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1.
Artigo em Inglês | MEDLINE | ID: mdl-34609596

RESUMO

CD47, a transmembrane protein, acts as a "do not eat me" signal that is overexpressed in many tumor cell types, thereby forming a signaling axis with its ligand signal regulatory protein alpha (SIRPα) and enabling the tumor cells to escape from macrophage-mediated phagocytosis. Several clinical trials with CD47 targeting agents are underway and have achieved impressive results preliminarily. However, hematotoxicity (particularly anemia) has emerged as the most common side effect that cannot be neglected. In the development of CD47 targeting agents, various methods have been used to mitigate this toxicity. In this review, we summarized five strategies used to alleviate CD47 blockade-induced hematotoxicity, as follows: change in the mode of administration; dual targeting bispecific antibodies of CD47; CD47 antibodies/SIRPα fusion proteins with negligible red blood cell binding; anti-SIRPα antibodies; and glutaminyl-peptide cyclotransferase like inhibitors. With these strategies, the development of CD47 targeting agents can be improved.

2.
J Affect Disord ; 296: 189-197, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34607060

RESUMO

BACKGROUND: The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. METHODS: Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. RESULTS: Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%-1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%-57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. LIMITATIONS: The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. CONCLUSIONS: Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.

3.
Lancet Psychiatry ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34559991

RESUMO

BACKGROUND: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. METHODS: The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. FINDINGS: 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. INTERPRETATION: Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. FUNDING: National Health Commission and Ministry of Science and Technology of People's Republic of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

4.
Chin J Nat Med ; 19(9): 648-655, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34561075

RESUMO

Ocotillol (OT)-type ginsenosides, one subtype of ginsenosides, consist of a dammarane skeleton and a tetrahydrofuran ring. Most naturally-occurring OT-type ginsenosides exist in Panax species, particularly in Panax quinquefolius, which may be attributed to the warm and humid climate of its native areas. Till now, merely 28 types of naturally-occurring OT-type ginsenosides have been isolated. In contrast, semi-synthesized OT-type ginsenosides are attracted considerable attentions. These ginsenosides can be obtained through oxidation and cyclization of side chains of dammarane-type ginsenosides, and other methods, which may change their physical and chemical properties and further improve their bioavailabilities. It is also notable that the pharmacological activities of ginsenosides are closely related to the stereoisomers caused by the configuration at C-20. Semi-synthesis of OT-type ginsenosides can facilitate our understanding of the biosynthesis, transformation and metabolism of OT-type ginsenosides in the body. This review will systematically summarize the research progress on naturally-occurring and semi-synthetic OT-type ginsenosides, which provides a theoretical basis for their bioactivity-guided research.

5.
Cladistics ; 37(5): 518-539, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34570931

RESUMO

Comprising about 82% of the extant fern species diversity, Polypodiales are generally believed to have diversified in the Late Cretaceous. We estimated the divergence times of Polypodiales using both penalized likelihood and Bayesian methods, based on a dataset consisting of 208 plastomes representing all 28 families and 14 fossil constraints reflecting current interpretations of fossil record. Our plastome phylogeny recovered the same six major lineages as a recent nuclear phylogeny, but the position of Dennstaedtiineae was different. The present phylogeny showed high resolution of relationships among the families of Polypodiales, especially among those forming the Aspleniineae. The divergence time estimates supported the most recent common ancestor of Polypodiales and its closest relative dating back to the Triassic, establishment of the major lineages in the Jurassic, and a likely accelerated radiation during the late Jurassic and the Early Cretaceous. The estimated divergence patterns of Polypodiales and angiosperms converge to a scenario in which their main lineages were established simultaneously shortly before the onset of the Cretaceous Terrestrial Revolution, and further suggest a pre-Cretaceous hidden history for both lineages. The pattern of simultaneous diversifications shown here elucidate an important gap in our understanding of the Terrestrial Revolution that shaped today's ecosystems.

