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1.
Artigo em Inglês | MEDLINE | ID: mdl-34629254

RESUMO

BACKGROUND AND AIMS: High hemoglobin A1c (HbAlc) level is associated with increased cardiovascular disease risk and thromboembolic events [1]. The study sought to explored the association between HbAlc and left atrial appendage flow velocity (LAAV) among non-valvular atrial fibrillation (AF) patients. METHODS AND RESULTS: A total of 249 consecutive non-valvular AF patients who underwent transesophageal echocardiography (TEE) were divided into two subgroups according to the median of LAAV level (<45 cm/s, ≥45 cm/s). Blood samples and other baseline clinical data of all patients were collected and analyzed. The low LAAV group included 126 patients and the high LAAV group included 123 patients. Patients in the low LAAV group were older and had a higher percentage of persistent AF, chronic heart failure, and higher CHA2DS2-VASc score (P < 0.05). HbAlc level in the low LAAV group was significantly higher than the high LAAV group [6.1 (5.7-6.5)% vs 5.9 (5.6-6.2)%, P = 0.010]. The low LAAV group had larger left atrial diameter (LAD), left atrial area (LAA), higher left atrial pressure (LAP), and lower left ventricular ejection fraction (LVEF) (P < 0.05). Spearman rank correlation analysis showed that the HbAlc level was negatively correlated with LAAV (r = -0.211, P = 0.001). Multivariate analysis indicated that female gender (OR = 2.233, 95% CI 1.110-4.492, P = 0.024), persistent AF (OR = 6.610, 95% CI 3.109-14.052, P < 0.001), and HbAlc (OR = 1.903, 95% CI 1.092-3.317, P = 0.023) were independent factors that associated with low LAAV in AF patients. CONCLUSION: Increased HbAlc level is associated with decreased LAAV and may reflect a low contractile function of the left atrial appendage.

2.
Nat Genet ; 53(10): 1493-1503, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34594040

RESUMO

How two subgenomes in allo-tetraploids adapt to coexistence and coordinate through structure and expression evolution requires extensive studies. In the present study, we report an improved genome assembly of allo-tetraploid common carp, an updated genome annotation of allo-tetraploid goldfish and the chromosome-scale assemblies of a progenitor-like diploid Puntius tetrazona and an outgroup diploid Paracanthobrama guichenoti. Parallel subgenome structure evolution in the allo-tetraploids was featured with equivalent chromosome components, higher protein identities, similar transposon divergence and contents, homoeologous exchanges, better synteny level, strong sequence compensation and symmetric purifying selection. Furthermore, we observed subgenome expression divergence processes in the allo-tetraploids, including inter-/intrasubgenome trans-splicing events, expression dominance, decreased expression levels, dosage compensation, stronger expression correlation, dynamic functionalization and balancing of differential expression. The potential disorders introduced by different progenitors in the allo-tetraploids were hypothesized to be alleviated by increasing structural homogeneity and performing versatile expression processes. Resequencing three common carp strains revealed two major ecotypes and uncovered candidate genes relevant to growth and survival rate.

3.
BMC Cardiovasc Disord ; 21(1): 429, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507544

RESUMO

BACKGROUND: Homocysteine (Hcy) is considered to be a risk factor for cardiovascular and cerebrovascular diseases. Few studies have evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the population with healthy physical examination and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. METHODS: Measurements of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA, and related metabolic risk factors were selected for analysis from 8063 medical examination samples collected from February 2017 to April 2020. The relationship between Hcy and other biochemical indicators were evaluated with the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). RESULTS: Among 8063 cases, the age, BMI, SBP, and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P < 0.001), and the proportion of males, smoking, and drinking were higher than the low-Hcy group, the difference was statistically significant (P < 0.001); Hcy of the abnormal GLU group is higher than the normal GLU group (P = 0.002) and the Hcy of abnormal TG and HDL is higher than that of the normal blood lipid group (P < 0.001); Hcy of people with abnormal UA and Urea was higher than that of people with normal renal function (P < 0.001, P = 0.007). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (ß = - 0.038, SE = 0.016, P = 0.019), lnCr was positively correlated with lnHcy (ß = 0.055, SE = 0.016, P < 0.001), lnUA and lnHcy were positive correlated (ß = 0.043, SE = 0.019, P = 0.022). CONCLUSION: Hcy is closely related to HDL-c, Cr, and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.

