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1.
Zhongguo Zhen Jiu ; 41(10): 1147-52, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34628749

RESUMO

The appropriate sample size estimation is very important in the design of clinical trials. However, insufficient or inappropriate sample size estimation is still a prominent problem in the currently published acupuncture and moxibustion clinical trials. At present, the superiority test, non-inferiority test and equivalence test have been widely used in acupuncture and moxibustion clinical trials. This article focuses on the application, calculation methods and PASS11 software using of these three hypothesis test types. In view of the problems in the estimation of sample size in acupuncture and moxibustion clinical trials, the particularity of sample size estimation in acupuncture and moxibustion is summarized from the aspects of parameter setting, ratio of intervention group and control group, and multi-group comparison, in order to guide acupuncture clinical researchers to correctly estimate sample size when conducting clinical trials.


Assuntos
Terapia por Acupuntura , Acupuntura , Moxibustão , Ensaios Clínicos como Assunto , Tamanho da Amostra
2.
Life Sci ; 286: 120039, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34637797

RESUMO

AIM: This study investigated the roles of bone morphogenetic protein-4 (BMP4) and ROS in diabetic endothelial dysfunction and explored whether Salvianolic acid B (Sal B) improved endothelial function by affecting BMP4-ROS in diabetic mice. MAIN METHODS: db/db mice were orally administrated with Sal B (10 mg/kg/day) for one week while db/m + mice were injected with adenoviral vectors delivering BMP4 (3 × 108 pfu) and then received one week-Sal B treatment. ROS levels were assayed by DHE staining. Protein expression and phosphorylation were evaluated by Western blot. Aortic rings were suspended in myograph for force measurement. Flow-mediated dilatations in the second-order mesenteric arteries were determined by pressure myograph. KEY FINDINGS: We first revealed the existence of a BMP4-ROS cycle in db/db mice, which stimulated p38 MAPK/JNK/caspase 3 and thus participated in endothelial dysfunction. One week-treatment or 24 h-incubation with Sal B disrupted the cycle, suppressed p38 MAPK/JNK/caspase 3 cascade, and improved endothelium-dependent relaxations (EDRs) in db/db mouse aortas. Importantly, in vivo Sal B treatment also improved flow-mediated dilatation in db/db mouse second order mesenteric arteries. Furthermore, in vivo BMP4 overexpression induced oxidative stress, stimulated p38 MAPK/JNK/caspase 3, and impaired EDRs in db/m + mouse aortas, which were all reversed by Sal B. SIGNIFICANCE: The present study demonstrates that Sal B ameliorates endothelial dysfunction through breaking the BMP4-ROS cycle and subsequently inhibiting p38 MAPK/JNK/caspase 3 in diabetic mice and provides evidence for the additional new mechanism underlying the benefit of Sal B against diabetic vasculopathy.

3.
Cell Discov ; 7(1): 99, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34697287

RESUMO

Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8+ T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.

4.
Front Pharmacol ; 12: 723922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504429

RESUMO

Background: Endothelial barrier dysfunction plays a key role in atherosclerosis progression. The primary pathology of obstructive sleep apnea-hypopnea syndrome is chronic intermittent hypoxia (IH), which induces reactive oxygen species (ROS) overproduction, endothelial barrier injury, and atherosclerosis. Salidroside, a typical pharmacological constituent of Rhodiola genus, has documented antioxidative, and cardiovascular protective effects. However, whether salidroside can improve IH-aggravated endothelial barrier dysfunction and atherosclerosis has not been elucidated. Methods and results: In normal chow diet-fed ApoE-/- mice, salidroside (100 mg/kg/d, p. o.) significantly ameliorated the formation of atherosclerotic lesions and barrier injury aggravated by 7-weeks IH (21%-5%-21%, 120 s/cycle). In human umbilical vein endothelial cells (HUVECs), exposure to IH (21%-5%-21%, 40 min/cycle, 72 cycles) decreased transendothelial electrical resistance and protein expression of vascular endothelial cadherin (VE-cadherin) and zonula occludens 1. In addition, IH promoted ROS production and activated ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway. All of these effects of IH were reversed by salidroside. Similar to salidroside, ROCK-selective inhibitors Y26732, and Fasudil protected HUVECs from IH-induced ROS overproduction and endothelial barrier disruption. Furthermore, salidroside increased intracellular cAMP levels, while the PKA-selective inhibitor H-89 attenuated the effects of salidroside on IH-induced RhoA/ROCK suppression, ROS scavenging, and barrier protection. Conclusion: Our findings demonstrate that salidroside effectively ameliorated IH-aggravated endothelial barrier injury and atherosclerosis, largely through the cAMP/PKA/RhoA signaling pathway.

