1.Associations between exposure to perfluoroalkyl substances and estimated glomerular filtration rate in population without kidney disease
Ruifang LIU ; Hongbo LIU ; Shu NI ; Jiemin WEI ; Yu CHEN ; Kun MEN ; Jingyun ZHANG ; Liangpo LIU ; Ze YANG ; Naijun TANG
Journal of Environmental and Occupational Medicine 2023;40(4):448-455
Background Perfluoroalkyl substances (PFASs) are classified as persistent organic pollutants and have been widely detected in human. Studies investigating the associations between PFASs exposure and estimated glomerular filtration rate (eGFR) yielded inconsistent results, and little is known about the effects of PFASs on eGFR in population without kidney disease. Objective To explore the associations of exposure to PFASs with eGFR and renal dysfunction in population without kidney disease. Methods A total of 609 participants with an eGFR > 60 mL·min−1·1.73 m−2 and without renal impairment matched for sex and age (1∶1) were recruited from endocrinology department and medical examination center of two hospitals in Tianjin, China, from April 2021 to March 2022. Each subject was interviewed using a structured questionnaire to collect information about sex, age, height, weight, disease history, smoking, alcohol intake, etc. Clinical parameters were obtained from medical record, such as fasting blood glucose (FBG), creatinine (Cre), total cholesterol (TC), and triglyceride (TG). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by professionals using standard methods. The serum concentrations of PFASs were determined by liquid chromatography/mass spectrometry. Multivariable linear and logistic regression models were performed to evaluate the associations of PFASs exposure with eGFR and renal dysfunction, respectively. Subgroup analyses stratified by age and sex were also performed to assess the modified effects of covariates on the associations of PFASs exposure with eGFR. Results There were 283 males, accounting for 46.5% of the total population. The mean age of the participants was (56.86±12.47) years, and the average body mass index (BMI) was (25.59±3.84) kg·m−2. Perfluoro-n-octanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoro-n-nonanoic acid (PFNA), perfluoro-n-decanoic acid (PFDA), perfluoro-n-undecanoic acid (PFUnDA), sodium 1H, 1H, 2H, 2H-perfluoro-1-octanesulfonate (6:2 FTS), and perfluoropentane sulfonic acid (PFPeS) were positive in more than 75% of serum samples, and the corresponding median concentrations were 9.50, 1.67, 17.22, 1.86, 1.41, 0.78, 0.42, and 0.43 μg·L−1, respectively. After full adjustments of sex, age, BMI, hypertension, diabetes, TC, TG, smoking, and drinking, the linear regression models showed that log2-transformed PFHxS concentration was negatively associated with eGFR (b=−1.160, 95%CI: −2.280, −0.410). Compared with the lowest exposure tertile, the estimated change of eGFR in the highest tertile for PFHxS was significantly decreased (b=−2.471, 95%CI: −4.574, −0.368). Furthermore, compared with males, the negative association of PFHxS with eGFR was strengthened among females (female: b=−1.281, 95%CI: −2.388, −0.174; male: b=−0.781, 95%CI: −2.823, 1.261, Pinteraction=0.043). Conclusion A significant negative association between serum PFHxS and eGFR is observed in the sampled population without kidney disease, and females are more susceptible to PFASs exposure than the males.
2.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
;
Female
;
Humans
;
Aged
;
Natriuretic Peptide, Brain
;
Simendan/therapeutic use*
;
Non-ST Elevated Myocardial Infarction
;
Heart Failure/drug therapy*
;
Peptide Fragments
;
Arrhythmias, Cardiac
;
Biomarkers
;
Prognosis
3.Effect of complete revascularization in acute coronary syndrome after 75 years old: insights from the BleeMACS registry.
Ge WANG ; Xiu-Huan CHEN ; Si-Yi LI ; Ze-Kun ZHANG ; Wei GONG ; Yan YAN ; Shao-Ping NIE ; José P HENRIQUES
Journal of Geriatric Cardiology 2023;20(10):728-736
BACKGROUND:
The prognostic benefit of complete revascularization in elderly patients (aged over 75 years) with multi-vessel disease and acute coronary syndrome (ACS) is currently unclear. This study aimed to determine the long-term prognostic impact of complete revascularization in this population.