4.
Fam Relat ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34548727

RESUMO

Objective: The current study aimed to examine the economic impact of COVID-19 virus on family dynamics and college-age children's mental health in China and to identity personal and social or relational resilience factors that could buffer the negative consequences of COVID-19. Background: Since an outbreak of COVID-19 was first reported in China in December 2019, it has profoundly changed the lives of families and children of all ages. In particular, it has created challenges among families with college-age young adult children. Method: Using a sample of 484 college students from 21 universities in China, an online survey design was utilized to obtain information from these students on their family demographics and economic situation, parent-child interactions, and individual well-being during COVID-19. Results: Results from structural equation modeling suggested that family income loss due to COVID-19 was related to economic pressure. Economic pressure was associated with negative interactions between parents and young adult children, which were associated with problems in young adult children's mental health (i.e., anxiety and depressive symptoms). Further, self-control was found to buffer the association between family income loss and economic pressure, and respect for family was found to weaken the association between economic pressure and negative parent-child interactions. Conclusion: Findings supported the hypotheses of the negative impacts of COVID-19 on young adult children's mental health and the resilience factors that buffered the negative impacts. Implications: Implications to family researchers, family life educators, practitioners, and policymakers were discussed.

5.
Int Immunopharmacol ; 100: 108066, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492536

RESUMO

Severe acute lung injury (ALI) cause significant morbidity and mortality worldwide. MicroRNAs (miRNAs) are possible biomarkers and therapeutic targets for ALI. We aimed to explore the role of miR-762, a known oncogenic factor, in the pathogenesis of ALI. Levels of miR-762 in lung tissues of LPS-treated ALI mice and blood cells of patients with lung injury were measured. Injury of human lung epithelial cell line A549 was induced by LPS stimulation. A downstream target of miR-762, NFIX, was predicted using online tools. Their interactions were validated by luciferase reporter assay. Effects of targeted regulation of the miR-762/NFIX axis on cell proliferation, apoptosis, and inflammatory responses were tested in vitro in A549 cells in vivo with an ALI mouse model. We found that upregulation of miR-762 expression and downregulation of NFIX expression were associated with lung injury. Either miR-762 inhibition or NFIX overexpression in A549 lung cells significantly attenuated LPS-mediated impairment of cell proliferation and viability. Notably, increasing expressions of miR-762 inhibitor or NFIX in vivo via airway lentivirus infection alleviated the LPS-induced ALI in mice. Further, targeted downregulation of miR-762 expression or upregulation of NFIX expression in A549 cells markedly down-regulates NF-κB/IRF3 activation, and substantially reduces the production of inflammatory factors, including TNF-α, IL-6, and IL-8. This study reveals a novel role for the miR-762/NFIX pathway in ALI pathogenesis and sheds new light on targeting this pathway for diagnosis, prevention, and therapy.

6.
Chemistry ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490934

RESUMO

A copper-catalyzed conjugate silylation of various cyclobutenone derivatives with Me2 PhSiZnCl ⋅ 2LiCl or (Me2 PhSi)2 Zn ⋅ xLiCl (x≤4) to generate ß-silylated cyclobutanones is reported. Trapping the intermediate enolate with ClP(O)(OPh)2 affords silylated enol phosphates that can be further engaged in Kumada cross-coupling reactions to yield silylated cyclobutene derivatives.

