1.Mechanism of salidroside in inhibiting expression of adhesion molecules in oxLDL-induced endothelial cells by regulating ferroptosis mediated by SIRT1/Nrf2.
Meng ZHANG ; Min XIAO ; Jing-Jing LI ; Jiang-Feng LI ; Guang-Hui FAN
China Journal of Chinese Materia Medica 2025;50(10):2787-2797
This article investigated the effect and mechanism of salidroside(SAL) on the expression of adhesion molecules in oxidized low-density lipoprotein(oxLDL)-induced mouse aortic endothelial cell(MAEC). The oxLDL-induced endothelial cell injury model was constructed, and the safe concentration and action time of SAL were screened. The cells were divided into control group, oxLDL group, low and high concentration groups of SAL, and ferrostatin-1(Fer-1) group. The cell viability was detected by CCK-8 assay; lactate dehydrogenase(LDH) leakage was measured by colorimetry; the expression of intercellular adhesion molecule 1(ICAM-1) and recombinant vascular cell adhesion molecule 1(VCAM-1) were detected by immunofluorescence; Fe~(2+),glutathione(GSH),malondialdehyde(MDA),and 4-hydroxynonenal(4-HNE) levels were detected by kit method; reactive oxygen species(ROS) was detected by DCFH-DA probe; the levels of glutathione peroxidase 4(GPX4),silent mating type information regulation 2 homolog 1(SIRT1), and nuclear factor erythroid 2-related factor 2(Nrf2) were determined by using Western blot. The inhibitors of Nrf2 and SIRT1 were used, and endothelial cell were divided into control group, oxLDL group, SAL group, ML385 group(Nrf2 inhibitor), and EX527 group(SIRT1 inhibitor). The ultrastructure of mitochondria was observed by electron microscope; mitochondrial membrane potential(MMP) was detected by flowcytometry; the expressions of SIRT1,Nrf2,solute carrier family 7 member 11(SLC7A11),GPX4,ferroportin 1(FPN1),ferritin heavy chain 1(FTH1),ICAM-1, and VCAM-1 were detected by Western blot. The results showed that similar to Fer-1,low and high concentrations of SAL could improve cell viability, inhibit LDH release and the expression of ICAM-1 and VCAM-1 in oxLDL-induced endothelial cells(P<0.05 or P<0.01). It was related to increase in GSH level, decrease in Fe~(2+),ROS,MDA, and 4-HNE level, and up-regulation of SIRT1,Nrf2, and GPX4 expression to inhibit ferroptosis(P<0.05 or P<0.01). The intervention effect of high concentration SAL was the most significant. ML385 and EX527 could partially offset the protection of SAL on mitochondrial structure and MMP and reverse the ability of SAL to up-regulate the expression of SIRT1,Nrf2,SLC7A11,GPX4,FPN1, and FTH1 and down-regulate the expression of ICAM-1 and VCAM-1(P<0.05 or P<0.01).To sum up, SAL could reduce the expression of ICAM-1 and VCAM-1 in oxLDL-induced endothelial cell, which may relate to activation of SLC7A11/GPX4 antioxidant signaling pathway mediated by SITR1/Nrf2, up-regulation of FPN1 and FTH1 expression, and inhibition of ferroptosis.
