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1.
Chin J Integr Med ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34755287

RESUMO

OBJECTIVE: To verify the efficacy of Quxie Capsule in patients with metastatic colorectal cancer (mCRC). METHODS: It was a block randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into 2 groups at a 1:1 ratio. The patients in the treatment group received conventional therapy including chemotherapy, radiotherapy, targeted therapy and supportive care, and Chinese herbal medicine combined with Quxie Capsule (each capsule of 0.4 g was orally administered at 50 mg/kg, twice daily, day 1-20, in a 30-day course) for 3 months. The patients in the control group received conventional therapy and Chinese herbal medicine combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed according to therapy lines, right or left-sided colon, targeted therapy and RAS gene status to determine the differences in PFS and OS between the two groups. Patients were followed up every 3 months until December 31st, 2018. RESULTS: Median follow-up time was 19.4 months. The median OS was 23.9 months in the treatment group [95% confidence interval (CI) 15.9-28.5] vs. 14.3 months in the control group (95% CI 11.3-21.4, P<;0.05). Hazard ratio (95% CI) was 0.55 (0.31-0.95, P=0.040). There were no significant differences between the two groups in PFS (P>0.05). In the subgroups of ⩾second-line therapy, non-targeted therapy, RAS gene wild type and left-sided colon, the treatment group showed a significant survival benefit compared with the control group (P<;0.05 or P<;0.01), respectively. CONCLUSION: Quxie Capsule can reduce the risk of death and prolong the OS of patients with mCRC. (Registration No. ChiCTR-IOR-16009733).

2.
Rheumatol Ther ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806155

RESUMO

INTRODUCTION: This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. METHODS: Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity. RESULTS: A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62-68.20%) and 56.89% for the INF group (95% CI 50.90-62.74%). The difference between the two groups was 5.65% with a 95% CI of - 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable. CONCLUSIONS: GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34718432

RESUMO

OBJECTIVE: To quantify temporal trend of sex- and age-specific disability-adjusted life years (DALYs) for musculoskeletal disorders (MSK) by region and cause. METHODS: Data were collected from Global Burden of Diseases Study 2019. Estimated annual percentage change (EAPC) by sex, age, region, and cause was calculated to examine the temporal trend of age-standardized DALY rate (ASDR). The socio-demographic index (SDI) and risk exposures are also examined. RESULTS: Between 1990 and 2019, global ASDR in MSK remained almost stable by sex and age group, but decreased mostly among females aged 0-14 years (EAPC = -0.27). Such age- and sex- trend pattern was nearly the same by SDI, except for high SDI regions, where ASDR extensively increased in subgroups but those aged 15-49 years. The trend in ASDR of MSK for females and males aged 50-74 and 75+ years increased in about 80% countries and territories. The greatest increase was in El Salvador for males aged 15-49 years (EAPC = 1.30), followed by Nicaragua. Association between EAPC and SDI was positive in developing regions, particularly among females aged 15-49 years, and negative in developed regions. Decreased trend in ASDR mainly driven by the decrease in LBP, while the increased trend was largely due to other MSK and gout across sexes and age groups. CONCLUSIONS: There are great disparities in the age- and sex-specific trend in ASDR by cause at global, regional, and national level. More differentiated prevention and management strategies are needed for MSK.

4.
Ann Rheum Dis ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556485

RESUMO

OBJECTIVES: We previously identified a hypomorphic variant, p.Arg90His (p.R90H) of neutrophil cytosolic factor 1 (NCF1, a regulatory subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 complex), as an putative causal variant for systemic lupus erythematosus (SLE), and established a knock-in (KI) H90 variant in the C57BL/6 background to study how this variant promotes lupus development. METHODS: Wild type (WT) and KI littermates were assessed for immune profiles and lupus-like features. Disease activity and renal damage of patients with SLE were assessed by systemic lupus erythematosus disease activity index (SLEDAI) and renal items of systemic lupus international collaborating clinics (SLICC), respectively. RESULTS: Compared with WT littermates, 5-week-old homozygous KI mice had reduced oxidative burst, splenomegaly, elevated type I interferon (IFN-I) scores, increased ratios of splenic follicular T helper 2 (Tfh2) to either T follicular regulatory (Tfr) or Tfh1 cells, increased ANA+ follicular, germinal centre and plasma cells without spontaneous kidney disease up to 1 year of age. Pristane treatment exacerbated the immune dysregulation and induced IFN-I-dependent kidney disease in 36-week-old H90 KI female mice. Decreased efferocytosis of macrophages derived from KI mice and patients with homozygous H90 SLE promoted elevated ratios of Tfh2/Tfr and Tfh2/Tfh1 as well as dysregulated humoral responses due to reduced voltage-gated proton channel 1 (Hv1)-dependent acidification of phagosome pH to neutralise the decreased electrogenic effect of the H90 variant, resulting in impaired maturation and phagosome proteolysis, and increased autoantibody production and kidney damage in mice and patients with SLE of multiple ancestries. CONCLUSIONS: A lupus causal variant, NCF1-H90, reduces macrophage efferocytosis, enhances Tfh2 responses and promotes autoantibody production and kidney damage in both mice and patients with SLE.

