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1.
Oncogene ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862460

RESUMO

In many types of cancer, tumor cells prefer to use glycolysis as a major energy acquisition method. Here, we found that the 18fluoro-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-based markers were positively associated with the expression of programmed cell death ligand 1 (PD-L1), pyruvate kinase M2 (PKM2), both of which indicate poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the regulatory mechanism of PD-L1 remains elusive. In this study, we confirmed that transforming growth factor-beta1 (TGF-ß1) secreted by tumor-associated macrophages (TAMs) was a key factor contributing to the expression of PD-L1 in PDAC cells by inducing the nuclear translocation of PKM2. Using co-immunoprecipitation and chromatin immunoprecipitation assays, we demonstrated that the interaction between PKM2 and signal transducer and activator of transcription 1 (STAT1) was enhanced by TGF-ß1 stimulation, which facilitated the transactivation of PD-L1 by the binding of PKM2 and STAT1 to its promoter. In vivo, PKM2 knockdown decreased PD-L1 expression in PDAC cells and inhibited tumor growth partly by promoting natural killer cell activation and function, and the combination of PD-1/PD-L1 blockade with PKM2 knockdown limited tumor growth. In conclusion, PKM2 significantly contributes to TAM-induced PD-L1 overexpression and immunosuppression, providing a novel target for immunotherapies for PDAC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34845632

RESUMO

Maintaining or increasing grain yields while also reducing the emissions of field agricultural greenhouse gases is an important objective. To explore the multifactor effects of nitrogen fertilizer on nitrous oxide (N2O) emissions and the yield of potato fields and to verify the applicability of the denitrification-decomposition (DNDC) model when used to project the N2O emission load and yield, this research chooses a potato field in Shenyang northeast China from 2017 to 2019 as the experiment site. The experiment includes four nitrogen levels observing the emission of N2O by static chamber/gas chromatograph techniques. The results of this study are as follows: (1) DNDC has a good performance regarding the projection of N2O emissions and yields. The model efficiency index EFs were 0.45 ~ 0.88 for N2O emissions and 0.91, 0.85, and 0.85 for yields from 2017 to 2019. (2) The annual precipitation, soil organic carbon, and soil bulk density had the most significant influence on the accumulated N2O emissions during the growth period of potatoes. The annual precipitation, annual average temperature, and CO2 mass concentration had the most significant influences on yield. (3) Under the premise of a normal water supply, sowing potatoes within 5 days after the 5-day sliding average temperature in this area exceeds 10℃ can ensure the temperature required for the normal growth of potatoes and achieve the purpose of maintaining and increasing yield. (4) The application of 94.5 kg·hm-2 nitrogen and 15 mm irrigation represented the best results for reducing N2O emissions while also maintaining the yield in potato fields.

4.
EBioMedicine ; 74: 103722, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34839263

RESUMO

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411 .

5.
Front Plant Sci ; 12: 717077, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484281

RESUMO

Speed breeding by artificial control of photothermal conditions facilitates generation advancement but was limited in scale and cost. In this study, we demonstrated a cost-saving off-site summer nursery pattern, taking full advantage of shorter daylength and higher temperature with lower latitude compared to the origin of the soybean cultivars used in the study. This substantially reduced the generation cycles under totally natural conditions. Using this approach, two generations of soybean cultivars from Northeastern Spring Planting Region (NE) and Yellow-Huai-Hai Valleys Summer Planting Region (YHH) were successfully obtained in Beijing and Hainan, respectively, compared to one generation in origin. Fresh-seeding method was also used to further shorten the generation duration by 7-10 days, thereby allowing at least four generations per year. Using DNA markers to define haplotypes of maturity genes E1-E4, we proposed a model to predict the optimum adaptation region of the advanced generation lines. Taken together, we present a speed-breeding methodology combining off-site nursery, fresh-seeding method, and marker-assisted selection, aimed at accelerating soybean improvement.

