Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 619
Filtrar
1.
Clin Chem Lab Med ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32172226

RESUMO

Background As the number of patients increases, there is a growing understanding of the form of pneumonia sustained by the 2019 novel coronavirus (SARS-CoV-2), which has caused an outbreak in China. Up to now, clinical features and treatment of patients infected with SARS-CoV-2 have been reported in detail. However, the relationship between SARS-CoV-2 and coagulation has been scarcely addressed. Our aim is to investigate the blood coagulation function of patients with SARS-CoV-2 infection. Methods In our study, 94 patients with confirmed SARS-CoV-2 infection were admitted in Renmin Hospital of Wuhan University. We prospectively collect blood coagulation data in these patients and in 40 healthy controls during the same period. Results Antithrombin values in patients were lower than that in the control group (p < 0.001). The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. Moreover, D-dimer and FDP values in patients with severe SARS-CoV-2 infection were higher than those in patients with milder forms. Compared with healthy controls, prothrombin time activity (PT-act) was lower in SARS-CoV-2 patients. Thrombin time in critical SARS-CoV-2 patients was also shorter than that in controls. Conclusions The coagulation function in patients with SARS-CoV-2 is significantly deranged compared with healthy people, but monitoring D-dimer and FDP values may be helpful for the early identification of severe cases.

2.
PLoS One ; 15(3): e0230779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214358

RESUMO

BACKGROUND: Beijing is a national and international hub potentially containing a broad diversity of HIV variants. Previous studies on molecular epidemiology of HIV in Beijing pooled together samples from residents and non-residents. Pooling residents and non-residents has potentially introduced bias and undermined a good assessment and the intervention among the autochthonous population. Here, we aimed to define HIV subtype diversity and investigate the TDR in Beijing residents exclusively. METHODS: We analyzed the demographic, clinical, and virological data collected between 2001 and 2016 from residents in Beijing. A population-based sequencing of the HIV pol gene was carried out using plasma specimens. Phylogenetic analysis was performed in order to classify sequences into their corresponding subtypes using an automated subtyping tool, the Context-Based Modeling for Expeditious Typing (COMET). Furthermore, the drug resistance mutations were determined using the World Health Organization list for surveillance of TDR mutations. RESULTS: Data on TDR were available for 92% of 2,315 individuals with HIV infection, of whom 7.1% were women. The bioinformatic analysis of HIV strains from this study revealed that a combined 17 subtypes were circulating in Beijing, China between 2001 and 2016. The most common ones were CRF01_AE, CRF07_BC, and subtype B in Beijing during this period. The overall prevalence of TDR was 4.5% (95% confidence intervals[CI]: 3.6%-5.4%), with a declining trend over the period of spanning 2001 through 2016. In-depth class-specific analysis revealed that the prevalence of TDR for the nucleoside reverse-transcriptase inhibitors (NRTIs) was 1.0% (95% CI: 0.6-1.5), 0.9% (95% CI:0.6-1.4) for non-NRTIs and 2.8% (95% CI:2.1-3.5) for protease inhibitors. The prevalence of TDR was lower in individuals infected with the CRF07_BC HIV strain than those infected with CRF01_AE. CONCLUSIONS: Our data showed that the HIV epidemic in Beijing displayed a high genetic heterogeneity and a low and declining prevalence of TDR. In sharp contrast to Europe and North America, the declining trend of TDR between 2001 through 2016 was noticed while there was a widespread distribution of antiretroviral treatment in Beijing, China.

3.
AIDS Res Ther ; 17(1): 9, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138739

RESUMO

BACKGROUND: The aim of this study was to assess trends in drug resistance and associated clinical and programmatic factors at a national level during the rapid scale up of ART. METHODS: Logistic regression was used to identify the factors associated with HIVDR. Variables associated with drug resistance in multivariable logistic regression were included in the Cochran-Armitage test for trend. RESULTS: A total of 11,976 patients were enrolled in the study. The prevalence of HIVDR among patients who received ART for 9-24 months during 2003-2008, 2009-2012, and 2013-2015 significantly decreased (15.5%, 6.3%, and 2.3%, respectively, P < 0.01). With respect to the class of antiretroviral, there were substantial increases in resistance to both non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) (2003-2008, 2009-2012, and 2013-2015: 49.7%, 58.9%, and 73.0%, respectively, P < 0.01). The prevalence of DR to protease inhibitors (PIs) was low, which supported their continued use as second-line therapy in China. CONCLUSIONS: Our results provide evidence for the effectiveness of China's "Treat All" approach to guide policy makers to improve training for healthcare providers and education on ART adherence among patients.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32186933

