1.Impact of ferroptosis-related gene expression on cardiovascular outcomes in chronic renal failure
Xuelan LIN ; Kexin LIU ; Xiao GE ; Yiming YU ; Lifang CAO
International Journal of Laboratory Medicine 2025;46(19):2378-2384,2390
Objective To investigate the relationship between ferroptosis-related genes[heme oxygenase-1(HO-1),solute carrier family 7 member 11(SLC7A11),and long-chain acyl-coenzyme A synthetase 4(ACSL4)]expression and cardiovascular events in patients with chronic renal failure(CRF),aiming to pro-vide clinical insights for risk assessment of cardiovascular complications.Methods A total of 124 CRF pa-tients(CRF group)admitted to the hospital from January 2020 to January 2023 and 124 healthy people(con-trol group)who underwent physical examination in the hospital during the same period were selected as the research objects.The levels of ferroptosis-related gene HO-1,SLC7A11 and ACSL4 were detected and com-pared between the two groups.CRF patients were followed up for 12 months after discharge,and they were di-vided into concurrent group(n=56)and non-concurrent group(n=66)according to the occurrence of cardio-vascular events.Spearman correlation analysis was used to investigate the correlation between iron death relat-ed genes HO-1,SLC7A11,ACSL4 and cardiovascular events in CRF patients.Univariate and multivariate Lo-gistic regression analysis were used to investigate the influencing factors of cardiovascular events in CRF pa-tients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of iron death re-lated genes HO-1,SLC7A11,and ACSL4 for cardiovascular events in CRF patients.Results Serum HO-1 and SLC7A11 levels in CRF group were lower than those in control group(P<0.05),and the ACSL4 level was higher than that in control group(P<0.05).The serum HO-1 and SLC7A11 levels in concurrent group were lower than those in non-concurrent group(all P<0.05),and the serum ACSL4 level was higher than that in non-concurrent group(P<0.05).Ferroptosis-related genes HO-1 and SLC7A11 were negatively correlated with cardiovascular events(r=-0.708,—0.721,P<0.05),while ACSL4 was positively correlated with car-diovascular events(r=0.699,P<0.05).High serum ACSL4 expression and high cTnT level were risk fac-tors for cardiovascular events in CRF patients(P<0.05),and high hemoglobin level and high serum HO-1 and SLC7A11 expression were protective factors for cardiovascular events in CRF patients(P<0.05).ROC curve analysis results showed that the area under the curve(AUC)of serum HO-1,SLC7A11,ACSL4,hemo-globin and cTnT alone for predicting cardiovascular events in CRF patients were 0.787,0.735,0.773,0.651 and 0.782,respectively.The AUC of the combined prediction of ferroptosis-related genes was 0.837,and the AUC of the combined application of five factors was 0.880.According to Delong's test,the AUC of both com-bined application models was significantly higher than those of individual application(P<0.05).The nomo-gram model showed that all ferroptosis-related genes were positively expressed(HO-1<1.5,SLC7A11<1.15,ACSL4≥2.75),and the risk of developing concurrent cardiovascular events in CRF patients could reach over 75%.Conclusion The expression of serum HO-1 and SLC7A11 in CRF patients is decreased,and the ACSL4 expression is increased,which is closely related to cardiovascular events,and the combined detection of three indexes has high value in predicting cardiovascular events in CRF patients.
2.Cannabidiol inhibits neuronal endoplasmic reticulum stress and apoptosis in rats with multiple concussions by regulating the PERK-eIF2α-ATF4-CHOP pathway.
Yujia YANG ; Lifang YANG ; Yaling WU ; Zhaoda DUAN ; Chunze YU ; Chunyun WU ; Jianyun YU ; Li YANG
Journal of Southern Medical University 2025;45(6):1240-1250
OBJECTIVES:
To explore the effects of cannabidiol on endoplasmic reticulum stress and neuronal apoptosis in rats with multiple concussions (MCC).
METHODS:
SD rats were randomized into sham group, MCC group, 1% tween20 (TW) treatment group, and low-dose (10 mg/kg) and high-dose (40 mg/kg) cannabidiol treatment groups. In all but the sham group, MCC models were established using a metal pendulum percussion device, after which the rats received daily intraperitoneal injections of the corresponding agents for 2 weeks. The expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-Akt and pro-caspase-3 in the brain tissue of the rats were detected with qRT-PCR, Western blotting and immunofluorescence staining. The core targets of cannabidiol in treatment of traumatic brain injury (TBI) were identified by network pharmacology analysis, and molecular docking was carried out to simulate the interaction of cannabidiol with the factors related to endoplasmic reticulum stress and apoptosis.
