1.Association between the triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular diseases in people living with human immunodeficiency virus: Evidence from a retrospectively cohort study 2005-2022
Liqin SUN ; Yinsong LUO ; Xinyun JIA ; Hui WANG ; Fang ZHAO ; Lukun ZHANG ; Bin JU ; Haiyan WANG ; Duo SHAN ; Yun HE ; Hongzhou LU ; Jiaye LIU
Chinese Medical Journal 2024;137(22):2712-2719
Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.
2.Effects of Radix Angelica sinensis and Radix Hedysari ultrafiltration on oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation and its mechanism
Li-Rong WANG ; Ling-Yun WANG ; Xiao-Jing LI ; Hui-Lin ZHAO ; Yao-Hui HUO ; Hui CHAI ; Kai LIU
Chinese Pharmacological Bulletin 2024;40(8):1501-1509
Aim To investigate the effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration(RAS-RH)on oxidative stress and inflammatory injury of human umbilical vein endothelial cells(HUVECs)induced by ionizing radiation.Methods The model of HUVECs damage induced by 6 Gy X-rays was estab-lished.HUVECs were treated with different concentra-tions of RAS-RH(100,200,400 μg·L-1).The proliferative activity of HUVECs was detected by CCK-8 method,the structural changes of mitochondria were observed by transmission electron microscope,the level of ROS was detected by DCFH-DA probe,the change of intracellular mitochondrial membrane potential was detected by JC-1 kit,and the apoptosis and cycle were detected by flow cytometry.The contents of IL-6 and TNF-α in cells were detected by ELISA.The activities of MDA,CAT,SOD and GSH-PX were detected by biochemical kit.The gene expression levels of Nrf2,HO-1,NF-κB,eNOS and IL-6 were detected by qRT-PCR,and the expression levels of Nrf2,HO-1,eNOS,NF-κB,p-NF-κB and IL-6 protein were detected by Western blot.Results Compared with the model group,RAS-RH could increase the activity of HUVECs induced by ionizing radiation,decrease the rate of ap-optosis,decrease the level of intracellular ROS,re-duce the injury of intracellular mitochondria,increase the level of mitochondrial membrane potential,promote the expression of Nrf2,HO-1 and eNOS,and inhibit the expression of NF-κB and IL-6.Conclusions RAS-RH has anti-radiation,antioxidant and anti-in-flammatory effects,which may reduce the oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation by activating the activity of Nrf2/HO-1 signal pathway,thus promoting the activity of cell proliferation.
3.Multiple cross displacement amplification coupled with a gold nanoparticle-based lateral flow biosensor for detection of Listeria ivanovii
Hui LI ; Yi WANG ; Yan WANG ; Chang-Yun YE
Chinese Journal of Zoonoses 2024;40(7):605-612
A method using multiple cross displacement amplification combined with a lateral flow biosensor to detect Liste-ria ivanovii was developed and evaluated in this study.The L.ivanovii-MCDA-LFB assay used a set of ten primers spanning ten distinct regions of smcl,and was performed at a constant temperature of 64 ℃ to evaluate its specificity,sensitivity and feasibility.The specificity of MCDA-LFB assay was 100%in L.ivanovii and non-L.ivanovii strains.The limit of detection of the MCDA-LFB assay in pure culture and in L.ivanovii artificial contaminated feces was 10 fg and 6.8× 102 CFU/g,respec-tively.The detection results of the L.ivanovii-MCDA-LFB assay were identical to those of traditional culture-based methods(ISO 11290-1)in 195 wild rat intestinal feces samples.Detection could be achieved by boiling the template with the second en-richment solution.Thus,our rapid L.ivanovii-MCDA-LFB method with favorable sensitivity and specificity may provide a useful tool for detecting L.ivanovii in food surveillance,and medical and laboratory research.
4.ABO*A2.08 Subtype Allele Identification and Protein Structure Analysis in Newborns
Xin LIU ; Lian-Hui WANG ; Jin SHU ; Zi-Heng XU ; Xiu-Yun XU
Journal of Experimental Hematology 2024;32(1):225-230
Objective:To study the serological characteristics of ABO*A2.08 subtype and explore its genetic molecular mechanism.Methods:ABO blood group identification was performed on proband and her family members by routine serological methods.ABO genotyping and sequence analysis were performed by polymerase chain reaction-sequence specific primer(PCR-SSP),and direct sequencing of PCR products from exons 6 and 7 of ABO gene were directly sequenced and analyzed.The effect of gene mutation in A2.08 subtype on structural stability of GTA protein was investigated by homologous protein conserved analysis,3D molecular modeling and protein stability prediction.Results:The proband's serological test results showed subtype Ax,and ABO genotyping confirmed that the proband's genotype was ABO*A207/08.Gene sequencing of the proband's father confirmed the characteristic variation of c.539G>C in the 7th exon of ABO gene,leading to the replacement of polypeptide chain p.Arg180Pro(R180P).3D protein molecular modeling and analysis suggested that the number of hydrogen bonds of local amino acids in the protein structure was changed after the mutation,and protein stability prediction showed that the mutation had a great influence on the protein structure stability.Conclusion:The mutation of the 7th exon c.539G>C of ABO gene leads to the substitution of polypeptide chain amino acid,which affects the structural stability of GTA protein and leads to the change of enzyme activity,resulting in the A2.08 phenotype.The mutated gene can be stably inherited.
