1.Epidural fibrous scar formation in rabbits following autologous ligamentum flavum intervention
Debao ZHANG ; Peng WANG ; Kun LI ; Shaojie ZHANG ; Zhijun LI ; Shuwen LI ; Yimin WU
Chinese Journal of Tissue Engineering Research 2025;29(6):1168-1175
BACKGROUND:It has been proved clinically that adhesion of fibrous scar with the dura mater or nerve root after lumbar operation is an important factor for postoperative symptoms,such as postoperative pain and numbness. OBJECTIVE:To verify the inhibitory effect of autologous ligamentum flavum on the formation of epidural fibrous scar after lumbar surgery and explore the possible molecular biological mechanism. METHODS:Forty-eight Japanese white rabbits(6-8 months old)were randomly divided into three groups:a ligamentum flavum preservation group,a ligamentum flavum non-preservation group,and an autologous fat reposition group.A lumbar laminectomy model was established in all the three groups of rabbits,and rabbit epidural tissues were collected at 3 and 6 weeks after modeling.Hematoxylin-eosin staining was used to observe histological changes and the number and density of fibroblasts,VG staining was used to observe the percentage of collagen fiber area,and immunohistochemistry was used to observe the expression of transforming growth factor β1 and Smad3 proteins. RESULTS AND CONCLUSION:Hematoxylin-eosin staining results revealed that fibroblasts in the ligamentum flavum preservation group were few and loosely arranged,while the cells in the ligamentum flavum non-preservation and autologous fat reposition groups were more numerous and closely arranged.The number density of fibroblasts in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P<0.05);however,there was no significant difference between the latter two groups.VG staining results showed that the collagen fibers in the ligamentum flavum preservation group were sparse and distributed unevenly,while a lot of red collagen fibers were gathered in the ligamentum flavum non-preservation and autologous fat reposition groups.The area percentage of collagen fibers in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P<0.05),but there was no significant difference between the latter two groups.The results of immunohistochemistry showed that the degree of positive staining of retained histone the ligamentum flavum preservation group was significantly lower than that of the other two groups.The absorbance value of transforming growth factor β1 and Smad3 in the ligamentum flavum preservation group was significantly lower than that in the other two groups at 3 and 6 weeks after surgery(P<0.05),but there was no significant difference between the latter two groups.To conclude,there are different degrees of epidural fibrous scar formation after lumbar surgery.If the ligamentum flavum is preserved,it can help to reduce the number of epidural fibroblasts as well as the formation of collagen fibers,thus reducing the adhesion of the fibrous scar tissue to the dural sac and nerve root.The mechanism is not only a purely mechanical blockade,but also to reduce the formation of epidural fibrous scar by interfering with the transforming growth factor β1/Smad3 signaling pathway.
2.Gut microbiota and osteoporotic fractures
Wensheng ZHAO ; Xiaolin LI ; Changhua PENG ; Jia DENG ; Hao SHENG ; Hongwei CHEN ; Chaoju ZHANG ; Chuan HE
Chinese Journal of Tissue Engineering Research 2025;29(6):1296-1304
BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.
