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1.
Orthop Surg ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942538

RESUMO

OBJECTIVE: To investigate the biomechanical effect of different intervertebral reconstructive heights on adjacent segments following C5 /C6 anterior cervical discectomy and fusion (ACDF) through finite element analysis. METHODS: A finite element model of intact C4 -C7 segments was developed and validated for the present study. Five additional C4 -C7 postoperative models were constructed with 100%, 125%, 150%, 175%, and 200% of the benchmark height of C5 /C6 on the basis of the intact model. The changes in intradiscal pressure (IDP) and range of motion (ROM) of adjacent segments before and after reconstruction of C5 /C6 were analyzed. RESULTS: For the upper adjacent segment (C4 /C5 ), the IDPs under the different loading conditions all increased after reconstruction. The maximum IDPs were 0.387, 0.489, 0.491, and 0.472 MPa under flexion, extension, axial rotation, and lateral bending, respectively, observed at the reconstructive height of 200%. The minimum IDPs were observed at 150% reconstructive height under all loading conditions except extension, and were 57, 86 and 81% of the maximum IDPs under flexion, axial rotation, and lateral bending, respectively. The minimum IDP under extension occurred when the reconstructive height is 125% of the benchmark height. For the lower adjacent segment (C6 /C7 ), the IDPs of postoperative models under all loading conditions also increased compared to the preoperative model. The maximum IDPs after reconstruction under flexion, extension, axial rotation, and lateral bending were 0.402, 0.411, 0.461, and 0.497 MPa, respectively, when the height of the reconstruction was 200% of the benchmark. The minimum IDPs were observed after a reconstruction at 150% of the benchmark, and were 59%, 85%, 82%, and 81% of the maximum IDPs under flexion, extension, axial rotation, and lateral bending loading conditions. CONCLUSIONS: The reconstructive height is an important factor affecting the IDP and the ROM of adjacent segments after ACDF. To delay the adjacent segment disease, an intervertebral reconstructive height of 150% is an appropriate height in C5 /C6 ACDF.

2.
BMC Microbiol ; 21(1): 138, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947329

RESUMO

BACKGROUND: Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis. RESULTS: In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic "pathogens" (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic "pathogens" associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect. CONCLUSIONS: Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.

3.
Aging (Albany NY) ; 132021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973531

RESUMO

Calcific aortic valve disease (CAVD) is associated with increased morbidity and mortality. We aimed to elucidate the 30-year epidemiology of CAVD globally. Global CAVD incidence, prevalence, and deaths increased 3.51-, 4.43-, and 1.38-fold from 1990 to 2019, respectively, without any decreasing trends, even after age standardization. In 2019, Slovenia had the highest age-standardized rate (ASR) of CAVD incidence (62.21/100,000 persons) and prevalence (1,080.06/100,000) whereas Cyprus had the highest ASR of deaths (8.20/100,000). Population aging was an important contributor to incidence. Compared with women, more men had CAVD and men had earlier peaks in disease prevalence. High systolic blood pressure, diet high in sodium, and lead exposure were the main risk factors for deaths owing to CAVD. The estimated annual percentage change, a measure to estimate the variation of ASR, was significantly associated with the ASR and sociodemographic index (SDI) in 2019 for incidence and prevalence across all 204 countries and territories (all p<0.0001). With increased lifespan and risk factors, the overall burden of CAVD is high and remains on the rise, with differences by sex, age, and SDI level. Our findings serve to sound the alarm for organizations, institutions, and resources whose primary purpose is to improve human health.

4.
Adv Healthc Mater ; : e2100198, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33938637

RESUMO

Photodynamic therapy (PDT) often suffers from the exacerbated tumor hypoxia and the heterogeneous distribution of photosensitizers, leading to an inefficient ROS productivity and availability. In this work, a mitochondria targeted O2 economizer (designated as Mito-OxE) is developed to improve PDT efficiency by alleviating tumor hypoxia and enhancing the subcellular localization of photosensitizers. Specifically, the photosensitizer of protoporphyrin IX (PpIX) is modified with the hydrophilic polyethylene glycol and the lipophilic cation of triphenylphosphine (TPP) to fabricate the biocompatible mitochondria targeted photosensitizers (designated as Mito-PSs). And Mito-OxE is prepared by using Mito-PSs to load the mitochondrial oxidative phosphorylation inhibitors of atovaquone (ATO). Benefiting from the targeting capability of TPP, Mito-OxE can selectively accumulate in mitochondria after cellular uptake. Subsequently, the mitochondrial respiration would be suppressed to with the participation of ATO, resulting in a local hypoxia mitigation for enhanced PDT. Compared with Mito-PSs, Mito-OxE maximizes the therapeutic effect against hypoxic tumors under light irradiation. This design of mitochondria targeted O2 economizer would advance the development of targeted drug delivery system for effective PDT regardless of hypoxic microenvironment.