RESUMO

Diabetes (especially type II), is one of the primary threats to cardiovascular health. Wound healing defects and vascular dysfunction are common in these patients, while the main cause of deterioration is sustained high plasma glucose. microRNA, a non-coding RNA, has critical regulatory functions in maintaining homeostasis. miR-126-3p is a potential biomarker of diabetes and a pro-angiogenic factor, and its plasma level decreases in diabetic patients. Previous studies revealed the pro-angiogenic character of gasotransmitter hydrogen sulfide (H2S). However, little is known about the relationship between H2S and miR-126-3p when extracellular glucose level is high, let alone their influences on deteriorated endothelial cell migration, a key component of angiogenesis, which is crucial for wound healing. Thus, our study aimed to explore its relationship and functions. Both exogenous and endogenous H2S could upregulate miR-126-3p level in HUVECs or muscle tissue. High glucose decreased H2S level and the protein expression of H2S producing enzyme CSE in HUVECs, however, DNA - methyltransferase 1 (DNMT1) protein level was upregulated. CSE overexpressing not only increased miR-126-3p level via decreasing DNMT1 protein level, but also rescued deteriorated cell migration in HUVECs treated with high glucose. DNMT1 overexpressing decreased miR-126-3p level and inhibited migration of HUVECs, whereas DNMT1 silencing improved cell migration. In conclusions, high glucose decreased endogenous H2S and miR-126-3p levels, and increased DNMT1 expression, thus induced migration dysfunction of HUVECs. Treatment with exogenous H2S or overexpressing endogenous producing enzyme CSE would recuse the migration dysfunction through H2S-DNMT1-miR-126-3p.

5.
Nanoscale ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129396

RESUMO

Phonon-assisted single-photon upconversion, which was not previously reported in organic materials, has been demonstrated in the 6-pentaceneone crystal through the linear pumping power dependent anti-Stokes photoluminescence (ASPL), nanoseconds PL lifetime and quenched ASPL at low temperature. Furthermore, the 6-pentaceneone crystal can be mechanically exfoliated to ultrathin flakes and it exhibits thickness-dependent photoluminescence.

6.
Pregnancy Hypertens ; 20: 19-26, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32145524

RESUMO

OBJECTIVE: To investigate the relationship between platelet-activating factor acetylhydrolase (PAF-AH) gene (PLA2G7) G994T (V279F, rs76863441) and R92H (rs1805017) polymorphisms and risk of preeclampsia (PE) in Chinese women. STUDY DESIGN: This is a case-control study of 273 patients with PE and 530 healthy pregnant women. MAIN OUTCOME MEASURES: PLA2G7 genotypes were determined by polymerase chain reaction amplification and restriction analysis. Plasma PAF-AH, apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH), total high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH), apoE-containing HDL-associated PAF-AH (apoE-H-PAF-AH) activities, and clinical, metabolic, and oxidative stress parameters were also analyzed. RESULTS: The frequencies of the GT + TT genotype (14.7 versus 9.2%, P = 0.019) and T allele (7.5% versus 4.6%) of PLA2G7 G994T polymorphism were significantly higher in patients with PE than in the control subjects. The GT + TT genotypes remained a significant predictor for PE in a regression model including age, body mass index (BMI), plasma PAF-AH, H-PAF-AH, apoE-H-PAF-AH and apoB-PAF-AH activities as covariates (odds ratio (OR) = 4.926, 95% confidence interval (CI): 1.707-14.219, P = 0.003). The ratio of apoB-PAF-AH to H-PAF-AH activities was significantly higher, while serum triglyceride levels were lower in patients with the GT genotype compared with patients with the GG genotype (P < 0.05). No significant differences were observed in the frequencies of the R92H genotype and allele between the PE and control groups. CONCLUSIONS: The PLA2G7 G994T, but not R92H, genetic polymorphism is associated with the risk of PE in Chinese women.