5.
Sci Rep ; 11(1): 18591, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545152

RESUMO

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.


Assuntos
Poluição do Ar/efeitos adversos , Água Potável , Exposição Ambiental/efeitos adversos , Lúpus Eritematoso Sistêmico/epidemiologia , Poluição da Água/efeitos adversos , Adulto , China/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
6.
Arthritis Res Ther ; 23(1): 250, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587995

RESUMO

OBJECTIVE: Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of patients with primary Sjögren's syndrome and to correlate these findings with their disease activity. METHODS: Fifty-two patients with primary SS and 52 sex- and age-matched healthy control subjects were included. All of them underwent clinical and laboratory examination. Olfactory functions were evaluated using olfactory function assessment by computerized testing including the three stages of smell: threshold, identification, and memory of the different odors. RESULTS: All the olfactory scores (olfactory threshold, identification, and memory) in patients with pSS were significantly decreased than the control group (all P < 0.01). Patients had higher proportion of anosmia (13.5% vs 0%) and hyposmia (19.2% vs 11.5%) than controls (χ2 = 10.526, P < 0.01). Multivariable regression analysis revealed that ESSDAI and the symptoms of dryness, fatigue, and limb pain had negative influence on olfactory function (adjusted R2 = 0.381, 0.387, 0.513, and 0.614, respectively). ESSPRI showed significantly negative association with olfactory threshold, identification, memory, and total scores. Olfactory identification and memory scores were decreased in pSS patients with thyroid dysfunction or hypocomplementemia (P < 0.05). Smell threshold scores were decreased in pSS patients with anti-SSA antibody or anti-nuclear antibody compared with those without those autoantibodies (P < 0.01). CONCLUSION: Our findings indicate that olfactory functions are impaired in pSS patients. There was a close correlation between olfactory dysfunction and disease severity and immunological abnormalities. Immune and systemic inflammation dysregulation might play a role in the mechanism of this defect.


Assuntos
Transtornos do Olfato , Síndrome de Sjogren , Fadiga , Humanos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Dor , Índice de Gravidade de Doença , Síndrome de Sjogren/complicações
7.
IEEE Trans Image Process ; 30: 8658-8670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34554912

RESUMO

Formulated as a conditional generation problem, face animation aims at synthesizing continuous face images from a single source image driven by a set of conditional face motion. Previous works mainly model the face motion as conditions with 1D or 2D representation (e.g., action units, emotion codes, landmark), which often leads to low-quality results in some complicated scenarios such as continuous generation and large-pose transformation. To tackle this problem, the conditions are supposed to meet two requirements, i.e., motion information preserving and geometric continuity. To this end, we propose a novel representation based on a 3D geometric flow, termed facial flow, to represent the natural motion of the human face at any pose. Compared with other previous conditions, the proposed facial flow well controls the continuous changes to the face. After that, in order to utilize the facial flow for face editing, we build a synthesis framework generating continuous images with conditional facial flows. To fully take advantage of the motion information of facial flows, a hierarchical conditional framework is designed to combine the extracted multi-scale appearance features from images and motion features from flows in a hierarchical manner. The framework then decodes multiple fused features back to images progressively. Experimental results demonstrate the effectiveness of our method compared to other state-of-the-art methods.

8.
Chin J Integr Med ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432206

RESUMO

BACKGROUND: The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients' adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer. METHODS: A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy. DISCUSSION: This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518).