5.
Am J Clin Pathol ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519765

RESUMO

OBJECTIVES: Recent clinical trials have demonstrated significant clinical benefits from novel therapeutic compounds in breast cancer patient with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) score of 1+ or 2+ and negative in situ hybridization (ISH) result. A new concept of "HER2-low" breast cancer has been proposed and applied in the recent and ongoing clinical trials. In this article, we review the literature on the topic of HER2-low breast cancer. METHODS: A literature search in PubMed was performed using key words related to HER2-low breast cancer. Major relevant studies that were presented in international breast cancer conferences were also included. RESULTS: HER2-low breast cancer is currently defined as breast cancer with HER2 IHC score of 1+ or 2+ and negative ISH result. It likely represents a group of tumors with significant biological heterogeneity. Reports of clinical activity using the next generation of HER2-targeting antibody-drug conjugates in HER2-low breast cancers suggest that some strategies of targeting HER2 might be effective in this patient population while raising considerable concerns over limitations in our current testing methodologies and our ability to accurately identify such patients. CONCLUSIONS: The promising efficacy of novel HER2-targeted therapy in advanced HER2-low breast cancers has raised the possibility for changing the clinical interpretation of HER2 status in breast cancer to include a HER2-low category; however, the definition of HER2-low breast cancer, the corresponding reliable and accurate quantitative HER2 testing methodology, and the biology of HER2-low breast cancer remain poorly defined.

6.
Clin Chim Acta ; 522: 70-76, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34390687

RESUMO

BACKGROUND: Inflammatory response plays a critical role in the initiation and progression of type 2 diabetes mellitus (T2DM). Myeloperoxidase (MPO), a leukocyte-derived protagonist, exerts its proinflammatory properties in many complications. We explored the associations between serum extracellular vesicle (EV)-derived MPO as well as serum MPO and T2DM. METHODS: We performed a cross-sectional study in 151 individuals, including 93 patients with T2DM and 58 non-T2DM controls. The concentrations of serum EV-derived MPO and serum MPO were measured by Luminex Assay. RESULTS: Our data showed that serum EV-derived MPO concentrations and serum MPO concentrations were significantly higher in T2DM patients compared with non-T2DM subjects. In addition, multivariate logistic regression analysis revealed that serum EV-derived MPO as well as serum MPO was independently associated with the presence of T2DM even after adjusting for confounding factors (OR = 1.836 /1 ng EV-derived MPO, 95% CI = 1.395-2.417, P < 0.001; OR = 4.135 /10 ng serum MPO, 95% CI = 2.285-7.483, P < 0.001). Furthermore, serum MPO showed marginally higher discriminatory accuracy than serum EV-derived MPO in screening T2DM (AUC = 0.858; AUC = 0.779). CONCLUSION: Increased concentrations of the inflammatory marker MPO either in serum or in serum EVs were independently associated with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Biomarcadores , Estudos Transversais , Humanos , Peroxidase
7.
Life Sci ; 283: 119866, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352257