5.
Psychiatry Res ; 300: 113937, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33895443

RESUMO

Cognitive impairments are the hallmark of schizophrenia and prominent in the early episode stage. However, the underlying pathological mechanisms of cognitive impairments are not fully understood. This study aimed to investigate the abnormal functional connectivity (FC) of the cerebellar dentate nucleus (DN) and its correlation with cognitive impairments in patients with drug-naive and first-episode schizophrenia. Resting-state functional magnetic resonance imaging data were acquired in 47 patients and 43 healthy controls. Cognitive functions were assessed by number sequence span, verbal category fluency, digit-symbol coding tests. The results showed that the patients had deficits in all three cognitive tests compared to the controls. Furthermore, the increased FC of DN with the bilateral postcentral gyrus and decreased FC of DN with the right inferior temporal gyrus and regional cerebellum (e.g., Vermis 4-5 and Crus I) were observed in the patient group compared to the control group. Importantly, these abnormal DN FC significantly correlated with cognitive tests (e.g., number sequence span and digit-symbol coding) and clinical symptoms (e.g., negative symptom) in the patient group. The results suggested that abnormal FC of DN with cortical and subcortical regions was associated with cognitive impairments and symptom severity and might be an underlying neural mechanism in schizophrenia.

6.
Hum Cell ; 34(3): 918-931, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33813726

RESUMO

Gallbladder carcinoma (GBC) is a lethal biliary tract malignant neoplasm. Patient-derived primary cancer cell lines (PDPCs) are appropriate models to explore biological characteristics and potential therapeutics; however, there is a lack of PDPCs in GBC. In this study, we aimed to establish and characterize the GBC PDPCs, and further investigated the intra-tumor heterogeneity (ITH). Multi-region sampling (3-9 regions) of the operable tumor tissue samples was used to establish PDPCs. Short tandem repeat genotyping for cell authentication and karyotyping was performed, followed by whole-exome sequencing and RNA sequencing to assess the ITH at the genetic and transcriptional levels, respectively. Thirty-eight PDPCs were successfully established from seven GBC patients and characterized. ITH was observed with a median of 38.3% mutations being heterogeneous (range, 26.6-59.4%) across all patients. Similar with other tumor types, TP53 mutations were always truncal. In addition, there were three genes, KMT2C, CDKN2A, and ARID1A, with truncal mutations in at least two patients. A median of 370 differentially expressed genes (DEGs) was identified per patient. Distinct expression patterns were observed between major histocompatibility complex (MHC) class I and II genes. We found the expression of MHC class II genes in the PDPC samples was closely regulated by CIITA, while that of MHC class I genes were not correlated with CIITA expression. The PDPCs established from GBC patients can serve as novel in vitro models to identify the ITH, which may pave a crucial molecular foundation for enhanced understanding of tumorigenesis and progression.

7.
Vaccines (Basel) ; 9(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808531

RESUMO

K48-linked ubiquitination determining antigen degradation and the endosomal recruitments of p97 and Sec61 plays vital roles in dendritic cell (DC) cross-presentation. Our previous studies revealed that nicotine treatment increases bone marrow-derived dendritic cell (BM-DC) cross-presentation and promotes BM-DC-based cytotoxic T lymphocyte (CTL) priming. But the effect of nicotine on K48-linked ubiquitination and the mechanism of nicotine-increased BM-DC cross-presentation are still uncertain. In this study, we first demonstrated that ex vivo nicotine administration obviously increased K48-linked ubiquitination in BM-DC. Then, we found that K48-linked ubiquitination was essential for nicotine-augmented cross-presentation, BM-DC-based CTL priming, and thereby the superior cytolytic capacity of DC-activated CTL. Importantly, K48-linked ubiquitination was verified to be necessary for nicotine-augmented endosomal recruitments of p97 and Sec61. Importantly, mannose receptor (MR), which is an important antigenic receptor for cross-presentation, was exactly catalyzed with K48-linked ubiquitination by the treatment with nicotine. Thus, these data suggested that K48-linked ubiquitination contributes to the superior adaptive immunity of nicotine-administrated BM-DC. Regulating K48-linked ubiquitination might have therapeutic potential for DC-mediated immune therapy.