METHODS:
We conducted this study using data obtained from the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) registry, which was carried out from 2003 to 2014. The objective was to categorize older patients diagnosed with ACS into two groups: those who underwent complete revascularization and those who did not. Propensity score matching and the Kaplan-Meier analysis were employed to examine differences in one-year clinical outcomes. The primary endpoint was major adverse cardiovascular event (MACE), which encompassed a combination of all-cause mortality and myocardial infarction.
RESULTS:
Out of 1263 patients evaluated, 445 patients (35.2%) received complete revascularization. Patients who underwent complete revascularization had a higher prevalence of hypertension and prior percutaneous coronary intervention compared to those who did not. During the one-year follow-up period, complete revascularization was associated with a significantly decreased risk of MACE [13.7% vs. 20.5%, hazard ratio (HR) = 0.63, 95% CI: 0.45-0.88, P = 0.007] and a lower risk of myocardial infarction (5.9% vs. 9.9%, HR = 0.55, 95% CI: 0.33-0.92, P = 0.02). However, it was not linked to a lower risk of all-cause death (9.5% vs. 13.5%, HR = 0.68, 95% CI: 0.45-1.02, P = 0.06). Similar results were observed in the subgroup analysis.
CONCLUSIONS
Long-term clinical improvements were observed in ACS patients aged over 75 years with multi-vessel disease who achieved complete revascularization. Therefore, adhering to guidelines for complete revascularization should be recommended for elderly patients.
4.Diagnostic efficiency and incremental value of myocardial blood flow quantification by CZT SPECT for patients with coronary artery disease.
Ze Kun PANG ; Jiao WANG ; Yue CHEN ; Hong Xin CHU ; Meng Yan ZHANG ; Jian Ming LI
Chinese Journal of Cardiology 2022;50(5):494-500
Objective: To investigate the diagnostic efficiency and incremental value of quantitative myocardial blood flow measurements by Cadmium-Zine-Telluride (CZT) single photon emission computed tomography (SPECT) dynamic myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) compared with traditional semi-quantitative measurements by MPI. Methods: This is a retrospective, cross-sectional study. We retrospectively analyzed clinical data of patients with suspected or known CAD, who underwent the dynamic MPI quantitative blood flow measurement of CZT SPECT in TEDA International Cardiovascular Hospital from October 2018 to December 2020. Clinical data, semi-quantitative parameters (stress score (SS), rest score (RS) and different score (DS)) and myocardial quantitative blood flow parameters (rest myocardial blood flow (rMBF), stress myocardial blood flow (sMBF) and myocardial flow reserve (MFR)) were analyzed. According to the results of coronary angiography, patients were divided into the stenosis group and the control group with coronary artery stenosis ≥50% or ≥75% as the diagnosis criteria. The differences of quantitative and semi-quantitative parameters between the two groups were compared, and the diagnostic efficacy was compared by receiver operating characteristic(ROC) curve. Results: A total of 98 patients with a mean age of (62.1±8.7) years were included in the study, including 66 males (67%). At the patient level, with the positive standard of coronary artery stenosis≥50%, the left ventricle (LV) stress MBF (LV-sMBF) ((1.36±0.45) ml·min-1·g-1) and LV-MFR (1.45±0.43) of the stenosis group were lower than the LV-sMBF ((2.09±0.64) ml·min-1·g-1) and LV-MFR (2.17±0.54) of control group; summed SS and summed DS were higher than control group (all P<0.05). With the positive standard of coronary artery stenosis ≥75%, the LV-sMBF ((1.19±0.34) ml·min-1·g-1) and LV-MFR (1.34±0.35) of stenosis group were lower than the LV-sMBF ((1.94±0.63) ml·min-1·g-1) and MFR (2.00±0.58) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). At the vascular level, with coronary artery stenosis ≥50% as the diagnosis criteria, the sMBF ((1.26±0.49) ml·min-1·g-1) and MFR (1.35±0.46) of stenosis group were lower than the sMBF ((1.95±0.70) ml·min-1·g-1) and MFR (2.05±0.65) of control group; SS and DS were higher than control group (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the sMBF ((1.12±0.41) ml·min-1·g-1) and MFR (1.25±0.38) of stenosis group were lower than the sMBF ((1.84±0.70) ml·min-1·g-1) and MFR (1.93±0.66) of control group; all semi-quantitative parameters were higher than control group (all P<0.05). With coronary artery stenosis≥50% as the diagnosis criteria and CAG as the reference standard, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.830 (0.783-0.877). The sensitivity (86.1% vs. 61.5%), specificity (82.6% vs. 73.8%), positive predictive value (77.8% vs. 62.5%), negative predictive value (89.3% vs. 73.0%) and accuracy (84.0% vs. 68.7%) were all higher than the semi-quantitative parameters (all P<0.05). With coronary artery stenosis≥75% as the diagnosis criteria, the AUC and 95%CI of myocardial quantitative blood flow parameters indicated by ROC curve for diagnosis of CAD were 0.832(0.785-0.879). The sensitivity (89.2% vs. 67.6%), negative predictive value (95.5% vs. 86.2%) and accuracy (80.6% vs. 68.0%) were all higher than semi-quantitative parameters (all P<0.05). Conclusion: Compared with traditional SPECT MPI derived semi-quantitative parameters, diagnostic efficacy for CAD is higher using CZT SPECT quantitative myocardial blood flow parameters, this strategy thus has additional diagnostic benefits and incremental value on the diagnosis of CAD.
Aged
;
Constriction, Pathologic
;
Coronary Angiography
;
Coronary Artery Disease/diagnostic imaging*
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Coronary Stenosis/diagnostic imaging*
;
Cross-Sectional Studies
;
Humans
;
Male
;
Middle Aged
;
Myocardial Perfusion Imaging/methods*
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Retrospective Studies
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Tomography, Emission-Computed, Single-Photon/methods*
5.Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma.
Ze Kun WANG ; Jiang Hu ZHANG ; Xue Song CHEN ; Qing Feng LIU ; Jing Bo WANG ; Run Yu WU ; Ye ZHANG ; Kai WANG ; Yuan QU ; Xiao Dong HUANG ; Jian Ping XIAO ; Li GAO ; Guo Zhen XU ; Jun Lin YI ; Jing Wei LUO
Chinese Journal of Oncology 2022;44(2):185-191
Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.
Carcinoma, Adenoid Cystic/pathology*
;
Humans
;
Paranasal Sinus Neoplasms/therapy*
;
Prognosis
;
Proportional Hazards Models
;
Retrospective Studies
6.Equol and its enantiomers inhibited urethane-induced lung cancer in mice.
Xue YU ; Yong Qiu ZOU ; Ying WANG ; Ze Kun CHEN ; De Fu MA
Journal of Peking University(Health Sciences) 2022;54(2):244-248
OBJECTIVE:
To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice.
METHODS:
A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison.
RESULTS:
A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups.
CONCLUSION
Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.
