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1.
BMC Med ; 19(1): 322, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34923987

RESUMO

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

2.
Wei Sheng Yan Jiu ; 50(5): 722-727, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34749863

RESUMO

OBJECTIVE: To understand the physical activity and regular exercise status and influencing factors of people with high risk of chronic diseases among Beijing residents, and to provide science basis for health education strategies and intervention measures. METHODS: 13 200 participants aged 18-79 were selected by stratified cluster sampling method for questionnaire survey in 2017.3448 participants without hypertension, diabetes and dyslipidemia met the criteria of high risk population. The metabolic equivalent of physical activity was calculated by referring to the summary of physical activity in the United States and the global physical activity questionnaire. RESULTS: 1794 male(52.0%) and 1654 female(48.0%) are included in this study. 862(25.0%) are 18-29 years old, 778(22.6%) are 30-39 years old, 640(18.6%) are 40-49 years old, 709(20.6%) are 50-59 years old, and 193(13.3%) are 60-79 years old. 684 participants(18.6%) are low physical activity level, 1480 participants(42.9%) are medium level and 1284 respondents(37.2%) are high level. The rate of never exercising is 60.2%. Multivariate analysis shows female(OR=1.32, 95%CI 1.11-1.55), aged 40-49(OR=1.34, 95%CI 1.04-1.72) and aged 50-59(OR=1.76, 95%CI 1.36-2.28) participants are likely to have high level physical activity. Participants with high education level(OR=0.78, 95%CI 0.66-0.93) and insufficient intake of fruits and vegetables(OR=0.73, 95%CI 0.64-0.84) are likely to have low physical activity level. Female(OR=1.46, 95%CI 1.22-1.76), participants with insufficient intake of fruits and vegetables(OR=1.44, 95%CI 1.24-1.69) are likely never to exercise. Participants with high education level(OR=0.46, 95%CI 0.38-0.55), high school education(OR=0.63, 95%CI 0.53-0.75), no job(OR=0.67, 95%CI 0.56-0.81) are likely to exercise. CONCLUSION: The population with high risk of chronic diseases in Beijing City was lack of physical activity. Gender, age, education level, fruit and vegetable intake are the influencing factors of physical activity level, while gender, fruit and vegetable intake, education level, marriage, employment and fruit and vegetable intake are the influencing factors of exercise.


Assuntos
Dieta , Verduras , Adolescente , Adulto , Idoso , Pequim/epidemiologia , Doença Crônica , Exercício Físico , Frutas , Humanos , Pessoa de Meia-Idade , Adulto Jovem
3.
Anal Chem ; 93(46): 15225-15230, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34752059

RESUMO

The detection of microRNA (miRNA) in human serum has great significance for cancer prevention. Herein, a novel self-powered biosensing platform is developed, which effectively integrates an enzymatic biofuel cell (EBFC)-based self-powered biosensor with a matching capacitor for miRNA detection. A catalytic hairpin assembly and hybrid chain reaction are used to improve the analytical performance of EBFC. Furthermore, the matching capacitor is selected as an auxiliary signal amplifying device, and graphdiyne is applied as substrate material for EBFC. The results confirm that the developed method obviously increases the output current of EBFC, and the sensitivity can reach 2.75 µA/pM, which is 786% of pure EBFC. MiRNA can be detected in an expanded linear range of 0.1-100000 fM with a detection limit of 0.034 fM (S/N = 3). It can offer a selective and sensitive platform for nucleotide sequence detection with great potential in clinical diagnostics.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Técnicas Eletroquímicas , Grafite , Humanos , Limite de Detecção , MicroRNAs/genética
4.
Front Public Health ; 9: 733314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796159