9.
Front Immunol ; 12: 675542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394075

RESUMO

Autoreactive T cells play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). TGF-ß type I receptor (TGFßRI) is pivotal in determining T cell activation. Here, we showed that TGFßRI expression in naïve CD4+ T cells was decreased in SLE patients, especially in those with high disease activity. Moreover, IL-6 was found to downregulate TGFßRI expression through JAK/STAT3 pathway in SLE patients. In vitro, the JAK inhibitor tofacitinib inhibited SLE T cell activating by upregulating TGFßRI expression in a dose-dependent manner. In MRL/lpr mice, tofacitinib treatment ameliorated the clinical indicators and lupus nephritis, as evidenced by reduced plasma anti-dsDNA antibody levels, decreased proteinuria, and lower renal histopathological score. Consistently, tofacitinib enhanced TGFßRI expression and inhibited T cell activation in vivo. TGFßRI inhibitor SB431542 reversed the effects of tofacitinib on T cell activation. Thus, our results have indicated that tofacitinib can suppress T cell activation by upregulating TGFßRI expression, which provides a possible molecular mechanism underlying clinical efficacy of tofacitinib in treating SLE patients.


Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ativação Linfocitária/efeitos dos fármacos , Piperidinas/farmacologia , Pirimidinas/farmacologia , Receptor do Fator de Crescimento Transformador beta Tipo I/fisiologia , Linfócitos T/efeitos dos fármacos , Adulto , Animais , Feminino , Humanos , Interleucina-6/fisiologia , Janus Quinases/fisiologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Pessoa de Meia-Idade , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Fator de Transcrição STAT3/fisiologia , Linfócitos T/imunologia , Adulto Jovem
10.
Lancet Reg Health West Pac ; 10: 100128, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34327344

RESUMO

Background: There is heterogeneity in the clinical manifestations and responses to drugs in RA patients due to variety of factors such as genes and environment. Despite advances in the treatment of rheumatoid arthritis (RA), approximately 40% of RA patients still do not achieve primary clinical outcomes in randomized trials, and its low remission rate and high economic consumption remain unresolved, especially in developing countries. Iguratimod (IGU) is a new disease-modifying anti-rheumatic drug (DMARD) with a low price that has demonstrated good efficacy and safety in clinical trials and was approved for active RA in China and Japan. As the most populous country in the Western Pacific region, it is warranted to conduct a study with a large scale of patients in a real-life setting. Our study confirms the new option for RA patients, which is potentially benificial for public health in developing countries. Methods: This was a nationwide, prospective real-world study of IGU. Eligible subjects were active adult RA patients who aged 18 to 85 with or without multiple comorbidities such as hypertension and diabetes with DMARDs at a stable dosage for at least 12 weeks, or without ongoing DMARDs. A two-stage design was used for this study. In the first stage (the first 12 weeks), IGU 25 mg bid was added as monotherapy or to the background therapy, and in the second stage (the latter 12 weeks), adjustment of RA medicines other than IGU was allowed according to the participants' disease activity. The primary endpoints were American College of Rheumatology 20% response (ACR20) 24 weeks and adverse events during 24 weeks. The secondary endpoints were ACR50 and ACR70 over 24 weeks, the changes of DAS28 and Health Assessment Questionnaire (HAQ) at week 12 and week 24 from baseline. The trial was registered with ClinicalTrials.gov, number NCT01554917. Findings: Between March 2012 and January 2015, 1759 participants were enrolled, of whom 81•5% (1433/1759) completed the study. Notably, 1597 patients in the full analysis set were assessed for the effectiveness and 1751 patients were in the safety analysis set; 71•9% (1148/1597) of the patients achieved the primary endpoint of ACR20 response at week 24, and 51•7% (906/1751) patients had at least 1 adverse event (AE). The incidence of the clinical significant AE (grade≥3) of special interest was 3•4% (54 patients for grade 3 and 6 patients for grade 4), and 0•7% (13/1751) of patients developed SAEs associated with IGU. The most common clinical significant AEs were infection in 0•6% (10/1751) of the patients, abdominal discomfort in 0•5% (9/1751) of the patients including 0•2% (3/1751) gastric ulcer, fracture in 0•4% (7/1751), and increased alanine aminotransferase (ALT) in 0•2% (3/1751) of the patients. The secondary endpoint of ACR50 and ACR70 response rates at week 24 were 47•4% (757/1597) and 24•0% (384/1597). DAS28 was 4•11±1•27 and 3•75±1•32 at week 12 and 24, which was significantly decreased -1•40±1•10 and -1•75±1•26 compared with baseline (P<0•001) respectively. Changes in HAQ at week 12 and 24 from baseline were -7•4 ± 9•18 and -8•5 ± 9•97, respectively (all P<0•001). Stratified analysis results showed that the patients with shorter disease duration, male gender had better response to IGU. There was no significant difference in ACR20/50/70 responses between elderly patients(≥65 years) and younger patients(<65 years), IGU monotherapy or combined with other DMARDs. However, more fractures (1•1% vs 0•5%; P = 0•64) and infections (8•7% vs 7•9%; P = 0•69) were observed in elderly patients in our study. Interpretation: Our results confirmed the effectiveness and safety of IGU as a new DMARD for active patients with RA as monotherapy or combination therapy. Funding: This study was supported by "the 11th Five-Year-Plan for Science and Technology Support Program (2012ZX09104-103-01)".