Animals
;
Body Weight
;
Equol
;
Genistein
;
Lung Neoplasms/prevention & control*
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Male
;
Mice
;
Mice, Inbred C57BL
;
NF-E2-Related Factor 2
;
Superoxide Dismutase
;
Urethane/toxicity*
7. Panax notoginseng saponins regulates hematopoietic function of bone marrow in aplastic anemia mice via TLR4/TLR2-NF-kB pathway
Shan-Shan CHEN ; Ze-Bin WU ; Kun MA ; Xiao-Min ZHANG ; Ling-Ling ZHU
Chinese Pharmacological Bulletin 2022;38(7):1052-1058
Aim To explore the effects of Panax notog- inseng saponins( PNS) on hematopoietic functions anrl regulation on the TLR4/TLR2-NF-kB signaling path¬way in immune-mediated aplastic anemia ( AA ) C57 mice.Methods C57BL/6 mice were randomly divid¬ed into control group, total body irradiation group ( TBI) , model group, cyclosporine treatment group, PNS low-dose group, medium-dose group and high-dose group.The immune-mediated A A mice model was es¬tablished by total body irradiation with 5.0 Gy X-ray and mixed lymphocyte infusion.The body weight was measured, the spleen and thymus index was calculated , bone marrow pathology, the levels of peripheral blood triline cells,bone marrow nucleated cells( BMCs) and the levels of serum TNF-cx , 1L-2 , 1L-10 were detected, and the expression of CD1 lc and proteins related to the TLR4/TLR2-N F- k B pathway were detected 15 days later.Results Compared with control group, body weight, thymus index, the number of peripheral blood triline cells, BMCs and serum 1L-10 levels of the mice in model group significantly decreased ( P < 0.05 ) , while spleen index, the serum TNF-a, IL-2 levels and the protein expression of CD 11 c, TLR4, TLR2 , MvD88 , Akt and NF-kB in hone marrow significantly increased ( P <0.05).Compared with model group, after PNS treatment, hodv weight, thymus index, the number of peripheral blood triline cells, BMCs and serum IL-10 levels increased.Spleen index,serum TNF-cx,lL-2 lev¬els and the expression of CD11 c, TLR4, TLR2, NF-kB and Akt in bone marrow decreased, and the therapeutic effect was not dose-dependent.There was no signifi¬cant change in the expression of MvD88 and MAPK proteins.Conclusions PNS can improve AA bone marrow injury, regulate immune disoders and promote hematopoiesis, which may be related to the regulation of the number of DCs and the TLH4/TLH2 - Akt- NF-kB pathway in bone marrow.
8.The expression and significance of TRPM8 among chronic rhinosinusitis with nasal polyps.
Xiao Ting TONG ; Pei Qiang LIU ; Hui Qin ZHOU ; Jing JIN ; Kun Yu LIU ; Jing Yu HUANG ; Wei ZHANG ; Shi Ming CHEN ; Ze Zhang TAO ; Yu XU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(10):1059-1065
Objective: To compare the expression and difference of melastatin-related transient receptor potential 8(TRPM8) among chronic rhinosinusitis, nasal polyps and normal mucosa tissues. And to explore the significant expression of TRPM8 among CRSwNP. Methods: Fifty-one patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from February 2019 to January 2020 were recruited, including 33 males and 18 females, aged from 14 to 65 years old (34.55±1.689).Immunohistochemistry was used to detected the expression of TRPM8 protein among CRSsNP(17),CRSwNP (17) and control tissuses(17). In addition, the correlation between the expression of TRPM8 protein in CRSwNP patients and preoperative CT Lund-Mackay scores and preoperative VAS scores and sinonasal outcome test-20 scores was analyzed, respectively. The primary human nasal epithelial cells were cultured in vitro and the expression of TRPM8 was detected by quantitative real-time PCR and western blotting . The tissue in control group, chronic rhinosinusitis without nasal polyps (CRSsNP) group and the CRSwNP group were collected and grinded into tissue homogenized. The expression of TRPM8 protein was detected by western blotting after 24 h stimulation after homogenate was added into the medium of RPMI 2650 and primary nasal epithelial cells. Results: Compared with the control, the expression of TRPM8 was significantly up-regulated in nasal polyps (t=6.852, P<0.05). TRPM8 was mainly expressed in epithelial cells. The expression of TRPM8 in the epithelial cells of CRSsNP had no difference with the control group (t=1.980, P>0.05). In addition, the expression of TRPM8 in CRSwNP patients was positively correlated with the preoperative CT Lund-Mackay scores and VAS scores and SNOT-20 scores (r=0.512, P<0.05;r=0.853, P<0.01;r=0.814, P<0.01). After cultured primary epithelial cells in vitro, the expression level of TRPM8 in epithelial cells derived from nasal polyp was significantly higher than that in control group (t=8.845, P<0.05). By adding the homogenization of control and CRSsNP and CRSwNP tissues, the expression of TRPM8 in RPMI 2650 cells and primary nasal epithelial cells was changed and that was significantly increased after adding the homogenization of the group of CRSwNP. Conclusion: TRPM8 is highly expressed in nasal polyps epithelial cells, suggesting that TRPM8 may be involved in the pathogenesis of nasal polyps regulated by nasal epithelial cells.