7.
Virol J ; 17(1): 17, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014042

RESUMO

BACKGROUND: Anhui Province in China is facing a severe HIV epidemic with an increasing number of newly diagnosed cases. METHODS: In this study, HIV genetic characteristics in the province were investigated. Newly reported HIV-positive individuals from 15 districts of Anhui Province were enrolled and interviewed. Total viral RNA was extracted from plasma isolated from blood samples. We amplified and sequenced an HIV pol fragment of the 1062 bp. The sequences were used for determination of HIV subtypes and the presence of drug resistance mutations. Transmission networks were constructed to explore possible relationships. And all of assembled partial pol genes were submitted to the Stanford HIV Drug Resistance Database website to find the transmitted drug resistance. RESULTS: Partial pol gene sequences were obtained from 486 cases. The results showed that MSM was the most dominant transmission route (253, 52.06%), followed by heterosexual transmission (210, 43.21%) and blood-borne transmission (1, 0.21%). Many subtypes were identified, including CRF01_AE (226, 46.50%), CRF07_BC (151, 31.07%), subtype B (28, 5.76%), CRF08_BC (20, 4.12%), CRF55_01B (15, 3.09%), CRF68_01B (7, 1.44%), CRF67_01B (3, 0.62%), CRF57_BC (2, 0.41%), CRF59_01B (2, 0.41%), CRF79_0107 (2, 0.41%), subtype C (2, 0.41%), CRF64_BC (1, 0.21%), and circulating recombinant forms (URFs) (27, 5.55%). Four transmission subnetworks containing high transmission risk individuals (with degree ≥4) were identified based on CRF01_AE and CRF07_BC sequences, including two CRF01_AE transmission subnetworks constituted by elderly people with average ages of 67.9 and 61.5 years. Infection occurred most likely through heterosexual transmission, while the other two CRF07_BC transmission subnetworks consist mainly of MSMs with average ages of 31.73 and 34.15. The level of HIV-transmitted drug resistance is 3.09%. CONCLUSIONS: The simultaneous spread of multiple HIV subtypes in Anhui province underscores that close surveillance of the local HIV epidemic is necessary. Furthermore, the elderly people were frequently involved, arguing for behaviour intervention in this specific population besides the MSM risk group.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32079407

RESUMO

Recombinant forms contribute substantially to the genetic diversity of HIV-1. Recent studies have also revealed that three major viral strains (CRF07_BC, CRF01_AE, and subtype B) have been cocirculating among MSM in Anhui, suggesting a high probability of generating new recombinants. Here, we reported a novel CRF01_AE and CRF07_BC HIV-1 recombinant form in men who have sex with men (MSM) in Fuyang city of China. Two near full-length sequences (NFLG) named FY184, FY208 were successfully obtained. The genomic composition analysis of the NFLG reveals that it was divided into four segments by three breakpoints, with two regions of CRF07_BC inserted into a CRF01_AE backbone's gag, pol regions. The CRF01_AE regions were originated from a sub-cluster lineage of CRF01_AE, which mainly circulating among MSM in China. The emergence of a novel recombinant of CRF01_AE/CRF07_BC is indicative of the increasing genetic diversity of the HIV epidemic in MSM in Anhui.

9.
J Diabetes Res ; 2020: 3483427, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32090118

RESUMO

Background: Paraoxonase 1 (PON1) is a calcium-dependent multifunctional enzyme that binds to high-density lipoproteins. The physiological function of PON1 is related to its lactonase activity. However, this activity has not been analyzed in women with gestational diabetes mellitus (GDM). The present study investigated the lactonase activities and status of PON1 and their association with PON1 genetic variants and oxidative stress indices in Chinese women with GDM. Methods: This is a case-control study of 347 women with GDM and 288 women with uncomplicated pregnancies. PON1 levels and lactonase activities were analyzed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL), respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC) levels, and PON1 genetic variants and oxidative stress indices in Chinese women with GDM. Results: PON1 lactonase activity and levels of TOS, TAC, and MDA were higher in the GDM women compared with the control women. The PON1 -108C→T genetic variation decreased the levels and lactonase activities of PON1 in a genotype-dependent manner in the patient and control groups. GDM patients with the PON1 -108TT genotype displayed lower NLA than those with the -108CC or -108CT genotype. GDM patients with the RR genotype of PON1 192Q/R polymorphism had significantly lower PON1 lactonase activities and NLA and tended to have decreased PON1 levels compared with those with the QQ or QR genotype. Multivariable regression analysis revealed that the PON1 -108C/T or 192Q/R variations, apolipoprotein (apo) A1, apoB, TAC, MDA, or age was significant predictors of the levels, lactonase activities, or NLA of PON1. Conclusions: The lactonase activities of PON1 are increased in women with GDM. PON1 genetic variants, increased oxidative stress, and abnormalities in lipoproteins may be associated with these changes.PON1 genetic variants and oxidative stress indices in Chinese women with GDM.