7.
Environ Pollut ; 285: 117509, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34380217

RESUMO

Humans benefit from nuclear technologies but consequently experience nuclear disasters or side effects of iatrogenic radiation. Hematopoietic system injury first arises upon radiation exposure. As an intricate new layer of genetic control, the posttranscriptional m6A modification of RNA has recently come under investigation and has been demonstrated to play pivotal roles in multiple physiological and pathological processes. However, how the m6A methylome functions in the hematopoietic system after irradiation remains ambiguous. Here, we uncovered the time-varying epitranscriptome-wide m6A methylome and transcriptome alterations in γ-ray-exposed mouse bone marrow. 4 Gy γ-irradiation rapidly (5 min and 2 h) and severely impaired the mouse hematopoietic system, including spleen and thymus weight, blood components, tissue inflammation and malondialdehyde (MDA) levels. The m6A content and expression of m6A related enzymes were altered. Gamma-irradiation triggered dynamic and reversible m6A modification profiles and altered mRNA expression, where both m6A fold-enrichment and mRNA expression most followed the (5 min_up/2 h_down) pattern. The CDS enrichment region preferentially upregulated m6A peaks at 5 min. Moreover, the main GO and KEGG pathways were closely related to metabolism and the classical radiation response. Finally, m6A modifications correlated with transcriptional regulation of genes in multiple aspects. Blocking the expression of m6A demethylases FTO and ALKBH5 mitigated radiation hematopoietic toxicity. Together, our findings present the comprehensive landscape of mRNA m6A methylation in the mouse hematopoietic system in response to γ-irradiation, shedding light on the significance of m6A modifications in mammalian radiobiology. Regulation of the epitranscriptome may be exploited as a strategy against radiation damage.


Assuntos
Medula Óssea , Sistema Hematopoético , Adenosina/análogos & derivados , Animais , Sistema Hematopoético/metabolismo , Metilação , Camundongos , RNA Mensageiro/metabolismo
8.
Chin Med J (Engl) ; 134(14): 1669-1680, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34397593

RESUMO

BACKGROUND: The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer, but the effects on safety and survival are still controversial. The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery (NACS) and surgery alone (SA) for locally advanced gastric cancer. METHODS: Databases (PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar) were explored for relative studies from January 2000 to January 2021. The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale, respectively. The Review Manager software (version 5.3) was used to perform this meta-analysis. The overall survival was evaluated as the primary outcome, while perioperative indicators and post-operative complications were evaluated as the secondary outcomes. RESULTS: Twenty studies, including 1420 NACS cases and 1942 SA cases, were enrolled. The results showed that there were no significant differences in overall survival (P = 0.240), harvested lymph nodes (P = 0.200), total complications (P = 0.080), and 30-day post-operative mortality (P = 0.490) between the NACS and SA groups. However, the NACS group was associated with a longer operation time (P < 0.0001), a higher R0 resection rate (P = 0.003), less reoperation (P = 0.030), and less anastomotic leakage (P = 0.007) compared with SA group. CONCLUSIONS: Compared with SA, NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage. While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.


Assuntos
Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
9.
Cancer Biol Med ; 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34369136

RESUMO

The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body, including the mouth, lung, intestines, skin, and vagina. These microbial communities are involved in many essential functions, such as metabolism, immunity, host nutrition, and diseases. Recent studies have focused on the microbiota associated with cancers, particularly the oral and intestinal microbiota. Radiotherapy, the most effective cytotoxic modality available for solid tumors, contributes to the treatment of cancer patients. Mounting evidence supports that the microbiota plays pivotal roles in the efficacy and prognosis of tumor radiotherapy. Here, we review current research on the microbiota and cancer development, and describe knowledge gaps in the study of radiotherapy and the microbiota. Better understanding of the effects of the microbiome in tumorigenesis and radiotherapy will shed light on future novel prevention and treatment strategies based on modulating the microbiome in cancer patients.