Sirtuin 1/genetics*
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Animals
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Ferroptosis/drug effects*
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Lipoproteins, LDL/metabolism*
;
NF-E2-Related Factor 2/genetics*
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Mice
;
Endothelial Cells/cytology*
;
Glucosides/pharmacology*
;
Phenols/pharmacology*
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Cell Adhesion Molecules/genetics*
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Reactive Oxygen Species/metabolism*
;
Intercellular Adhesion Molecule-1/genetics*
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Vascular Cell Adhesion Molecule-1/genetics*
;
Cell Survival/drug effects*
2.Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
Ying-Juan TANG ; Jia-Cheng DAI ; Song YANG ; Xiao-Shi YU ; Yao ZHANG ; Hai-Long SU ; Zhi-Yuan LIU ; Zi-Xuan XIANG ; Jun-Cheng LIU ; Hai-Xia HE ; Jian LIU ; Yuan-Shan HAN ; Yu-Hong WANG ; Man-Shu ZOU
China Journal of Chinese Materia Medica 2025;50(16):4538-4545
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals
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Male
;
Rats
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Nucleus Accumbens/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
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Depression/complications*
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Membrane Glycoproteins/genetics*
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Rats, Sprague-Dawley
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Sleep Initiation and Maintenance Disorders/complications*
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Neurons/metabolism*
;
Receptors, Immunologic/genetics*
;
Signal Transduction/drug effects*
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Synapses/metabolism*
3.miR-207 targets autophagy-associated protein LAMP2 to regulate the mechanism of macrophage-mycobacterium tuberculosis interaction.
Wenya DU ; Yumei DAI ; Linzhi YUE ; Tao MA ; Lixian WU
Chinese Journal of Cellular and Molecular Immunology 2025;41(2):97-104
Objectives miR-207 has been identified as being expressed in natural killer (NK) cell exosomes that play a role in disease progression; however, to date, there are no studies specifically linking miR-207 to tuberculosis (TB). Methods Bioinformatics methods employed for prediction, followed by a dual luciferase reporter assay to determine whether lysosome-associated membrane protein 2 (LAMP2) is targeted by miR-207. The experiments were divided into four groups using the liposome transfection method (OP-LAMP2 group: co-transfected with miR-207 mimics and LAMP2 overexpression plasmid; EP group: co-transfected with mimics NC and null-loaded plasmid; siLAMP2 group: transfected with siLAMP2; and siLAMP2-NC group: transfected with siLAMP2-NC). TB infection was modeled using H37Ra-infected Ana-1 cells. The impact of LAMP2 on intracellular mycobacterial load and clearance of extracellular residual mycobacteria were assessed by tuberculosis colony-forming unit counting. Flow cytometry was used to assess the total apoptosis rate. Real-time fluorescent quantitative PCR was conducted to determine the relative expression of LAMP2, apoptosis genes, pyroptosis genes, and autophagy genes. Western blot analysis was performed to measure the relative expression of LAMP2 proteins, apoptosis proteins, pyroptosis proteins, and autophagy proteins. Results Dual luciferase reporter assay test showed that there was a targeting relationship between LAMP2 and miR-207. The transfection model was successfully constructed under real-time fluorescent quantitative PCR and Western blot statistical analysis, and microscopic observation. The infection model was successfully established under microscopic observation. Colony forming unit counting revealed that the number of colonies in the OP-LAMP2 group was lower than that in the EP group, while the number of colonies in the siLAMP2 group was higher than that in the siLAMP2-NC group. Flow cytometry assay revealed that the total apoptosis in OP-LAMP2 group was lower than that in EP group, and the total apoptosis in siLAMP2 group was higher than that in siLAMP2-NC group. Real-time fluorescence quantitative PCR and Western blot analysis revealed that the relative expression of apoptosis and pyroptosis-related proteins and genes in the control group was lower in the OP-LAMP2 group compared to the EP group, and higher in the siLAMP2 group compared to the siLAMP2-NC group. Real-time fluorescence quantitative PCR detected that the relative expression of autophagy positively regulated genes Microtubule-associated protein 1 light chain 3(LC3)and Beclin1 in the OP-LAMP2 group was higher in the OP-LAMP2 group compared to the EP group, and lower in the siLAMP2 group compared to the siLAMP2-NC group, while the relative expression of negatively regulated autophagy genes followed the opposite trend to that of autophagy positively regulated genes. The relative expression of autophagy-related proteins was consistent with the trend of autophagy genes. Conclusions miR-207 enhances macrophage apoptosis, cellular pyroptosis and inhibits autophagy, promoting survival of Mycobacterium tuberculosis by targeting the autophagy-related protein LAMP2, thus offering a novel therapeutic direction for tuberculosis.