10.
AIDS ; 34(4): 609-619, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31895143

RESUMO

OBJECTIVES: Fifteen years after the roll-out of antiretroviral treatment (ART) in China, there is limited information available on transmitted HIV drug resistance (TDR). This study aimed to characterize the epidemiology of TDR in China. DESIGN: We conducted a prospective cross-sectional observational study. METHODS: We analyzed the demographic, clinical, and virological data of individuals with newly diagnosed HIV infection using data from the Beijing HIV laboratory network collected between 2001 and 2017. We did population-based sequencing of the pol gene on plasma specimens and identified TDR mutations using the WHO list for surveillance of TDR mutations. RESULTS: Data on TDR were available for 91% of the 10 115 individuals with newly diagnosed HIV infection tested, of whom 19.2% were from rural areas. The overall prevalence of TDR was 4.1% [95% confidence interval (CI): 3.7-4.5%], with a declining trend over the period 2001-2017. In the multivariable analysis, the risk of TDR differed significantly according to sex [odds ratio (OR) for women vs. men: 0.41, 95% CI: 0.22-0.69, P = 0.002]; infection type (OR for CRF07_BC vs. CRF01_AE: 0.24, 95% CI: 0.16-0.36, P < 0.001); and sampling period (OR for 2009-2012 vs. 2001-2008: 0.57, 95% CI: 0.41-0.79; P = 0.01), and was significantly higher among individuals from Hebei province than in those from Beijing (OR: 1.43, 95% CI: 1.05-1.96; P = 0.02). CONCLUSION: In China, the prevalence of TDR among individuals with newly diagnosed HIV infection is relatively low. Trends in TDR should be assessed in other countries with a high TDR burden.

11.
Chem Rec ; 20(2): 102-119, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31250979

RESUMO

Multi-shelled hollow spheres metal oxides, namely materials with more than three shells, have attracted increasing attention due to their unique structure. The preparation methods of typical metal oxides including NiO, Co3 O4 and ZnO etc. have been summarized in this review. Simultaneously, the parameters that influence the ultimate morphologies, shell number as well as the compositions have also been discussed. The potential application fields in energy conversion and storage, electromagnetic wave absorption, photocatalysis that related to the unique structure are also highlighted. Finally, the future researches of multi-shelled hollow spheres metal oxides are further discussed.

12.
J Obstet Gynaecol ; : 1-6, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790312

RESUMO

Preeclampsia (PE) is a serious gestational idiopathic hypertensive disease, threatening both maternal and foetal safety. As a systemic disease, the initial-onset symptoms (IOSs) and clinical manifestations of PE can vary widely from patient to patient. However, a lack of evidence-based data on IOS and their relationship to their corresponding clinical features and pregnancy outcomes persists. We hypothesised that there would be a significant difference between the morbidity time, subsequent organ dysfunction and the status of mother and foetus in PE patients with different IOS. Moreover, early identification of the characteristics of the PE patients with different IOS could improve pregnancy outcomes through individualised prevention or intervention. This study aimed to analyse maternal and foetal condition and pregnancy outcomes of PE patients with different IOS, and to explore the disease progression and characteristics of maternal and foetal outcomes for different IOS, so as to provide the basis for future maternal and foetal monitoring of PE patients.Impact statementWhat is already known on this subject? In 2013, the American College of Obstetricians and Gynecologists revised their definition of PE, sparking a heated debate. Subsequently in 2015, China updated its guidelines to define PE as hypertensive pregnancy accompanied by involvement of any other organ or organ system, to include the heart, lungs, liver and kidneys, among others. However, IOS can be varied in PE, so the maternal management and foetal monitoring should be classified through different IOS. No evidence-based data on IOS in PE patients exist.What the results of this study add? Significant differences in mean morbidity times and mean delivery times were demonstrated among patients with different IOS; medians of the interval from morbidity to delivery were between 4 and 6 weeks. Significant differences in laboratory values were found in patients with different IOS. In patients that did not present with proteinuria as an IOS, 89.1% experienced proteinuria following diagnosis. Patients with the most severe complications presented with hypertension as an IOS. Follow-up visits demonstrated different foetal weight medians.What the implications are of these findings for clinical practice and/or further research? IOS could be an indicator to help evaluate the potential for different maternal and foetal complications and PE outcomes. Moreover, the duration of treatment for PE maybe 4-6 weeks.