RESUMO

Objective: This study aims to estimate the prevalence of dementia and Alzheimer's disease (AD) and associated risk factors among the general Chinese population. Methods: We carried out a nationwide study including 24,117 participants aged 60 years and older in China using a multistage clustered sampling. Dementia and AD were diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the criteria issued by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. Face-to-face interviews were administered by the trained interviewers to obtain information on demographics, lifestyle factors, and previous diseases. Results: The overall weighted prevalence of dementia was 4.22% (95%CI 2.27-6.17%) for people aged 60 years and older, was higher in women than in men and increased with age. Daily tea drinking and daily exercises were the protective factors for both dementia and AD. Engaging in social and intellectual activities was significantly associated with a lower risk of dementia and AD. Conclusions: A large number of population with dementia posed a significant challenge to China where the population is rapidly aging. The increase of public awareness, building more care facilities, and training dementia specialists and professional caregivers are all urgently needed and should be the future priorities of dementia care in China.

5.
ACS Appl Mater Interfaces ; 13(46): 54974-54980, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34779193

RESUMO

In this study, graphdiyne (GDY) was first reported as a substrate material for sodium-ion batteries (SIBs). The creative hybridization of GDY and molybdenum disulfide (MoS2) endows the composite with unique heterostructural and morphological advantages that boost the charge transport rate and enhance the battery discharge properties. Electrochemical results indicated that the MoS2@GDY anode displays a considerable discharge capacity of up to 328 mAh g-1 at 1000 mA g-1. A capacity retention of 93% even at testing current back to 200 mA g-1 suggests superior rate characteristics. An outstanding stable cyclic performance of 217 mAh g-1 is obtained at a high testing density. The attractive results not only demonstrate that GDY could be used not only as an effective conductive substrate to prevent the host material from agglomerating in the electrochemical process but also provide a novel design for fabricating efficient electrode materials for future energy-storage systems.

6.
Front Endocrinol (Lausanne) ; 12: 743962, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675880

RESUMO

Aims/Hypothesis: We aimed to explore whether and to what extent overweight or obesity could increase the risk of hypertension, and further to estimate the roles of genetic and early-life familial environmental factors in their association. Methods: This prospective twin study was based on the Chinese National Twin Registry (CNTR), which collected information from self-report questionnaires. We conducted unmatched case-control analysis to examine the association between overweight or obesity and hypertension. And further to explore whether genetics and familiar environments shared within a twin pair, accounted for their association via co-twin matched case-control design. Generalized estimating equation (GEE) models and conditional logistic regressions were used in the unmatched and matched analyses, respectively. Then, we used logistic regressions to test the difference in odds ratios (ORs) between the unmatched and matched analyses. Finally, through bivariate twin model, the roles of genetic and environmental factors in the body mass index (BMI)- hypertension association were estimated. Results: Overall, we included a total of 30,617 twin individuals, of which 7533 (24.6%) twin participants were overweight or obesity and 757 (2.5%) developed hypertension during a median follow-up time of 4.4 years. In the GEE model, overweight or obesity was associated with a 94% increased risk of hypertension (OR=1.94, 95% confidence interval (CI): 1.64~2.30). In the conditional logistic regression, the multi-adjusted OR was 1.80 (95% CI: 1.18~2.74). The difference in OR between unmatched and matched analyses was significant (P=0.016). Specifically, overweight or obesity was not associated with hypertension risk in the co-twin design when we full controlled genetic and familiar environmental factors (OR=0.89, 95 CI: 0.46~1.72). After controlling for age and sex, we found the positive BMI-hypertension association was mainly explained by a genetic correlation between them (r A= 0.59, 95% CI: 0.44~1.00). Conclusions/Interpretation: Genetics and early-life environments shared by participants within a twin pair appear to account for the association between overweight or obesity and hypertension risk.