Lysosomal-Associated Membrane Protein 2/metabolism*
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MicroRNAs/metabolism*
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Mycobacterium tuberculosis/physiology*
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Autophagy/genetics*
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Humans
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Macrophages/metabolism*
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Apoptosis/genetics*
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Tuberculosis/metabolism*
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Cell Line
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Pyroptosis/genetics*
4.Preparation and Evaluation of Clinical-Grade Human Umbilical Cord-Derived Mesenchymal Stem Cells with High Expression of Hematopoietic Supporting Factors.
Jie TANG ; Pei-Lin LI ; Xiao-Yu ZHANG ; Xiao-Tong LI ; Fu-Hao YU ; Jia-Yi TIAN ; Run-Xiang XU ; Bo-Feng YIN ; Li DING ; Heng ZHU
Journal of Experimental Hematology 2025;33(3):892-898
OBJECTIVE:
To prepare clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSC) with high expression of hematopoietic supporting factors and evaluate their stem cell characteristics.
METHODS:
Fetal umbilical cord tissues were collected from healthy postpartum women during full-term cesarean section. Wharton's jelly was mechanically separated and hUC-MSCs were obtained by explant culture method and enzyme digestion method in an animal serum-free culture system with addition of human platelet lysate. The phenotypic characteristics of hUC-MSCs obtained by two methods were detected by flow cytometry. The differences in proliferation ability between the two groups of hUC-MSCs were identified through CCK-8 assay and colony forming unit-fibroblast (CFU-F) assay. The differences in multilineage differentiation potential between the two groups of hUC-MSCs were identified through induction of adipogenic, osteogenic, and chondrogenic differentiation. The mRNA expression levels of hematopoietic supporting factors such as SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in the two groups of hUC-MSCs were identified by real-time fluorescence quantiative PCR(RT-qPCR).
RESULTS:
The results of flow cytometry showed that hUC-MSCs obtained by the two methods both expressed high levels of CD73, CD90 and CD105, while lowly expressed CD31, CD45 and HLA-DR. The results of CCK-8 and CFU-F assay showed that the proliferation ability of hUC-MSCs obtained by explant culture method was better than those obtained by enzyme digestion method. The results of the triple lineage differentiation experiment showed that there was no significant difference in multilineage differentiation potential between the two grous of hUC-MSCs. The results of RT-qPCR showed that the mRNA expression levels of hematopoietic supporting factors SCF, IL-3, CXCL12, VCAM1 and ANGPT1 in hUC-MSCs obtained by explant cultrue method were higher than those obtained by enzyme digestion method.
CONCLUSION
Clinical-grade hUC-MSCs with high expression levels of hematopoietic supporting factors were successfully cultured in an animal serum-free culture system.
Humans
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Mesenchymal Stem Cells/metabolism*
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Umbilical Cord/cytology*
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Cell Differentiation
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Female
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Cell Proliferation
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Cells, Cultured
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Chemokine CXCL12/metabolism*
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Angiopoietin-1/metabolism*
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Vascular Cell Adhesion Molecule-1/metabolism*
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Stem Cell Factor/metabolism*
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Flow Cytometry
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Pregnancy
5.Investigation on the Role of Medical Recombinant Human-Derived Collagen Functional Dressings in Wound Healing.
Xiaoxiao GAI ; Xiaoxia SUN ; Wenqian MA ; Zhenhua LIN ; Xinyuan LI ; Chenghu LIU
Chinese Journal of Medical Instrumentation 2025;49(4):415-422
OBJECTIVE:
To investigate the biological effect of medical recombinant human-derived collagen functional dressings in wound healing.