3.Skin contact of cobalt and its compounds in workers of hard metal tool manufacturing enterprises
Wubin LIU ; Fangda PENG ; Chunmin ZHANG ; Yina YANG ; Chunguang DING
Journal of Environmental and Occupational Medicine 2025;42(3):349-353
Background China is the world's largest producer and consumer of cobalt. Skin exposure to excess cobalt can cause symptoms such as contact dermatitis. At present, there are few studies on skin contact of cobalt and its compounds. Objective To investigate the skin contact characteristics of cobalt and its compounds. Methods A cross-sectional study was conducted in February 2024 involving 70 workers from a hard metal tool manufacturing company and the workers were divided into four groups according to their job positions: powder mixing, sintering, automatic pressing, and grinding processing. General demographic information was collected through questionnaires. Workplace air samples were collected using personal samplers, and cobalt concentrations in workplace air were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Skin samples were collected from the workers' foreheads using cotton swabs, and urine samples were collected within 30 min after the end of their shift. Urine specific gravity was measured immediately after collection, and disqualified samples were discarded. Cobalt concentrations in the swab extracts and urine were determined by inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis was performed using Kruskal-Wallis test for multiple group comparisons, Mann-WhitneyU test for pairwise comparisons, Chi-square test for categorical variables, and Spearman's rank correlation analysis to examine the correlations among air, dermal, and urinary cobalt levels. Results The 8 h time-weighted average (TWA) cobalt concentration was (2.30±2.15) μg·m−3 (
4.Correlation Between Quality of Life and Traditional Chinese Medicine Syndromes in Patients with Myasthenia Gravis
Yibin ZHANG ; Qi LU ; Baitong WANG ; Yixun QI ; Hanying XU ; Peng XU ; Meijin SONG ; Peixi ZHAO ; Zhiguo LYU ; Jian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):275-281
ObjectiveThis study aimed to explore the correlation between the quality of life (QOL) and different traditional Chinese medicine (TCM) syndromes in patients with myasthenia gravis (MG), identifying potential influencing factors to provide new insights for clinical interventions and improving the QOL of patients with MG. MethodsA questionnaire survey was conducted on 93 adults with MG who visited the Department of Neurology at the Affiliated Hospital of Changchun University of Chinese Medicine from March 2023 to January 2024. Statistical analysis was performed on the clinical data collected using SPSS 24.0 software. ResultsAmong the 93 patients with MG, the average score for myasthenia gravis quality of life-15 (MGQOL-15) was 17.65±6.27, and that for the 36-item short form health survey (SF-36) was (106.13±11.83) scores. The QOL was rated as good for 16 patients and moderate for 77 patients. There were no statistically significant differences in the scores of MGQOL-15, SF-36, and their individual scales by gender or education level. Age showed statistically significant differences in MGQOL-15 and the role physical (RP) scale (P<0.05), and occupational type showed significant differences in the vitality (VT) scale (P<0.01). The Myasthenia Gravis Foundation of America (MGFA) classification had statistical significance on the total SF-36 score (P<0.01), VT scale (P<0.01), role emotional (RE) scale (P<0.05), social functioning (SF) scale (P<0.05), and physical functioning (PF) scale (P<0.01). Among patients with different TCM syndromes, there were significant differences in MGQOL-15 scores (F=4.919, P<0.01). Moreover, significant differences were observed in SF-36 scores (P<0.01), VT scale (P<0.01), RE scale (P<0.05), mental health (MH) scale (P<0.01), and SF scale (P<0.05). ConclusionFactors affecting the QOL of patients with MG include age, occupational type, and clinical classification of MG. Specifically, a greater impact on the QOL of older patients is observed, while physical laborers have a poorer QOL compared to non-physical laborers. Patients classified as MGFA type Ⅱ and higher have a poorer QOL. Additionally, there is a potential correlation between the QOL and TCM syndromes, with patients presenting with spleen and kidney Qi deficiency having a lower QOL than those with spleen and stomach Qi deficiency or Qi and Yin deficiency, which is particularly evident in the VT, RE, MH, and SF scales.