6.
Vaccine ; 39(42): 6189-6194, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34538698

RESUMO

BACKGROUND: Pneumococcal vaccines have been developed to protect infants and young children from pneumococcal diseases. Vaccination coverage studies are important in determining a population's vaccination status and strategically adjusting national immunization programs (NIP). In this paper, we aim to describe the coverage of pneumococcal conjugate vaccines (PCVs) immunization for birth cohorts from 2012 to 2020 and discussed the factors influencing the coverage. METHODS: Vaccination data were collected via the vaccination information database in Shanghai, China, for children born from 2012 to 2020. The population data used in this study were collected from each community from 2012 to 2020. The coverage of initial immunization (1st dose), basic immunization (three doses) and full immunization (3 + 1 doses) for PCVs was calculated according to the number of doses received. As vaccination coverage was assessed each year, Annual Growth Rate (AGR) was used to describe the variation trend of vaccination coverage. Immunization time and completeness of different PCVs were also analyzed. RESULTS: The total number of births from 2012 to 2020 was 38,268 in Huangpu District, Shanghai, China. The initial immunization coverage of PCVs increased from 12.26% in 2012 to 49.65% in 2020, and the highest coverage was 50.61% in 2019. The cumulative vaccination coverage of PCVs was 19.4% for initial immunization and 16.8% for basic immunization from 2012 to 2020. And cumulative full immunization coverage of PCVs was 12.3% from 2012 to 2019. The PCVs coverage of most vaccination statuses showed an obvious upward trend from 2017 to 2020. CONCLUSIONS: Despite an upward trend in vaccination coverage of PCVs, the vaccination coverage of initial, basic and full immunization among children is still low. And given the heavy burden of Streptococcus pneumoniae (Sp) among children in China and the fact that the current vaccination coverage cannot effectively protect children, it is recommended that the government include PCVs into the NIP as soon as possible.

7.
Pharmacol Res ; 173: 105870, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34500061

RESUMO

Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide. Nannocystin ax (NAN), a 21-membered cyclodepsipeptide initially isolated from myxobacteria of the Nannocystis genus, was found to target the eukaryotic elongation factor 1A (eEF1A). The current study was designed to evaluate the anticancer effect and underlying mechanisms of NAN with in vitro and in vivo models. Results showed that NAN induced G1 phase cell cycle arrest and caspase-independent apoptosis in HCT116 and HT29 human CRC cells. NAN significantly downregulated cyclin D1 level in a short time, but NAN did not affect the transcription level and ubiquitin-dependent degradation of cyclin D1. Furthermore, NAN treatment directly targeted eEF1A and partially decreased the synthesis of new proteins, contributing to the downregulation of cyclin D1. Besides, NAN significantly suppressed tumor growth in the zebrafish xenograft model. In conclusion, NAN triggered G1 phase cell cycle arrest through cyclin D1 downregulation and eEF1A-targeted translation inhibition and promoted caspase-independent apoptosis in CRC cells.

8.
JAMA ; 326(10): 916-925, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519801

RESUMO

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Main Outcomes and Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Método Duplo-Cego , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/secundário , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Placebos , Intervalo Livre de Progressão , Qualidade de Vida , Análise de Sobrevida
9.
BMC Public Health ; 21(1): 1561, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404376

RESUMO

BACKGROUND: Published studies examining the association between childhood maltreatment (CM) and self-harm (SH) among adolescents have been accumulated. It is possible that resilience serves as a moderator or mediator in CM-SH association, nevertheless, this topic has never been thoroughly investigated. METHODS: In this population-based cross-sectional study, we surveyed 3146 students aged 10-17 in southwest China. The Childhood Trauma Questionnaire (CTQ), the Modified version of Adolescents Self-Harm Scale (MASHS), and the Resilience Scale for Chinese Adolescents (RSCA) were used to measure CM, SH, and resilience. Correlational analyses, hierarchical multivariate linear regression, and structural equation modeling (SEM) were performed to test the moderation and mediation of resilience in CM-SH association. RESULTS: Findings revealed that, resilience with its five dimensions, CM, and SH were significantly correlated with each other. Resilience partially moderated and mediated the association between CM and SH. Besides, among all dimensions of resilience, emotion regulation, interpersonal assistance, and family support presented the strongest mediation in CM-SH association. CONCLUSIONS: Our results highlight the importance of resilience in CM related SH among Chinese teenagers. Resilience-oriented intervention could be considered in SH intervention measures for adolescents who had experienced CM.