RESULTS:
Compared with the sham-operated rats, the rat models of MCC showed significantly increased mRNA expressions of PERK, eIF2α and CHOP and protein expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-AKT and pro-caspase-3 in the cerebral cortex. CBD treatment, especially at the high dose, obviously increased the expression of p-Akt and lowered the expression levels of the other factors tested in the rat models. Network pharmacology analysis indicated interactions of the core targets of CBD with the factors related to endoplasmic reticulum stress and TBI, and molecular docking study showed a high binding energy of CBD with multiple factors pertaining to endoplasmic reticulum stress and apoptosis.
CONCLUSIONS
MCC induce endoplasmic reticulum stress and apoptosis in rat brain tissues, for which CBD, especially at a high dose, provides neuroprotective effects by inhibiting endoplasmic reticulum stress and cell apoptosis.
Animals
;
Endoplasmic Reticulum Stress/drug effects*
;
Apoptosis/drug effects*
;
Rats, Sprague-Dawley
;
Activating Transcription Factor 4/metabolism*
;
Transcription Factor CHOP/metabolism*
;
Rats
;
Eukaryotic Initiation Factor-2/metabolism*
;
Signal Transduction/drug effects*
;
eIF-2 Kinase/metabolism*
;
Cannabidiol/pharmacology*
;
Neurons/metabolism*
;
Brain Concussion/metabolism*
;
Male
;
Molecular Docking Simulation
3.The effects of cannabidiol on the expression of NLRP3 inflammasome following multiple cerebral concussions in rats
Chunze YU ; Lifang YANG ; Zhaoda DUAN ; Yujia YANG ; Chunyun WU ; Jianyun YU ; Li YANG
Chinese Journal of Neuroanatomy 2024;40(1):98-104
Objective:To investigate the effects of cannabidiol(CBD)on the NOD-like receptor protein 3(NLRP3)inflammasome in the brains of rats with multiple cerebral concussions(MCC).Methods:Rats were subjec-ted to the MCC model and divided into Sham,MCC,vehicle(MCC+TW),CBD-L(10 mg/kg),and CBD-H(40 mg/kg)groups.Immunofluorescence double staining was used to observe changes in NLRP3 and microglial cells in the brain,and Western Blot was performed to detect the expression changes of the NLRP3 inflammasome.Results:A sig-nificant increase in lectin-positive microglial cells of the cortex with enlarged cell bodies and elevated immunofluores-cence intensity of NLRP3 in the activated microglial cells was revealed by immunofluorescence double staining following MCC(P<0.05).The immunofluorescence intensity of NLRP3 in the activated microglial cells was downregulated by the administration of CBD,with a more pronounced effect observed in the CBD-H group compared to the CBD-L group(P<0.05).The expression of NLRP3,caspase-1,and apoptosis-associated speck-like protein(ASC)in the cortex,hippocampus,and basal ganglia of rats following MCC was significantly increased,as shown by Western Blot analysis(P<0.05),and cortical areas are more elevated.The expression of these proteins in different brain regions was reduced by CBD-10 and CBD-40 intervention(P<0.05).Conclusion:Cannabidiol can reduce the inflammatory response of multiple cerebral concussions rats through NLRP3 inflammasome and protect nerve tissue.
4.Efficacy of SedLine Brain Function Monitor-guided total intravenous anesthesia for children undergoing hypospadias surgery
Rui MA ; Yu MAO ; Pei QIN ; Xin LIU ; Chan LI ; Juanning WANG ; Wei DING ; Lifang YANG
Chinese Journal of Anesthesiology 2024;44(11):1361-1365
Objective:To evaluate the efficacy of SedLine Brain Function Monitor-guided total intravenous anesthesia for children undergoing hypospadias surgery.Methods:This was a randomized controlled trial. A total of 161 children, aged 1-10 yr, with American Society of Anesthesiologists Physical Status classification ⅠorⅡ, scheduled for elective hypospadias surgery, were divided into SedLine group (S group, n=83) and control group (C group, n=78) using a random number table method. In group S, 95% spectral edge frequency (SEF 95) was maintained at 14-18 Hz, and the patient state index (PSI) was maintained at 25-50 during surgery. In group C, mean arterial pressure was maintained at 60-80 mmHg, and heart rate was maintained at 80-110 beats/min during surgery. PSI and SEF 95 were recorded before induction (T 1), at 0, 5 and 10 min after intubation (T 2-4), at the beginning of surgery (T 5), at 30 min and 1 h after surgery (T 6, 7), and at the end of surgery (T 8). The anesthetic duration, operation time, time from withdrawal to extubation, postanesthesia care unit duration, consumption of propofol and remifentanil, intraoperative adverse events, 5-point Likert scale scores, and emergence delirium scores were recorded. Results:Compared to C group, the total anesthesia time, time from withdrawal to extubation and postanesthesia care unit duration were significantly shortened, the consumption of propofol for both induction and maintenance was reduced, the PSI at T 5-8, SEFL 95 at T 2-6, and SEFR 95 at T 2-8 were increased, and the incidence of intraoperative body movement and incidence of emergence agitation were decreased in S group ( P<0.05). Conclusions:SedLine Brain Function Monitor-guided total intravenous anesthesia provides better efficacy when used for the children undergoing hypospadias surgery.