12.
Big Data ; 9(5): 343-357, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34287015

RESUMO

The accuracy of the prediction of stock price fluctuations is crucial for investors, and it helps investors manage funds better when formulating trading strategies. Using forecasting tools to get a predicted value that is closer to the actual value from a given financial data set has always been a major goal of financial researchers and a problem. In recent years, people have paid particular attention to stocks, and gradually used various tools to predict stock prices. There is more than one factor that affects financial trends, and people need to consider it from all aspects, so research on stock price fluctuations has also become extremely difficult. This paper mainly studies the impact of leading indicators on the stock market. The framework used in this article is proposed based on long short-term memory (LSTM). In this study, leading indicators that affect stock market volatility are added, and the proposed framework is thus named as a stock tending prediction framework based on LSTM with leading indicators (LSTMLI). This study uses stock markets in the United States and Taiwan, respectively, with historical data, futures, and options as data sets to predict stock prices in these two markets. We measure the predictive performance of LSTMLI relative to other neural network models, and the impact of leading indicators on stock prices is studied. Besides, when using LSTMLI to predict the rise and fall of stock prices in the article, the conventional regression method is not used, but the classification method is used, which can give a qualitative output based on the data set. The experimental results show that the LSTMLI model using the classification method can effectively reduce the prediction error. Also, the data set with leading indicators is better than the prediction results of the single historical data using the LSTMLI model.


Assuntos
Memória de Curto Prazo , Redes Neurais de Computação , Previsões , Humanos
13.
Redox Biol ; 44: 102010, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34082381

RESUMO

Activated microglia are an important type of innate immune cell in the brain, and they secrete inflammatory cytokines into the extracellular milieu, exert neurotoxicity to surrounding neurons and are involved in the pathogenesis of many brain disorders. Quercetin (Qu), a natural flavonoid, is known to have anti-inflammatory and antioxidant properties. Previous studies have shown that both increased reactive oxygen species (ROS) stress and decreased autophagy participate in the activation of microglial. In the current study, we showed that Qu significantly attenuated LPS-induced inflammatory factor production, cell proliferation and NF-κB activation of microglia. Importantly, Qu decreased the levels of NLR family, pyrin domain containing three (NLRP3) inflammasome and pyroptosis-related proteins, including NLRP3, active caspase-1, GSDMD N-terminus and cleaved IL-1ß. Further study indicated that this anti-inflammatory effect of Qu was associated with mitophagy regulation. Importantly, Qu promoted mitophagy to enhance damaged mitochondrial elimination, which then reduced mtROS accumulation and alleviated NLRP3 inflammasome activation. Then, we confirmed that Qu treatment protected primary neurons against LPS-induced microglial toxicity and alleviated neurodegeneration in both depression and PD mouse models. Further IL-1ß administration blunted these neuroprotective effects of Qu in vitro and in vivo. This work illustrated that Qu prevents neuronal injury via inhibition of mtROS-mediated NLRP3 inflammasome activation in microglia through promoting mitophagy, which provides a potential novel therapeutic strategy for neuroinflammation-related diseases.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Microglia , Mitofagia , Quercetina , Espécies Reativas de Oxigênio
14.
J Comput Assist Tomogr ; 45(4): 557-563, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34176880