5.Impact of initial screening strategies on compliance with colonoscopy for colorectal carcinoma in residents aged 50 years and above
Fang XIANG ; Zhihao HU ; Yawei WANG ; Yiying ZHANG ; Fang HUANG ; Qian PENG ; Hongjie YU ; Chaowei FU
Shanghai Journal of Preventive Medicine 2025;37(2):140-144
ObjectiveTo compare colonoscopy compliance rates under different screening strategies, to explore ways to enhance colonoscopy compliance among residents with colorectal carcinoma. MethodsResidents aged between 50‒80 years were recruited through extensive community outreach and voluntary participation. A total of 210 630 residents who participated in the colorectal carcinoma screening program in Jiading District, Shanghai, between 2013 and 2019 were selected as the research subjects. All subjects underwent a colorectal carcinoma risk assessment questionnaire survey and two fecal occult blood tests (FOBT). Positive results in the initial screening were defined as a positive questionnaire survey or a positive result in at least one FOBT. Participants with positive initial screening results were advised to undergo colonoscopy screening in a hospital. Colonoscopy results were collected from hospital reports and physician follow-ups. Compliance with colonoscopy was analyzed under different screening strategies to identify possible factors influencing residents’ willingness to undergo the procedure. ResultsA total of 21 403 individuals (10.16%) were identified as positive with the questionnaire survey, 31 595 individuals (15.00%) tested positive with at least one FOBT. Combined questionnaire and FOBT positivity was observed in 3 501 individuals (1.66%). Among the 48 453 individuals with positive initial screening results, 17 230 (35.56%) underwent colonoscopy, and a total of 315 cases of colorectal cancer were detected. The sensitivity, specificity value of FOBT initial screening were 83.81% and 84.66%, respectively. According to the combined risk assessment and FOBT initial screening preliminary screening, the lowest colonoscopy compliance rate (25.63%) was observed among individuals with only a positive questionnaire, and the highest compliance rate (52.55%) was among those with both positive questionnaire survey and two positive FOBT results. Multivariate analysis revealed that FOBT positivity had the greatest impact on colonoscopy compliance. Those with one positive FOBT test result were 2.64 times more likely to undergo colonoscopy screening than those with negative FOBT results, while individuals with two positive FOBT results were 3.18 times more likely to do so. After adjusting for FOBT results, individuals with positive questionnaire survey results were 1.43 times more likely to undergo colonoscopy screening than those with negative results (95%CI: 1.34‒1.52). Compared to questionnaire-based risk assessment, FOBT results were more influential in determining compliance with colonoscopy. ConclusionThe choice of initial screening method significantly impacts residents’ compliance with colonoscopy. While implementing colorectal carcinoma screening programs, it is necessary to strictly adhere to screening protocols, including risk assessment and FOBT. Additionally, efforts should be made to raise public awareness, encouraging residents to actively participate in risk assessments and FOBT, thereby improving their compliance with colonoscopy.
6.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
Xin-Die WANG ; Da-Li FENG ; Xiang CUI ; Su ZHOU ; Peng-Fei ZHANG ; Zhi-Qiang GAO ; Li-Li ZOU ; Jun WANG
Progress in Biochemistry and Biophysics 2025;52(4):804-819
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.
7.Geographical Inference Study of Dust Samples From Four Cities in China Based on ITS2 Sequencing
Wen-Jun ZHANG ; Yao-Sen FENG ; Jia-Jin PENG ; Kai FENG ; Ye DENG ; Ke-Lai KANG ; Le WANG
Progress in Biochemistry and Biophysics 2025;52(4):970-981
ObjectiveIn the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by the internal transcribed spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms. MethodsITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using Linear Discriminant Analysis Effect Size (LEfSe) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples. ResultsAmong the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted. ConclusionSignificant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.
8.Association between ambient ozone exposure during pregnancy and risk of preterm birth in Guangdong Province
Peng HU ; Shanshan RAN ; Qingmei LIN ; Yin YANG ; Zilong ZHANG ; Xiaoling GUO ; Yonggui GAO ; Jinde ZHAO ; Hualiang LIN
Journal of Environmental and Occupational Medicine 2025;42(4):379-384
Background Air pollution exposure has a significant impact on maternal and child health. However, the research on the association between ambient ozone (O3) exposure during pregnancy and the risk of premature birth in newborns is limited, and the conclusions are inconsistent. Objective To investigate the association of ambient O3 exposure during pregnancy with the risk of preterm birth in Guangdong Province. Methods Data of pregnant women in Guangzhou from 2013 to 2019 and Foshan from 2018 to 2023 were collected, and O3 concentrations during different trimesters were assessed according to maternal residential addresses. Bilinear interpolation was used to evaluate the concentrations of air pollution. A cohort study design was adopted in our study. Restricted cubic spline curves were used to evaluate the exposure-response relationship between O3 exposure and preterm