10.
Soc Sci Med ; 285: 114288, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34358946

RESUMO

RATIONALE: One of the biggest challenges for mothers returning to work after childbirth is breastfeeding. Studies documented the physical health benefits of breastfeeding for mothers and children. However, research findings concerning the longitudinal effects of breastfeeding on maternal and children's mental health are mixed. OBJECTIVE: The current study investigated the longitudinal effects of the length of breastfeeding on maternal psychopathological symptoms and infants' problem behaviors, among a sample of low-income working mothers. METHODS: The sample included 285 infants and their mothers (primarily minority, low-income, and single) who returned to work 3-month postpartum, recruited from an ethnically diverse and economically disadvantaged area in a southern U.S. state. Mothers' breastfeeding behaviors were assessed four times in the first year postpartum, and mothers' psychopathological symptoms and their infants' problem behaviors were reported by mothers two times, at 12-month and 24-month postpartum. RESULTS: Path models revealed that high maternal psychopathological symptoms in infancy worsened the effect of breastfeeding on child externalizing behaviors in toddlerhood. Likewise, very high infant externalizing behaviors worsened the effect of breastfeeding on maternal hostility one year later. CONCLUSIONS: This study suggests the need for implementing prevention interventions with a lifecycle approach and continued, tailored professional breastfeeding support after hospital discharge among at-risk working mothers. Findings of this study can inform public policy by highlighting the importance of considering joint breastfeeding support and mental health counseling in the delivery of services to mothers and their infants who live in under-resourced environments and struggle with maternal psychopathology.

11.
BMC Cancer ; 21(1): 974, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461860

RESUMO

BACKGROUND: This study compared the long-term efficacy of different durations of adjuvant chemotherapy for patients with gastric cancer after radical gastrectomy with D2 lymphadenectomy. METHODS: We retrospectively identified 428 patients with stage II-III gastric cancer who underwent D2 gastrectomy between 2009 and 2016. Patients were divided into four groups according to the duration of adjuvant chemotherapy, including 0 week (no adjuvant, group A), 20 to 24 weeks (completed 7-8 cycles every 3 weeks or 10-12 cycles every 2 weeks, group B), and 12 to18 weeks (completed 4-6 cycles every 3 weeks or 6-9 cycles every 2 weeks, group C), and less than 12 weeks (received up to 3 cycles every 3 weeks or 5 cycles every 2 weeks, group D). The chemotherapy regimens included XELOX, SOX, and FOLFOX. 5-year overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: The 5-year OS rates for groups A, B, C, and D were 52.3, 73.7, 72.0, and 53.3%, respectively, and the 5-year DFS rates were 50.0, 68.0, 65.4, and 50.0%, respectively. OS and DFS were higher in group B than in groups A and D. Similarly, patients in group C were more likely to have higher OS and DFS than those in groups A and D. Meanwhile, there were no significant differences in OS and DFS between groups B and C. The multivariate analysis confirmed with high statistical significance the efficacy of complete courses of adjuvant chemotherapy, and, among them, the similar impact of 4-6/6-9 and 7-8/10-12 cycles, resulting in similar HRs vs Group A (0.52 and 0.42, respectively). CONCLUSIONS: To reduce toxicity and maintain efficacy, XELOX or SOX chemotherapy regimens administered for 4-6 cycles every 3 weeks or FOLFOX regimen for 6-9 cycles every 2 weeks might be a favorable option for patients with stage II-III gastric cancer after D2 gastrectomy. Prospective multicenter clinical trials with adequate sample sizes are necessary to verify these findings.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/mortalidade , Gastrectomia/mortalidade , Excisão de Linfonodo/mortalidade , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Adulto Jovem
12.
FASEB J ; 35(8): e21787, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34320242

RESUMO

Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sex-specific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.