6.
Cell Death Dis ; 12(10): 876, 2021 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-34564711

RESUMO

Chondroitin polymerizing factor (CHPF) is an important glycosyltransferase involved in the biosynthesis of chondroitin sulfate. However, the relationship between CHPF and gastric cancer has not been fully investigated. CHPF expression in gastric cancer tissues was detected by immunohistochemistry and correlated with gastric cancer patient prognosis. Cultured gastric cancer cells and human gastric epithelial cell line GES1 were used to investigate the effects of shCHPF and shE2F1 on the development and progression of gastric cancer by MTT, western blotting, flow cytometry analysis of cell apoptosis, colony formation, transwell and gastric cancer xenograft mouse models, in vitro and in vivo. In gastric cancer tissues, CHPF was found to be significantly upregulated, and its expression correlated with tumor infiltration and advanced tumor stage and shorter patient survival in gastric cancer. CHPF may promote gastric cancer development by regulating cell proliferation, colony formation, cell apoptosis and cell migration, while knockdown induced the opposite effects. Moreover, the results from in vivo experiments demonstrated that tumor growth was suppressed by CHPF knockdown. Additionally, E2F1 was identified as a potential downstream target of CHPF in the regulation of gastric cancer, and its knockdown decreased the CHPF-induced promotion of gastric cancer. Mechanistic study revealed that CHPF may regulate E2F1 through affecting UBE2T-mediated E2F1 ubiquitination. This study showed, for the first time, that CHPF is a potential prognostic indicator and tumor promoter in gastric cancer whose function is likely carried out through the regulation of E2F1.

7.
Small ; 17(44): e2102689, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34553830

RESUMO

Recently, the application of metal-organic frameworks (MOFs) in thermal energy storage has attracted increasing research interests. MOF-ammonia working pairs have been proposed for controlling/sensing the air quality, while no work has yet been reported on the immense potential of MOFs for thermal energy storage up till now. Herein, the feasibility of thermal energy storage using seven MOF-ammonia working pairs is experimentally assessed. From ammonia sorption stability and sorption thermodynamics results, it is found that MIL-101(Cr) exhibits both high ammonia sorption stability and the largest sorption capacity of ≈0.76 g g-1 . Compared with MIL-101(Cr)-water working pair, MIL-101(Cr)-ammonia working pair improves the sorption capacity by over three times with evaporation temperature lower than 8.4 °C. Due to stable ammonia sorption stability and negligible hysteresis, MIL-101(Cr) and ZIF-8(Zn) are tested at condensation/evaporation temperature of 30 °C/10 °C. The thermal energy storage density (reaching over 1200 kJ kg-1 ) and coefficient of performance of MIL-101(Cr)-based system are both higher than ZIF-8(Zn)-based one due to larger average isosteric enthalpy and cycle sorption capacity. This experimental work paves the way for developing the high efficient and stable thermal energy storage system with MOF-ammonia working pairs especially for critical conditions with low evaporation temperature and high condensation temperature.

8.
J Immunother ; 44(9): 339-347, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34545012

RESUMO

Protein kinase D3 (PKD3) has been involved in various aspects of tumorigenesis and progression in many kinds of cancer types. However, whether PKD3 regulates immune escape in tumor microenvironment is rarely reported. Here, we explored the function and mechanism of PKD3 in reconstructing the immune escape niche of oral squamous cell carcinoma (OSCC). Both the Western blotting analysis in OSCC cells and the gene expression correlation analysis from The Cancer Genome Atlas shows that the expression of Fas and programmed cell death-ligand 1 (PD-L1) was positively correlated with PKD3, while major histocompatibility complex-I (MHC-I) was negatively correlated with PKD3. Knockdown of PKD3 significantly decreased the expression of Fas and PD-L1 and increased the expression of MHC-I. Furthermore, when PKD3 was overexpressed in oral precancerous cells, Fas, PD-L1, and MHC-I showed an opposite trend to that observed when PKD3 was knocked down. In addition, PKD3 knockdown decreased the secretion of transforming growth factor ß, CC-chemokine ligand 21, interleukin-10 by OSCC cells. Finally, the tumor cell antigen, which was extracted from PKD3 knockdown OSCC cells, significantly induced the growth and activation of T lymphocytes. These results demonstrate that PKD3 promotes the immune escape of OSCC cells by regulating the expression of Fas, PD-L1, MHC-I, transforming growth factor ß, CC-chemokine ligand 21, interleukin-10, and plays a key role in reconstructing the tumor immune escape niche.

