU ; Zhongzheng XIANG ; Yuanyuan ZENG ; Meiling SHEN ; Xiaorong KOU ; Qinjie WU ; Changyang GONG
Acta Pharmaceutica Sinica B 2024;14(2):821-835
Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.
2.Prevalence and influencing factors analysis of the polycystic ovary syndrome among female college students in Fuzhou City, Jiangxi Province
Ling LEI ; Xiaoyun YAO ; Jue FU ; Jia LYU ; Chang LIU ; Liping WU ; Yuxuan ZENG ; Huajuan YAO
Shanghai Journal of Preventive Medicine 2024;36(2):163-167
ObjectiveTo investigate the prevalence of polycystic ovary syndrome (PCOS) among female college students at a university in Fuzhou City, Jiangxi Province, and to facilitate early detection and intervention of PCOS. MethodsUsing a stratified sampling method, a total of 450 female freshmen were randomly selected for PCOS screening. A self-designed questionnaire was used for data collection, covering menstrual status, high androgen signs, lifestyle, dietary habits, and awareness of PCOS. Sample t test and χ2 test were used to compare the basic information and dietary habits between PCOS and non-PCOS cases. The correlation between various indicators and the prevalence of PCOS was analyzed by a logistic regression model. ResultsA total of 12 PCOS cases were identified, with a prevalence rate of 2.99%. PCOS cases exhibited statistically significant differences compared to non-PCOS cases in terms of waist-to-hip ratio, waist circumference, abdominal obesity, the proportion of overweight or obese individuals, and a preference for sweet food (all P<0.05). Multivariate logistic regression analysis revealed a significant correlation between preference for sweet food and the occurrence of PCOS (OR=4.858, 95%CI=1.199‒19.675,P=0.027), as well as a significant correlation with PCOS accompanied by abdominal obesity (OR=7.083, 95%CI=0.773‒64.937, P=0.048). Among the female college students surveyed, 37.90% had never heard of PCOS, 51.62% were only familiar with the name of the disease, and 10.47% had attempted to search for PCOS-related information. ConclusionThe prevalence of PCOS among female college students should not be overlooked and unhealthy dietary habits may be a crucial factor contributing to the occurrence of PCOS during this period. Early screening for PCOS during puberty is crucial.
3.HU value of chest CT vertebral body in the opportunistic screening of type 2 diabetes mellitus osteoporosis
Liping WANG ; Tianxing LIAN ; Yongrong HU ; Hongsheng YANG ; Zhimou ZENG ; Hao LIU ; Bo QU
Chinese Journal of Tissue Engineering Research 2024;28(6):950-954
BACKGROUND:Some studies have shown that the hounsfield units(HU)value based on lumbar CT can be used to screen osteoporosis.At present,the number of patients with pulmonary infection has increased;the number of patients with pulmonary infection and type 2 diabetes is also increasing,which increases the utilization rate of chest CT. OBJECTIVE:To investigate the role of lumbar 1 vertebral body HU value based on chest CT in the screening of type 2 diabetes mellitus osteoporosis. METHODS:The clinical data of 244 patients with type 2 diabetes mellitus treated in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022 were analyzed retrospectively.The bone mineral density was obtained by dual-energy X-ray absorptiometry.According to WHO's diagnostic criteria for osteoporosis,the subjects were divided into the non-osteoporosis group(n=120)and the osteoporosis group(n=124).The general condition,T value and HU value of lumbar 1 vertebra in chest CT were compared,and the relationship between the HU value and T value of each position was analyzed and the accuracy of type 2 diabetes mellitus osteoporosis was evaluated. RESULTS AND CONCLUSION:(1)There was no significant difference in sex,age,body mass index,glycosylated hemoglobin,mean blood glucose,calcium(Ca),phosphorus(P),time of type 2 diabetes mellitus,history of hypertension and history of hyperlipidemia between the two groups(P>0.05).(2)The HU value was positively correlated with the lowest T value of the hip(r=0.619,P<0.01);the HU value was positively correlated with the hip T value(r=0.584,P<0.01),and the HU value was positively correlated with the femoral neck T value(r=0.641,P<0.01).When the HU value was 98,the prediction of type 2 diabetes mellitus osteoporosis had good accuracy,and the sensitivity was 70.8%.(3)It is concluded that the HU value of the lumbar 1 vertebra based on chest CT examination is of good value for osteoporosis screening in patients with type 2 diabetes mellitus,and may be an opportunistic and cost-free supplementary screening method for type 2 diabetes mellitus osteoporosis.