RESUMO

OBJECTIVE: To explore the role of diffusion kurtosis magnetic resonance (MR) imaging in the noninvasive identification of synovitis in hand arthritis. METHODS: A total of 30 patients with rheumatoid arthritis (RA) and 10 patients suspected of RA were enrolled in the prospective study. A 3.0-T MR imaging including the diffusion kurtosis MR imaging sequence (b = 0, 500, 1000, 1500, 2000 s·mm2) was performed. A total of 210 regions of interest were confirmed and diffusion kurtosis MR imaging parameters were generated. The suspected synovitis or effusion was scored on a scale of 0 (effusion) to 3 (mild, moderate, severe synovitis), according to RA-MR imaging scoring system. The performance of diffusion kurtosis MR imaging parameters (the apparent diffusion coefficient [ADC], diffusion coefficient [D], and kurtosis [K]) in distinguishing different synovitis scores was evaluated. RESULTS: There were significant differences in ADC, D, and K values among different synovitis scores (all P < 0.001). Synovitis scores were negatively correlated with the ADC and D values significantly (r = -0.725, -0.757, respectively, all P < 0.001), but positively correlated with the K values significantly (r = 0.429, P < 0.001). The area under the curve values of D, ADC, and K values were 0.884, 0.874, and 0.728 for differentiating score 1-3 from score 0, respectively. Diffusion coefficient and ADC had similar diagnostic performance, and both were higher than K in detecting synovitis. No significant difference was found between the ADC and D values in detecting synovitis. CONCLUSIONS: The diffusion kurtosis MR imaging may be feasible as a noninvasive method for the diagnosis and grading of synovitis in the hands of RA patients, and the D and ADC values showed similar diagnostic performance, both of which were higher than K values.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Sinovite/diagnóstico por imagem , Adulto , Artrite Reumatoide/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Membrana Sinovial/diagnóstico por imagem , Sinovite/complicações
15.
Integr Cancer Ther ; 20: 15347354211021654, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34116595

RESUMO

OBJECTIVE: To evaluate the effectiveness of Chinese Herbal Medicine (CHM) on leukopenia/neutropenia induced by chemotherapy in adults with colorectal cancer (CRC). METHODS: Eight electronic databases were searched from their inception to June 2020. Randomized controlled trials with clarified sequence generation were qualified. Two reviewers independently conducted the screening and data extraction. Methodological quality was assessed using the Risk of Bias tool. RevMan 5.4 was applied to the meta-analysis. RESULTS: Twenty-seven studies involving 1867 participants were qualified, of which 26 were included in the quantitative synthesis. Meta-analysis showed that CHM significantly reduced the incidence of leukopenia induced by chemotherapy (RR = 0.69; 95% CI 0.59-0.82), as well as the grade 3/4 leukopenia (RR = 0.71; 95% CI 0.55-0.90). Meanwhile,CHM decreased the occurrence of neutropenia (RR = 0.52, 95% CI 0.35-0.77), especially for the grades 3/4 neutropenia (RR = 0.42, 95% CI 0.27-0.64). Twenty-six of the included studies focused on the adverse events related to CHM. CONCLUSION: CHM may relieve neutropenia/leukopenia induced by chemotherapy in adults with colorectal cancer.


Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Neutropenia , Adulto , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Herbária , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Fitoterapia
16.
Integr Cancer Ther ; 20: 15347354211020105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34116615

RESUMO

INTRODUCTION: Spleen Deficiency Syndrome (SDS) is recognized as one of the most common Traditional Chinse Medicine (TCM) syndromes in patients with colorectal cancer (CRC). However so far there is no existing patient-reported outcome (PRO) to evaluate SDS. Our study aimed to develop and validate a PRO TCM-SDS scale for CRC in China. METHODS: We developed an initial 8-item TCM-SDS scale for CRC based on literature review and consultation with experts. We then pilot tested the scale (n = 40) and performed item revision. We conducted a survey study among CRC patients from oncology clinics at a TCM Hospital to further determine the reliability and validity of the scale. RESULTS: Among 100 patients finally enrolled and analyzed in the survey study, 46% were female with median age of 60 years old, 77% had left side tumors and 23% had stage IV disease. Factor loading indicated that there were three domains within TCM-SDS scale. The final TCM-SDS scale involves 5 items including "I feel loss of appetite," "I feel abdomen fullness," "I feel my arms and legs lack strength," "I feel short of breath when talking," and "My stool is formless" (Cronbach's alpha coefficient 0.76). We calculated the total score of the scale by summing the 5 individual items and normalizing them to a value maximum of 10, with higher scores indicating greater burden of spleen deficiency syndrome. The average spleen deficiency score for all patients was 3.55 ± 1.54. Among them, those who had stage IV disease had higher scores than stage I-III patients (4.30 vs 3.38, P = .015). Test-retest reliability after 2 weeks showed Pearson coefficient of 0.67 and all items were highly related (P < .001). Compared with healthy controls, CRC patients had significantly higher spleen deficiency scores (3.55 vs 3.23, P = .045). CONCLUSION: The patient-reported TCM-SDS scale for CRC showed adequate initial reliability and validity. The development of the scale provided an outcome measurement tool, which could facilitate future studies to better evaluate the role of TCM in treating CRC.