7.
Ann Palliat Med ; 10(11): 11244-11254, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34670386

RESUMO

BACKGROUND: At present, some cancer patients experience hyperprogressive disease (HPD) after receiving immunotherapy. This study used the Response Evaluation Criteria in Solid Tumors 1.1 to evaluate the incidence of HPD in patients receiving immune checkpoint inhibitors (ICIs) for treating primary liver cancer (PLC) and to explore the risk factors for HPD. METHODS: This retrospective, single-center study included patients with PLC who were treated with ICIs. The RECIST 1.1 was used to determine patients with HPD. Univariate and multivariate regression analyses were performed to explore the risk factors for HPD, and clinical variables with prognostic significance for HPD were included to establish a risk model. RESULTS: Among 129 patients with PLC treated with ICIs, HPD occurred in 13 patients (10.1%). In the multivariate regression analysis, lymph node metastasis and lung metastasis were risk factors for HPD. The area under the curve of the risk model, established by including lymph node metastasis, lung metastasis, neutrophil-lymphocyte ratio, albumin, and performance status, was 0.801 (P<0.001). The progression-free survival of HPD patients was significantly worse than that of non-HPD patients (P<0.001). CONCLUSIONS: In this study, 10.1% of patients with PLC had HPD. Compared with the non-HPD patients, lung metastasis and lymph node metastasis were independent risk factors of HPD.

8.
Diabetes Metab ; : 101278, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520837

RESUMO

OBJECTIVES: This study aimed to estimate the association between overweight and type 2 diabetes mellitus (T2DMM) in twins, and further to explore whether genetic and early-life environmental factors account for this association. METHODS: This study included 31,197 twin individuals from the Chinese National Twin Registry (CNTR). Generalised estimating equation (GEE) models were applied for unmatched case-control analysis. Conditional logistic regressions were used in co-twin matched case-control analysis. Logistic regressions were fitted to examine the differences in odds ratios (ORs) from the GEE models and conditional logistic regressions. Bivariate genetic model was used to explore the genetic and environmental correlation between body mass index (BMI) and T2DM. RESULTS: In the GEE model, overweight was associated with a higher T2DM risk (OR=2.71, 95% confidence interval (CI): 1.96∼3.73), compared with participants with normal BMI. In the multi-adjusted conditional logistic regression, the association was still significant (OR=2.60, 95% CI: 1.15∼5.87). The ORs from the unmatched and matched analyses were different (P = 0.042). Particularly, overweight could increase T2DM risk in monozygotic (MZ) twins, and the difference in ORs between the unmatched and matched designs was significant (P = 0.014). After controlling for age and sex, the positive BMI-T2DM association was partly due to a significant genetic correlation (rA= 0.31, 95% CI: 0.20∼0.41). CONCLUSIONS: Our findings suggest that genetics and early-life environments might account for the observed overweight-T2DM association. Genetic correlation between BMI and T2DM further provides evidence for the influence of overlap genes on their association.

9.
Twin Res Hum Genet ; 24(4): 228-233, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34542028

RESUMO

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1-2 years), preschool (3-5 years), primary or elementary school (6-11 years), and adolescence (10-18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0-18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.

10.
Mov Disord ; 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34390510

RESUMO

BACKGROUND: China's socioeconomic and population structures have evolved markedly during the past few decades, and consequently, monitoring the prevalence of Parkinson's disease (PD) is crucial. OBJECTIVE: This study aimed to investigate the prevalence of PD within Chinese communities, particularly in older people. METHODS: A nationwide study of 24,117 participants, aged 60 years or older, was carried out in 2015 using multistage clustered sampling. All participants were initially screened using a nine-item questionnaire, from which those suspected of having PD were examined by neurologists and a diagnosis was given, according to the 2015 Movement Disorder Society Clinical Diagnostic Criteria. RESULTS: The prevalence of PD was 1.37% (95% confidence interval 1.02%-1.73%) in people aged over 60 years. Thus, the estimated total number of people in China with PD could be as high as 3.62 million. CONCLUSIONS: Although the PD population prevalence percentage did not change significantly, the total number of PD sufferers has increased with the increased population, which poses a significant challenge in a rapidly aging population. © 2021 International Parkinson and Movement Disorder Society.

