OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

ObjectiveTo explore the potential mechanism of acupuncture with the method of soothing the liver and regulating the mind in improving depressive disorder. MethodsEighteen C57BL/6J mice were randomly divided into blank group， model group， and acupuncture group， with 6 mice in each group. The model group and the acupuncture group were subjected to depression induction by intraperitoneal injection of lipopolysaccharide （LPS）， while the blank group received an equal volume of normal saline once daily for seven consecutive days. Concurrently， the acupuncture group received "soothing the liver and regulating the mind" acupuncture intervention starting from the first day of modeling， once daily for 14 days； whereas the blank group and the model group were only restrained without acupuncture. The sucrose preference test was used to assess sucrose preference rate， the open-field test to measure center stay time and total travel distance， and the forced swim test to evaluate immobility time. Hematoxylin-eosin （HE） staining was performed to observe hippocampal morphological changes. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in hippocampal tissue. Western blot analysis was conducted to examine the protein expression levels of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the hippocampus. ResultsCompared to the blank group， the model group showed a significant reduction in sucrose preference rate， center stay time， and total travel distance， along with a significant increase in immobility time in the forced swim test， hippocampal IL-1β， IL-6， and TNF-α levels， as well as TLR4 and NF-κB protein expression （P＜0.01）， and the histological examination revealed blurred hippocampal neuronal boundaries， loose arrangement， and some neurons exhibiting nuclear pyknosis and deep staining. Compared to the model group， the acupuncture group demonstrated a significant increase in sucrose preference rate， center stay time， and total travel distance， along with a significant reduction in immobility time in the forced swim test， hippocampal IL-1β， IL-6， and TNF-α levels， and TLR4 and NF-κB protein expression （P＜0.01）， and the histological analysis showed that hippocampal neurons in the acupuncture group were more tightly arranged， with reduced nuclear pyknosis and deep staining. ConclusionAcupuncture with the "soothing the liver and regulating the mind" method can significantly improve depression-like behavior， potentially by inhibiting the hippocampal TLR4/NF-κB signaling pathway and alleviating inflammatory responses.

ObjectiveTo investigate the effect of Dingzhi Xiaowan （DZXW） in post-stroke cognitive impairment （PSCI） model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group， model group， low-dose DZXW group （1.43 g·kg^-1）， and high-dose DZXW group （2.56 g·kg^-1）， with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage， and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein （APP）， amyloid 42 （Aβ₄₂）， acetylcholinesterase （AChE）， and superoxide dismutase （SOD） were measured by enzyme-linked immunosorbent assay （ELISA）. Deoxyribonucleotide end transferase-mediated nick end labelling （TUNEL） assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase （PI3K）， protein kinase B （Akt）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor 1-alpha （HIF-1α）， B-cell lymphoma 2 （Bcl-2） homologous structural domain protein （Beclin1）， sequestosome 1 （p62）， microtubule-associated protein light chain 3 （LC3）， Bcl-2， and Bcl-2-associated X protein （Bax） in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly increased in the model group （P<0.01）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly decreased （P<0.01）. Compared with the model group， the latency， APP， Aβ₄₂， AChE， TUNEL positivity rate， ferric ion deposition， HIF-1α， Beclin1， Bax， and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups （P<0.05）， while the number of crossing platforms， SOD， p-PI3K， p-Akt， p-mTOR， p62， and Bcl-2 were significantly higher （P<0.05）. ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.