5.The Role of NK Cells in Allogeneic Hematopoietic Stem Cell Micro-Transplantation for Acute Myeloid leukemia
Ru-Yu LIU ; Chang-Lin YU ; Jian-Hui QIAO ; Bo CAI ; Qi-Yun SUN ; Yi WANG ; Tie-Qiang LIU ; Shan JIANG ; Tian-Yao ZHANG ; Hui-Sheng AI ; Mei GUO ; Kai-Xun HU
Journal of Experimental Hematology 2024;32(2):546-555
Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1%after 1 course and 73.7%after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.
6.Network pharmacology-based strategy for predicting therapy targets of apigenin on thyroid carcinoma
Shu-Bin LIANG ; Zhen LI ; Sheng-Nan WANG ; Yun-Hui WANG
Chinese Journal of Current Advances in General Surgery 2024;27(8):594-598
Objective:To explore the potential therapeutic targets of apigenin in the treat-ment of thyroid carcinoma by network pharmacology.Methods:The targets of apigenin were screened by HIT(High Throughput),Binding Database,SEA(Similarity Ensemble Approach),STITCH(Search Tool for Interactions of Chemicals),PharmMapper.Thyroid carcinoma related targets were mined from TTD(Therapeutic Target Database),DrugBank,CTD(Comparative Toxicogenomics Da-tabase),DisGeNET databases.The String database and Cytoscape 3.2.1 software were used to identify and screen out the hub targets of apigenin for thyroid carcinoma.The David database was used for Gene Ontology(GO)enrichment and KEGG signal pathway enrichment analysis of hub tar-gets.Finally,the Kaplan-Meier Plotter database was used to analyze the prognosis of hub targets.Results:175potential targets of apigenin and 168 potential targets related to thyroid carcinoma were included.37 overlapping targets of apigenin and thyroid carcinoma were obtained.32 hub targets were finally selected by network topology analysis.These hub targets of apigenin in the treatment of thyroid carcinoma were mainly enriched in involving HIF-1 signaling pathway,path-ways in cancer,etc.Finally,8 targets were screened to be associated with the survival and prog-nosis of thyroid carcinoma patients.Conclusion:Our study suggested that ALB,CCNA2,CCND1,CYP2C19,TERT,TTR,BCL2,CBR1 might be potential therapeutic targets for apigenin in the treatment of thyroid carcinoma.
7.Effects of Moluodan Dami Pills on chronic atrophic gastritis rats
Meng-Lei WANG ; Yi-Feng WU ; Jian-Liang SUI ; Miao-Miao YIN ; Hui-Yun LIU ; Qi-Chao LIU ; Zhuo-Chen WU ; Zhen WANG
Chinese Traditional Patent Medicine 2024;46(5):1476-1482
AIM To investigate the effects of Moluodan Dami Pills on chronic atrophic gastritis(CAG)rats and their mechanism.METHODS The rat models were randomly divided into the model group,the low-dose group and high-dose Moluodan Dami Pills groups(2.43 g/kg and 4.86 g/kg),and vitamin A group(0.32 g/kg),following the 16 weeks successful induction of CAG by five-factor modeling method,in contrast to another 10 normal rats of the control group.After 8 weeks corresponding administration,the rats of each group had their general physiological status and pH value of gastric juice assessed;their pathological changes of gastric mucosa observed by naked eyes combined with HE staining;their changes of gastrin-secreting cells(G cells)and somatostatin-secreting cells(D cells)in gastric mucosa observed by immunohistochemistry;and their serum levels of pepsinogen Ⅰ/pepsinogen Ⅱ(PG Ⅰ/PG Ⅱ)ratio,TNF-α and IL-6 detected by ELISA.RESULTS Compared with the model group,the groups intervened with Moluodan Damei Pills and vitamin A displayed lower pH values of gastric juice(P<0.05),improved pathological changes of gastric mucosa,increased G and D cells counts(P<0.05,P<0.01),increased ratio of serum PGⅠ/PGⅡ,and decreased levels of IL-6 and TNF-α(P<0.05,P<0.01).CONCLUSION Moluodan Dami Pills can effectively improve the symptoms of CAG rats through its influence on the number and secretion abilityof G and D cells,the levels of serum PG Ⅰ/PG Ⅱ ratio and inflammatory factors.