Assuntos
Restrição Calórica , Microbioma Gastrointestinal , Hematopoese/efeitos da radiação , Lesões por Radiação/complicações , Lesões por Radiação/terapia , Animais , Fezes/microbiologia , Feminino , Gastroenteropatias/terapia , Inflamação/terapia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores Sexuais , Organismos Livres de Patógenos Específicos
13.
Medicine (Baltimore) ; 100(28): e26586, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260538

RESUMO

ABSTRACT: To evaluate the characteristics and influential factors of breast density and establish a new model for predicting breast density in Chinese women, so as to provide a basis for breast cancer screening techniques and duration.A total of 9412 women who were selected from screening and intervention techniques for Breast and Cervical Cancer Project between April 2018 and June 2019 were enrolled in this study. Selected women were randomly assigned to training and validation sets in a ratio of 1:1. Univariable and multivariable analyzes were performed by Logistic regression model. Nomogram was generated according to the results of multivariate analysis. Calibration, area under curve (AUC) and akaike information criterion (AIC) were used for measuring accuracy of prediction model.There were 377 (4.0%) women in breast imaging reporting and data system (BI-RADS) A category, 2164 (23.0%) in B category, 5749 (61.1%) in C category and 1122 (11.9%) in D category. Age duration, educational attainment, history of benign diseases, breastfeeding history, menopausal status, and body mass index (BMI) were imputed as independent influential factors for breast density in multivariable analysis. The AUC and AIC of training and validation set were 0.7158, 0.7139, and 4915.378, 4998.665, respectively.This study indicated that age, educational attainment, history of benign breast disease, breastfeeding history, menopausal status and BMI were independent influential factors of breast density. Nomogram generated on the basis of these factors could relatively predict breast density, which in turn could be used for recommendations of breast cancer screening techniques.


Assuntos
Densidade da Mama/fisiologia , Mamografia/métodos , Modelos Estatísticos , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Aleitamento Materno , China , Feminino , Humanos , Menopausa/fisiologia , Pessoa de Meia-Idade , Nomogramas , Fatores Socioeconômicos
14.
Endocrine ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34296389

RESUMO

PURPOSE: Mitochondrial DNA (mtDNA) variations have been implicated in various cancer types. Several attempts have been made in benign parathyroid adenoma (PA); however, mtDNA variants and copy number alterations have not been investigated in parathyroid carcinoma (PC). The present study aimed to explore the variations in the mitochondrial genome in parathyroid neoplasms. METHODS: In this study, ultradeep targeted sequencing of mtDNA was performed in 12 cases with PC and 25 cases with PA. Germline and somatic variants in the mitochondrial genome were analysed according to clinical features. The mtDNA copy number relative to nuclear DNA was measured. RESULTS: A total of 821 germline variants and 23 somatic mutations were identified. All 160 germline nonsynonymous variants in the coding sequence (CDS) were predicted to be likely benign, and germline variants frequently occurred (26.3%) in the displacement loop region. Tumour somatic mutation in a CDS with heteroplasmic factor (HF) >0.8 showed a higher mtDNA copy number (p = 0.039). Using Spearman's rank test, tumour mtDNA copy number revealed a positive correlation with serum levels of intact parathyroid hormone and calcium. CONCLUSION: Our results demonstrate that null recurrent mtDNA mutational hotspots were PC specific. An increased mtDNA copy number in parathyroid neoplasms was associated with somatic CDS mutations with a high HF and major clinical features. Larger cohort investigations should be performed in future analyses.

15.
Lancet Oncol ; 22(8): 1081-1092, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34252374

RESUMO

BACKGROUND: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. METHODS: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. FINDINGS: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. INTERPRETATION: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. FUNDING: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/cirurgia , Adulto , Idoso , Capecitabina/administração & dosagem , Quimioterapia Adjuvante/métodos , Combinação de Medicamentos , Neoplasias Esofágicas/cirurgia , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem
16.
Adv Ther ; 38(8): 4258-4270, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34176089