11.
JAMA Netw Open ; 4(8): e2121106, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34398202

RESUMO

Importance: The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known. Objective: To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China. Design, Setting. and Participants: This cross-sectional study, the China Osteoporosis Prevalence Study, was conducted from December 2017 to August 2018. A random sample of individuals aged 20 years or older who represented urban and rural areas of China were enrolled, with a 99% participation rate. Main Outcomes and Measures: Weighted prevalence of osteoporosis, clinical fracture, and vertebral fracture by age, sex, and urban vs rural residence as determined by x-ray absorptiometry, questionnaire, and radiography. Results: A total of 20 416 participants were included in this study; 20 164 (98.8%; 11 443 women [56.7%]; mean [SD] age, 53 [13] years) had a qualified x-ray absorptiometry image and completed the questionnaire, and 8423 of 8800 (95.7%) had a qualified spine radiograph. The prevalence of osteoporosis among those aged 40 years or older was 5.0% (95% CI, 4.2%-5.8%) among men and 20.6% (95% CI, 19.3%-22.0%) among women. The prevalence of vertebral fracture was 10.5% (95% CI, 9.0%-12.0%) among men and 9.7% (95% CI, 8.2%-11.1%) among women. The prevalence of clinical fracture in the past 5 years was 4.1% (95% CI, 3.3%-4.9%) among men and 4.2% (95% CI, 3.6%-4.7%) among women. Among men and women, 0.3% (95% CI, 0.0%-0.7%) and 1.4% (95% CI, 0.8%-2.0%), respectively, with osteoporosis diagnosed on the basis of bone mineral density or with fracture were receiving antiosteoporosis treatment to prevent fracture. Conclusions and Relevance: In this cross-sectional study of an adult population in mainland China, the prevalence of osteoporosis and vertebral fracture were high and the prevalence of vertebral fracture and clinical fracture was similarly high in men and women. These findings suggest that current guidelines for screening and treatment of fractures among patients in China should focus equally on men and women and should emphasize the prevention of vertebral fractures.

12.
Front Oncol ; 11: 666145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221982

RESUMO

Purpose: Despite the success of targeted therapy in c-ros oncogene 1 (ROS1)-rearranged cancers, especially non-small cell lung cancer (NSCLC), the clinical significance of ROS1 de novo mutation has not yet been understood. We sought to elucidate the predictive effect of ROS1 mutation for immune checkpoint inhibitor (ICI) therapy in melanoma. Methods: The Cancer Genome Atlas [TCGA (n = 10967)] and Memorial Sloan Kettering Cancer Center [MSK (n = 10,945)] datasets, as well as two clinical cohorts of melanoma received ICI [CA209-038 (n = 73) and MEL-IPI (n = 110)], were included to explore the prevalence, prognostic effect, and immunotherapeutic predictive effect of ROS1 mutation in melanoma. Overall survival (OS) was defined as the primary outcome. Results: Overall, melanoma accounted for the highest proportion of ROS1 mutation (~20%) which made up the majority (~95%) of the ROS1-alterated cases. Remarkably, ROS1 mutation yielded longer OS from ICI than the wild-type counterpart in the MSK melanoma population [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.30-0.74], and two external melanoma cohorts (CA209-038: HR 0.42, 95% CI 0.20-0.89; MEL-IPI: HR 0.55, 95% CI 0.34-0.91), without affecting the prognosis of patients. Elevated tumor mutational burden and enrichment of DNA damage repair was observed in ROS1 mutated patients, providing an explanation for the favorable responses to ICI therapy. Precisely, ROS1 mutation in non-protein tyrosine kinase (PTK) domain but not PTK mutation was responsible for the immunotherapy-specific responses of the ROS1 mutated patients in melanoma. Conclusions: Collectively, ROS1 mutation, specifically the non-PTK mutation, is a potential predictor of ICI therapy in melanoma, which is distinct from the well-established role of ROS1 rearrangement for targeted therapy in NSCLC.