METHODS:
MTT assay and RTCA assay were used to detect cell toxicity and proliferation. Scratch assay and Transwell cell migration assay were used to detect cell motility and migration ability. Enzyme-linked immunosorbent assay was used to detect the contents of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-endothelial cell adhesion molecule (CD31) in the supernatant of four types of cells. After animal surgery, the surgical wound was taken at 1 week, 4 weeks and 13 weeks, respectively, for hematoxylin eosin (HE) staining and immunohistochemistry to observe the inflammatory response and CD31 expression of the wound.
RESULTS:
Medical recombinant human-derived collagen functional dressing promotes cell proliferation and migration, enhances wound angiogenesis by upregulating the expression of VEGF, FGF, and CD31 in human dermal vascular endothelial cells (HDVEC) and human vascular endothelial cells (HVEC), thereby improving local blood supply to the wound, regulating the inflammatory response of the wound, and accelerating wound healing.
CONCLUSION
Recombinant type Ⅲ humanized collagen plays an important role in wound healing.
Humans
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Wound Healing/drug effects*
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Recombinant Proteins/pharmacology*
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Animals
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Cell Proliferation
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Cell Movement
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Collagen/pharmacology*
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Vascular Endothelial Growth Factor A/metabolism*
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Bandages
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Platelet Endothelial Cell Adhesion Molecule-1/metabolism*
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Endothelial Cells
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Fibroblast Growth Factors/metabolism*
6.Clinical and genetic analysis of an individual with Lan-negative rare blood group due to variant of ABCB6 gene.
Xianguo XU ; Kairong MA ; Ying LIU ; Xiaozhen HONG ; Yanling YING ; Faming ZHU
Chinese Journal of Medical Genetics 2025;42(3):286-291
OBJECTIVE:
To investigate a case of antibodies against high-frequency erythrocyte antigens and elucidate the genetic mechanism underlying the blood group.
METHODS:
A Lan-negative patient referred to the Zhejiang Blood Center by Quzhou Hospital of Traditional Chinese Medicine in August 2016 was selected as the study subject. A retrospective study was conducted to collect the proband's clinical data. The proband's erythrocyte antigens and unexpected serum antibodies were identified using tube saline and microcolumn agglutination anti-human globulin methods. Antibody specificity was determined by treating erythrocytes with 7 enzymes and 2 chemical reducing agents. Genomic DNA was extracted from the proband's blood sample for whole genome sequencing (WGS) and erythrocyte blood group gene analysis, with validation by Sanger sequencing. Multiple bioinformatics tools were used to analyze the pathogenicity of the variant. The rare blood group and unexpected antibody specificity were comprehensively determined based on the results of serological and genetic testing. This study has been approved by the Zhejiang Provincial Blood Center Medical Ethics Committee(Ethics No.20190201).
RESULTS:
The proband was a 91-year-old Han Chinese male with prostatitis, cystitis, and malnutrition in conjunct with emaciation. He had a history of multiple erythrocyte transfusions without observable adverse reactions. Prior to the most recent transfusion, major crossmatch agglutination was observed, which prompted antibody identification. Antibodies against high-frequency antigens were detected in the proband's serum, with enzyme and reducing agent treatments ruling out antibody specificities associated with 17 blood group systems, e.g., MNS, LU, KEL. WGS analysis identified 4 525 SNPs and 1 046 INDEL variants among erythrocyte blood group genes. Further screening revealed that the proband had a rare blood group due to a homozygous rs755723161 variant. This variant in the ABCB6 gene (c.459delC) has led to a frameshifting mutation (p.Trp154GlyfsTer96), resulting in the Lan-negative rare blood group with a high-frequency antigen deficiency and the production of IgG anti-Lan antibodies in the serum.
CONCLUSION
This study has identified anti-Lan alloantibodies in a Lan-negative patient and, for the first time, elucidated the ABCB6 gene variant underlying the Lan-negative rare blood group in the Chinese population.