5.Factors influencing decision-to-delivery interval in emergency cesarean section in Guangzhou and its impact on maternal-infant outcomes
Huixiang LIU ; Huiyun XIAO ; Lifang ZHANG ; Yingfang WU ; Jia YU ; Songying SHEN ; Xiu QIU
Chinese Journal of Perinatal Medicine 2024;27(5):353-361
Objective:To investigate the factors influencing the decision to delivery interval (DDI) in emergency cesarean section in Guangzhou and the impact of DDI on maternal-infant outcomes.Methods:A retrospective study was conducted on clinical data of pregnant women who underwent emergency cesarean section at municipal and district maternal and child health hospitals in Guangzhou city in 2021. Per the classification method of emergency cesarean section and recommendations for DDI provided by National Institute for Health and Clinical Excellence guidelines, these subjects were classified into Category Ⅰ and Category Ⅱ cesarean sections. Each category was further divided into two subgroups based on DDI: the Category Ⅰ group into >30 min and ≤30 min subgroups, and the Category Ⅱ group into >75 min and ≤75 min subgroups. Chi-square test or Fisher's exact test, two independent samples t-test, Mann-Whitney U test, and logistic regression were used to analyze the potential factors influencing DDI and the impact of DDI on maternal-infant outcomes. Results:(1) Totally 502 women underwent urgent cesarean section, including 304 (60.6%) Category Ⅰ and 198 (39.4%) Category Ⅱ, were analyzed. Among the Category Ⅰ group, 30.3% (92/304) achieved a DDI of ≤30 min, while 37.4% (74/198) of Category Ⅱ cases had a DDI of ≤75 min. (2) For the Category Ⅰ cases, multivariate logistic regression showed that more patients under intravertebral anesthesia, than those under general anesthesia, had a DDI >30 min ( OR=14.04, 95% CI: 6.14-32.10) as well as more with ward-based emergencies than those with delivery room emergencies ( OR=3.21, 95% CI: 1.72-6.00, both P=0.001). Among the Category Ⅱ cases, logistic regression revealed that cesarean section during routine working hours was more likely to achieve DDI >75 min than that during resting hours ( OR=3.93, 95% CI: 2.03-7.63, P=0.001). The risk of DDI >75 min was higher in tertiary maternal and child health hospitals compared with secondary maternal and child health hospitals ( OR=2.45, 95% CI: 1.06-5.70, P=0.037). (3) Among the Category Ⅰ cases, compared with the DDI ≤30 min group, the DDI >30 min group had a lower risk of neonatal Apgar score ≤7 at 1 min ( OR=0.31, 95% CI: 0.14-0.69, P=0.004), but there was no significant difference in the risk of neonatal Apgar score ≤7 at 5 min ( OR=0.21, 95% CI: 0.04-1.17) or neonatal asphyxia ( OR=0.32, 95% CI: 0.07-1.44) between the two subgroups. In cases of Category Ⅱ cesarean sections, there was no significant difference in any maternal-infant outcomes between DDI ≤75 min and DDI >75 min subgroups. Conclusions:The location of emergency and types of anesthesia are the influencing factors of DDI for Category Ⅰ cesarean sections, while the operation time and level of maternal and child health hospital are the influencing factors of DDI for Category Ⅱ cesarean sections. We did not find any impact of DDI on maternal or infant outcome.