8.
Mol Cancer Ther ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879557

RESUMO

Immune checkpoint inhibitors (ICIs) therapy has been widely used to treat different human cancers, particularly advanced solid tumors. However, clinical studies have reported that ICI immunotherapy benefits only ~15% of colorectal cancer (CRC) patients, specifically those with tumors characterized by microsatellite instability (MSI), a molecular marker of defective DNA mismatch repair (dMMR). For the majority of CRC patients who carry proficient MMR (pMMR), ICIs have shown lilttle clinical benefit. In this study, we examined the efficacy of sulindac to enhance the response of pMMR CRC to anti-PD-L1 immunotherapy. We utilized CT26 syngeneic mouse tumor model to compare the inhibitory effects of PD-L1 antibody (Ab), sulindac, and their combination on pMMR CRC tumor growth. We found that mice treated with combination therapy showed a significant reduction in tumor volume, along with increased infiltration of CD8+ T lymphocytes in the tumor tissues. We also demonstrated that sulindac could downregulate PD-L1 by blocking NF-κB signaling, which in turn led to a decrease in exosomal PD-L1. Notably, PD-L1 Ab can be bound and consumed by exosomal PD-L1 in the blood circulation. Therefore, in combination therapy, sulindac downregulating PD-L1 leads to increased availability of PD-L1 Ab, which potentially improves the overall efficacy of anti-PD-L1 therapy. We also show that low-dose sulindac does not appear to have a systemic inhibitory effect on prostaglandin E2 (PGE2). In conclusion, our findings provide unique insights into the mechanism of action and efficacy for sulindac as an immunomodulatory agent in combination with anti-PD-L1 therapy for the treatment of pMMR CRC.

9.
Transplant Proc ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33888344

RESUMO

Acute myeloid leukemia (AML) is a rare malignancy with increased incidence in the kidney transplantation (KT) population for which immunosuppression has been implicated as a putative cause. The average time interval from KT to AML development is 5 years. We present the case of a 61-year-old man who was found to have peripheral blood blasts on a postoperative day 20 routine blood draw after an uneventful unrelated living donor kidney transplant. He subsequently had a bone marrow biopsy and next-generation sequencing (NGS)-based molecular testing, which demonstrated AML characterized by SMC1A and TET2 mutations. He received induction chemotherapy followed by hematopoietic cell transplantation (HCT) from the kidney donor, who happened to be matched at one haplotype. At 12 months after his HCT and 15 months after his KT, his AML remained in remission, normal renal function was preserved, no active graft-versus-host disease was present, and immunosuppression was tapering. With full donor-derived hematopoietic chimerism, we expect to be able to discontinue immunosuppression shortly, thereby achieving tolerance. The short time interval between KT and development of AML suggests the malignancy was likely present before KT. Modern NGS-based analysis offers a promising method of identifying transplant candidates with unexplained hematologic abnormalities on pre-KT testing who may benefit from formal hematologic evaluation.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33852512

RESUMO

BACKGROUND: This study attempted to investigate the impact of hepatopulmonary syndrome (HPS) on postoperative outcomes in hepatitis B virus-induced hepatocellular carcinoma (HBV-HCC) patients. METHODS: HBV-HCC patients undergoing primary curative hepatectomy for HCC in our hospital were diagnosed with HPS by contrast-enhanced echocardiography (CEE) and arterial blood gas analysis. Patients were divided into HPS, intrapulmonary vascular dilation (IPVD) (patients with positive CEE results and normal oxygenation) and control (patients with negative CEE results) groups. Baseline information, perioperative clinical data and postoperative pulmonary complications (PPCs) were compared among all groups. Cytokines in patient serums from each group (n = 8) were also assessed. RESULTS: Eighty-seven patients undergoing hepatectomy from October 2019 to January 2020 were analyzed. The average time in the postanaesthesia care unit (112.10 ± 38.57 min) and oxygen absorption after extubation [34.0 (14.5-54.5) min] in the HPS group was longer than in IPVD [81.81 ± 26.18 min and 16.0 (12.3-24.0) min] and control [93.70 ± 34.06 min and 20.5 (13.8-37.0) min] groups. There were no significant differences in oxygen absorption time after extubation between HPS and control groups. The incidence of PPCs, especially bi-lateral pleural effusions in the HPS group (61.9%), was higher than in IPVD (12.5%) and control (30.0%) groups. Increased serum levels of the growth-regulated oncogene, monocyte chemoattractant protein, soluble CD40 ligand and interleukin 8 might be related to delayed recovery in HPS patients. CONCLUSIONS: HPS patients with HBV-HCC suffer delayed postoperative recovery and are at higher risk for PPCs, especially bi-lateral pleural effusions, which might be associated with changes in certain cytokines.