9.
ACS Omega ; 6(34): 22020-22032, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34497896

RESUMO

Sewage sludge and waste biomass are unavoidable byproducts of municipal and industrial processes. Both materials have significant carbon contents. Activated coke with a developed pore structure can be obtained after its physical activation. In this study, sewage sludge and waste poplar bark were used as precursor materials to prepare activated coke by steam, carbon dioxide gas, and their mixtures. The effects of different concentrations of activation gas on the activated coke product were investigated. Through nitrogen adsorption analysis, it was found that activated coke has a higher specific surface area and better pore structure when activated in gas containing 20% steam. The activated coke prepared by carbon dioxide gas activation has higher microporosity than that prepared by steam activation. Infrared spectrum analysis shows that steam activation is beneficial to the formation of free hydroxyl functional groups. Through scanning electron microscopy analysis, the pores of activated coke prepared by steam activation appeared to extend deeper in the structure of the coke, while the pores of activated coke prepared by carbon dioxide activation appeared to have fine circular structures. The activated coke prepared by the activation of mixed gas appeared to have ablated particles on the surface due to the ablation of the pore structure. In order to prepare activated coke with excellent adsorption performance, the physical and chemical properties of activated coke under different activation conditions were studied in detail.

10.
Org Lett ; 23(20): 7724-7729, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34581590

RESUMO

A novel electrochemical radical selenylation of alkenes and activated arenes without external oxidants is reported. The diselenide was fully transformed into Se-centered radicals through electrochemical Se-Se bond activation. Three-component radical carbonselenation was successfully realized using styrenes to trap the RSe radical. Besides, the direct coupling of RSe radicals with activated arenes was further developed. Using this atom-economic protocol, diversity of unsymmetric aryl-aryl, aryl-alkyl, and alkyl-alkyl selenoethers was obtained regioselectively, which has potential application in biological chemistry.

11.
Stem Cells Int ; 2021: 9992381, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367295

RESUMO

Acute respiratory distress syndrome (ARDS) is difficult to treat and has a high mortality rate. Mesenchymal stem cells (MSCs) have an important therapeutic effect in ARDS. While the mechanism of MSC migration to the lungs remains unclear, the role of MSCs is of great clinical significance. To this end, we constructed vimentin knockout mice, extracted bone MSCs from the mice, and used them for the treatment of LPS-induced ARDS. H&E staining and Masson staining of mouse lung tissue allowed us to assess the degree of damage and fibrosis of mouse lung tissue. By measuring serum TNF-α, TGF-ß, and INF-γ, we were able to monitor the release of inflammatory factors. Finally, through immunoprecipitation and gene knockout experiments, we identified upstream molecules that regulate vimentin and elucidated the mechanism that mediates MSC migration. As a result, we found that MSCs from wild-type mice can significantly alleviate ARDS and reduce lung inflammation, while vimentin gene knockout reduced the therapeutic effect of MSCs in ARDS. Cytological experiments showed that vimentin gene knockout can significantly inhibit the migration of MSCs and showed that it changes the proliferation and differentiation status of MSCs. Further experiments found that vimentin's regulation of MSC migration is mainly mediated by Rab7a. Rab7a knockout blocked the migration of MSCs and weakened the therapeutic effect of MSCs in ARDS. In conclusion, we have shown that the Vimentin-Rab7a pathway mediates migration of MSCs and leads to therapeutic effects in ARDS.

12.
Hepatobiliary Surg Nutr ; 10(4): 498-506, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34430528

RESUMO

Background: The first-line chemotherapy regimen for advanced gallbladder cancer (GBC) is gemcitabine plus platinum (GP), despite its efficacy is limited. The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus oxaliplatin (GEMOX) as the first-line chemotherapy for unresectable locally advanced or metastatic GBC. Methods: The data of patients with unresectable locally advanced or metastatic GBC, who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, were retrieved. This retrospective study evaluated the clinical characteristics, survival outcomes and adverse events. Results: A total of 44 patients (n=25 in mFOLFIRINOX, n=19 in GEMOX) were included. There were no significant differences between groups in baseline characteristics. The median progression free survival (mPFS) was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group [P=0.021; hazard ratio (HR), 0.499; 95% CI, 0.266 to 0.937]. The median overall survival (mOS) was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group (P=0.019; HR, 0.471; 95% CI, 0.239 to 0.929). Disease control rate (DCR) was 76.0% in the mFOLFIRINOX group and 47.4% in the GEMOX group (P=0.051). The rate of grade 3-4 adverse events was 48% in the mFOLFIRINOX group and 36.8% in the GEMOX group (P=0.459). The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group, while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group. Conclusions: mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC, and the results need to be further verified by prospective clinical studies.