Assuntos
Maus-Tratos Infantis , Comportamento Autodestrutivo , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Humanos , Comportamento Autodestrutivo/epidemiologia , Estudantes , Inquéritos e Questionários
10.
Zhongguo Zhen Jiu ; 41(8): 845-50, 2021 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-34369692

RESUMO

OBJECTIVE: To explore the bidirectional regulation of acupuncture based on a subgroup analysis of multicenter randomized controlled trial of acupuncture with Tiaoshen Jianpi for irritable bowel syndrome (IBS). METHODS: A total of 519 patients were included in the analysis, including 137 patients with constipation type irritable bowel syndrome (IBS-C) (92 cases in the acupuncture group and 45 cases in the polyethylene glycol [PEG] group), and 382 patients with diarrhea type irritable bowel syndrome (IBS-D) (252 cases in the acupuncture group and 130 cases in the pinaverium group). The patients in the acupuncture group were given acupuncture at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) once every other day, 3 times a week. The patients in the PEG group received polyethylene glycol 4000 powder orally, and the pinaverium group received pinaverium bromide tablets orally. All were treated for 6 weeks. The IBS symptom severity score (IBS-SSS) was assessed at baseline, treatment period (2, 4, 6 weeks of treatment) and 12 weeks of follow-up, and the IBS quality of life (IBS-QOL) score was evaluated at the baseline period, 6 weeks of treatment and 12 weeks of follow-up. RESULTS: The total IBS-SSS scores of the two groups of IBS-C patients at 2, 4, 6 weeks of treatment and follow-up of 12 weeks were lower than those in the baseline period (P<0.01). The total IBS-SSS score in the IBS-C acupuncture group was lower than that in the PEG group at 12 weeks of follow-up (P<0.05). The total IBS-SSS scores of the two groups of IBS-D patients at 2, 4, 6 weeks of treatment and 12 weeks of follow-up were lower than those in the baseline period (P<0.01). The total IBS-SSS scores in the IBS-D acupuncture group were lower than those in the pinaverium group at 2, 4, 6 weeks of treatment and 12 weeks of follow-up (P<0.05). The total IBS-QOL scores at 6 weeks of treatment and 12 weeks of follow-up were higher than those in the baseline period in both groups of patients with IBS-C (P<0.01). The total IBS-QOL scores at 6 weeks of treatment and 12 weeks of follow-up were higher than those in the baseline period in both groups in patients with IBS-D (P<0.01). The total IBS-QOL score in the IBS-D acupuncture group was higher than that in the pinaverium group at 18 weeks of follow-up (P<0.05). CONCLUSION: Acupuncture with Tiaoshen Jianpi can improve the clinical symptoms and quality of life of patients with IBS-C and IBS-D, which can regulate different functional states (constipation and diarrhea) of the same disease (irritable bowel syndrome), reflecting the bidirectional regulation of acupuncture.


Assuntos
Terapia por Acupuntura , Síndrome do Intestino Irritável , Pontos de Acupuntura , Diarreia , Humanos , Síndrome do Intestino Irritável/terapia , Qualidade de Vida , Resultado do Tratamento
11.
Psychiatry Res Neuroimaging ; 317: 111351, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34403967

RESUMO

The mechanism of white matter (WM) microstructure alteration in major depressive disorder (MDD) is unknown. Serum neurofilament (NF) levels have been identified as promising biomarkers for axonal damage and degeneration in neurological disorders. Furthermore, elevated plasma NF levels were also reported in depressive patients with treatment resistance. The current study investigated the serum NF levels of first-episode, medication-naïve patients with different severities of MDD and assessed their relationships with WM integrity. Diffusion tensor images and serum NF levels of 82 MDD patients and 72 age- and sex-matched healthy controls (HCs) were taken. We found that serum NF levels were significantly higher in patients with MDD than those in HCs. Fractional anisotropy (FA) of six brain WM tracts (the body and genu of the corpus callosum, left superior and posterior corona radiata, and bilateral anterior corona radiata) in patients with MDD were lower than those in the HCs after family-wise error-correction for multiple comparisons. Negative correlations between serum NF levels in the severe group of MDD and the decreased FA of the left anterior corona radiata were found in MDD, which might contribute to an understanding of the pathophysiological mechanism of MDD.