11.
Acta Otolaryngol ; : 1-7, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823748

RESUMO

BACKGROUND: Congenital microtia-atresia affects patients in two specific ways: severe conductive hearing loss and difficulty in integrating into social environments due to auricle malformation. AIMS/OBJECTIVES: To investigate the safety and efficacy of single-stage auricular reconstruction and hearing rehabilitation in children with microtia and external auditory canal atresia. MATERIAL AND METHODS: From January 2016 to December 2019, we included 32 patients with microtia and external canal atresia who received auricle reconstruction with high-density polyethylene (Medpor) framework and three different hearing rehabilitation approaches at the Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Twenty patients underwent the traditional external auditory canal and middle ear repair (EACR), eight patients were implanted with Bonebridge (BB) devices, and four patients were implanted with bone-anchored hearing aid (BAHA) in one stage. Postoperative changes in auricle morphology and hearing and speech recognition and occurrence of complications were evaluated. RESULTS: After 6-24 months of follow-up, the auricle shape recovered well in all three groups, and the average score of 14 fine structures in the auricle was 9.43 (EACR), 10.67 (BB), and 9.75 (BAHA) points. The average score of auricle symmetry was 6.83 (EACR), 6.00 (BB), and 6.44 (BAHA) points. No significant differences in auricle shape were observed among the three groups (p > .05). After surgery, the average hearing improvement in the BB group was 43.33 dB, and the average speech recognition threshold declined to 42.28 dB. In the BAHA group, the average hearing improvement was 35 dB, and the average speech recognition threshold declined to 33.5 dB, similar to that of the BB group. However, in the EACR group, the average hearing improvement was only 4.13 dB, and the average speech recognition threshold declined to 11.36 dB. No vertigo, tinnitus, cerebrospinal fluid leakage, facial nerve paralysis, osseointegration failure, and other complications occurred in all the patients. In the EACR group, auricle stent fracture, ear canal restenosis, and canal atresia occurred in one patient each. In the BAHA group, two patients developed local ear infections. CONCLUSIONS AND SIGNIFICANCE: The procedure of single-stage auricular reconstruction and hearing rehabilitation for microtia is feasible and effective. The appropriate method of hearing reconstruction should be determined by evaluating the development of the inner and middle ear of the patients. For those patients with poor development of the mastoid and ossicular chain, hearing aid devices are recommended to achieve a stable and significant hearing effect.

12.
Int J Infect Dis ; 106: 281-288, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823283

RESUMO

BACKGROUND: The spatiotemporal trend of renal involvement in coronavirus disease 2019 (COVID-19) patients is still unclear. Therefore, the aim of this study was to reveal the dynamics of renal involvement superimposed COVID-19 according to time and space. METHODS: COVID-19 patients reporting renal involvement were included in this study. The following information was collected from relevant articles: first author, patient demographics, patient enrollment period, location, definition of acute kidney injury (AKI), prevalence of AKI, and use of renal replacement therapy (RRT). RESULTS: A total of 17 134 patients were finally included. The overall prevalence of AKI in COVID-19 patients was 19%, with 7% of them undergoing RRT. The overall risk of AKI in patients enrolled before March 1, 2020 (9%) was significantly lower than that after March 1, 2020 (36%) (P < 0.00001). Moreover, the overall risk of AKI outside Asia (35%) was significantly higher than that in Asia (10%) (P < 0.00001). Additionally, similar to patients requiring RRT, AKI patients were more likely to become seriously ill or even to die (P < 0.00001). CONCLUSIONS: This study found that renal involvement superimposed COVID-19, a comorbidity portending a poor prognosis, has become an increasingly serious problem over time and is more common outside Asia. Thus, more attention should be paid to the management of this specific group of patients.