RESUMO

AIMS: Morphine, a commonly used drug for anesthesia, affects lipid metabolism in different tissues, but the mechanism is currently unclear. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme responsible for the first step of triglyceride (TG) hydrolysis. Here we aim to investigate whether ATGL phosphorylation is involved in morphine-induced TG accumulation. MAIN METHODS: Oil red O staining and TG content analysis were used to detect the effect of morphine on lipid storage. A series of ATGL phosphoamino acid site mutant plasmids were constructed by gene synthesis and transfected to HL-1 cells to evaluate the phosphorylation levels of ATGL phosphoamino acid in morphine-treated HL-1 cells with immunoprecipitation and immunoblotting assay. KEY FINDINGS: Morphine acute treatment induced excessive accumulation of TG and decreased the phosphorylation level of ATGL Ser406 in HL-1 cells. Of note, the phosphorylation positive mutation of ATGL Ser406 to aspartic acid effectively reversed morphine-induced excessive accumulation of TG in HL-1 cells. SIGNIFICANCE: This discovery will help to fully understand the lipid regulation function of morphine in a new scope. In addition, it will expand the phosphorylation research of ATGL more comprehensively and provide powerful clues for lipid metabolism regulation.


Assuntos
Lipase/metabolismo , Morfina/farmacologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Triglicerídeos/biossíntese , Animais , Linhagem Celular , Masculino , Camundongos , Morfina/farmacocinética , Miocárdio/patologia , Miócitos Cardíacos/patologia , Fosforilação/efeitos dos fármacos
8.
Sci Total Environ ; 790: 148220, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380245

RESUMO

With changing numbers, compositions, emission standards and fuel quality of on-road vehicles, it is imperative to accordingly characterize and update vehicular emissions of carbonaceous aerosols for better understanding their health and climatic effects. In this study, a 7-day field campaign was conducted in 2019 in a busy urban tunnel (>30,000 vehicles day-1) in south China with filter-based aerosol samples collected every 2 h at both the inlet and the outlet for measuring carbonaceous aerosols and their light absorbing properties. Observed fleet average emission factor (EF) of total carbon (TC) was 13.4 ± 8.3 mg veh-1 km-1, and 17.4 ± 11.3 mg veh-1 km-1 if electric and LPG-driven vehicles were excluded; and fleet average EF of organic carbon (OC) and elemental carbon (EC) was 8.5 ± 6.6 and 4.9 ± 2.6 mg veh-1 km-1 (11.0 ± 8.8 and 6.3 ± 3.6 mg veh-1 km-1 if excluding electric and LPG vehicles), respectively. Regression analysis revealed an average TC-EF of 319.8 mg veh-1 km-1 for diesel vehicles and 2.1 mg veh-1 km-1 for gasoline vehicles, and although diesel vehicles only shared ~4% in the fleet compositions, they still dominate on-road vehicular carbonaceous aerosol emissions due to their over 150 times higher average TC-EF than gasoline vehicles. Filter-based light absorption measurement demonstrated that on average brown carbon (BrC) could account for 19.1% of the total carbonaceous light absorption at 405 nm, and the average mass absorption efficiency of EC at 635 nm and that of OC at 405 nm were 5.2 m2 g-1 C and 1.0 m2 g-1 C, respectively.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , Carbono/análise , China , Monitoramento Ambiental , Material Particulado/análise , Emissões de Veículos/análise
9.
PeerJ ; 9: e11785, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395072