13.
Cancer Manag Res ; 13: 4541-4551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135631

RESUMO

Background: Atezolizumab has been used to treat patients with liver metastasis (LM). However, whether atezolizumab is superior to standard of care therapy in an all-comer or selective population with LM is still uncertain. Methods: A pooled analysis based on 10 randomized controlled trials was conducted to evaluate the clinical benefit of atezolizumab versus standard therapy in patients stratified by liver metastatic status, followed by biomarker-based individual analyses of the non-small cell lung cancer (NSCLC) cohort (OAK and POPLAR studies) and urothelial cancer cohort (IMvigor210 study). Results: The pooled analysis demonstrated an overall survival (OS) improvement using atezolizumab treatment versus standard therapy across cancer types and treatment lines regardless of liver metastatic status. However, the efficacy of atezolizumab in patients with LM from the second-line setting was limited, based on the individual analysis of NSCLC cohorts (P = 0.053). PD-L1 strong expression emerged as a predominant biomarker (P = 0.015) to screen atezolizumab-advantageous patients with LM. Notably, the combination of PD-L1 and LM improved the predictive power for atezolizumab therapy in both NSCLC and urothelial cancer cohorts. Exploratory translational analysis revealed that strong expression of PD-L1 might have reversed the non-inflamed immune phenotype of liver metastasis, thus sensitizing these patients to immunotherapy. Conclusion: Our study demonstrated a preferable efficacy of atezolizumab in patients with LM as first-line therapy over standard of care therapy, while sensitive patients should be selected in second-line settings. PD-L1 was demonstrated as the most effective biomarker for screening atezolizumab-advantageous patients with LM.

14.
Oncoimmunology ; 10(1): 1909296, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33996262

RESUMO

Objectives: Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is heterogeneous in clinical practice. Materials and Methods: We retrospectively assessed the predicitive effect of the primary and metastatic lesion spectrum (baseline sum of the longest diameters [SLD], number of metastatic sites and specific organ metastases) on the efficacy of atezolizumab over docetaxel in OAK and POPLAR trial cohorts. A decision model, termed DSO (Diameter-Site-Organ), based on the spectrum was developed and validated for guiding ICB. Results: Higher SLD (>38 mm) and more metastatic sites (≥2) were characterized with pronounced overall survival (OS) benefits from atezolizumab versus docetaxel. Specifically, adrenal gland and brain metastases were identified as favorable predictors of atezolizumab treatment. The DSO model was developed in the discovery cohort to integrate the directive effect of the primary and metastatic lesion spectrum. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a significantly prolonged OS than docetaxel, whereas OS was generally similar between two treatments in patients with DSO score ≤ 0. Equivalent findings were also seen in the internal and external validation cohorts. Conclusions: The response to anti-PD-L1 therapy among patients varied with the primary and metastatic lesion spectrum. The DSO-based system might provide promising medication guidance for ICB treatment in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos
15.
Int J Low Extrem Wounds ; : 15347346211016696, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33939492

RESUMO

The treatment of the Cierny-Mader (C-M) type III-IV calcaneus osteomyelitis combining with the soft-tissue defect is sophisticated and difficult. The aim of this study is to introduce the application and availability of the modified distally based sural flap with an adipofascial extension to reconstruct these defects. We retrospectively reviewed the data of 37 patients with C-M type III-IV calcaneus osteomyelitis accompanied with soft-tissue defect between December 2004 and December 2019. A modified distally based sural flap with an adipofascial extension was conducted to reconstruct the defect. The patient's demographics, duration of the diseases, etiology, reconstruction outcomes, infection control rate, recurrence rate, amputation rate, and follow-up data were collected to evaluate the effectiveness and reliability of the modification. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot scale was applied to assess the function of the ankle and hindfoot. Thirty-four flaps survived uneventfully, 1 flap displayed marginal necrosis and 2 flaps (5.41%) developed partial necrosis. Using this modified flap alone or combining with some simple salvage methods reconstructed all of the defects successfully. The calcaneus osteomyelitis was cured successfully, and no recurrences were observed during the follow-up period. The AOFAS ankle and hindfoot scores were excellent in 27 patients and good in 8 patients. The distally based sural flap with an adipofacial extension is a simple and effective technique to reconstruct the calcaneus osteomyelitis combined with soft-tissue defect in 1 stage. Applications of the adipofacial extension to obliterate the dead space and the well-vascularized skin island to cover the defect are the guarantee of achieving good ankle and foot functions. However, this technique is not appropriate for the patients with calcaneum less than half weight-bearing area.