Humans
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Male
;
Blood Group Antigens/immunology*
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Aged, 80 and over
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Retrospective Studies
;
ATP-Binding Cassette Transporters
7.Clinical manifestations and genetic variation analysis in six Chinese pedigrees affected with Stargardt disease.
Lijuan ZHANG ; Tao MA ; Ruiqi ZHANG ; Ximei ZHANG
Chinese Journal of Medical Genetics 2025;42(5):547-555
OBJECTIVE:
To explore the correlation between clinical manifestations and genetic variations in six Chinese Stargardt disease pedigrees.
METHODS:
Six Stargardt disease pedigrees due to ABCA4 gene variants that visited Shanxi Eye Hospital from June 2021 June 2023 were selected as the study subjects. A retrospective study method was used to collect the clinical and family history data of all members of these pedigrees. Peripheral venous blood samples of the examinees were collected, and genomic DNA was extracted for trio-WES. Candidate variants of the ABCA4 gene were verified by family Sanger sequencing. According to the "Standards and Guidelines for the Classification of Sequence Variants" (hereinafter referred to as the "ACMG Guidelines") formulated by American College of Medical Genetics and Genomics (ACMG), the variant sites of the ABCA4 gene were classified for pathogenicity. This study has been approved by the Medical Ethics Committee of Shanxi Eye Hospital (Ethics No. SXYYLL-20200620).
RESULTS:
From June 2021 to June 2023, 7 patients (patient 1 to 7) from families with Stargardt disease with ABCA4 variants were selected as the study subjects. The age of the patients was between 7 to 53 years old, and the age of onset was between their 6 to 15 years old. All patients had exhibited moderate-to-severe visual impairment with macular atrophy, and yellow white spots were seen in all patients except patient II2 in family 5. Optical coherence tomography (OCT) results showed that all patients' macular fovea was significantly thinner, with IS/OS or ellipsoid zone disappeared. Autofluorescence showed low autofluorescence in the macula, and abnormalities dot autofluorescence in the paramacular and periphery retina. ERG grouping classified three pedigrees as Group 3, two as Group 1, and one as Group 2. Genetic analysis results showed that all pedigrees had autosomal recessive inheritance, five had compound heterozygous variants in the ABCA4, and one had homozygous variants. In total 11 pathogenic mutations were detected in the ABCA4 gene, of which 3 were found for the first time, including p.Glu1704Gly, p.Gly1965Glu and p.Ser1531Phe. Patients carrying nonsense or frameshift mutations include patient 1 (family 1, II1), patient 2 (family 1, II2), patient 4 (family 3, II1), patient 6 (family 5, II2), and patient 7 (family 6, II1), whose clinical manifestations are more severe than those of patient 3 (family 2, II2) and patient 5 (family 4, II1), whom carried missense mutations in terms of best corrected visual acuity (BCVA) damage.
CONCLUSION
The ABCA4 gene variations may be the genetic cause of the Stargardt disease in this study, and the discovery of the ABCA4 gene p.Glu1704Gly, p.Gly1965Glu, p.Ser1531Phe variants has enriched the mutational spectrum of Stargardt disease.
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle Aged
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Young Adult
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ATP-Binding Cassette Transporters/genetics*
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China
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Genetic Variation
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Macular Degeneration/congenital*
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Mutation
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Pedigree
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Retrospective Studies
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Stargardt Disease/genetics*
;
East Asian People/genetics*
8.Clinical and genetic analysis of a child with Stargardt disease type 1 caused by novel compound heterozygous variants of the ABCA4 gene.
Min ZHANG ; Yudie NING ; Tao HUANG ; Junfeng LV ; Xiaohe YAN
Chinese Journal of Medical Genetics 2025;42(8):974-980
OBJECTIVE:
To investigate the clinical features and pathogenesis of a child with Stargardt disease caused by variants of ABCA4 gene.
METHODS:
A child presented at Shenzhen Eye Hospital between September 5, 2020, and April 3, 2023 was selected as the study subject. Clinical data of the child were collected. Whole exome sequencing was performed on peripheral blood samples from the child and his parents. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (Ethics No.: 2022KYPJ072).