4.Analysis of laboratory tests and prevention strategies for hemolytic disease of the fetus and newborn caused by anti-M
Hecai YANG ; Xiaoli MA ; Yonglei LYU ; Dongdong TIAN ; Qunjuan ZENG ; Minglu GENG ; Yi CAO ; Liping WANG
Chinese Journal of Blood Transfusion 2024;37(6):648-653
Objective To analyze the application of serological test results in the diagnosis and treatment of anti-M-in-duced hemolytic disease of the fetus and newborn(HDFN),and to explore HDFN prevention strategies.Methods The se-rological test results of 12 cases of HDFN caused by anti-M diagnosed in our laboratory from January 2017 to December 2023 were retrospectively analyzed,including blood group identification of mothers and children,serum total bilirubin/hemoglo-bin/antibody titer test,and three hemolysis tests in newborns.Clinical data of the children and mothers were collected,in-cluding pregnancy history,blood transfusion history,prenatal antibody testing,history of intrauterine blood transfusion and gestational week of delivery,and the prognosis of the children was followed up.Results All 12 cases of fetal neonatal he-molytic disease due to anti-M were RhD+MN phenotype newborn born to RhD+NN mother,with maternal-fetal incompati-blility in MN blood groups.In the ABO blood group system,ABO incompatibility between mother and child accounted for 41.7%(5/12).None of the mothers had a history of blood transfusion,and the median titer of the test at 4℃was 32,and the median titer at 37℃was 4.The mothers of 3 cases had a history of multiple intrauterine blood transfusions,with an inci-dence of 25%(3/12).One case had an abnormal first pregnancy,with an incidence of 8.3%(1/12),and seven cases had an abnormal pregnancy with a miscarriage,with an incidence of abnormal pregnancy and birth history of 58.3%(7/12).There were 6 cases of premature labor,with an incidence of 50%(6/12).The mothers in three cases underwent regular ob-stetric examination and the specificity of the antibodies was determined,accounting for 25%(3/12).Twelve children had free antibodies with a median titer of 6 at 4℃and 2 at 37℃.Two children had anti-M antibodies that were not reactive at 37℃,with a negative rate of 16.7%(2/12).The positive rate of DAT and elution test was respectively 8.3%(1/12)and 16.7%(2/12)in the children.The median minimum hemoglobin value was 75 g/L,and all 12 children received blood transfusions.The median peak total bilirubin value was 157.5 μmol/L,and none of them reached the threshold for blood ex-change.The rate of delayed anemia was16.7%(2/12),the postnatal mortality rate was8.3%(1/12),and 11 children was free of growth and neurodevelopmental delay in prognosis.Conclusion Anti-M can cause severe HDFN,which can also oc-cur in primigravida.The intensity of antibody titer does not correlate with the severity of the disease,and it is prone to cause delayed anemia,which should be monitored regularly according to the serological characteristics of anti-M and clinical symp-toms,and should be treated timely.
5.Molecular biological analysis of RhD variant blood donors in Zhengzhou
Hecai YANG ; Qunjuan ZENG ; Xiaoli MA ; Yonglei LYU ; Minglu GENG ; Liping WANG
Chinese Journal of Blood Transfusion 2024;37(8):866-871
Objective To investigate the serological characteristics and gene mutation mechanism of RhD variant blood donors in Zhengzhou.Methods From January 2023 to December 2023,1 619 RhD-negative blood donors sent to our labora-tory were selected for the study,and RhD negative confirmation test and RhCE phenotype detection were applied by tube method and microcolumn gel indirect antiglobulin test method.RHD gene amplification and Sanger sequencing were used to detect RhD variant sample genotypes.Results A total of 69 cases of RhD variants were detected in the RhD negative con-firmation test,with a proportion of 4.26%(69/1 619).The RhCE phenotypes were ccEe,Ccee,CcEe and CCee.There were 17 genotypes and 15 phenotypes of the D variant.The RHD?weak partial 15 allele was the most frequent(33 cases),with a frequency of 47.83%(33/69),and the main phenotype was the ccEe.This was followed by the RHD?DVI.3 allele in 20 ca-ses with a frequency of 28.99%(20/69)and the predominant phenotype was Ccee.The RHD?weak partial 15/RHD?01EL.01 heterozygote was found in 3 cases with a frequency of 4.35%(3/69),all with the CcEe phenotype.Other rare genotypes were present in 13 cases with a frequency of 18.84%(13/69).Antibody screening was positive in 3 cases with a frequency of 4.35%(3/69).Two cases of female blood donors,both with history of pregnancy and childbirth,were identified as anti-D;one case of male donor was anti-M.Conclusion The RHD?weak partial 15 genotype was the most common among the RhD variants in blood donors in Zhengzhou,followed by the RHD?DVI.3 genotype.It plays an important role in guarantee-ing the safety of blood supply and guiding precision transfusion.
6.Qualitative research on cognitive appraisal of middle school students with mental illness after experiencing childhood trauma
SONG Liping, CHEN Jie, XIONG Change, ZENG Jing
Chinese Journal of School Health 2024;45(8):1101-1105
Objective:
To gain an in depth understanding of the cognitive appraisal of middle school students with mental illness after experiencing childhood trauma, so as to provide a reference for the development of effective interventions.