12.
Clin Interv Aging ; 16: 1347-1356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290497

RESUMO

Purpose: Malnutrition has been shown to be related to adverse clinical outcomes in patients with heart failure, hypertension, atrial fibrillation and other cardiovascular diseases. However, in the patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI), especially in the elderly, the association of nutritional state and all-cause mortality remains unknown. We aimed to investigate the association of malnutrition with all-cause mortality in the elder patients undergoing PCI. Patients and Methods: Based on the largest retrospective and observational cohort study from January 2007 to December 2017, the Controlling Nutritional Status (CONUT) score was applied to 21,479 consecutive patients with age ≥60 who undergoing PCI for nutritional assessment. Participants were classified as absent, mild, moderate and severe malnutrition by CONUT score. The Kaplan-Meier method was used to compare all-cause mortality among the above four groups. Multivariable Cox proportional hazard regression analyses were performed to examine the association of malnutrition with all-cause mortality. Results: According to the CONUT score, 48.19%, 15.08% and 0.94% patients were mildly, moderately and severely malnourished, respectively. During a median follow-up of 5.16 years (interquartile range: 3.02 to 7.89 years), 3173 (14.77%) patients died. Kaplan-Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with a worse nutritional status. Compared with normal nutritional state, malnutrition was associated with significantly increased risk for all-cause mortality (adjusted hazard ratio for mild, moderate and severe degrees of malnutrition, respectively: 1.20 [95% confidence interval (CI): 1.09 to 1.33], 1.32 [95% CI: 1.17 to 1.49] and 1.76 [95% CI: 1.33 to 2.33]). Conclusion: Malnutrition is prevalent among elderly patients with CAD undergoing PCI, and is strongly related to the all-cause mortality increasing. For elderly patients with CAD undergoing PCI, it is necessary to assess the status of nutrition, and evaluate the efficacy of nutritional interventions.


Assuntos
Doença da Artéria Coronariana/cirurgia , Desnutrição/mortalidade , Intervenção Coronária Percutânea/mortalidade , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
Pathol Oncol Res ; 27: 581534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257528

RESUMO

Objective: We conducted this study to characterize somatic genomic alterations in circulating tumor DNA (ctDNA) from patients with ovarian cancer and compare GAs detected in ctDNA with tissue databases. Methods: Hybrid capture-next generation sequencing genomic profiling of 150 genes was performed on ctDNA from 138 patients with ovarian cancer with 1,500× sequencing depth. The GAs detected in ctDNA were compared with those in our ovarian cancer tissue database (N = 488) and the Cancer Genome Atlas (TCGA) database (N = 489). Results: 115 patients (83%) had at least 1 GA detected in ctDNA. The most frequently altered genes detected in ctDNA were TP53 (72%), KRAS (11%), LRP1B (10%), ZNF703 (9%) and NF1 (8%). Comparative analysis with our tissue database showed similar frequencies of GAs per gene, although PIK3CA and KRAS mutations were more frequent in tissue and ctDNA, respectively (p < 0.05). Gene amplification and rearrangement were more frequent in ctDNA samples. The mutation frequency of homologous recombination repair associated-genes, VEGF signal/angiogenesis pathways, RAS pathways, NOTCH pathways and MSI-H ratio was not statistically different either in ctDNA or in tissue database. However, the mutation frequency of AKT, PIK3CA, PTEN and STK11 in PI3K/AKT/mTOR pathway was significantly lower than that in tissue samples (p < 0.05). Conclusions: Our results suggest that genomic profiling of ctDNA could detect somatic GAs in a significant subset of patients with ovarian cancer. Hybrid capture-NGS based on liquid biopsy has the potential capability to serve as a substitute to tissue biopsy and further studies are warranted.