RESUMO

Backgroud: This study's objectives were to compare the clinical, perinatal, and obstetrical outcomes of patients with different estradiol (E2) levels in fresh single-blastocyst-transfer (SBT) cycles under an early follicular phase prolonged regimen on the day of trigger. Methods: We recruited patients in fresh SBT cycles (n = 771) undergoing early follicular phase prolonged protocols with ß-hCG values above 10 IU/L between June 2016 and December 2018. Patients who met the inclusion and exclusion criteria were divided into four groups according to their serum E2 level percentages on the day of trigger: <25th, 25th-50th, 51st-75th, and >75th percentile groups. Results: Although the rates of clinical pregnancy (85.57% (166/194)), embryo implantation 86.60% (168/194), ongoing pregnancy (71.13% (138/194)), and live birth (71.13% (138/194)) were lowest in the >75th percentile group, we did not observe any significant differences (all P > 0.05). We used this information to predict the rate of severe ovarian hyperstimulation syndrome (OHSS) area under the curve (AUC) = 72.39%, P = 0.029, cut off value of E2 = 2,893 pg/ml with the 75% sensitivity and 70% specificity. The 51st-75th percentile group had the highest rates of low birth weight infants (11.73% (19/162), P = 0.0408), premature delivery (11.43% (20/175), P = 0.0269), admission to the neonatal intensive care unit (NICU) (10.49% (17/162), P = 0.0029), twin pregnancies (8.57% (15/175), P = 0.0047), and monochorionic diamniotic pregnancies (8.57% (15/175); P = 0.001). We did not observe statistical differences in obstetrics complications, including gestational diabetes mellitus (GDM), gestational hypertension, placenta previa, premature rupture of membranes (PROM), and preterm premature rupture of membranes (PPROM). Conclusion: We concluded that serum E2 levels on the day of trigger were not good predictors of live birth rate or perinatal and obstetrical outcomes. However, we found that high E2 levels may not be conducive to persistent pregnancies. The E2 level on the day of trigger can still be used to predict the incidence of early onset severe OHSS in the fresh SBT cycle.

10.
Curr Eye Res ; : 1-10, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34323621

RESUMO

PURPOSE: The overexpression of transforming growth factor-beta1 (TGF-ß1) after surgical excision often leads to excessive fibrosis, indicating the recurrence of pterygium. The aims of the present in vitro study were to investigate the role of RhoA/ROCK signaling in regulating fibrotic effects of primary human pterygium fibroblasts (HPFs), as well as to explore the possible mechanisms of these effects. METHODS: Pterygium samples were obtained from surgery, and profibrotic activation was induced by TGF-ß1. Cell proliferation was detected by CCK-8 assay; cell migration was detected by wound healing assay; quantitative real-time PCR and Western blot were used to detect the effects of TGF-ß1 and the role of RhoA/ROCK signaling in the synthesis of alpha-smooth muscle actin (a-SMA), type I and III collagen (COL1 and COL3), and matrix metalloproteinase-9 (MMP9) in HPFs. The changes of signaling pathways were detected by Western blot; and pharmaceutical inhibition of RhoA/ROCK signaling and its downstream MRFT-A/SRF transcription pathway were used to assess their possible mechanism in HPFs fibrosis. RESULTS: ROCK inhibitor Y-27632 decreased TGF-ß1-induced cell proliferation and migration, reduced the TGF-ß1-induced expression of profibrotic markers in HPFs, and suppressed TGF-ß1-induced nuclear accumulation of Myocardin-related transcription factor A (MRTF-A) as well as accompanied elevation of F/G-actin ratio in HPFs. MRTF-A/Serum response factor (SRF) inhibitor CCG-100602 attenuated the TGF-ß1-induced α-SMA expression and reduced myofibroblast activation in HPFs. CONCLUSIONS: RhoA/ROCK signaling played a pivotal role in TGF-ß1-induced fibrosis and myofibroblast activation in HPFs at least in part by inactivating the downstream MRTF-A/SRF transcriptional pathway.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34319490