13.
Sci Total Environ ; 798: 149211, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34375235

RESUMO

Climate warming has been proposed to increase primary production of natural grasslands in cold regions. However, how climate warming affects the production of artificial pastures in cold regions remains unknown. To address this question, we used open-top chambers to simulate warming in a major artificial pasture (forage oat) on the cold Tibetan Plateau for three consecutive years. Surprisingly, climate warming decreased aboveground and belowground biomass production by 23.1%-44.8% and 35.0%-46.5%, respectively, without a significant impact on their ratio. The adverse effects on biomass production could be attributed to the adverse effects of high-temperatures on leaf photosynthesis through increases in water vapor pressure deficit (by 0.05-0.10 kPa), damages to the leaf oxidant system, as indicated by a 46.6% increase in leaf malondialdehyde content, as well as reductions in growth duration (by 4.7-6.7 days). The adverse effects were also related to exacerbated phosphorus limitation, as indicated by decreases in soil available phosphorus and plant phosphorus concentrations by 31.9%-40.7% and 14.3%-49.4%, respectively, and increases in the plant nitrogen: phosphorus ratio by 19.2%-108.3%. The decrease in soil available phosphorus concentration could be attributed to reductions in soil phosphatase activities (by 9.6%-18.5%). The findings of this study suggest an urgent need to advance agronomic techniques and cultivate more resilient forage genotypes to meet the increasing demand of forage for feeding livestock and to reduce grazing damage to natural grasslands on the warming-sensitive Tibetan Plateau.


Assuntos
Plantas , Solo , Biomassa , Pradaria , Fotossíntese , Tibet
14.
Channels (Austin) ; 15(1): 516-527, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34414859

RESUMO

Estradiol regulates thyroid function, and chloride channels are involved in the regulation of thyroid function. However, little is known about the role of chloride channels in the regulation of thyroid functions by estrogen. In this study, the effects of estrogen on chloride channel activities in human thyroid Nthy-ori3-1 cells were therefore investigated using the whole cell patch-clamp technique. The results showed that the extracellular application of 17ß-estradiol (E2) activated Cl- currents, which reversed at a potential close to Cl- equilibrium potential and showed remarkable outward rectification and an anion permeability of I- > Br- > Cl- > gluconate. The Cl- currents were inhibited by the chloride channel blockers, NPPB and tamoxifen. Quantitative Real-time PCR results demonstrated that ClC-3 expression was highest in ClC family member in Nthy-ori3-1 cells. The down-regulation of ClC-3 expression by ClC-3 siRNA inhibited E2-induced Cl- current. The Cl- current was blocked by the estrogen receptor antagonist, ICI 182780 (fulvestrant). Estrogen receptor alpha (ERα) and not estrogen receptor beta was the protein expressed in Nthy-ori3-1 cells, and the knockdown of ERα expression with ERα siRNA abolished E2-induced Cl- currents. Estradiol can promote the accumulation of ClC-3 in cell membrane. ERα and ClC-3 proteins were partially co-localized in the cell membrane of Nthy-ori3-1 cells after estrogen exposure. The results suggest that estrogen activates chloride channels via ERα in normal human thyroid cells, and ClC-3 proteins play a pivotal role in the activation of E2-induced Cl- current.