14.
N Engl J Med ; 385(1): 46-58, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34192431

RESUMO

BACKGROUND: Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODS: We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTS: A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONS: Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Clin Lymphoma Myeloma Leuk ; 21(9): e699-e709, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34108127

RESUMO

BACKGROUND: Daratumumab plus bortezomib/dexamethasone (D-Vd) significantly improved outcomes versus Vd in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 CASTOR study. We report the results of a prespecified interim analysis of the phase 3 LEPUS study of D-Vd versus Vd in Chinese patients with RRMM. PATIENTS AND METHODS: Chinese patients with ≥ 1 prior line of therapy were randomized 2:1 to receive 8 cycles (21 days/cycle) of bortezomib (1.3 mg/m2 subcutaneously) and dexamethasone (20 mg orally/intravenously) ± daratumumab (16 mg/kg intravenously). The primary endpoint was progression-free survival (PFS). RESULTS: A total of 211 patients were randomized (D-Vd, 141; Vd, 70). After an 8.2-month median follow-up, D-Vd significantly prolonged PFS versus Vd (median, not reached vs. 6.3 months; hazard ratio, 0.28; 95% confidence interval, 0.17-0.47; P < .00001) and significantly improved the rates of overall response (83% vs. 65%; P = .00527), ≥ very good partial response (65% vs. 33%; P = .00002), ≥ complete response (33% vs. 11%; P = .00079), and minimal residual disease negativity (10-5 sensitivity; 22% vs. 3%; P = .0002). The PFS benefit of D-Vd versus Vd was maintained across prespecified subgroups, including patients with prior bortezomib treatment and with high-risk cytogenetics. Thrombocytopenia (D-Vd, 51%; Vd, 37%), lymphopenia (44%; 29%), and lung infection (30%; 22%) were the 3 most common grade 3/4 treatment-emergent adverse events. Although patients in both treatment groups experienced higher rates of grade 3/4 lymphopenia and infections versus patients in CASTOR, the safety profile was generally consistent with that of CASTOR. CONCLUSION: These data support the use of D-Vd in Chinese patients with RRMM.

16.
Transl Oncol ; 14(9): 101162, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34171557

RESUMO

The anti-phagocytosis signal, CD47, prevents phagocytosis when it interacts with signal-regulatory protein alpha (SIRPα) on macrophages. Given the vital role of CD47 in immune response, further investigation on the regulation of CD47 in tumor microenvironment is needed. Herein, we identified that interferon-gamma (IFN-γ), one of the most important cytokines in the immune and inflammatory response, up-regulated CD47 expression in cancer cells and this effect could be inhibited by the JAK1/2 inhibitor ruxolitinib, as well as siRNA-mediated silencing of JAK1, STAT1, and IRF1. The IFN-γ-induced surface expression of CD47 contributed to a stronger binding affinity to SIRPα and a decrease in phagocytosis of cancer cells by macrophages. Knockdown of JAK1, STAT1, or IRF1 by siRNA reversed the decreased phagocytosis caused by IFN-γ. Besides, analysis from TCGA revealed that IFNG had a positive correlation with CD47 in various types of cancer, which was supported by the increased surface CD47 expression after IFN-γ treatment in different types of cancer cells. The discovery of IFN-γ-induced up-regulation of CD47 in cancer cells unveils another feedback inhibitory mechanism of IFN-γ, thus providing insights into cancer immunotherapy targeting CD47.