RESUMO

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Larger tumor size is widely acknowledged to be associated with increased lymph node (LN) metastatic potential. However, the quantitative relationships between tumor size and LN metastasis or survival remain unclear. This study aims to quantify the objective relationship between tumor size and the prevalence of LN metastases across a spectrum primary tumor size. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 9958 patients with resected PDAC without distant metastasis. The prevalence of LN metastases, LN ratio (LNR), and N2/N1 ratio were assessed amongst different tumor sizes, and the relationships were displayed by matched curves. RESULTS: In the enrolled cohort, age, tumor site, grade, American Joint Committee on Cancer (AJCC) 8th node staging, tumor size, chemotherapy, and radiotherapy were identified as significant independent predictors for overall survival (OS) and cancer-specific survival (CSS). For tumors within 1-40 mm in size, the prevalence of node-positive disease is closely modelled using a logarithmic formula [0.249 × ln (size) + 0.452] × 100%. The prevalence plateaued between 70% and 80% beyond 40 mm. The mean LNR increased in a stepwise manner as tumor size increased from 1-5 mm (LNR = 0.024) to 41-45 mm (LNR = 0.177); then, beyond 45 mm, it plateaued near 0.170. N2/N1 ratio gradually increased along with tumor size from 1-5 mm (N2/N1 = 0.286) to 41-45 mm (N2/N1 = 1.016), and when tumor size reached to 41-45 mm or more, the ratio stabilized around 1.000. In addition, significant survival prediction by AJCC N staging was observed when tumors ranging between 16 and 45 mm in size. CONCLUSION: Regional LN involvement demonstrated a logarithmic growth with increasing tumor sizes in patients with resected PDAC . The probability of metastasis in each regional LN for resected PDAC with tumors greater than 40 mm in size was near 17.0% and their overall prevalence of LN metastasis was 70-80%. Among which, 50% of patients had an N2 stage. Such prediction may be a potential and promising tool for guiding lymphadenectomy in PDAC surgery.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Prognóstico
17.
World J Surg Oncol ; 19(1): 187, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172053

RESUMO

BACKGROUND: Postoperative symptomatic anastomotic leakage (AL) is a serious complication after low anterior resection (LAR) for rectal cancer. AL can potentially affect short-term patient outcomes and long-term prognosis. This study aimed to explore the risk factors and long-term survival of symptomatic AL after laparoscopic LAR for rectal cancer. METHODS: From May 2009 to May 2015, 298 consecutive patients who underwent laparoscopic LAR for rectal cancer with or without a defunctioning stoma were included in this study. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for symptomatic AL. Survival analysis was performed using Kaplan-Meier curves, and log-rank tests were used for group comparisons. RESULTS: Among the 298 patients enrolled in this study, symptomatic AL occurred in eight (2.7%) patients. The univariate analysis showed that age of ≤65 years (P = 0.048), neoadjuvant therapy (P = 0.095), distance from the anal verge (P = 0.078), duration of operation (P = 0.001), and pathological tumor (T) category (P = 0.004) were associated with symptomatic AL. The multivariate analysis demonstrated that prolonged duration of operation (P = 0.010) was an independent risk factor for symptomatic AL after laparoscopic LAR for rectal cancer. No statistically significant differences were observed in the 3-year (P = 0.785) and 5-year (P = 0.979) overall survival rates. CONCLUSIONS: A prolonged duration of operation increased the risk of symptomatic AL after laparoscopic LAR for rectal cancer. An impact of symptomatic AL on a long-term survival was not observed in this study; however, further studies are required. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry ( ChiCTR2000033413 ) on May 31, 2020.


Assuntos
Laparoscopia , Neoplasias Retais , Idoso , Anastomose Cirúrgica , Fístula Anastomótica , Humanos , Prognóstico , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Fatores de Risco
18.
J BUON ; 26(2): 490-498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076997