15.
J Neurosci ; 41(36): 7532-7545, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34326141

RESUMO

Acetaldehyde (ACD), the first metabolite of ethanol, is implicated in several of ethanol's actions, including the reinforcing and aversive effects. The neuronal mechanisms underlying ACD's aversive effect, however, are poorly understood. The lateral habenula (LHb), a regulator of midbrain monoaminergic centers, is activated by negative valence events. Although the LHb has been linked to the aversive responses of several abused drugs, including ethanol, little is known about ACD. We, therefore, assessed ACD's action on LHb neurons in rats. The results showed that intraperitoneal injection of ACD increased cFos protein expression within the LHb and that intra-LHb infusion of ACD induced conditioned place aversion in male rats. Furthermore, electrophysiological recording in brain slices of male and female rats showed that bath application of ACD facilitated spontaneous firing and glutamatergic transmission. This effect of ACD was potentiated by an aldehyde dehydrogenase (ALDH) inhibitor, disulfiram (DS), but attenuated by the antagonists of dopamine (DA) receptor (DAR) subtype 1 (SCH23390) and subtype 2 (raclopride), and partly abolished by the pretreatment of DA or DA reuptake blocker (GBR12935; GBR). Moreover, application of ACD initiated a depolarizing inward current (I ACD) and enhanced the hyperpolarizing-activated currents in LHb neurons. Bath application of Rp-cAMPs, a selective cAMP-PKA inhibitor, attenuated ACD-induced potentiation of EPSCs and I ACD Finally, bath application of ZD7288, a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channels, attenuated ACD-induced potentiation of firing, EPSCs, and I ACD These results show that ACD exerts its aversive property by exciting LHb neurons via multiple cellular mechanisms, and new treatments targeting the LHb may be beneficial for alcoholism.SIGNIFICANCE STATEMENT Acetaldehyde (ACD) has been considered aversive peripherally and rewarding centrally. However, whether ACD has a central aversive property is unclear. Here, we report that ACD excites the lateral habenula (LHb), a brain region associated with aversion and negative valence, through multiple cellular and molecular mechanisms. Intra-LHb ACD produces significant conditioned place aversion. These results suggest that ACD's actions on the LHb neurons might contribute to its central aversive property and new treatments targeting the LHb may be beneficial for alcoholism.


Assuntos
Acetaldeído/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Habenula/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Animais , Dissulfiram/farmacologia , Antagonistas de Dopamina/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Ácido Glutâmico/metabolismo , Habenula/fisiologia , Masculino , Neurônios/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Dopaminérgicos/metabolismo , Transmissão Sináptica/efeitos dos fármacos
16.
BMJ Open ; 11(6): e044157, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193479

RESUMO

OBJECTIVES: Sex as a biological variable affects response to opioids. However, few reports describe the prevalence of specific adverse reactions to commonly prescribed opioids in men and women separately. A large cohort was used to investigate sex differences in type and occurrence of adverse reactions associated with use of codeine, tramadol, oxycodone and hydrocodone. DESIGN: Retrospective cohort study. SETTING: Participants in the Right Drug, Right Dose, Right Time (RIGHT) Study. PARTICIPANTS: The medical records of 8457 participants in the RIGHT Study who received an opioid prescription between 1 January 2004 and 31 December 2017 were reviewed 61% women, 94% white, median age (Q1-Q3)=58 (47-66). PRIMARY AND SECONDARY OUTCOME MEASURES: Adverse reactions including gastrointestinal, skin, psychiatric and nervous system issues were collected from the allergy section of each patient's medical record. Sex differences in the risk of adverse reactions due to prescribed opioids were modelled using logistic regression adjusted for age, body mass index, race and ethnicity. RESULTS: From 8457 participants (of which 449 (5.3%) reported adverse reactions), more women (6.5%) than men (3.4%) reported adverse reactions to at least one opioid (OR (95% CI)=2.3 (1.8 to 2.8), p<0.001). Women were more likely to report adverse reactions to tramadol (OR (95% CI)=2.8 (1.8 to 4.4), p<0.001) and oxycodone (OR (95% CI)=2.2 (1.7 to 2.9), p<0.001). Women were more likely to report gastrointestinal (OR (95% CI)=3.1 (2.3 to 4.3), p<0.001), skin (OR (95% CI)=2.1 (1.4 to 3.3), p=0.001) and nervous system issues (OR (95% CI)=2.3 (1.3 to 4.2), p=0.004). CONCLUSIONS: These findings support the importance of sex as a biological variable to be factored into pain management studies.


Assuntos
Analgésicos Opioides , Caracteres Sexuais , Analgésicos Opioides/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Oxicodona/efeitos adversos , Estudos Retrospectivos
17.
BMC Pediatr ; 21(1): 314, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261469