16.
Virol Sin ; 36(4): 706-720, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33559831

RESUMO

Human respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5' to 3') a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed  temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Animais , Chlorocebus aethiops , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/genética , Vírus Sincicial Respiratório Humano/genética , Vacinas Atenuadas/genética , Células Vero , Replicação Viral
17.
J Reconstr Microsurg ; 37(7): 580-588, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33592636

RESUMO

BACKGROUND: This study is to describe the distribution of natural true anastomoses associated with the distally based perforator-plus sural neurocutaneous flap (sural flap), summarize our experience in the flap with high pivot point, and compare the outcomes between the flaps with high and low pivot points. METHODS: Five amputated lower limbs were perfused, and the integuments were radiographed. We retrospectively analyzed 378 flaps, which were divided into two groups: pivot points located ≤8.0 cm (low pivot point group) and >8.0 cm (high pivot point group) proximal to the tip of the lateral malleolus. Partial necrosis rates were compared between two groups. RESULTS: The arterial chain surrounding the sural nerve was linked by true anastomoses from the intermalleolar line to popliteal crease. True anastomoses existed among peroneal perforators and between these perforators and the arterial chain. There were 93 flaps with high pivot point and 285 flaps with low pivot point. Partial necrosis rates were 16 and 9.1% in the high and low pivot point group (p = 0.059), respectively. CONCLUSION: True anastomosis connections among peroneal perforators and the whole arterial chain around sural nerve enable the sural flap to survive with a greater length. The sural flap with high pivot point is a good option for reconstructing soft-tissue defects in the middle and distal leg, ankle, and foot, particularly when the lowest peroneal perforator presents damage, greater distance to the defects, discontinuity with the donor site, or anatomical variation.


Assuntos
Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Lesões dos Tecidos Moles , Tornozelo , , Humanos , Estudos Retrospectivos , Lesões dos Tecidos Moles/cirurgia , Nervo Sural
18.
J Leukoc Biol ; 109(1): 35-47, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33242368

RESUMO

The SARS-CoV-2 pandemic has led to hundreds of thousands of deaths and billions of dollars in economic damage. The immune response elicited from this virus is poorly understood. An alarming number of cases have arisen where COVID-19 patients develop complications on top of the symptoms already associated with SARS, such as thrombosis, injuries of vascular system, kidney, and liver, as well as Kawasaki disease. In this review, a bioinformatics approach was used to elucidate the immune response triggered by SARS-CoV-2 infection in primary human lung epithelial and transformed human lung alveolar. Additionally, examined the potential mechanism behind several complications that have been associated with COVID-19 and determined that a specific cytokine storm is leading to excessive neutrophil recruitment. These neutrophils are directly leading to thrombosis, organ damage, and complement activation via neutrophil extracellular trap release.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Transdução de Sinais/imunologia , Trombose/imunologia , Lesões do Sistema Vascular/imunologia , COVID-19/patologia , Citocinas/imunologia , Humanos , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/patologia , Síndrome de Linfonodos Mucocutâneos/virologia , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/virologia , Trombose/patologia , Trombose/virologia , Lesões do Sistema Vascular/patologia , Lesões do Sistema Vascular/virologia
19.
Front Oncol ; 11: 772604, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34976815