birth risk and explore potential exposure threshold of O3. Logistic regression models were used to evaluate the association of O3 exposure with preterm birth. Results A total of 702 924 pregnant women were included in this study, of whom 43 051 (6.12%) were preterm. The average O3 exposure concentrations of pregnant women during the first, second, third, and whole trimesters were 95.51, 97.51, 100.60, and 97.87 μg·m−3, respectively. We observed J-shaped associations between O3 exposure and preterm birth risk during the second, third, and whole trimesters of pregnancy using restricted cubic spline curves. This study found that there were threshold concentrations between O3 exposure and preterm birth risk during different gestational periods, and the threshold concentrations in the first, second, third, and whole trimesters were 112.32, 99.83, 111.74, and 112.46 μg·m−3, respectively. During the second, third, and whole trimesters of pregnancy, after adjusting for maternal age, baby sex, pre-pregnancy body mass index, mode of delivery, baby birth weight, gestational diabetes, and gestational hypertension, the odds ratios (OR) of preterm birth were 1.02 (95%CI: 1.01, 1.04), 1.02 (95%CI: 1.00, 1.03), and 1.17 (95%CI: 1.13, 1.21) for each 10 μg·m−3 increase in O3 concentration above the O3 threshold. No significant association was found between O3 exposure and the risk of preterm birth during the first trimester. Conclusion There is a nonlinear association between the risk of preterm birth and O3 exposure during pregnancy, and higher concentrations of O3 exposure during pregnancy are associated with the risk of preterm birth. Above the O3 threshold concentration during pregnancy, especially during the second, third, and whole trimesters, the risk of preterm birth elevates with the increase of O3 exposure concentrations.
9.Effect of pegylated interferon-α-2b therapy on cytotoxicity of virus-specific CD8+ T cells in HBeAg-negative patients with chronic hepatitis B virus infection
Lei QIN ; Guangpeng LI ; Peijun SHEN ; Lanfang ZHANG ; Xiaofei YANG ; Meijuan PENG ; Ye ZHANG
Journal of Clinical Hepatology 2025;41(4):628-636
ObjectiveTo investigate the change in the activity of hepatitis B virus (HBV)-specific CD8+ T cells after pegylated interferon-α-2b (PEG-IFN-α-2b) therapy in HBeAg-negative patients with chronic HBV infection. MethodsA total of 53 HBeAg-negative patients with chronic HBV infection who attended The First Affiliated Hospital of Xinxiang Medical University and Tangdu Hospital of Air Force Mdical University from April 2020 to June 2022 were enrolled and treated with PEG-IFN-α-2b (180 μg/week, subcutaneous injection) antiviral therapy. The study endpoint was HBsAg clearance (course of treatment<48 weeks) or 48 weeks (course of treatment≥48 weeks). Peripheral blood mononuclear cells were isolated at baseline and study endpoint, and peripheral blood T cell counts were measured. Enzyme-linked immunospot assay was used to measure the frequency of HBV-specific CD8+ T cells secreting perforin, granzyme B, and interferon-γ. A total of 17 HLA-A*02-restricted patients were selected, and CD8+ T cells were purified to establish direct- and indirect-contact co-culture systems for HBV-specific CD8+ T cells and HepG2.2.15 cells. The level of lactate dehydrogenase in supernatant was measured to calculate the mortality rate of HepG2.2.15 cells, and the levels of HBV DNA, cytotoxic molecules, and cytokines in supernatant were also measured. Flow cytometry was used to measure the expression of apoptosis ligands, and the cytotoxicity of HBV-specific CD8+ T cells was evaluated. The independent samples t-test or the paired t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test or the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsThe HBsAg clearance rate at study endpoint was 30.19% (16/53). There were no significant differences in peripheral blood T cell counts (CD3+, CD4+, and CD8+ T cells) between baseline and study endpoint (P>0.05). At study endpoint, there was a significant increase in the frequency of HBV-specific CD8+ T cells secreting perforin, granzyme B, and interferon-γ (U=177.50, t=11.90, U=186.50, all P<0.001), and the patients with HBsAg clearance had a significantly higher frequency of such HBV-specific CD8+ T cells than those without HBsAg clearance (U=120.50, t=2.73, U=121.50, all P<0.01). In the direct- and indirect-contact co-culture systems at study endpoint, HBV-specific CD8+ T cells induced a significant reduction in HBV DNA in the supernatant of HepG2.2.15 cells (all P<0.001) and significant increases in the secretion of interferon-γ and tumor necrosis factor-α (all P<0.05); in the direct-contact co-culture system, HBV-specific CD8+ T cells induced significant increases in the mortality rate of HepG2.2.15 cells (13.62%±3.27% vs 11.39%±2.40%, t=2.27, P=0.030) and the secretion of perforin and granzyme B (t=72.50, U=52.50, both P<0.05). In the direct- and indirect-contact co-culture systems, compared with HBV-specific CD8+ T cells from the patients without HBsAg clearance, the HBV-specific CD8+ T cells from patients with HBsAg clearance had a significantly greater reduction in HBV DNA (P<0.05) and significant increases in the secretion of interferon-γ and tumor necrosis factor-α (P<0.05). ConclusionPEG-IFN-α-2b therapy can help to achieve a relatively high HBsAg clearance rate in HBeAg-negative patients with chronic HBV infection, and the activity of HBV-specific CD8+ T cells is significantly enhanced, which is closely associated with HBsAg clearance.