RESUMO

PURPOSE: The aim of this study was to evaluate the effects of berberine on nitroglycerin (NTG) tolerance and explore the underlying mechanism involved. METHODS: NTG tolerance was induced by pre-exposure of Sprague-Dawley rat aortas to NTG in vitro or by pretreating Sprague-Dawley rats with an NTG patch in vivo. The aortas were pre-treated with berberine or PKC inhibitors for different durations of time before induction of NTG tolerance. NTG-induced vasorelaxations was measured on wire myograph. Primary vascular smooth cells (VSMCs) were used to dissect the underlying mechanism of berberine-induced inhibition of NTG tolerance. RESULTS: NTG tolerance induced by either prior exposure of rat aortas to NTG in vitro or pretreatment with an NTG patch in vivo was reversed by co-treatment with berberine, as well as the inhibitors of protein kinase C (PKC) and protein kinase C alpha (PKCα). The mechanistic study revealed that PKCα participated in the development of NTG tolerance as NTG increased the activity of PKCα with enriched PKCα membrane localization and elevated phosphorylation of PKCα in VSMCs, which was reversed by berberine or PKCα inhibitors. CONCLUSION: This study is probably the first demonstration that berberine reverses NTG tolerance through inhibiting PKCα activity in VSMCs and PKCα is an important contributor to the development of NTG tolerance. These new findings suggest that berberine could become a promising drug for prevention of NTG tolerance and that targeting PKCα in VSMCs is likely to be a potential therapeutic strategy for reversal of NTG tolerance in blood vessels.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34152510

RESUMO

PURPOSE: It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates ß3 adrenergic receptor (ß3 AR). However, the effect of selective ß3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. METHODS: We generated a CIH-induced atherosclerosis model through exposing ApoE-/- mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5-21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective ß3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. RESULTS: The expression of ß3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE-/- mice in CIH but not in normoxia. Mechanistically, mirabegron activated ß3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, ß3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. CONCLUSION: This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via ß3 AR-mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33995551

RESUMO

Background: Multiple primary outcomes are commonly used in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM). Analysis and interpretation of the results of CHM RCTs with many outcomes are not clear. No previous studies have systematically assessed the use of multiple primary outcomes in this area. This study aimed to assess the reporting of multiple primary outcomes and the statistical methods used to adjust multiplicity in RCTs of CHM. Methods: Search for RCTs of CHM published in English between January 2010 and December 2019 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was undertaken. We randomly selected 20% of the included RCTs as the analyzing sample of this study. The number of multiple primary outcomes, the methods used to adjust the multiplicity in statistical analysis and sample size estimate, and the trial information were collected. For RCTs that adopted multiple primary outcomes without the multiplicity adjustment, we used Bonferroni correction to adjust. Results: 227 CHM RCTs were included in our study. 92 (40.5%) failed to report what their primary outcome was. Of 135 (59.5%) RCTs that reported primary outcome, 93 (68.9%) reported one and 42 (31.1%) reported more than one primary outcome (range 2-5). Of 42 RCTs that reported multiple primary outcomes, only 5 adjusted for multiple outcomes. If multiplicity had been accounted for using Bonferroni correction, 10 (37.0%) RCTs that reported a significant result had demonstrated a nonsignificant result, giving the adjusted P value. Only one of the 42 RCTs calculated sample size based on multiple primary outcomes. Adopting multiple primary outcomes showed a slow growth trend with the publication year. The proportion of primary outcome reported explicitly in RCTs was different in terms of the nationality of the first author (P=0.004), in which mainland China has the lowest proportion (55.8%). The highest percentage of the studies with primary outcome reporting explicitation was mental and behavioural disorders (83.3%), and the most frequently adopting multiple primary outcomes were studies on the disease of the nervous system (66.7%). The percentage of reporting primary outcome explicitly was associated with sample size (P < 0.001); for the percentage of RCTs adopting multiple primary outcomes, there was no statistically significant difference (P=0.739). Conclusions: Multiple primary outcomes are prevalent in CHM RCTs. However, appropriate methods are not usually taken in most of the analyses to safeguard the inferences against multiplicity. Sample size estimation based on multiple primary outcomes is still lacking. These issues complicate the interpretability of trial results and can lead to spurious conclusions. Guidelines to improve analyzing and reporting for multiple primary outcomes in CHM RCTs are warranted.