[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Objective:To explore the safety and efficacy of shunt reduction using the Interlock-35 fibered interlocking detachable coil (IDC) occlusion system in the treatment of refractory hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS).Methods:From August 2022 to December 2023, at the Department of Gastroenterology of the Air Force Medical Center, the clinical data of patients with refractory HE after TIPS who were treated with shunt reduction using the Interlock-35 fibered IDC occlusion system were retrospectively collected, which included portal vein pressure gradient (PVPG), HE grades, blood ammonia levels, prothrombin time (PT), liver function parameters, and other related indicators. The primary indicators related to the efficacy of the shunt reduction included symptom improvement, and changes in PVPG, blood ammonia levels, and Child-Pugh score. The safety of shunt reduction was analyzed based on the incidence of complications such as gastrointestinal bleeding and ascites during the follow-up period. Paired t-test was used for statistical analysis. Results:A total of 21 patients were enrolled. Prior to shunt reduction, there were 5 cases with HE of grade 3 and 16 cases with HE of grade 2. Before operation, the blood ammonia was (103.14±27.69) mol/L; and the liver function Child-Pugh grade of 1 case was classified as grade A, 16 cases as grade B, and 4 cases as grade C. Shunt reduction was performed between 7 and 1 879 d, with a median time of 99 (54, 806) d after TIPS. The procedure was technically successful in all patients, with a total of 25 coils implanted. Before shunt reduction, the PVPG was (14.02±5.28) cmH 2O (1 cmH 2O=0.098 kPa), after shunt reduction procedure, the PVPG increased to (25.05±6.04) cmH 2O, and the difference was statistically significant ( t=-11.26, P<0.001). After operation, 16 patients returned to the hospital for follow-up examinations, with a median follow-up time of 114 (46, 195) d, the blood ammonia levels, PT, and Child-Pugh scores during the follow-up were all lower than those before operation ((78.19±27.85) μmol/L vs. (105.00±30.53) μmol/L, (14.09±1.65) s vs. (15.41±2.35) s, and 6.88±1.59 vs. 8.13±1.75, respectively), and the differences were statistically significant ( t=2.23, 3.23, and 2.61; P=0.040, <0.001, =0.020). There was no statistically significant in PVPG between during follow-up and immediately post-procedure ((28.91±6.20) cmH 2O vs. (25.22±5.92) cmH 2O, P>0.05). During the follow-up period, HE symptoms disappeared in 12 patients among the 16 patients who returned to hospital for follow-up, however gastrointestinal bleeding occurred in 5 patients and ascites occurred in 3 patients; additionally, 4 patients experienced intermittent HE symptoms (grade 1 in 3 cases, grade 2 in 1 case). After operation, 5 patients were followed up via telephone, among them, 3 patients died, and 2 patients experienced intermittent HE (grade 1) which could be spontaneously restored with dietary adjustments and(or) medication. Conclusions:Interlock-35 fibered IDC occlusion system for shunt reduction is a feasible and effective treatment for refractory HE after TIPS. It can effectively improve symptoms and decrease liver function score. After shunt reduction, early follow-up and adjustment of flow reduction can help reduce the occurrence of severe complications.

BACKGROUND:Long non-coding RNA(LncRNA)plays an important role in nervous system development and neurological diseases.Previous studies by the research team have demonstrated that human umbilical cord mesenchymal stem cells overexpressing erythropoietin(EPO-MSCs)under ischemic and hypoxic conditions have better neuroprotective functions and significantly activate the expression of LncRNA XIST.Research suggests that XIST is related to the pathogenesis of hypoxic-ischemic encephalopathy,but the role and mechanism of its regulation by EPO-MSCs in protecting ischemic-hypoxic neurons remain unclear.OBJECTIVE:To explore the new mechanism by which LncRNA XIST,in response to EPO-MSC signaling,affects the apoptosis of ischemic-hypoxic SH-SY5Y cells.METHODS:(1)SH-SY5Y cell lines with knockdown of LncRNA XIST(sh-XIST)and negative control(NC-XIST)were constructed through lentiviral transfection.Oxygen-glucose deprivation was used to induce ischemic-hypoxic injury in the cells.Transwell chambers were used to create a non-contact co-culture system with EPO-MSCs,sh-XIST,and NC-XIST ischemic-hypoxic SH-SY5Y cells.Cell proliferation ability was detected using the CCK-8 assay.Cell migration ability was assessed using the scratch assay,and cell apoptosis was measured by flow cytometry.(2)RNA-seq bioinformatics analysis was performed to screen for differentially expressed genes and pathways between sh-XIST and NC-XIST cell lines.Dual-luciferase experiments were used to verify the relationship between miR-124-3p and the target genes XIST and GRIN1.qRT-PCR was conducted to validate the expression levels of downstream miR-124-3p and GRIN1 genes.(3)miR-124-3p inhibitors and mimics were added to verify phenotypic changes in SH-SY5Y cells after ischemic-hypoxic injury and co-culture with EPO-MSCs.RESULTS AND CONCLUSION:(1)Compared with the NC-XIST group,SH-SY5Y cells in the sh-XIST group showed reduced proliferation and migration abilities and increased apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs.(2)Dual-luciferase experiments showed that miR-124-3p interacted with the target gene XIST.SH-SY5Y cells transfected with miR-124-3p mimics and co-cultured with EPO-MSCs showed decreased apoptosis after ischemic-hypoxic injury,while SH-SY5Y cells transfected with miR-124-3p inhibitors showed increased apoptosis after co-culture with EPO-MSCs.(3)Transcriptomic sequencing and bioinformatics analysis of sh-XIST revealed significant downregulation of the neuroactive ligand-receptor pathway and the key receptor gene GRIN1 for central nervous system development.(4)Dual-luciferase experiments showed that miR-124-3p interacted with GRIN1.GRIN1 expression was significantly downregulated in the sh-XIST group after ischemic-hypoxic injury compared with the NC-XIST group.These findings indicate that LncRNA XIST promotes GRIN1 expression by upregulating miR-124-3p,thereby reducing cell apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs and enhancing proliferation and migration.sh-XIST can block this protective function.