Adolescent
;
Adult
;
Aged
;
Chronic Disease
;
Endoscopy
;
Female
;
Humans
;
Male
;
Membrane Proteins
;
Middle Aged
;
Nasal Polyps
;
Rhinitis
;
Sinusitis
;
TRPM Cation Channels
;
Young Adult
9.The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop.
Yao-Dong CHEN ; Fang-Yu CAI ; Yu-Ze MAO ; Yong-Sheng YANG ; Kun XU ; Xiao-Fang LIU ; Wen-Wen FAN ; Wu CHEN ; Feng-Qi JIANG ; Hui ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2021;19(11):815-824
Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.
Animals
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Apoptosis
;
Cell Line, Tumor
;
Cell Movement
;
Cell Proliferation
;
Feedback
;
Female
;
HeLa Cells
;
Humans
;
Interleukin-6/genetics*
;
Janus Kinase 1
;
Mice
;
Mice, Nude
;
Quinolizidines
;
STAT3 Transcription Factor/genetics*
;
Signal Transduction
;
Uterine Cervical Neoplasms/drug therapy*
10.The effect of procyanidin on periprosthetic osteolysis caused by TCP wear particles in the mouse calvaria and its mechanism.
Kun LIN ; Jia-Hao CHEN ; Ze-Hao FANG ; Cheng-Long YE ; Chao-Jie HAN ; Ming YAN ; Jian FANG ; Yun ZHANG
Chinese Journal of Applied Physiology 2019;35(3):250-255
OBJECTIVE:
To investigate the protective effects of procyanidin on periprosthetic osteolysis caused by tricalcium phosphate (TCP) wear particles in the mouse calvaria and its mechanism.
METHODS:
Forty-eight male ICR mice were randomly divided into sham group, TCP group, and procyanidin (0.2 mg/kg, 1 mg/kg, 5 mg/kg)-treated group (n=12). A periprosthetic osteolysis model in the mouse calvaria was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2 day post-operation, procyanidin (1 mg/kg, 5 mg/kg) was locally injected to the calvaria under the periosteum every other day. After 2 weeks, all the mice were sacrificed to collect the blood samples and the calvaria. Periprosthetic osteolysis and osteoclastogenesis in the mouse calvaria were observed by tartrate resistant acid phosphatase (TRAP) staining and HE staining. mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 in the periprosthestic bone tissue were examined by real-time fluorescence quantitative PCR. Serum contents of total anti-oxidation capacity (T-AOC) and MDA, and superoxide dismutase (SOD) activity were determined by chemical colorimetry. Protein expressions of autophagic biomarkers such as Beclin-1 and LC-3 in periprosthetic bone tissue of the calvaria were examined by Western blot.
RESULTS:
Compared with sham group, periprosthetic osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1, and serum MDA content were increased significantly in the TCP group (P<0.05), whereas serum T-AOC level and SOD activity were decreased. The protein expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were both up-regulated markedly in the mouse calvaria of TCP group (P<0.05). Compared with TCP group, osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 and serum MDA content were decreased obviously in the procyanidine group (P<0.05), serum T-AOC level and SOD activity were increased, the expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were down-regulated obviously in the mouse calvaria of procyanidin group (P<0.05).
CONCLUSION
Procyanidin has a protective effect of periprosthetic osteolysis caused by TCP wear particles in the mouse calvaia, its mechanism may be mediated by inhibition of oxidative stress and autophagy.
Animals
;
Autophagy
;
Biflavonoids
;
pharmacology
;
Calcium Phosphates
;
adverse effects
;
Catechin
;
pharmacology
;
Male
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Mice
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Mice, Inbred ICR
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Osteolysis
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Oxidative Stress
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Proanthocyanidins
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pharmacology
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Prostheses and Implants
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adverse effects
;
Random Allocation
;
Skull

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