18.
Endocrine ; 74(2): 290-299, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34125410

RESUMO

PURPOSE: To identify the specific glucose metrics derived from maternal continuous glucose monitoring (CGM) data, which were associated with a higher percentile of offspring birth weight. METHODS: In this cohort study, we recruited singleton pregnant women with GDM who underwent CGM for 5-14 days at a mean of 28.8 gestational weeks between Jan 2017 and Nov 2018. Commonly used single summary glucose metrics of glucose exposure (including mean 24-h, daytime, and nighttime glucose level) and variability (including J-index and mean amplitude of glycaemic excursions) were derived from CGM data. A novel comprehensive glucose metric-hours per-day spent in a severe variability glucose mode (HSSV)-was identified using the spectral clustering method, which reflects both glucose level and variability. Multiple linear regression models were used to estimate the associations of sex- and gestational age-adjusted birth weight percentile with CGM parameters. RESULTS: Ninety-seven women comprising 127,279 glucose measurements were included. Each 1-SD increase in maternal nighttime mean glucose level and HSSV was associated with 6.0 (95% CI 0.4, 11.5) and 6.3 (95% CI 0.4, 12.2) percentage points increase in birth weight percentile, respectively. No associations were found between other glucose metrics and birth weight percentile. CONCLUSION: Nighttime mean glucose level has a comparable effect size to HSSV in association with fetal growth, suggesting that endogenous hyperglycemia might drive the association between maternal hyperglycemia and birth weight. Further studies need to examine the effect of lowering nighttime glucose level and/or HSSV on preventing fetal overgrowth in GDM women.

19.
Int Urol Nephrol ; 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34173178

RESUMO

PURPOSE: Malnutrition is a common comorbidity of coronary artery disease (CAD) and is often associated with adverse events. The malnutrition often means lower cholesterol, albumin and high lymphocyte, as risk factors of Contrast-Induced Acute Kidney Injury (CI-AKI). We aim to evaluate the association between malnutrition and CI-AKI following coronary angiography (CAG) in CAD patients. METHODS: We analyzed 3170 CAD patients with variables of nutritional status (Controlling Nutritional Status score (CONUT)) from the prospective multicenter study, REICIN (NCT01402232) including 4,271 consecutive patients undergoing CAG from January 2013 to February 2016. Patients were divided into the normal group (CONUT score 0-1) and malnutrition group (CONUT score > 1). The association of malnutrition and the risk of CI-AKI was examined in all CAD patients using multivariable logistics regression analysis. RESULTS: Among the 3170 patients (mean age: 63.1 ± 10.7 years), 1865 (58.8%) suffered from malnutrition, 111 (3.5%) developed CI-AKI, including 23 (1.76%) in normal group and 88 (4.72%) in malnutrition group (p < 0.01). The malnourished patients were older, and likely had anemia and worse cardiorenal function. After adjustment for confounders, the risk of CI-AKI was 1.04 times higher in the malnutrition group than in the normal group (adjusted OR: 2.04, 95% CI 1.28-3.38, p < 0.01). CONCLUSIONS: Among CAD patients undergoing CAG, malnutrition is extremely common and associated with a double risk of CI-AKI. Further studies are needed to investigate the potential renal protection of intervening malnutrition in CAD patients.

20.
Shanghai Kou Qiang Yi Xue ; 30(2): 210-213, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-34109365

RESUMO

PURPOSE: To investigate the clinical effect of modified posterior dental splint in the treatment of anterior disk displacement without reduction of the temporomandibular joint (TMJ). METHODS: Eight-nine patients with anterior disk displacement without reduction of the TMJ who were treated in Stomatology Hospital of Guangzhou Medical University from October 2016 to October 2017 were selected in the study. 47 patients in the first group were treated by modified posterior dental splint, while 42 patients in the second group were treated by stabilization splint. The patients' pain index, mouth opening degrees were collected before treatment,3 months, 6 months, and 1 year after treatment. Statistical analysis of the data was performed using SPSS 18.0 software package, multivariate test was used to compare the indicators between the two groups. RESULTS: The effect of modified posterior dental splint on treating limited mouth opening was better than those of stabilization splint(P<0.05). In the treatment of joint pain, the two splints had no significant difference(P>0.05). CONCLUSIONS: Modified posterior dental splint is a new type of splint for the treatment of TMJ disorders. It is suitable for clinical application.


Assuntos
Luxações Articulares , Transtornos da Articulação Temporomandibular , Humanos , Luxações Articulares/terapia , Placas Oclusais , Contenções , Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/terapia
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