13.
Acta Pharmacol Sin ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792341

RESUMO

Cancer is a highly heterogeneous disease in term of molecular signature even though it is originated from the same tissue type. Cancer heterogeneity may occur during its development or treatment, which is the main cause resulting in drug resistance and recurrence. Precision medicine refers to matching the right medicine to the right patients based on their molecular signatures. Therefore, a thorough understanding of the mechanism of tumorigenesis and drug resistance is essential to precision medicine. CRISPR-cas9 system is a powerful tool for gene editing and CRISPR-based high-throughput screening has been widely applied especially in searching for tumor-driven or synergistic lethal genes aiming to overcome drug resistance. In this review, we describe the progress of CRISPR-cas9-based unbiased screening in precision medicine including identification of new drug targets, biomarkers and elucidation of mechanisms leading to drug resistance. The existing challenges as well as the future directions are also discussed.

14.
Curr HIV Res ; 17(6): 441-451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778107

RESUMO

BACKGROUND: Pretreatment drug resistance (PDR) poses an increasing threat to the success of antiretroviral treatment (ART) programs in China. We aimed to conduct a survey of PDR among HIV patients in an area in Southwest China with extensive drug trafficking. METHODS: Consecutive cross-sectional surveys were conducted in Liangshan Prefecture of Sichuan Province from 2009 to 2018 based on the WHO-recommended method. PDR was identified by testing pol region sequences with the Stanford HIVdb algorithm (version 7.0). PDR prevalence and related factors were assessed by multivariable logistic regression. The transmission of HIV drug resistance was analyzed using a genetic transmission network. RESULTS: HIV-1 pol genes from 1889 patients were successfully amplified. The distribution of HIV- 1 genotypes was as follows: CRF07_BC (94.0%), CRF08_BC (2.3%), CRF01_AE (2.0%) and others (1.4%). Of the participants, 6.9% (95% CI: 4.1-8.1%) had pretreatment resistance to 12 antiretroviral drugs recommended by the WHO, and nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitors (PI) resistance were identified among 1.4% (95% CI: 0.7-3.4%), 5.8% (95% CI: 1.2-8.7%) and 0.4% (95% CI: 0.1- 3.0%) of the patients, respectively. In the multivariate logistic model, the prevalence of PDR was 1.52-fold higher among intravenous drug users (IDUs) than among patients infected by heterosexual transmission (95% CI: 1.07-2.38; P=0.049), and the prevalence of PDR among patients diagnosed from 2017-2018 was 2.03-fold higher than that among patients diagnosed from 2009-2016 (95% CI: 1.18-5.76; P=0.018). A total of 26 clusters containing PDR and a rapidly growing drug resistancerelated cluster containing the E138Q and V179D mutations were identified by genetic transmission network analysis. CONCLUSION: The results show a moderate overall level of PDR prevalence and rapidly growing drug resistance over time. Preventive intervention should be focused on controlling the HIV epidemic among drug users, and surveillance is urgently needed to monitor the trend of PDR.

15.
Materials (Basel) ; 12(23)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766593

RESUMO

An experimental study with respect to the effect of an alternating electropulsing on grain refinement in pure aluminum was reported. The macrostructural observation with the mold preheated to different temperature and embedded the metal mesh indicated that the change of electric current-associated free energy related with the position of crystal nuclei (ΔGem) and forced convection dominated the generation of fine equiaxed grains (FEG). Under electropulsing with 480 A, ΔGem induced the dissociation of crystal nuclei from the upper interface of the electrode and the melt, leading to the generation of FEG. For a larger current intensity, FEG originated from the dissociation of crystal nuclei on the side wall besides the upper interface due to ΔGem and the forced convection. Furthermore, the model coupling the dissociation of crystal nuclei and dendrite fragmentation due to the forced convection and the dissociation of crystal nuclei due to ΔGem was presented to explain the formation mechanism of FEG in pure aluminum under electropulsing.