14.
Genomics ; 113(4): 2572-2582, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34052320

RESUMO

Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder characterized by an extremely elevated serum level of low-density lipoprotein cholesterol (LDL-C) and accelerated premature atherosclerotic cardiovascular diseases (ASCVD). However, the detailed mechanism of how the pathogenic mutations of HoFH trigger the acceleration of ASCVD is not well understood. Therefore, we performed high-throughput RNA and small RNA sequencing on the peripheral blood RNA samples of six HoFH patients and three healthy controls. The gene and miRNA expression differences were analyzed, and seven miRNAs and six corresponding genes were screened out through regulatory network analysis. Validation through quantitative PCR of genes and miRNAs from 52 HoFH patients and 20 healthy controls revealed that the expression levels of hsa-miR-486-3p, hsa-miR-941, and BIRC5 were significantly upregulated in HoFH, while ID1, PLA2G4C, and CACNA2D2 were downregulated. Spearman correlation analysis found that the levels of ID1, hsa-miR-941, and hsa-miR-486-3p were significantly correlated with additional ASCVD risk factors in HoFH patients. This study represents the first integrated analysis of transcriptome and miRNA expression profiles in patients with HoFH, a rare disease, and as a result, six differentially expressed miRNAs/genes that may be related to atherosclerosis in HoFH are reported. The miRNA-mRNA regulatory network may be the critical regulation mechanism by which ASCVD is accelerated in HoFH.

15.
J Am Soc Cytopathol ; 10(4): 391-398, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33906830

RESUMO

INTRODUCTION: We investigated the prevalence and carcinogenic risks of individual high-risk human papillomavirus (HR-HPV) in all types of cervical cytology specimens in the Shanghai population. METHODS: A total of 124,251 cases with cotesting of cytology and HPV genotyping between October 2017 and February 2020 were included. RESULTS: The overall HPV positive rate was 24.3%, with 22.9% for HR-HPV and 6.1% for low-risk HPV. The top five most common HR-HPV subtypes were HPV 52/16/58/53/39 in the entire studied population, and HPV 16/53/56/51/39 in women with abnormal cytology. The most prevalent subtypes in negative/LSIL, HSIL, and glandular lesions were HPV 52, 16, and 18, respectively. HPV 16, 33, 26, 18, 58, and 82 were the most common subtypes significantly associated with an increased risk for HSIL + cytology. HPV 16/18 were present in 53.6% and 66.7%, and HPV 16/18/31/33/45/52/58 were identified in 90.3% and 80.1% of HSIL and squamous cell carcinoma cytology, respectively. HPV 16/18 and HPV 16/18/31/33/45/52/58 were detected in 37.0% and 44.4% of women with cytologic interpretation of in situ and invasive adenocarcinoma. CONCLUSIONS: This large-scale study identified the most common HPV subtypes in each cytology category, and the carcinogenic risks of individual HR-HPV in the studied Shanghai population. The results would provide valuable information for the development of next-generation HPV vaccines and cervical cancer screening programs for the Chinese population, and, more specifically, the Shanghai metropolitan population.

16.
Cell Death Dis ; 12(4): 357, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824286

RESUMO

Mesenchymal stem cells (MSCs) are one of the most widely clinically trialed stem cells, due to their abilities to differentiate into multiple cell lineages, to secrete regenerative/rejuvenative factors, and to modulate immune functions, among others. In this study, we analyzed human umbilical-cord-derived MSCs from 32 donors and revealed donor-dependent variations in two non-correlated properties, (1) cell proliferation, and (2) immune modulatory functions in vitro and in vivo, which might explain inconsistent clinical efficacies of MSCs. Through unbiased transcriptomic analyses, we discovered that IFN-γ and NF-κB signaling were positively associated with immune modulatory function of MSCs. Activation of these two pathways via IFN-γ and TNF-α treatment eradicated donor-dependent variations. Additional transcriptomic analyses revealed that treatment with these two factors, while having abolished donor-dependent variations in immune modulatory function, did not overall make different donor-derived MSCs the same at whole transcriptomic levels, demonstrating that the cells were still different in many other biological perspectives, and may not perform equally for therapeutic purposes other than immune modulation. Pre-selection or pre-treatment to eradicate MSC variations in a disease-treatment-specific manner would therefore be necessary to ensure clinical efficacies. Together this study provided novel insights into the quality control perspective of using different-donor-derived MSCs to treat inflammation-related clinical conditions and/or autoimmune diseases.