RESULTS:
The child was a 10-year-old male presenting with uncorrected visual acuity of 0.1 in both eyes without improvement with refractive correction. Fundus photography showed diffusely distributed yellow-white flecks in the macular region. FAF revealing central hypofluorescence surrounded by a hyperfluorescent ring, and OCT demonstrating significant foveal thinning (right eye: 45 μm; left eye: 50 μm) with ellipsoid zone disruption. Whole exome sequencing and Sanger sequencing revealed that the child has harbored compound heterozygous variants of the ABCA4 gene, namely c.2384G>T (p.Gly795Val) and c.2903G>A (p.Arg968Glu), which were inherited from his phenotypically normal parents and consistent with an autosomal recessive inheritance. This specific combination of the variants was previously unreported. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG) guidelines, both variants were classified as likely pathogenic (PM2_Supporting+PM3+PP3+PP4; PM1+PM2_Supporting+PP3+PP4).
CONCLUSION
The novel compound heterozygous variants of the ABCA4 gene probably underlay the genetic etiology of Stargardt disease type 1 in this child. Above finding has expanded the mutational spectrum of the ABCA4 gene among the Chinese population and provided further evidence for understanding the genetic heterogeneity and genotype-phenotype correlation of the Stargardt disease.
Humans
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Male
;
Child
;
ATP-Binding Cassette Transporters/genetics*
;
Stargardt Disease/genetics*
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Heterozygote
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Mutation
;
Exome Sequencing
;
Macular Degeneration/congenital*
9.Phenotypic and genotypic analysis of five fetuses with Harlequin ichthyosis due to variants of ABCA12 gene.
Yimo ZENG ; Juan ZHU ; Jing WU ; Chen LI ; Yiming QI ; Jiaqi LU ; Ruiman LI ; Aihua YIN
Chinese Journal of Medical Genetics 2025;42(11):1302-1307
OBJECTIVE:
To explore the clinical and genetic characteristics of five fetuses with Harlequin ichthyosis (HI).
METHODS:
Five fetuses with HI diagnosed at Guangdong Women and Children Hospital between 2017 and 2024 were selected as study subjects. Clinical and laboratory data were collected and reviewed. Whole exome sequencing (WES) was carried out, and candidate variants were verified by bioinformatic analysis. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 202401024).
RESULTS:
The five fetuses had presented with ectropion, eclabium and contracture and flexion of fingers and toes. WES revealed that all had harbored compound heterozygous or homozygous variants of the ABCA12 gene. Among the eight types of variants, five were unreported previously.
CONCLUSION
The compound heterozygous or homozygous variants of the ABCA12 gene probably underlay the HI in the five fetuses. Clinicians should be vigilant about the possibility of HI in fetus with ectropion, eclabium, and contracture and flexion of fingers and toes.
Humans
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Ichthyosis, Lamellar/genetics*
;
Female
;
ATP-Binding Cassette Transporters/genetics*
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Pregnancy
;
Genotype
;
Phenotype
;
Exome Sequencing
;
Fetus
;
Mutation
;
Male
;
Adult
10.Impact and clinical significance of different types of fluid resuscitation on the glycocalyx in patients with early sepsis and septic shock: a single center, prospective, randomized controlled trial.
Lipeng DONG ; Xinhui WU ; Congcong ZHAO ; Shengmei GE ; Zhihong LIU
Chinese Critical Care Medicine 2025;37(3):237-244
OBJECTIVE:
To evaluate the risks and benefits of different resuscitation fluids in patients with early sepsis and septic shock by observing and comparing clinical indicators, clinical outcomes, and the concentration changes of glycocalyx biomarkers, and to determine how to appropriately select suitable resuscitation fluids for sepsis patients to aid fluid therapy.