RESUMO

BACKGROUND: Eczema is usually the first allergic manifestation to appear in life attributed to gene-environment interactions. IL13, IL4, MS4A2 and ILR4A are four key inflammatory genes associated with atopy. This study aimed to explore gene-environment interactions on eczema in early life among the above four genes and environmental factors in Chinese Han children. METHODS: Five hundred ninety-seven children from a birth cohort who completed two-year follow-up were enrolled and their cord blood was collected. Subjects were genotyped for six polymorphisms in the aforementioned four genes. The children were followed at 6, 12 and 24 months, with epidemiologic information and medical history of eczema collected by questionnaire and eczema assessed by dermatologists. RESULTS: Among the 597 children, 168 were diagnosed with eczema and the others were not after 2 years of follow-up. MS4A2 rs569108 GG genotype (P = 1.68E-02, odds ratio (OR) = 4.66) and antibiotic use (P = 3.75E-4, OR = 2.02) were found independently associated with development of childhood eczema. Children with both antibiotic use and MS4A2 rs569108 GG genotype were more likely to develop eczema than those with only antibiotic use or GG homozygote (OR = 6.24 VS. 2.04 or 4.68). CONCLUSIONS: MS4A2 rs569108 polymorphism and antibiotic use were solely associated with eczema, and they interacted with each other to increase the risk of developing the disease in Chinese Han toddlers. Long-term follow-up along with functional and replication studies are still needed.


Assuntos
Dermatite Atópica , Eczema , Receptores de IgE/genética , Antibacterianos , Estudos de Coortes , Dermatite Atópica/genética , Eczema/genética , Humanos , Lactente , Polimorfismo Genético , Estudos Prospectivos
18.
Ann Surg ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34225294

RESUMO

OBJECTIVE: To investigate postoperative functional connectivity alterations across impaired cognitive domains and their causal relationships with systemic inflammation. BACKGROUND: Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether functional connectivity alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remain unclear. METHODS: Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for TNF-α and IL-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations and cytokines. RESULTS: Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC functional connectivity with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased TNF-α and decreased executive function up to day 7 after cardiac surgery. CONCLUSIONS: The decreased functional connectivity of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits following cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.

19.
J Cancer Res Ther ; 17(3): 613-618, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269289

RESUMO

Pancreatic cancer (PC) is a lethal disease with extremely high mortality. Although surgical resection is the optimal therapeutic approach for PC, about 30%-40% of those patients are not candidates for surgical resection when diagnosed. Chemotherapy and radiotherapy also could not claim a desirable effect on PC. The application of interventional radiology approaches is limited by unavoidable damage to the surrounding vessels or organs. By the superiority of mechanism and technology, IRE could ablate the tumor by creating irreversible pores on the membrane of PC cells with other tissues like vessels and pancreatic ducts untouched. This consensus gathers the theoretical basis and clinical experience from multiple Chinese medical centers, to provide the application principles and experience from Chinese experts in the IRE field.

20.
Am J Cardiol ; 155: 121-127, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34315566

RESUMO

Undiagnosed dilated cardiomyopathy (DC) can be asymptomatic or present as sudden cardiac death, therefore pre-emptively identifying and treating patients may be beneficial. Screening for DC with echocardiography is expensive and labor intensive and standard electrocardiography (ECG) is insensitive and non-specific. The performance and applicability of artificial intelligence-enabled electrocardiography (AI-ECG) for detection of DC is unknown. Diagnostic performance of an AI algorithm in determining reduced left ventricular ejection fraction (LVEF) was evaluated in a cohort that comprised of DC and normal LVEF control patients. DC patients and controls with 12-lead ECGs and a reference LVEF measured by echocardiography performed within 30 and 180 days of the ECG respectively were enrolled. The model was tested for its sensitivity, specificity, negative predictive (NPV) and positive predictive values (PPV) based on the prevalence of DC at 1% and 5%. The cohort consisted of 421 DC cases (60% males, 57±15 years, LVEF 28±11%) and 16,025 controls (49% males, age 69 ±16 years, LVEF 62±5%). For detection of LVEF≤45%, the area under the curve (AUC) was 0.955 with a sensitivity of 98.8% and specificity 44.8%. The NPV and PPV were 100% and 1.8% at a DC prevalence of 1% and 99.9% and 8.6% at a prevalence of 5%, respectively. In conclusion AI-ECG demonstrated high sensitivity and negative predictive value for detection of DC and could be used as a simple and cost-effective screening tool with implications for screening first degree relatives of DC patients.


Assuntos
Inteligência Artificial , Cardiomiopatia Dilatada/diagnóstico , Ecocardiografia/métodos , Programas de Rastreamento/métodos , Função Ventricular Esquerda/fisiologia , Algoritmos , Cardiomiopatia Dilatada/fisiopatologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
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