RESUMO

Background: Homologous recombination deficiency (HRD) is characterized by overall genomic instability and has emerged as an indispensable therapeutic target across various tumor types, particularly in ovarian cancer (OV). Unfortunately, current detection assays are far from perfect for identifying every HRD patient. The purpose of this study was to infer HRD from the landscape of copy number variation (CNV). Methods: Genome-wide CNV landscape was measured in OV patients from the Australian Ovarian Cancer Study (AOCS) clinical cohort and >10,000 patients across 33 tumor types from The Cancer Genome Atlas (TCGA). HRD-predictive CNVs at subchromosomal resolution were identified through exploratory analysis depicting the CNV landscape of HRD versus non-HRD OV patients and independently validated using TCGA and AOCS cohorts. Gene-level CNVs were further analyzed to explore their potential predictive significance for HRD across tumor types at genetic resolution. Results: At subchromosomal resolution, 8q24.2 amplification and 5q13.2 deletion were predominantly witnessed in HRD patients (both p < 0.0001), whereas 19q12 amplification occurred mainly in non-HRD patients (p < 0.0001), compared with their corresponding counterparts within TCGA-OV. The predictive significance of 8q24.2 amplification (p < 0.0001), 5q13.2 deletion (p = 0.0056), and 19q12 amplification (p = 0.0034) was externally validated within AOCS. Remarkably, pan-cancer analysis confirmed a cross-tumor predictive role of 8q24.2 amplification for HRD (p < 0.0001). Further analysis of CNV in 8q24.2 at genetic resolution revealed that amplifications of the oncogenes, MYC (p = 0.0001) and NDRG1 (p = 0.0004), located on this fragment were also associated with HRD in a pan-cancer manner. Conclusions: The CNV landscape serves as a generalized predictor of HRD in cancer patients not limited to OV. The detection of CNV at subchromosomal or genetic resolution could aid in the personalized treatment of HRD patients.

20.
Obes Facts ; 13(6): 538-547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33232966

RESUMO

OBJECTIVE: Metabolic syndrome (MetS) is one of the major public health problems worldwide. The aim of this study was to investigate the prevalence and associated risk factors of MetS in Beijing to formulate targeted policies. METHODS: Data from the 2017 Beijing Chronic Disease and Risk Factors Surveillance were used in this study, in which multistage stratified cluster sampling was adopted to collect a representative sample of 12,597 Beijing residents aged from 18 to 79 years. According to the definition of the International Diabetes Federation, the weighted prevalence of MetS and clustering of MetS components were estimated. The Rao-Scott adjusted χ2 test was used to test differences in MetS and components rates, and complex sampling unconditional logistic regression was used to explore influencing factors of MetS. RESULTS: The prevalence of MetS was 25.59% (95% CI 23.77-27.41), and the proportion of men and women was 30.53% (95% CI 28.32-32.75) and 20.44% (95% CI 18.29-22.58), respectively. The proportion of central obesity, high fasting plasma glucose, high triglyceride, low high-density lipoprotein cholesterol, and high blood pressure (BP) was 42.02, 27.96, 32.87, 27.25, and 43.06%, respectively. A total of 29.60% (95% CI 27.55-31.74) participants presented at least three components of MetS. The results from complex sampling unconditional logistic regression revealed that the risk factors for having MetS included being 45-59 years old, being 60-79 years old, being male, living in a rural area, education with junior middle school level, education with primary school or below level, harmful use of alcohol, inappropriate sleep time, and having an unhealthy waist-to-height ratio (WHtR); the OR values were 1.55 (95% CI 1.32-1.81), 1.94 (95% CI 1.62-2.31), 1.51 (95% CI 1.34-1.70), 1.27 (95% CI 1.06-1.52), 1.38 (95% CI 1.13-1.68), 1.44 (95% CI 1.13-1.84), 1.50 (95% CI 1.14-1.99), 1.23 (95% CI 1.10-1.37), and 238.20 (95% CI 92.54-613.12), respectively. CONCLUSIONS: The prevalence of MetS is still in a rising trend in Beijing. Strategies aimed at prevention and control of high BP should be prioritized to reduce the occurrence of MetS. WHtR is more important to evaluate MetS. Health education and personalized lifestyle intervention should be promoted to keep a healthy WHtR and waist circumference. An appropriate sleep time should be kept, and harmful alcohol drinkers should limit or abstain from alcohol.


Assuntos
Síndrome Metabólica/epidemiologia , Adolescente , Adulto , Idoso , Pequim , Feminino , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Razão Cintura-Estatura , Adulto Jovem
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