6.Preliminary application of pseudovirus in evaluating the immunogenicity of recombinant poliovirus vaccines and in rat potency tests
Yueyue LIU ; Lifang DU ; Shi CHEN ; Rongrong ZHAO ; Fan ZHENG ; Ling DING ; Zhijing MA ; Jing ZHANG ; Meng MA ; Suhua ZHAO ; Yu LIANG ; Qiming LI ; Yaru QUAN
Chinese Journal of Microbiology and Immunology 2024;44(9):778-783
Objective:To preliminarily investigate the applicability of a poliovirus pseudovirus-based neutralization assay in evaluating the immunogenicity of recombinant poliovirus vaccines and their in vivo potency in rats. Methods:Serum samples from rats immunized with recombinant poliovirus vaccines were tested using both the pseudovirus neutralization assay and the live-virus neutralization assay with Sabin strain. The consistency and correlation of the two methods were analyzed using the Kappa test and Spearman′s rank correlation.Results:For the neutralizing antibodies against typeⅠ, Ⅱ, and Ⅲ polioviruses, the Kappa values for consistency analysis of the two methods were 0.914, 1.000, and 0.751, respectively ( P<0.001), and the correlation coefficients ( R values) were 0.833, 0.927, and 0.859, respectively ( P<0.001). Conclusions:The test results of the two methods are consistent and show a good correlation, indicating that the pseudovirus neutralization assay can be applied to evaluating the immunogenicity of poliovirus vaccines and also can be used in rat potency tests.
7.Development and validation of an Assessment Scale of Proactive Health Behavior Ability for the Disabled Elderly in Nursing Homes
Yangli OU ; Xiaoyan LIAO ; Ying PENG ; Hong ZHANG ; Shaohua YIN ; Liyu CHEN ; Xue XIONG ; Xiuli YU ; Lifang TONG ; Yan XIE ; Dan HUO ; Jun SHEN
Chinese Journal of Nursing 2024;59(21):2579-2586
Objective To develop the assessment scale of proactive health behavior ability for the disabled elderly in nursing homes and to test its reliability and validity.Methods The first draft of the scale was formed by literature review,qualitative interviews and Delphi method.From December 2023 to March 2024,525 disabled elderly people from 9 nursing homes in Sichuan Province and Chongqing City were selected as the survey subjects,and item analysis and reliability and validity test were carried out on the scale.30 disabled elderly people were re-investigated after 2 weeks to calculate the retest reliability of the scale.Results The scale consisted of 4 dimensions and 27 items.Exploratory factor analysis extracted 4 common factors,with the cumulative vanance contribution rate of 65.992%,and confirmatory factor analysis showed that the modified model fitting index was within acceptable range.The content validity index at item level was 0.917-1.000,and that at scale level was 0.997.The Cronbach's α coefficient,test-retest reliability and split-half reliability of the total scale were 0.944,0.997 and 0.882,respectively.Conclusion The scale has good reliability and validity,and it can be used to evaluate the proactive health behavior ability of the disabled elderly in nursing homes.
8.Single extract of Forsythia Suspense versus the prepared drug in pieces:comparison of their anti-inflammatory,antitumor and antibacterial effects in zebrafish
Xindeng GUO ; Zhuolin GUO ; Dongmei SUN ; Lifang ZOU ; Jinying OU ; Linzhong YU ; Zibin LU ; Huihui CAO ; Junshan LIU
Journal of Southern Medical University 2024;44(3):594-604
Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.
9.Single extract of Forsythia Suspense versus the prepared drug in pieces:comparison of their anti-inflammatory,antitumor and antibacterial effects in zebrafish
Xindeng GUO ; Zhuolin GUO ; Dongmei SUN ; Lifang ZOU ; Jinying OU ; Linzhong YU ; Zibin LU ; Huihui CAO ; Junshan LIU
Journal of Southern Medical University 2024;44(3):594-604
Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.
10.Quantitative Evaluation of High-Quality Development Policies of Public Hospitals at Provincial Level Based on PMC Index Model
Zihan LANG ; Yixuan WU ; Lifang ZHOU ; Lingfeng XU ; Qianqian YU
Chinese Hospital Management 2024;44(10):1-4,9
Objective It evaluates the high-quality development policies of public hospitals at the provincial level in China,and provides theoretical basis and countermeasures for formulating and optimizing the high-quality develop-ment policies of public hospitals.Methods The ROST CM 6.0 software was used to conduct text mining for 11 sample policies,and the Policy Modeling Consistency(PMC)index model was constructed to evaluate the sample policies quantitatively.Results The average PMC index of 11 sample policies included in the study was 7.16 points,of which 8 were excellent grades and 3 were qualified grades.The first-level variables X5 service system(0.82),X8 Party leadership(0.91)and X6 organization and operation(0.94)scored higher;X2 policy timeliness(0.52),X7 cultural construction(0.68)and X4 service capability(0.71)scored low.Conclusion The content of the high-quality develop-ment policy of public hospitals at the provincial level is basically in line with the national policy,and is relatively excel-lent in the aspects of organization and operation,service system and party leadership,etc.,but there are some weaknesses in the aspects of policy timeliness,cultural construction and service capacity,etc.,which can be op-timized and improved from the aspects of improving service capacity,supplementing long-term policies and strengthening hospital cultural construction.

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