RESUMO

PURPOSE: Although the acceptance of laparoscopy-assisted gastrectomy (LAG) for the treatment of gastric cancer (GC) has been increasing, it is still controversial that LAG is an applicable treatment method for elderly patients since elderly patients are usually complicated with other diseases. Therefore, this study aimed to investigate the prognostic differences between elderly patients and non-elderly patients after receiving LAG. METHODS: Patients (n = 306) who received LAG for the treatment of GC from April 2009 to December 2014 were included in the study. The patients were divided into the elderly group (≥ 65 years old, n = 120) and the non-elderly group (< 65 years old, n=186). The postoperative outcomes as well as the morbidity and the survival rates were compared between the two groups. RESULTS: American Society of Anesthesiologists (ASA) score and comprehensive complication index (CCI) score in the elderly group were significantly higher than those in the non-elderly group (p<0.05). In terms of surgical outcomes, there was no significant difference in blood loss or postoperative hospital stay between the elderly group and the non-elderly group. As for postoperative comorbidities, there were significant differences in intraperitoneal hemorrhage and pleural effusion between the elderly group and the non-elderly group. Moreover, the median follow-up time was 38.5 months, and the overall survival of elderly patients with comorbidities was significantly lower than that of the elderly patients without comorbidities (p<0.05). CONCLUSIONS: LAG can be performed safely and successfully in the elderly population with acceptable postoperative and long-term results.

19.
Front Endocrinol (Lausanne) ; 12: 631680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054720

RESUMO

Purpose: Hyperparathyroidism is the third most common endocrine disease. Parathyroid adenoma (PA) accounts for approximately 85% of cases of primary hyperparathyroidism, but the molecular mechanism is not fully understood. Herein, we aimed to investigate the genetic and transcriptomic profiles of sporadic PA. Methods: Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) of 41 patients with PA and RNA-seq of 5 normal parathyroid tissues were performed. Gene mutations and characterized expression changes were identified. To elucidate the molecular mechanism underlying PA, unsupervised consensus clustering of RNA-seq data was performed. The correlations between the sequencing data and clinicopathological features of these patients were analyzed. Results: Previously reported PA driver gene mutations, such as MEN1 (9/41), mTOR (4/41), ZFX (3/41), CASR (3/41), EZH2 (2/41) and FAT1 (2/41), were also identified in our cohort. Furthermore, somatic mutation of EZH1, which had not been reported in PA, was found in 4 samples. RNA-seq showed that the expression levels of 84 genes were upregulated and 646 were downregulated in PA samples compared with normal samples. Unsupervised clustering analysis of RNA-seq data clustered these patients into 10 subgroups related to mutation or abnormal expression of a group of potential pathogenic genes. Conclusion: MEN1, EZH2, CASR, EZH1, ZFX, mTOR and FAT1 mutations in PA were revealed. According to the RNA-seq data clustering analysis, cyclin D1, ß-catenin, VDR, CASR and GCM2 may be important factors contributing to the PA gene expression profile.

20.
Mol Cell Biochem ; 476(9): 3449-3460, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33974232

RESUMO

Heart failure is a syndrome with symptoms or signs caused by cardiac dysfunction. In clinic, four stages (A, B, C, and D) were used to describe heart failure progression. This study was aimed to explore plasma metabolomic and lipidomic profiles in different HF stages to identify potential biomarkers. Metabolomics and lipidomics were performed using plasma of heart failure patients at stages A (n = 49), B (n = 61), and C+D (n = 26). Analysis of Variance (ANOVA) was used for screening dysregulated molecules. Bioinformatics was used to retrieve perturbed metabolic pathways. Univariate and multivariate receiver operating characteristic curve (ROC) analyses were used for potential biomarker screening. Stage A showed significant difference to other stages, and 142 dysregulated lipids and 134 dysregulated metabolites were found belonging to several metabolic pathways. Several marker panels were proposed for the diagnosis of heart failure stage A versus stage B-D. Several molecules, including lysophosphatidylcholine 18:2, cholesteryl ester 18:1, alanine, choline, and Fructose, were found correlated with B-type natriuretic peptide or left ventricular ejection fractions. In summary, using untargeted metabolomic and lipidomic profiling, several dysregulated small molecules were successfully identified between HF stages A and B-D. These molecules would provide valuable information for further pathological researches and biomarker development.


Assuntos
Biomarcadores/sangue , Insuficiência Cardíaca/diagnóstico , Lipidômica/métodos , Lipídeos/sangue , Metaboloma , Idoso , Estudos de Casos e Controles , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC
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