Methods:
From March to September in 2023, 21 middle school students with childhood trauma experiences and mental illnesses were selected from outpatient and inpatient departments through purposive sampling in a tertiary grade A psychiatric hospital in Wuhan. Semistructured interviews were conducted and the seven steps of Colaizzi phenomenology were used to analyze the data and extract themes.
Results:
A total of 3 themes and 11 subthemes were extracted:insufficient awareness of childhood trauma (lack of selfawareness, lack of awareness of primary caregivers), multiple hurtful experiences after experiencing childhood trauma (complex negative affective experiences, multiple physical discomfort, pessimistic attitudes toward life, social impairment, and academic impairment), and influences on childhood trauma experiences (personality traits, inappropriate personal coping styles, poor upbringing environment, and difficulty in obtaining social support).
Conclusions
Middle school students with mental illnesses and their caregivers generally lack knowledge about childhood trauma, which brings widespread harm and are affected by multiple factors. It should jointly strengthen the popularization of scientific knowledge, intervene in a timely manner, and thereby reduce the adverse consequences of childhood trauma experiences.
7.The current state and hotspots of post-cardiac arrest brain injury: a visualization analysis based on CiteSpace
Xiaoye MO ; Wei HE ; Liyuan ZENG ; Xiangmin LI ; Xiaogang LI ; Liping ZHOU ; Zheng LI
Chinese Journal of Emergency Medicine 2024;33(7):1026-1031
Objective:This study examined the development trend and research hotspot of cardiopulmonary brain resuscitation in the last ten years by a visual analysis of the literature on post-cardiac arrest brain injury.Methods:English articles were acquired from the Web of Sciences (WOS) core database. CiteSpace 5.8.R3 software was used to analyze annual publications, countries, institutions, authors. We identified the trending research areas by analyzing collaborative networks, keywords co-occurrence, burst detection analysis, timeline and time-zone diagrams.Results:The search included 10 867 articles in the WOS core database from Jan 1, 2013 to Oct 25, 2023. In the last ten years, the top 3 nations were the United States, China, and Japan, with the United States having the most citation of 3691 and an centrality of 0.47. The author with the highest number of publications was Hans Friberg from Sweden. The top 5 most frequent keywords in WOS were cardiac arrest, cardiopulmonary resuscitation, resuscitation, survival, outcome. Keyword cluster analysis showed 4 clusters, including: #0 of-hospital cardiac arrest, #1 traumatic brain injury, #2 targeted temperature management, #3 global cerebral ischemia. Keyword burst showed that the top 5 ranked by strength are mild hypothermia, emergency cardiovascular care, neuron specific enolase, cerebral ischemia, epinephrine, and the top 5 ranked by the year of burst begins are out-of-hospital cardiac arrest, cpr, epinephrine, coma, and task force. The timeline and time zone charts indicated that, starting in 2017, the main fields of study concentration were traumatic brain injury and out-of-hospital cardiac arrest. Additionally, extracorporeal membrane, intensive care, risk factors, and electroencephalography were identified as new high-frequency keywords.Conclusions:Over the past ten years, the research hotspots on post-cardiac arrest brain injury include out-of-hospital cardiac arrest, traumatic brain injury, and target temperature control. The research development trends will be extracorporeal membrane oxygenation, critical care, and EEG.
8.Investigation of the inhibitory potential of caffeic acid phenethyl ester on prion replication, amplification, and fibril formation in vitro
Zhiyue CHAO ; Xiaoxi JIA ; Jiafeng ZENG ; Yuezhang WU ; Kang XIAO ; Liping GAO ; Qi SHI ; Xiaoping DONG ; Cao CHEN
Chinese Journal of Preventive Medicine 2024;58(7):1011-1019
Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.
9.Clinical application of split liver transplantation: a single center report of 203 cases
Qing YANG ; Shuhong YI ; Binsheng FU ; Tong ZHANG ; Kaining ZENG ; Xiao FENG ; Jia YAO ; Hui TANG ; Hua LI ; Jian ZHANG ; Yingcai ZHANG ; Huimin YI ; Haijin LYU ; Jianrong LIU ; Gangjian LUO ; Mian GE ; Weifeng YAO ; Fangfei REN ; Jinfeng ZHUO ; Hui LUO ; Liping ZHU ; Jie REN ; Yan LYU ; Kexin WANG ; Wei LIU ; Guihua CHEN ; Yang YANG
Chinese Journal of Surgery 2024;62(4):324-330
Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.
10.Investigation of the inhibitory potential of caffeic acid phenethyl ester on prion replication, amplification, and fibril formation in vitro
Zhiyue CHAO ; Xiaoxi JIA ; Jiafeng ZENG ; Yuezhang WU ; Kang XIAO ; Liping GAO ; Qi SHI ; Xiaoping DONG ; Cao CHEN
Chinese Journal of Preventive Medicine 2024;58(7):1011-1019
Objective:To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrP Sc). Methods:The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrP Sc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrP Sc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results:CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrP Sc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrP Sc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10 -6 mol/L. Conclusions:CAPE inhibits PrP Sc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.


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