16.
Stem Cell Res Ther ; 10(1): 357, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779679

RESUMO

BACKGROUND: The degenerative disc disease (DDD) is a major cause of low back pain. The physiological low-glucose microenvironment of the cartilage endplate (CEP) is disrupted in DDD. Glucose influences protein O-GlcNAcylation via the hexosamine biosynthetic pathway (HBP), which is the key to stem cell fate. Thiamet-G is an inhibitor of O-GlcNAcase for accumulating O-GlcNAcylated proteins while 6-diazo-5-oxo-L-norleucine (DON) inhibits HBP. Mechanisms of DDD are incompletely understood but include CEP degeneration and calcification. We aimed to identify the molecular mechanisms of glucose in CEP calcification in DDD. METHODS: We assessed normal and degenerated CEP tissues from patients, and the effects of chondrogenesis and osteogenesis of the CEP were determined by western blot and immunohistochemical staining. Cartilage endplate stem cells (CESCs) were induced with low-, normal-, and high-glucose medium for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. CESCs were induced with low-glucose and high-glucose medium with or without Thiamet-G or DON for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. Sox9 and Runx2 O-GlcNAcylation were measured by immunofluorescence. The effects of O-GlcNAcylation on the downstream genes of Sox9 and Runx2 were determined by Q-PCR and western blot. RESULTS: Degenerated CEPs from DDD patients lost chondrogenesis, acquired osteogenesis, and had higher protein O-GlcNAcylation level compared to normal CEPs from LVF patients. CESC chondrogenic differentiation gradually decreased while osteogenic differentiation gradually increased from low- to high-glucose differentiation medium. Furthermore, Thiamet-G promoted CESC osteogenic differentiation and inhibited chondrogenic differentiation in low-glucose differentiation medium; however, DON acted opposite role in high-glucose differentiation medium. Interestingly, we found that Sox9 and Runx2 were O-GlcNAcylated in differentiated CESCs. Finally, O-GlcNAcylation of Sox9 and Runx2 decreased chondrogenesis and increased osteogenesis in CESCs. CONCLUSIONS: Our findings demonstrate the effect of glucose concentration on regulating the chondrogenic and osteogenic differentiation potential of CESCs and provide insight into the mechanism of how glucose concentration regulates Sox9 and Runx2 O-GlcNAcylation to affect the differentiation of CESCs, which may represent a target for CEP degeneration therapy.

17.
Gynecol Oncol ; 155(3): 436-443, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31604662

RESUMO

OBJECTIVE: Human papillomavirus (HPV) 16/18 genotyping is an effective method for triage of high-risk (hr) HPV-positive women in primary hrHPV screening for cervical cancer. The present study aimed to evaluate whether co-infected with other hrHPV types will affect the risk of cervical carcinogenesis in HPV16/18 positive women. METHODS: A total of 313,704 women aged ≥30 years were screened in China. Among them, 4,933 HPV16/18-positive participants underwent colposcopy-directed biopsy. The HPV genotypes were identified using the Cobas HPV genotyping system. Multinomial logistic regression was used to model different HPV16/18 infection patterns. RESULTS: The overall prevalence rates of hrHPV and HPV16/18 were 7.85% (24,456/311,382) and 1.95% (6,086/311,382) respectively. Among HPV16/18 positive individuals, 33.24% (2,023/6,086) were co-infection with multiple types. Of the 4933 women who underwent colposcopy, their HPV16/18 infection patterns were as follows: 52.38% (2,584/4,933) HVP16 only, 23.54% (1,161/4,933) HPV16 + other hrHPVs, 14.98% (739/4,933) HPV18 only, 6.83% (337/4,933) HPV18 + other hrHPVs, 1.13% (56/4,933) HPV16 + 18, 1.13% (56/4,933) HPV16 + 18+other hrHPVs. After adjusting for cofactors, compared with single HPV16 infection, the risk of developing cervical intraepithelial neoplasia (CIN) grade 3 or greater (CIN3+) was significantly lower in HPV16 + other hrHPVs group (odds ratio [OR] = 0.637, 95% confidence interval [CI] = 0.493-0.822). CONCLUSION: HPV16/18 co-infection with other hrHPVs is a common phenomenon. Different HPV16/18 infection patterns may influence the risk of cervical carcinogenesis. HPV16 co-infected with other hrHPVs appears to have a lower associated risk of CIN3+ in ≥30 years old women.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Carcinogênese , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Coinfecção/epidemiologia , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prevalência , Neoplasias do Colo do Útero/virologia
19.
Theranostics ; 9(20): 5937-5955, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534530