13.
Methods Mol Biol ; 2300: 133-139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33792878

RESUMO

MicroRNAs (miRNAs) are a class of small noncoding single-stranded RNA molecules containing 18-22 nucleotides that play an important role in the regulation of gene expression at the post-transcriptional and translational levels. Loss-of-function studies are the fundamental strategy to examine miRNA function and target genes in cellular and molecular biology. Traditional methods for miRNA loss-of-function studies include miRNA-specific antisense inhibitors, miRNA sponges, and genetic knockout. However, efficiency, specificity, and stability of these methods are not adequate. Our study suggests that CRISPR/Cas9 is an economic, convenient, and innovative strategy with high efficiency, specificity, and stability for the modulation of miRNA expression. Herein, we describe a detailed protocol for knocking out miRNA genes in vitro and in vivo with the CRISPR/Cas9 system.

14.
Transplant Cell Ther ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33840625

RESUMO

Disease relapse after hematopoietic cell transplantation (HCT) is a major cause of treatment failure for patients with acute myeloid leukemia (AML). Maintenance therapy after HCT for patients with targetable mutations such as mutated IDH1 or IDH2 may improve outcomes, and clinical trials evaluating this strategy are ongoing. However, clinical outcomes of IDH1- and IDH2-mutated AML patients after HCT have not been well described. The primary objective of this study was to describe the clinical characteristics and post-HCT outcomes of IDH-mutated AML patients. Survival outcomes included progression-free survival (PFS), overall survival, and cumulative incidences of relapse and nonrelapse mortality. In this multicenter retrospective analysis, 112 adult patients with IDH1- or IDH2-mutated AML who underwent HCT and did not receive an IDH inhibitor as maintenance therapy after HCT were identified at Massachusetts General Hospital, Dana Farber Cancer Institute, and Ohio State University. Mutation testing was performed using next-generation sequencing panels. Patient characteristics were collected retrospectively, and their survival outcomes were analyzed. Univariate and multivariate analyses were performed. The median patient age was 64.1 years. The median follow-up was 27.5 months. Among patients, 78.5% had intermediate- or adverse-risk disease by European LeukemiaNET criteria. Fifty-eight percent of patients received intensive induction chemotherapy, 82% of patients underwent HCT during first complete remission (CR) or CR with incomplete hematologic recovery (CRi), and 34% of patients received myeloablative conditioning. Frequently detected co-mutations were DNMT3A (35.7%), NPM1 (33.1%), and FLT3-ITD (13.4%); TP53 mutations were detected in 3.6% of patients. For IDH1-mutated patients transplanted during first CR/CRi, the 1- and 2-year PFS was 75% and 58%, respectively. For IDH2-mutated patients transplanted in first CR/CRi, the 1- and 2-year PFS was 64% and 58%, respectively. The 2-year cumulative incidence of relapse was 31% and 25% for IDH1- and IDH2-mutated cohorts, respectively. Multivariable analysis suggested first CR/CRi and age ≤60 was associated with improved outcomes for IDH2-mutated patients. To date, this is the largest multicenter study of outcomes of IDH-mutated AML patients after HCT. Our analysis provides important benchmarks for analysis and interpretation of results emerging from clinical trials evaluating maintenance IDH1 and IDH2 inhibitor therapy for AML patients after HCT.