Assuntos
Neoplasias Colorretais , Medicina Tradicional Chinesa , China , Neoplasias Colorretais/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Reprodutibilidade dos Testes , Baço , Inquéritos e Questionários , Síndrome
17.
Front Immunol ; 12: 668760, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093566

RESUMO

Resolvin D1 (RvD1) prompts inflammation resolution and regulates immune responses. We explored the effect of RvD1 on systemic lupus erythematosus (SLE) and investigated the correlation between RvD1 and Treg/Th17 imbalance, which is one of the major factors contributing to the pathogenesis of disease. SLE patients and healthy controls were recruited to determine plasma RvD1 levels. MRL/lpr lupus model was used to verify rescue of the disease phenotype along with Treg/Th17 ratio. Purified naive CD4+ T cells were used to study the effect of RvD1 on Treg/Th17 differentiation in vitro. Furthermore, small RNA Sequencing and transfection were performed successively to investigate downstream microRNAs. The result showed that the RvD1 level was significantly lower in active SLE patients compared with inactive status and controls. Moreover, The SLE disease activity index (SLEDAI) score had a significant negative correlation with RvD1 level. As expected, RvD1 treatment ameliorated disease phenotype and inflammatory response, improved the imbalanced Treg/Th17 in MRL/lpr mice. In addition, RvD1 increased Treg while reduced Th17 differentiation in vitro. Furthermore, miR-30e-5p was verified to modulate the Treg/Th17 differentiation from naïve CD4+ T cells as RvD1 downstream microRNA. In conclusion, RvD1 effectively ameliorates SLE progression through up-regulating Treg and down-regulating Th17 cells via miR-30e-5p.


Assuntos
Anti-Inflamatórios/farmacologia , Diferenciação Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Lúpus Eritematoso Sistêmico/prevenção & controle , MicroRNAs/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adulto , Animais , Estudos de Casos e Controles , Células Cultivadas , Citocinas/sangue , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/sangue , Feminino , Humanos , Mediadores da Inflamação/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Camundongos Endogâmicos MRL lpr , MicroRNAs/genética , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Adulto Jovem
18.
Nat Commun ; 12(1): 3073, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031386

RESUMO

Follicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.


Assuntos
Formação de Anticorpos/imunologia , Vacinas contra Influenza/imunologia , Leptina/metabolismo , Animais , Anticorpos Antivirais/imunologia , Diferenciação Celular , Feminino , Homeostase , Humanos , Imunização , Influenza Humana/prevenção & controle , Leptina/deficiência , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Vacinação/métodos
19.
Sci Adv ; 7(19)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952522

RESUMO

Morphing structures are often engineered with stresses introduced into a flat sheet by leveraging structural anisotropy or compositional heterogeneity. Here, we identify a simple and universal diffusion-based mechanism to enable a transient morphing effect in structures with parametric surface grooves, which can be realized with a single material and fabricated using low-cost manufacturing methods (e.g., stamping, molding, and casting). We demonstrate from quantitative experiments and multiphysics simulations that parametric surface grooving can induce temporary asynchronous swelling or deswelling and can transform flat objects into designed, three-dimensional shapes. By tuning the grooving pattern, we can achieve both zero (e.g., helices) and nonzero (e.g., saddles) Gaussian curvature geometries. This mechanism allows us to demonstrate approaches that could improve the efficiency of certain food manufacturing processes and facilitate the sustainable packaging of food, for instance, by creating morphing pasta that can be flat-packed to reduce the air space in the packaging.

20.
Chin Med J (Engl) ; 134(12): 1457-1464, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34039871

RESUMO

BACKGROUND: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. METHODS: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48. RESULTS: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed. CONCLUSIONS: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. TRIAL REGISTRATION: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , China , Difosfonatos , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Tecnécio/uso terapêutico , Resultado do Tratamento
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