Assuntos
Doenças Autoimunes/metabolismo , Proliferação de Células/fisiologia , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/metabolismo , Doenças Autoimunes/imunologia , Células Cultivadas , Humanos , Imunomodulação/imunologia , Interferon gama/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia
17.
Appl Immunohistochem Mol Morphol ; 29(4): 287-292, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33818537

RESUMO

We investigate L1 cell adhesion molecule (L1CAM) expression in estrogen receptor (ER)-positive/human epidermal growth factor receptor (HER2)-negative breast carcinomas. The finding of a potential correlation between high L1CAM expression and recurrent/metastatic disease in luminal A and B breast carcinomas may be helpful for risk stratification and open opportunities for targeted therapies. 304 cases comprising 152 cases of ER-positive, progesterone receptor (PR)-positive/negative, and HER2-negative recurrent/metastatic breast carcinomas and 152 nonrecurrent controls were included. ER, PR, HER-2, Ki-67 status, Nottingham grade, tumor size, tumor stage, number of foci, lymph node status, lymphovascular invasion, phenotype, laterality, age at diagnosis and first distant or local recurrence were recorded. L1CAM positive cases showed increased specificity for recurrence and these patients were significantly younger than L1CAM negative ones. Compared with L1CAM negative recurrent cases, L1CAM positive ones had a noticeably higher Ki-67, tended to be larger and recurred sooner. All L1CAM positive recurrent/metastatic cases were of the luminal B subtype compared with 67.3% of the L1CAM negative cases. L1CAM is highly specific for recurrence in a subset of breast cancer patients and may be associated with more aggressive behavior, particularly in luminal B breast cancers with higher Ki-67 expression. Further investigation about the prognostic value of L1CAM is warranted.

18.
J Cancer ; 12(10): 2815-2824, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854582

RESUMO

Objective: In this prospective, population-based study, we evaluated the utility of high-risk human papillomavirus (HR-HPV) genotyping for triaging women with atypical squamous cells of undetermined significance (ASC-US) in the Chinese rural area. Methods: A total of 40,000 women were recruited from rural areas of Shanxi Province, China, between June 2014 and December 2014. Women with Pap results of ASC-US underwent HPV genotyping, colposcopy and histopathological examination. For those with normal cervixes or cervical intraepithelial neoplasia (CIN) 1 on the initial evaluation, a 2-year follow-up study was performed. Results: The reporting rate of ASC-US was 5.76% (2,304/40,000) in the study population. The detection rates of CIN 2 or above (CIN2+) and CIN 3 or above (CIN3+) in women with ASC-US were 7.28% and 1.75%, respectively. HPV 16 (39.53%), HPV 58 (17.83%), and HPV 52 (15.50%) were the three most prevalent HR-HPV genotypes among all women with ASC-US cytology. The five most common HR-HPV genotypes in CIN3+ lesions were HPV16, HPV58, HPV33, HPV31 and HPV18. Compared with the 15 HR-HPV testing, genotyping for a combination of HPV16/18/31/33/58 increased specificity significantly with virtually no loss of sensitivity for detecting CIN2+ and CIN3+ lesions, as well as significantly reduced colposcopy referral rate (23.15% vs 33.70%, p<0.01). In addition, in the 2-year follow-up period, women with infection of HPV16, 18, 31, 33 or 58 genotypes were the most likely population (92%, 23/25) to develop CIN2 lesion. Conclusion: Our results demonstrate that genotyping for a combination of HPV16/18/31/33/58 provides a more efficient and cost-effective model to risk-stratify women with ASC-US in the Chinese rural population.