Objective:To investigate the correlation between preoperative calcitonin levels and upper mediastinal lymph node metastasis in medullary thyroid carcinoma (MTC).Methods:A retrospective analysis was conducted on 249 MTC patients who underwent surgery at the Cancer Hospital, Chinese Academy of Medical Sciences between January 2010 and December 2021. Based on postoperative pathology, patients were categorized into the upper mediastinal lymph node metastasis group ( n=41) and the non-upper mediastinal lymph node metastasis group ( n=208). Clinicopathological features were compared, and survival outcomes were assessed using Kaplan-Meier analysis. Receiver operating characteristic (ROC) curves were employed to determine the predictive efficacy and optimal cutoff value of preoperative calcitonin for the upper mediastinal lymph node metastasis group. Logistic regression identified independent risk factors for the upper mediastinal lymph node metastasis group. Results:Compared to the non-upper mediastinal lymph node metastasis group, the upper mediastinal lymph node metastasis group demonstrated a higher proportion of male patients, elevated levels of carcinoembryonic antigen and calcitonin, increased multifocality, larger primary tumor size, higher rates of extrathyroidal extension, advanced T and N stages, and greater incidences of lymph node metastasis and extracapsular invasion (all P＜0.01). Patients with upper mediastinal lymph node metastasis exhibited significantly lower overall survival than those without upper mediastinal lymph node metastasis ( P＜0.001). ROC curve analysis revealed an area under the curve of 0.783 for preoperative calcitonin in predicting upper mediastinal lymph node metastasis, with an optimal cutoff value of 1 865 pg/ml (sensitivity 71.79%, specificity 75.53%). Multivariate logistic regression analysis identified preoperative calcitonin levels >1 865 pg/ml ( OR=5.31, 95% CI: 1.77-15.94) and >15 metastatic lymph nodes ( OR=4.90, 95% CI: 1.87-12.89) as independent risk factors for the upper mediastinal lymph node metastasis group. Conclusions:Preoperative calcitonin＞1 865 pg/ml suggests a higher likelihood of MTC with upper mediastinal lymph node metastasis. For individuals with suspected upper mediastinal lymph node metastasis on imaging, combining preoperative calcitonin levels can reduce false-positive rates.

Objective:To investigate the influential factors of lung function injury in occupational exposure workers in carbon industry.Methods:In January 2024, a judgment sampling method was employed, with 230 occupational exposure workers in the carbon industry as the study subjects. They were divided into abnormal group and normal group according to whether there was lung function injury in occupational health examination. The basic information of workers in carbon industry was collected by questionnaire, their lung function was measured, urine and blood samples were collected after work, and 1-hydroxypyrene, 1-hydroxynaphthalene and 2-hydroxynaphthalene concentrations and the percentage of DNA in the comet tail and Olive tail distance in peripheral blood lymphocytes were determined. The differences in indicators of lung function, urine and blood samples between the two groups were compared by Mann-Whitney test and t-test. The influencing factors of lung function injury were analyzed by logistic regression. Results:The forced vital capacity (FVC) %[88% (86%, 92%) ], forced expiratory volume in the first second (FEV 1) %[92% (88%, 95%) ] and FEV 1.0/FVC%[96% (91%, 102%) ] of occupational exposure workers in the carbon industry in the normal lung function group ( n=118) were significantly higher than those in the abnormal lung function group [ n=112, 83% (80%, 87%), 84% (80%, 88%), 86% (79%, 91%) ], the differences were statistically significant ( P<0.05). 1-Hydroxypyrene[9.28 (2.96, 25.94) μg/g], 1-hydroxynaphthalene[2.48 (1.47, 4.37) μg/g], percentage of DNA in the comet tail [11.83% (5.30%, 21.45%) ] and Olive tail distance [2.30 (0.82, 4.77) μm] in the abnormal lung function workers was significantly higher than those in the normal group[2.57 (1.17, 9.34) μg/g, 1.70 (0.94, 2.89) μg/g, 6.75% (2.55%, 12.60%), 1.25 (0.43, 2.34) μm], and the differences were statistically significant ( P<0.05). Logistic regression analysis showed that sex, working age, job type, percentage of comet tail DNA in peripheral blood, Olive tail distance and 1-hydroxypyrene were all factors influencing lung function injury in occupational exposure workers in carbon industry ( P<0.05) . Conclusion:The percentage of DNA in the comet tail, Olive tail distance in peripheral blood lymphocytes and 1-hydroxypyrene may be markers of lung function injury in workers exposed to carbon industry. Working age and job type are occupational factors affecting lung function injury. Occupational protection should be strengthened and a reasonable operating system should be established to ensure the health of occupational workers.