8.Simultaneou determination of twenty-eight constituents in Dayuan Drink by UPLC-MS/MS
Yu-Jie HOU ; Xin-Jun ZHANG ; Ming SU ; Xin-Rui LI ; Yue-Cheng LIU ; Yu-Qing WANG ; Dan-Dan SUN ; Hui ZHANG ; Kang-Ning XIAO ; Long-Yun DUAN ; Lei CAO ; Zhen-Yu XUAN ; Shan-Xin LIU
Chinese Traditional Patent Medicine 2024;46(11):3545-3552
AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.
9.Role of peroxisome proliferator-activated receptor signaling pathway in acne inversa by high-throughput sequencing: a preliminary study
Yanyan HE ; Xiao MA ; Yun HUI ; Wenzhu WANG ; Baoxi WANG ; Rong ZENG ; Haoxiang XU
Chinese Journal of Dermatology 2024;57(4):309-315
Objective:To explore the role of peroxisome proliferator-activated receptor (PPAR) signaling pathway in the pathogenesis of acne inversa (AI) .Methods:Skin tissue samples were obtained from 8 AI patients and 4 healthy controls from Hospital of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College from 2013 to 2019, and high-throughput sequencing was performed for tissue-specific mRNA expression profiling. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were carried out. Real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to verify the results of high-throughput sequencing.Results:Analysis of the specific expression profiles showed that 2 738 differentially expressed genes were screened out in the AI patients compared with the healthy controls, of which 1 328 genes were significantly up-regulated and 1 410 genes were significantly down-regulated. GO analysis demonstrated that the positive regulation of interferon γ secretion, T cell receptor complex and C-X-C chemokine receptor activity were significantly enriched in the AI lesions. KEGG analysis demonstrated that the signaling pathways associated with primary immuno‐deficiency, PPAR, and chemokine-chemokine receptor interaction were significantly enriched in the AI lesions. GSEA demonstrated that the PPAR signaling pathway was significantly weakened in the AI lesions. The mRNA expression levels of PPARA and PPARG were significantly lower in the AI patients (0.336 ± 0.120, 0.253 ± 0.078, respectively) than in the healthy group (1.000 ± 0.146, 1.000 ± 0.172, t = 3.50, 3.95, respectively, both P < 0.05), so were their protein levels. However, there was no significant difference in the PPARD mRNA expression level between the two groups ( t = 0.34, P = 0.750). The mRNA expression levels of nuclear hormone receptor 9-cis retinoid X receptor alpha (RXRA), RXRG and fatty acid-binding protein 4 were significantly lower in the AI patients than in the healthy controls ( t = 2.96, 2.96, 4.62, respectively, all P < 0.05) . Conclusion:The PPAR signaling pathway was restrained and lipid metabolism was disordered in AI patients.
10.Chassis damage assessment for protective emergency ambulance
Xin LIU ; Yun-Jiang ZHU ; Hui-Min REN ; Yun-Dou WANG ; Chen SU
Chinese Medical Equipment Journal 2024;45(6):23-27
Objective To explore the effectiveness of the protective emergency ambulance chassis against damage from explosive weapons such as grenades and mines.Methods A 12 mm-thick polyethylene(PE)protective plate and a composite ceramic PE protective plate(1 mm-thick aluminum plate+6 mm-thick B4C ceramic+12 mm-thick high molecular weight polyethylene fiber)were involved in for the protection of the chassis of an emergency ambulance under the premise of meeting the ambulance's protective requirements.Theoretical calculations and simulations were used to analyze the blast damage effects of a 62 g TNT grenade on the PE protective plate and a 6 000 g TNT equivalent mine on the composite ceramic PE protective plate.Results The PE protective plate and composite ceramic PE protective plate were able to withstand the destructive effects of a grenade and a mine at a blast distance of 1.1 m,respectively,and no significant damage was observed in either case.Conclusion The PE protective plate and composite ceramic PE protective plate meet the requirements for mobility,lightweight and protection against damage from explosive weapons such as grenades and mines,and references are provided for designing protection schemes of the protective emergency ambulance chassis.[Chinese Medical Equipment Journal,2024,45(6):23-27]

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