19.
Biochem Biophys Res Commun ; 548: 182-188, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33647794

RESUMO

Intermittent hypoxia (IH), a main characteristic of obstructive sleep apnea (OSA) syndrome, is an independent risk factor of cardiovascular complications. However, the mechanism has not been fully elucidated. Growing evidence has revealed alterations of extracellular vesicle (EV) contents, mostly miRNAs, playing a pathogenic role in cardiovascular complications. In current study, we attempt to compare the disparity of myocardial EV miRNA components after IH or normoxia treatment and determine whether EVs from IH-treated cardiomyocytes could affect endothelial function. 63 differentially expressed miRNAs were identified in EVs from IH-exposed cardiomyocytes by miRNA chip assay. Among them, 16 miRNAs with homologous sequence in mouse and human were verified by qPCR assay and 11 miRNAs were proved with the same tendency as miRNA chip assay. KEGG predicted that the function of differentially expressed miRNA was enriched to Akt signaling pathway. Notably, EVs from IH-exposed cardiomyocytes dramatically impaired endothelial-dependent relaxation and inhibited Akt/eNOS expression in endothelial cells. This study provides the first evidence that IH significantly alters myocardial EV miRNA composition and reveals a novel role of myocardial EVs in endothelial function under IH status, which will help to understand the OSA- or IH-related endothelial dysfunction from a new scope.


Assuntos
Células Endoteliais/metabolismo , Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Hipóxia Celular/genética , Vesículas Extracelulares/ultraestrutura , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Miocárdio/metabolismo , Reprodutibilidade dos Testes
20.
Biochem Pharmacol ; 186: 114502, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33684391

RESUMO

OBJECTIVE: Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality. Apnea-induced chronic intermittent hypoxia (CIH) is a primary pathophysiological manifestation of OSA that promotes various cardiovascular alterations, such as aortic vascular remodeling. In this study, we investigated the association between angiopoietin-like proteins 8 (ANGPTL8) and CIH-induced aortic vascular remodeling in mice. METHODS: C57BL/6J male mice were divided into four groups: Normoxia group, ANGPTL8-/- group, CIH group, CIH + ANGPTL8-/- group. Mice in the normoxia group and ANGPTL8-/- group received no treatment, while mice in the CIH and CIH + ANGPTL8-/- group were subjected to CIH (21%-5% O2, 180 s/cycle, 10 h/day) for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization, and aortic wall collagen abundance were assessed in vivo. Immunohistochemistry and Western-blot were used to detect endoplasmic reticulum stress (ERS) and aortic vascular smooth muscle cell proliferation. ANGPTL8 shRNA and ANGPL8 overexpression were used in aortic vascular smooth muscle cells to investigate the mechanism of ANGPTL8 in CIH. RESULTS: Compared to the control group, CIH exposure significantly increased intima-media thickness (IMT), elastic fibers disorganization, and aortic wall collagen abundance. CIH also significantly increased blood pressure, induced hyperlipidemia, as well as the expression of ERS protein activating transcription factor-6 (ATF6) and aortic vascular smooth muscle cell proliferation. Contrary, ANGPTL8-/- significantly mitigated the CIH-induced vascular remodeling; ANGPTL8-/- decreased CIH-induced hypertension and hyperlipidemia, inhibited the protein expression of ATF6, and aortic vascular smooth muscle cell proliferation. Moreover, our in vitro study suggested that CIH could induce ANGPTL8 expression via hypoxia-inducible factor (HIF-1α); ANGPTL8 induced proliferation of aortic vascular smooth muscle cells via the ERS pathway. CONCLUSION: ANGPTL8-/- can prevent CIH-induced aortic vascular remodeling, probably through the inhibition of the ERS pathway. Therefore, ANGPTL8 might be a potential target in CIH-induced aortic vascular remodeling.


Assuntos
Proteínas Semelhantes a Angiopoietina/deficiência , Modelos Animais de Doenças , Hipóxia/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Remodelação Vascular/fisiologia , Proteínas Semelhantes a Angiopoietina/genética , Animais , Células Cultivadas , Feminino , Humanos , Hipóxia/complicações , Hipóxia/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Gravidez , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/genética
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