RESUMO

Prolonged occlusion of multiple microvessels causes microvascular injury. G protein-coupled receptor 124 (GPR124) has been reported to be required for maintaining central nervous system (CNS) angiogenesis and blood-brain barrier integrity. However, the molecular mechanisms by which GPR124 regulates pericytes during ischemia have remained elusive. Methods: A microsphere embolism-induced ischemia model was used to evaluate the expression of GPR124 following microsphere embolism. Immunocytochemistry and stochastic optical reconstruction microscopy imaging were used to assess the expression and distribution of GPR124 in human brain vascular pericytes (HBVPs) and after the treatment with 3-morpholino-sydnonimine (SIN-1) or oxygen-glucose deprivation (OGD). The effect of GPR124 knockdown or overexpression on HBVP migration was analyzed in vitro using wound healing assays and a microfluidic device. GPR124 loss-of-function studies were performed in HBVPs and HEK293 cells using CRISPR-Cas9-mediated gene deletion. Time-lapse imaging was used to assess dynamic changes in the formation of filopodia in an individual cell. Finally, to explore the functional domains required for GPR124 activity, deletion mutants were constructed for each of the N-terminal domains. Results: GPR124 expression was increased in pericytes following microsphere embolism. Morphological analysis showed localization of GPR124 to focal adhesions where GPR124 bound directly to the actin binding protein vinculin and upregulated Cdc42. SIN-1 or OGD treatment redistributed GPR124 to the leading edges of HBVPs where GPR124 signaling was required for pericyte filopodia formation and directional migration. Partial deletion of GPR124 domains decreased SIN-1-induced filopodia formation and cell migration. Conclusion: Taken together, our results provide the first evidence for a role of GPR124 in pericyte migration under ischemic conditions and suggest that GPR124 was essential for Cdc42 activation and filopodia formation.

20.
AIDS Res Hum Retroviruses ; 35(11-12): 1095-1102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31544479

RESUMO

Older people living with HIV (PLWH) may have delayed diagnosis and access to care and therefore have poorer disease outcomes. Little is known about HIV care and disease outcomes among older PLWH in China. This retrospective cohort study used data from all adult HIV/AIDS cases during 1988-2017 in Chongqing, China from two national databases. We compared demographic and behavioral profiles, HIV care, virologic suppression, and mortality between two age groups of 18-49 and ≥50 years. Multivariate logistic and cox regression analyses were used to calculate adjusted odds ratio (AOR) and adjusted hazard ratio (AHR) among older versus younger PLWH. Of 46,580 adult HIV/AIDS cases, 76.1% were men and 38.2% were 50 years of age or older. The proportion of older cases in men increased from 2.4% in 2002 to 51.8% in 2017, and in women from 3.3% to 57.9%. Older PLWH had a lower CD4 count than their younger counterparts at HIV diagnosis (median 323 vs. 391 cells/µL; p < .001). The average time from HIV diagnosis to initiation of antiretroviral therapy (ART) were 6.3 months among older and 12.8 months among younger PLWH (p < .001). Nearly one tenth (9.6%) had virologic failure within 12 months of ART initiation, and the odds of virologic failure among older PLWH was 80% higher [AOR 1.8; 95% confidence interval (CI), 1.1-3.0] than among younger ones after controlling for calendar year of initiating ART and other covariates. The mortality rate within 12 months of initiating ART was 9.8 deaths per 100 person years, and the risk of mortality among older PLWH was three times among younger ones (AHR, 3.1; 95% CI, 2.1-4.6). Older people represented an increasing proportion of new HIV/AIDS cases and were more likely to have virologic failure and mortality within 12 months of ART initiation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA