1.Analysis of the clinical effect of tirofiban in the treatment of early neurological deterioration in patients with acute ischemic stroke
Xiaohui LI ; Xiaomin LI ; Mingyang WEI ; Huimin GUO ; Chen WANG ; Jianbin ZHANG ; Zhiqiang ZHAO
China Pharmacy 2025;36(10):1221-1225
OBJECTIVE To investigate the efficacy and safety of tirofiban for early neurological deterioration in patients with acute ischemic stroke. METHODS A total of 126 patients with early neurological deterioration of acute ischemic stroke who were admitted to the Department of Neurology, Heji Hospital Affiliated to Changzhi Medical College from January 2022 to December 2023 were selected and divided into observation group and control group according to random number table method, with 63 cases in each group. All patients received standardized treatment such as lipid-lowering and blood pressure-lowering therapy. Based on the standard treatment, patients in the control group additionally took Aspirin enteric-coated tablets 100 mg+Clopidogrel bisulfate tablets 75 mg orally (once a day, for 14 consecutive days). The patients in the observation group received Tirofiban hydrochloride and sodium chloride injection based on the standardized treatment [first intravenous infusion of 0.40 μg/(kg·min) for 30 min, and then continuous intravenous infusion of 0.10 μg/(kg·min) for 47.5 h]; subsequently, patients were given Aspirin enteric-coated tablets (100 mg) and Clopidogrel bisulfate tablets (75 mg) once a day for 14 consecutive days. The clinical efficacy, the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS) score, and hemorheological indexes before and after treatment were compared between the two groups, and the adverse reactions were recorded. RESULTS The total effective rate (87.30%) of the observation group was significantly higher than that of the control group (71.43%) (P<0.05). NIHSS scores of the two groups at 1st, 7th and 14th day after treatment, the mRS score at 90th day after treatment, and the platelet aggregation rate, whole blood viscosity, plasma viscosity and fibrinogen at 14th day after treatment were significantly lower than those before treatment in the same group, and the observation group was significantly lower than the control group at the same period (P<0.05). The total incidences of adverse reactions such as nausea, headache, fever, gastrointestinal bleeding, oral and nasal mucosal bleeding and thrombocytopenia in both groups of patients were 28.57% respectively, with no statistically significant difference (P>0.05). CONCLUSIONS For patients with early neurological deterioration in acute ischemic stroke, the addition of tirofiban can accelerate the recovery of neurological function, improve blood hyperviscosity and platelet aggregation, and improve the prognosis of patients with good safety.
2.Systemic comparison of molecular characteristics in different skin fibroblast senescent models.
Xiaokai FANG ; Shan ZHANG ; Mingyang WU ; Yang LUO ; Xingyu CHEN ; Yuan ZHOU ; Yu ZHANG ; Xiaochun LIU ; Xu YAO
Chinese Medical Journal 2025;138(17):2180-2191
BACKGROUND:
Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models.
METHODS:
Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models.
RESULTS:
In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids.
CONCLUSIONS
Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans
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Fibroblasts/drug effects*
;
Cellular Senescence/physiology*
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Skin/metabolism*
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Child
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Transcriptome/genetics*
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Aged
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Ultraviolet Rays
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Cells, Cultured
;
Galactose/pharmacology*
3.Prevotella nigrescens exacerbates periodontal inflammation and impairs cognitive function in mice.
Qi CHEN ; Tiantian XIA ; Yongqiang ZHOU ; Mingyang CHANG ; Nan HU ; Yanmei YANG ; Zhong LI ; Yue GAO ; Bin GU
Journal of Southern Medical University 2025;45(3):453-460
OBJECTIVES:
To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice.
METHODS:
Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.
RESULTS:
After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.
CONCLUSIONS
Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals
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Periodontitis/microbiology*
;
Mice
;
Mice, Inbred C57BL
;
Cognition
;
Alveolar Bone Loss
;
Hippocampus/pathology*
;
Male
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Inflammation
;
Maze Learning
4.Effect of Liangxue Tuizi Formula (凉血退紫方) on RAF/MEK/ERK Pathway in Skin Tissue and Serum NETs Biomarkers in Henoch-Schönlein Purpura Model Rats with Blood Heat Syndrome
Yingying JIANG ; Manxiang YANG ; Zhenhua YUAN ; Leying XI ; Mingyang CAI ; Diya MA ; Yifan LI ; Yuhang NIU ; Runze LIU ; Jiawen CAO ; Xilin CHEN ; Xianqing REN
Journal of Traditional Chinese Medicine 2025;66(23):2475-2483
ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula (凉血退紫方, LXTZF) in treating Henoch-Schönlein Purpura (HSP) by examining its regulatory effect on neutrophil extracellular trap (NETs) dysregulation via the rapidly accelerated fibrosarcoma kinase (RAF)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group (n=14) and a modeling group (n=56). Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin (OVA) induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups (n=10 per group), model group, compound glycyrrhizin group, LXTZF group, RAF inhibitor group, and LXTZF + RAF agonist group. Additionally, 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling, rats in the blank control group and the model group received 1 ml/(100 g·d) ultrapure water via oral administration, in addition to 0.5 ml/(kg·d) 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/(kg·d) LXTZF granule suspension via gavage, 13.5 mg/(kg·d) compound glycyrrhizin suspension via gavage, respectively. The RAF inhibitor group received 1 mg/(kg·d) GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration; the LXTZF + RAF agonist group received 7.5 g/(kg·d) LXTZF granule suspension via gavage and 1 mg/(kg·d) paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention, skin tissue histopathology was examined by hematoxylin and eosin (H&E) staining, immunoglobulin A (IgA) deposition was assessed via immunofluorescence, serum levels of neutrophil elastase (NE), tumor necrosis factor-α (TNF-α), and vascular cell adhesion molecule-1 (VCAM-1) were measured using enzyme-linked immunosorbent assay (ELISA), serum myeloperoxidase (MPO) level was determined by a colorimetric assay; the mRNA expression levels of RAF, MEK, and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction (RT-qPCR); and the protein expression of RAF, MEK, ERK, as well as phosphorylated MEK (p-MEK) and phosphorylated ERK (p-ERK), were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal, whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups, neutrophil infiltration and haemorrhagic exudation reduced markedly, with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group, rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue, elevated serum levels of NE, MPO, TNF-α and VCAM-1, increased mRNA expression of RAF, MEK, ERK1 and ERK2, as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios (P<0.05). Compared with the model group, the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue, along with decreased serum levels of NE, MPO, TNF-α, and VCAM-1 (P<0.05). In LXTZF group and RAF inhibition groups, reduced mRNA expression of RAF, MEK, ERK1, and ERK2 was observed in rat skin tissue, alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios (P<0.05). Compared with LXTZF + RAF agonist group, the compound glycyrrhizin group, LXTZF group, and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue, decreased serum NE, MPO, TNF-α, and VCAM-1 levels, and decreased MEK mRNA expression and p-MEK/MEK ratio (P<0.05). ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue, and suppressing excessive formation of NETs, thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.
5.The effect of renal denervation on patients with heart failure treated by guideline-directed management and therapy
Mingyang XIAO ; Xian YANG ; Xue KUANG ; Wenjiang CHEN ; Jie YANG ; Yuehui YIN
Chinese Journal of Clinical Medicine 2025;32(6):953-959
Objective To explore whether renal denervation (RDN) could improve the left ventricular ejection fraction (LVEF) of patients with heart failure (HF) on the basis of guideline-directed management and therapy (GDMT). Methods From January 1, 2023 to August 31, 2024, HF patients diagnosed as dilated cardiomyopathy (DCM) who underwent RDN in the Second Affiliated Hospital of Chongqing Medical University were retrospectively enrolled, all patients had received GDMT for at least three months but the LVEF remained below 55%. Parameters of transthoracic echocardiography (TTE) at baseline, during GDMT, and after RDN were compared to analyze whether RDN can further improve the LVEF of patients on the basis of GDMT. Results A total of 7 HF patients diagnosed with DCM were enrolled, the mean age was (52.86±9.86) years old, and 5(71.4%) were male. After an average of (9.29±8.06) months of GDMT, LVEF significantly increased from baseline (34.86%±10.22%) to (44.57%±5.59%, P=0.024).Three months after RDN, LVEF was further significantly improved (54.43%±9.05%, P=0.026). The average follow-up after RDN was (11.00±4.12) months. The LVEF remained stable (54.86%±7.10%, P=0.805), and no adverse events occurred in the patients. Conclusions RDN can further enhance the LVEF of HF patients on the basis of GDMT.
6.Analysis of specimen quality of intersphincteric resection for rectal cancer in the Chinese Transanal Total Mesorectal Excision Registry Collaborative database: a nationwide registered study
Pengyu WEI ; Mingyang REN ; Quan WANG ; Hong ZHANG ; Chienchih CHEN ; Qing XU ; Yi XIAO ; Dan MA ; Zhicong FU ; Dehai XIONG ; Yang LI ; Hongwei YAO ; Zhongtao ZHANG
Chinese Journal of Digestive Surgery 2024;23(6):819-825
Objective:To investigate the specimen quality of intersphincteric resection with transabdominal transanal mixed approach for rectal cancer in the Chinese Transanal Total Mesorectal Excision Registry Collaborative (CTRC) database.Methods:The retrospective case-control study was conducted. Based on the concept of real-world research, the clinicopathological data of 281 pati-ents with rectal cancer in the CTRC database who underwent intersphincteric resection with trans-abdominal transanal mixed approach in 19 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15,2017 to December 31,2023 were collected. There were 196 males and 85 females, aged 61(range, 27-87)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations; (4) analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resec-tion for rectal cancer. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The chi-square test was used for univariate analysis. Logistic regression model was used for multivariate analysis. Results:(1) Preoperative examinations. Of the 281 patients, 234 cases underwent preoperative pelvic magnetic resonance imaging (MRI) examina-tion. There were 2 cases in clinical stage T0, 3 cases in clinical stage T1, 58 cases in clinical stage T2, 137 cases in clinical stage T3, 24 cases in clinical stage T4, 3 cases in clinical stage Tx, 7 cases missing clinical T staging data. There were 87 cases in clinical stage N0, 68 cases in clinical stage N1, 60 cases in clinical stage N2, 9 cases in clinical stage Nx, 10 cases missing clinical N staging data. There were 30 cases with mesorectal fascia invasion, 53 cases with extramural venous invasion. The distance from lower margin of tumor to anal margin was 41.9(range, 1.0-80.0)mm. (2) Neoadjuvant therapy. Of the 281 patients, 125 cases underwent neoadjuvant therapy, including 39 cases receiving chemo-therapy alone, 6 cases receiving short-course simultaneous chemoradiotherapy, 5 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 48 cases receiving long-course simultaneous chemoradiotherapy, 2 cases receiving other treatments, and 25 cases missing neoadju-vant therapy data. (3) Postoperative examinations. Of the 281 patients, 249 cases achieved R 0 resection, 9 cases achieved R 1 resection, and there were 23 cases missing surgical margin data. The maximum tumor diameter, the number of lymph nodes harvested and positive rate of vessel carcinoma embolus were 30.0(range, 0.5-200.0)mm, 13(range, 0-70) and 27.55%(73/265) in 281 patients. There were 252 patients with circumferential margin records, showing positive in 15 cases, with a positive rate as 5.95%(15/252). The minimum distance from deep part of tumor to circumferential margin was 7.0(range, 0-150.0)mm in 252 patients. There were 85 cases with distal margin records, showing positive in 1 case, and the distance from lower margin of tumor to distal margin was 10.0(range, 0-202.0)mm. There were 273 patients with specimen integrity records, which showed intact specimen in 208 cases, fair specimen in 58 cases, poor specimen in 4 cases, unevaluated specimen in 3 cases. There were 7 cases with rectal perforation. Of the 281 patients, cases in pathological stage T0, Tis, T1, T2, T3, T4 were 14, 5, 22, 107, 113, 12, respectively, and there were 8 cases missing pathological T staging data. Of the 281 patients, cases in pathological stage N0, N1a, N1b, N1c, N2a, N2b were 176, 27, 27, 11,20, 12, respectively, and there were 8 cases missing pathological N staging data. Of the 281 patients, there were 4 cases with distant metastasis, 262 cases without distant metastasis, 5 cases not evaluated, and 10 cases missing tumor metastasis data. Of the 125 patients undergoing neoadjuvant therapy, there were 85 cases with tumor regression grade records, including 16 cases as grade 1, 27 cases as grade 2, 19 cases as grade 3, 15 cases as grade 4, 8 cases as grade 5. (4) Analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer. Results of univariate analysis showed that preoperative T staging on preoperative pelvic MRI, mesorectal fascia invasion, extramural venous invasion, pathological T staging, and pathological N staging were related factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer ( P<0.05). Conclusions:Intersph-incteric resection with transabdominal transanal mixed approach has good specimen quality and low positive rate of surgical margin. T staging on preoperative pelvic MRI may be related to positive circumferential margin after intersphincteric resection for rectal cancer.
7.Roxadustat attenuates heat stress-induced apoptosis and senescence in renal tubular epithelial cells by upregulating HIF-1α
Yongwei SONG ; Ling WANG ; Wenting CHEN ; Mingyang ZHANG ; Xuesen YANG ; Huanzi DAI
Journal of Army Medical University 2024;46(10):1092-1099
Objective To investigate the effect and underlying mechanism of roxadustat on apoptosis and senescence of renal tubular epithelial cell line HK-2 induced by heat stress.Methods After HK-2 cells were treated with different concentrations of roxadustat(10,20,30,40 and 50 μmol/L)for 24 h,CCK-8 assay was used to determine the optimal intervention concentration of roxadustat.HK-2 cells were divided into 4 groups(n=3):control group,roxadustat group(30 μmol/L,24 h),heat-stress group(43 ℃,2 h),and heat-stress+roxadustat group(30 μmol/L roxadustat treatmnet for 24 h followed by heat-stress 2 h).Cell viability was detected by CCK-8 assay.Expression of hypoxia-inducible factor-1α(HIF-1α),Cleaved Caspase-3,p16 and p21 at protein level was detected by Western blotting.Immunofluorescence assay was employed to observe the distribution of HIF-1α.β-galactosidase staining kit was utilized to detect SA-β-Gal activity.TUNEL staining was used to measure cell apoptosis.Results The highest cell viability was observed in the cells after 30 μmol/L roxadustat treatment.Heat stress resulted in a significant decrease in cell viability(P<0.05),elevated protein levels of HIF-1α,Cleaved Caspase-3,p16 and p21(P<0.05),enhanced SA-β-Gal activity(P<0.05)and increased percentage of TUNEL-positive cells(P<0.05)when compared with the cells in the control group.In comparison with the heat-stress group,the heat-stress+roxadustat group showed significant decrease in the protein levels of Cleaved Caspase-3,p16 and p21(P<0.05),reduced activity of SA-β-Gal[(65.44±5.00)%vs(77.15±2.61)%,P<0.05]and decreased percentage of TUNEL-positive cells[(16.73±2.20)%vs(46.40±13.87)%,P<0.05],but increase in cell viability[(86.33±4.51)%vs(66.33±8.50)%,P<0.05]as well as HIF-1α protein expression(P<0.05).Furthermore,immunofluorescence assay showed that HIF-1α was mainly distributed in the nucleus and perinucleus.Conclusion Roxadustat attenuates heat stress-induced apoptosis and senescence of renal tubular epithelial cells by upregulating HIF-1α.
8.Endovascular treatment for symptomatic non-acute long-segment occlusion of the internal carotid artery: comparison with drug therapy
Yue ZHU ; Chao HOU ; Shuxian HUO ; Qin YIN ; Xianjun HUANG ; Wen SUN ; Guodong XIAO ; Yong YANG ; Hongbing CHEN ; Min LI ; Mingyang DU ; Ruidong YE
International Journal of Cerebrovascular Diseases 2024;32(8):576-584
Objective:To investigate the clinical outcome of endovascular treatment vs. drug treatment in patients with symptomatic non-acute long-segment occlusion of the internal carotid artery. Methods:Based on prospective cohort registration research data, patients with symptomatic non-acute long-segment occlusion of internal carotid artery were retrospectively included. They were divided into a drug treatment group and an endovascular treatment group according to the actual treatment received. The latter was further divided into a successful recanalization group and an unsuccessful recanalization group. The endpoint events included ipsilateral ischemic stroke, any stroke, and all-cause death. Multivariate logistic regression analysis was used to compare the endpoint events between groups during the perioprocedural period (within 30 days), and multivariate Cox proportional hazards model was use to compare the endpoint events between the groups during the long-term follow-up. Results:A total of 684 patients were included, of which 570 (83.33%) were male, median aged 63 years (interquartile range, 56-70 years). Three hundred and fifty-three patients (51.6%) received drug treatment; 331 (48.4%) received endovascular treatment, of which 161 (48.6%) had successful recanalization. The median follow-up time was 1 223 days (interquartile range, 646.5-2 082 days), with 109 patients (15.9%) experiencing stroke recurrence events (including 87 ipsilateral ischemic stroke) and 78 (11.4%) experiencing all-cause mortality. The risk of any stroke during the perioprocedural period in the successful recanalization group was significantly higher than that in the drug treatment group (odds ratio 3.679, 95% confidence interval 1.038-13.036; P=0.044), but the risk of ipsilateral ischemic stroke recurrence (risk ratio 0.347, 95% confidence interval 0.152-0.791; P=0.012) and all-cause mortality (risk ratio 0.239, 95% confidence interval 0.093-0.618; P=0.003) during the long-term follow-up were significantly lower than those in the drug treatment group. Conclusions:In patients with symptomatic non-acute long-segment occlusion of the internal carotid artery, endovascular treatment can increase the risk of stroke recurrence within 30 days, but successful recanalization can reduce the risks of long-term ipsilateral ischemic stroke recurrence and all-cause mortality.
9.Disease burden due to PM2.5 pollution before and after air quality improvement in Shijiazhuang
Yue QU ; Fangting ZENG ; Fengge CHEN ; Mingyang GUAN
Journal of Environmental and Occupational Medicine 2024;41(3):294-302
Background Air pollution has gradually become a major environmental and public health problem faced by countries around the world. Hazy weather not only affects the health of the population, but also poses a threat to social and public safety. China has successively promulgated policies such as the "Ten Articles on Atmosphere" and the Three-year action plan to fight air pollution, aiming to improve ambient air quality. It is clear that the Beijing-Tianjin-Hebei region has accomplished the set targets and improved air quality according to the environmental monitoring data of 2017. Objective To assess air quality improvements through the evaluation of the disease burden due to fine particulate matter (PM2.5) pollution in Shijiazhuang City before and after the air quality improvement from 2014 to 2021, including fatalities and health economic losses attributed to PM2.5 pollution. Methods Data on causes of death, PM2.5 concentrations, the number of permanent residents at the end of the year, gross regional product, and disposable income per capita in urban areas of Shijiazhuang were collected from 2014 to 2021. Total, non-accidental, circulatory, and respiratory deaths due to PM2.5 pollution were estimated by global exposure mortality models (GEMM). Health and economic losses due to selected diseases were calculated by value of statistical life (VOSL). Results During the study period, the average annual concentration of PM2.5 in Shijiazhuang was highest in 2014, and began to decline year by year in 2017, but all exceeded the current national limit of the second level of ambient air quality standards (35 μg·m−3). The total deaths, non-accidental deaths, circulatory disease deaths, and respiratory disease deaths attributed to PM2.5 pollution from 2014 to 2021 were 41326, 40246, 21792, and 5022, respectively; the associated health economic losses were 37.362, 36.369, 19.695, and 4.535 billion yuan, respectively. From the perspective of improved air quality, both the number of attributed deaths and health economic losses had declined in a volatile manner since 2017, with a significant decrease in 2019. If the average annual concentration of PM2.5 reached the second-level limit of China's ambient air quality standard (35 μg·m−3), the total deaths, non-accidental deaths, and deaths from circulatory diseases and respiratory diseases due to PM2.5 pollution would deducted by about 17000, 16000, 9000, and 2000, respectively; the corresponding health and economic losses would decreased by 15.201, 14.761, 7.959, and 1.859 billion yuan, respectively. If the average annual concentration of PM2.5 reached the latest PM2.5 air quality guidelines (5 μg·m−3) proposed by the World Health Organization, the total deaths, non-accidental deaths, circulatory disease deaths, and respiratory disease deaths due to PM2.5 pollution would deducted by 36000, 35000, 19000, and 4000, respectively, and the corresponding health and economic losses would reduced by 32.673, 31.796, 17.211, and 3.969 billion yuan, respectively. Conclusion PM2.5 pollution can lead to severe mortality burden and economic loss. Under the implementation of the State Council's "Ten Articles on Atmosphere" and the Three-year action plan to fight air pollution, Shijiazhuang's PM2.5 concentration and health economic losses have been significantly reduced, and further control of PM2.5 pollution can achieve greater health benefits and economic gains, affirming the positive results of local air pollution prevention work.
10.Nuanxinkang Inhibits Endothelial-to-Mesenchymal Transition to Reduce Plaque Formation in Mice with Obstructive Sleep Apnea-Hypopnea Syndrome Comorbid with Atherosclerosis
Mingyang WANG ; Lingjun WANG ; Birong LIANG ; Zixin CHEN ; Yanhong CAO ; Yubing ZHANG ; Shuxian LI ; Jing LIU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):789-797
Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P<0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P<0.01).The number of CD31 positive cells in the plaque were significantly decreased(P<0.01),and the number of Vimentin positive cells were significantly increased(P<0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P<0.01),and HDL-C level was significantly decreased(P<0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P<0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P<0.05,P<0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P<0.05,P<0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P<0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P<0.05,P<0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P<0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P<0.05,P<0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P<0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P<0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.

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