10.Sulodexide alleviates renal fibrosis following prolonged ischemia-reperfusion injury by protecting vascular endothelial glycocalyx
Chaoyu HU ; Peng ZHANG ; Chao SUN ; Shuyong MO ; Yanfeng WANG
Organ Transplantation 2025;16(3):404-415
Objective To investigate the protective effects and mechanisms of sulodexide on renal fibrosis induced by prolonged warm ischemia. Methods An in vivo ischemia-reperfusion injury (IRI) model was established in rats, which were randomly divided into Sham group, IRI 60 min group (IRI group), and IRI 60 min + sulodexide group (IRI+SDX group), with 20 rats in each group. Pathological examination was used to evaluate renal tissue injury and fibrosis levels in each group. Immunohistochemistry was performed to detect the expression levels of kidney injury molecule (KIM)-1, intercellular adhesion molecule (ICAM)-1, von Willebrand factor (vWF), transforming growth factor (TGF)-β, α-smooth muscle actin (SMA), and type I collagen (COL-1). Immunofluorescence staining was used to detect CD31 expression. Real-time quantitative polymerase chain reaction was employed to measure the expression of KIM-1, ICAM-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in renal tissues. Transmission electron microscopy was used to observe the structure of the renal glycocalyx. Evans blue dye was injected to assess renal vascular permeability. Rat survival was recorded, and serum levels of syndecan (SDC)-1, heparan sulfate (HS) and serum creatinine were measured. An ex vivo perfusion model was also established, with rats randomly assigned to either the hypothermic oxygenated machine perfusion (HOPE) group or the HOPE+SDX group (five rats per group). Perfusion parameters were recorded after 2 hours of ex vivo perfusion. Results One day after reperfusion, compared with the Sham group, the IRI group exhibited more severe renal tissue injury, higher tubular injury scores, increased expression of KIM-1, ICAM-1 and vWF, decreased CD31 expression, elevated serum levels of SDC-1 and HS, increased vascular permeability, and higher expression of TNF-α, IL-1β and IL-6. Compared with the IRI group, the IRI+SDX group showed reduced renal tissue injury, lower tubular injury scores, decreased expression of KIM-1, ICAM-1 and vWF, increased CD31 expression, lower serum levels of SDC-1 and HS, decreased vascular permeability, and reduced expression of TNF-α, IL-1β and IL-6 (all P < 0.05). Ten days after reperfusion, renal tissue injury was further alleviated in the IRI+SDX group. Twenty-five days after reperfusion, the IRI+SDX group exhibited decreased expression of TGF-β, α-SMA, and COL-1, as well as reduced collagen deposition area (all P < 0.05). Compared with the HOPE group, the HOPE+SDX group showed increased renal perfusion flow and decreased intrarenal vascular resistance (both P < 0.01). Conclusions Sulodexide may alleviates renal IRI and fibrosis caused by prolonged warm ischemia by inhibiting inflammatory responses and protecting vascular endothelial glycocalyx.

Result Analysis
Print
Save
E-mail