15.
Transplant Cell Ther ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33789836

RESUMO

Hematopoietic cell transplantation (HCT) is a potentially curative therapy for hematologic malignancies, but it often results in significant toxicities and impaired quality of life (QOL). Although the value of patient-reported outcomes (PROs) is increasingly recognized in HCT, data are limited regarding the relationship between PROs and HCT complications. We conducted a secondary data analysis of 250 patients who were hospitalized for autologous or allogeneic HCT at Massachusetts General Hospital from 2011 through 2016. We assessed QOL (Functional Assessment of Cancer Therapy-General), mood (Hospital Anxiety and Depression Scale), and fatigue (FACT-Fatigue) at baseline. We abstracted from the Electronic Health Record (1) hospitalization during the first 100 days after HCT, (2) days alive and out of the hospital in the first 100 days after HCT, and (3) cumulative incidence of acute graft-versus-host disease (GVHD) among allogeneic HCT recipients. We assessed the association of baseline PROs with HCT complications using multivariable models adjusting for patient and transplant characteristics. Overall, 44.4% (111/250) of patients underwent an autologous HCT, 25.2% (63/250) received a myeloablative allogeneic HCT, and 30.4% (76/250) underwent a reduced-intensity allogeneic HCT. In multivariable logistic regression, higher anxiety (odds ratio [OR] = 1.14, P = .004) was associated with higher likelihood of rehospitalization within 100 days after HCT. In multivariable Poisson regression, lower fatigue (ß = 0.003, P = .015) was associated with increased days alive and out of the hospital in the first 100 days post-HCT. In multivariable logistic regression, lower baseline QOL (OR = 0.97, P = .034), higher fatigue (OR = 0.95, P = .004), and higher depression (OR = 1.15, P = .020) were associated with increased likelihood of acute GVHD. Baseline PROs are associated with health care utilization after HCT and risk of acute GVHD in allogeneic HCT recipients. These findings underscore the potential utility of pretransplantation PROs as important prognostic factors for HCT.

16.
Blood ; 137(11): 1447-1448, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33734331
17.
BMC Plant Biol ; 21(1): 130, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673810

RESUMO

BACKGROUND: Cytoplasmic male sterility (CMS), which naturally exists in higher plants, is a useful mechanism for analyzing nuclear and mitochondrial genome functions and identifying the role of mitochondrial genes in the plant growth and development. Polima (pol) CMS is the most universally valued male sterility type in oil-seed rape. Previous studies have described the pol CMS restorer gene Rfp and the sterility-inducing gene orf224 in oil-seed rape, located in mitochondria. However, the mechanism of fertility restoration and infertility remains unknown. Moreover, it is still unknown how the fecundity restorer gene interferes with the sterility gene, provokes the sterility gene to lose its function, and leads to fertility restoration. RESULT: In this study, we used multi-omics joint analysis to discover candidate genes that interact with the sterility gene orf224 and the restorer gene Rfp of pol CMS to provide theoretical support for the occurrence and restoration mechanisms of sterility. Via multi-omics analysis, we screened 24 differential genes encoding proteins related to RNA editing, respiratory electron transport chain, anther development, energy transport, tapetum development, and oxidative phosphorylation. Using a yeast two-hybrid assay, we obtained a total of seven Rfp interaction proteins, with orf224 protein covering five interaction proteins. CONCLUSIONS: We propose that Rfp and its interacting protein cleave the transcript of atp6/orf224, causing the infertility gene to lose its function and restore fertility. When Rfp is not cleaved, orf224 poisons the tapetum cells and anther development-related proteins, resulting in pol CMS mitochondrial dysfunction and male infertility. The data from the joint analysis of multiple omics provided information on pol CMS's potential molecular mechanism and will help breed B. napus hybrids.

18.
Health Qual Life Outcomes ; 19(1): 78, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685488

RESUMO

BACKGROUND: To evaluate the interaction of depression and anxiety with the development of recurrent pregnancy loss (RPL). METHODS: A nested case-control study involving 2558 participants was conducted with data from the prospective Miscarriage Woman Cohort study between 2017 and 2019 in the province of Gansu, China. The questionnaire data, self-rating anxiety scale and self-rating depression scale were collected after each participant's first miscarriage. Information on RPL outcomes was obtained from the medical records within the subsequent 2 years. All patients diagosed RPL were recruited as cases whilst a randomly selected group of women with only one miscarriage in the past were recruited as controls. The logistic regression and the interaction effects between anxiety and depression and RPL were analysed. RESULTS: The prevalence of anxiety (n = 325, 28.7% vs. n = 278, 19.5%) and depression symptoms (n = 550, 48.6% vs. n = 589, 41.3%) for the 1132 RPL cases were higher than 1426 non-RPL controls (P < 0.001). After adjusting for possible confounding variables, the odds ratio (OR) value, reflecting the multiplicative interaction, was 1.91 (95% CI 1.50-2.44, P < 0.001) for cases with both anxiety and depression symptoms compared with the non-RPL group. The relative excess risk of interaction value, reflecting the additive interaction between anxiety and depression to RPL was 1.15 (95% CI 0.32-4.21). Moreover, the adjusted OR for RPL cases with mild anxiety and severe depression was 2.77 (95% CI 1.07-44.14, P < 0.001), for RPL cases with severe anxiety and mild depression was 4.23 (95% CI 1.01-22.21, P < 0.001), for RPL cases with severe anxiety and moderate depression was 4.34 (95% CI 1.03-21.28, P < 0.001) and for RPL cases with severe anxiety and severe depression was 5.95 (95% CI 1.09-45.09, P < 0.05). CONCLUSIONS: Either depression or anxiety alone could increase the risk of subsequent RPL. Anxiety and depression had a synergistic effect after the first miscarriage which increased the development of subsequent RPL disease.