METHODS:
A single center, prospective, randomized controlled trial was conducted. Patients with early sepsis and septic shock who have required fluid resuscitation after capacity status assessment admitted to the department of critical care medicine of Fourth Hospital of Hebei Medical University from April to October 2023 were enrolled. Patients were randomly assigned to either the experimental group (balanced crystalloid solution+albumin) or the control group (balanced crystalloid solution) by a random number table method. Clinical data of both groups of patients before and after resuscitation at 3, 8, and 24 hours were monitored, and blood samples were collected, enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of plasma glycocalyx biomarker syndecan-1. The 28-day and 90-day survival rates and complications were also assessed.
RESULTS:
A total of 66 patients were enrolled, including 44 in the experimental group and 22 in the control group. The baseline data of two groups were balanced and comparable. There was no statistically significant difference in the plasma concentration of syndecan-1 between the experimental group and the control group before and after resuscitation, and both showed a trend of first increasing and then decreasing. However, the plasma syndecan-1 level in the control group at 8 hours and 24 hours after resuscitation were significantly higher than the baseline level before resuscitation [ng/L: 19.02 (14.41, 27.80), 18.95 (12.40, 22.50) vs. 14.67 (11.57, 21.14), both P < 0.05], while there was no statistically significant difference at any time point within the experimental group. The correlation analysis between plasma syndecan-1 level and lactic acid, albumin, and sequential organ failure assessment (SOFA) in all patients showed that a positive correlation between syndecan-1 level and SOFA score before resuscitation (r = 0.247, P = 0.046), and a negative correlation between syndecan-1 level and albumin level at 24 hours after resuscitation (r = -0.308, P = 0.012). There were no statistically significant differences in 28-day and 90-day mortality, length of hospital stay, length of intensive care unit (ICU) stay, duration of mechanical ventilation, blood purification time, number of organ injuries, and complications between the two groups. However, the baseline albumin level in the experimental group was significantly lower than that in the control group (g/L: 28.7±4.5 vs. 31.6±4.2, P < 0.05). Analysis of clinical treatment data showed that compared with the control group, the experimental group had lower absolute lactate level at 8 hours and 24 hours after resuscitation [mmol/L: 8 hours was 1.30 (1.00, 1.88) vs. 1.60 (1.30, 3.05), 24 hours was 1.15 (0.80, 1.78) vs. 1.55 (1.08, 2.05), both P < 0.05], and higher lactate clearance rate [8 hours was 45% (27%, 56%) vs. 20% (-4%, 46%), 24 hours was 55% (34%, 70%) vs. 34% (-14%, 59%), both P < 0.05]. However, there were no statistically significant differences in the amount of fluid resuscitation, use of vasoactive drugs, and oxygenation index between the two groups during the resuscitation process. Multivariate Logistic regression analysis showed that body mass index (BMI) was independently correlated with 90-day mortality [odds ratio (OR) = 1.991, 95% confidence interval (95%CI) was 1.023-3.387, P = 0.043].
CONCLUSIONS
There are no significant difference in plasma syndecan-1 level during fluid resuscitation of early sepsis and septic shock patients using balanced crystalloid fluid and balanced crystalloid fluid combined with albumin resuscitation, and there are no statistically significant differences in the impact on 28-day and 90-day prognosis, length of hospital stay, complications, and other aspects of the patients. However, compared to balanced crystalloid fluid, the combination of balanced crystalloid fluid and albumin for fluid resuscitation in sepsis patients has lower lactate level and better lactate clearance effect, but further validation is still needed through large-scale randomized controlled trials.
Humans
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Clinical Relevance
;
Crystalloid Solutions/administration & dosage*
;
Fluid Therapy/methods*
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Glycocalyx/metabolism*
;
Isotonic Solutions/administration & dosage*
;
Prospective Studies
;
Resuscitation/methods*
;
Sepsis/therapy*
;
Shock, Septic/therapy*
;
Syndecan-1/blood*

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