Assuntos
Aborto Habitual/psicologia , Ansiedade/epidemiologia , Depressão/epidemiologia , Aborto Habitual/epidemiologia , Adulto , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Gravidez , Prevalência , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Adulto Jovem
19.
Br J Clin Pharmacol ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33754371

RESUMO

AIMS: This study aims to evaluate the effects of dexmedetomidine on organ function, inflammation response, and oxidative stress in elderly patients following iatrogenic lower limb ischaemia-reperfusion (IR) during unilateral total knee arthroplasty. METHODS: Following unilateral total knee arthroplasty, 54 elderly patients were randomized to receive either intraoperative intravenous injection of dexmedetomidine (n = 27) or equivalent volume of 0.9% saline (n = 27). Blood samples were harvested at 5 minutes before lower limb tourniquet release (baseline); and 1, 6 and 24 hours after tourniquet release. Surrogate markers of cardiac, pulmonary, hepatic and renal function, oxidative stress, inflammatory response, along with parasympathetic and sympathetic activity were recorded and analysed. RESULTS: The levels of blood xanthine oxidase, creatine kinase, lactic acid and respiratory index increased in patients following tourniquet-induced lower limb IR injury. Dexmedetomidine administration decreased the respiratory index (P = .014, P = .01, and P = .043) and the norepinephrine level (P < .001) at 1, 6 and 24 hours; and decreased the xanthine oxidase level (P = .049, P < .001) at 6 and 24 hours after tourniquet release compared with the Control group. Other measurements, including creatine kinase isoenzyme, lactate dehydrogenase, creatinine, urea nitrogen, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, malondialdehyde, interleukin-1, interleukin-6 and tumour necrosis factor-α, were not statistically significantly different between the 2 groups. CONCLUSIONS: Intraoperative dexmedetomidine administration in elderly patients dampens the deterioration in respiratory function and suppresses the oxidative stress response in elderly patients following iatrogenic lower limb IR injury.

20.
Clinics (Sao Paulo) ; 76: e1816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787653

RESUMO

OBJECTIVE: This study aimed to identify the most useful ultrasound (US) features associated with definite neonatal necrotizing enterocolitis (NEC) and their prognostic values, particularly the calculated markers combined with important features. METHODS: A total of 213 suspected NEC cases were collected from the neonatal department of our hospital from January 2015 to August 2017. Each infant received both X-ray and US examinations. RESULTS: No differences were found in sex composition and delivery modes between groups. NEC-positive neonates had poorer prognosis compared to negative ones. The NEC group showed a higher frequency of abnormal signals. US showed higher NEC-related frequencies in different parameters. A variable (named predictor in US [PUS]) with five features was constructed. For NEC diagnosis, this variable provided a much higher area under the curve Q2 (AUC) (0.965) than other parameters. In this model, PUS had a cutoff value of 0.376 with a 0.900 sensitivity and 0.922 specificity. In prognosis, the closest factors were selected to draw a receiver operating characteristic curve, as well as a novel calculated variable US prognostic (USPro) marker. USPro had a much higher AUC (0.86) than other single features and showed a cutoff value of 0.18145, with 0.75 sensitivity and 0.84 specificity. This variable had a weaker power in prognosis when compared with PUS in diagnosis. CONCLUSIONS: The application of abdominal color Doppler US can provide high accuracy and sensitivity in NEC diagnosis and also contribute to its prognosis, without induction of radiation. Suspected neonates should be examined using this technique as early as possible.


Assuntos
Enterocolite Necrosante , Doenças do Recém-Nascido , Enterocolite Necrosante/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Prognóstico , Curva ROC , Ultrassonografia
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