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1.
J Affect Disord ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35038478

RESUMO

OBJECTIVE: To investigate the prevalence of psychotic depression and the differences in sociodemographic and clinical characteristics and prescription patterns of psychotropic medications between patients with psychotic depression (PD) and patients with nonpsychotic depression (NPD) in China. METHODS: We conducted a cross-sectional study in 13 major psychiatric hospitals or the psychiatric units of general hospitals in China from September 1, 2010, to February 28, 2011. PD was defined according to the psychotic disorder section of the Mini International Neuropsychiatric Interview (MINI). The sociodemographic and clinical characteristics and the prescription patterns of psychotropic medications were compared between the PD and NPD groups. Multivariate logistic regression analysis was used to investigate factors associated with an increased likelihood of PD. RESULTS: Among 1172 MDD patients, the prevalence of psychotic features was 9.2% in the present study. The logistic regression analysis indicated that unmarried (OR=2.08, p<0.001), frequent depressive episodes (OR=2.10, p=0.020), depressive episodes with suicidal ideation and attempts (OR=1.91, p=0.004), and patients who were prescribed any antipsychotics (OR=2.94, p<0.001) were associated with psychotic features in patients with MDD. LIMITATIONS: Cross-sectional design, retrospective recall of some data CONCLUSION: The prevalence of PD is high in China, and there were some differences in demographic and clinical characteristics between patients with PD and patients with NPD. Clinicians should regularly assess psychotic symptoms and consider intensive treatment and close monitoring when treating subjects with PD.

2.
Sci Total Environ ; 817: 152766, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35007603

RESUMO

Integrons are genetic elements that can facilitate rapid spread of antibiotic resistance by insertion and removal of genes. However, knowledge about the diversity and distribution of gene cassettes embedded in class 1 integron is still limited. In this study, we sequenced integron gene cassettes using nanopore sequencing and quantified antibiotic resistance genes (ARGs) and integrase genes in the manured soils and sewages of a bioreactor. The results showed that class 1 integron integrase genes were the most abundant in soils and sewages compared with class 2 and class 3 integrase genes. Long-term manure application exacerbated the enrichment of total ARGs, integrase genes and antibiotic resistance-associated gene cassettes, while antibiotics and heavy metals showed no impact on the overall resistome profile. Sewage treatment could efficiently remove the absolute abundance of integrase genes (~3 orders of magnitude, copies/L) and antibiotic resistance gene cassettes. The resistance gene cassettes mainly carried the ARGs conferring resistance to aminoglycoside and beta-lactams in soils and sewages, some of which were persistent during the sewage treatment. This study underlined that soil and sewage were potential reservoirs for integron-mediated ARGs transfer, indicating that anthropogenic activity played a vital role in the prevalence and diversity of resistance gene cassettes in integrons.

3.
Oncogene ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34999736

RESUMO

Macrophages are increased in human benign prostatic hyperplasia and prostate cancer. We generate a Pb-Csf1 mouse model with prostate-specific overexpression of macrophage colony-stimulating factor (M-Csf/Csf1). Csf1 overexpression promotes immune cell infiltration into the prostate, modulates the macrophage polarity in a lobe-specific manner, and induces senescence and low-grade prostatic intraepithelial neoplasia (PIN). The Pb-Csf1 prostate luminal cells exhibit increased stem cell features and undergo an epithelial-to-mesenchymal transition. Human prostate cancer patients with high CSF-1 expression display similar transcriptional alterations with the Pb-Csf1 model. P53 knockout alleviates senescence but fails to progress PIN lesions. Ablating epithelial Gp130 but not Il1r1 substantially blocks PIN lesion formation. The androgen receptor (AR) is downregulated in Pb-Csf1 mice. ChIP-Seq analysis reveals altered AR binding in 2482 genes although there is no significant widespread change in global AR transcriptional activity. Collectively, our study demonstrates that increased macrophage infiltration causes PIN formation but fails to transform prostate cells.

4.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268985

RESUMO

BackgroundIts critical to identify COVID-19 patients with a higher death risk at early stage to give them better hospitalization or intensive care. However, thus far, none of the machine learning models has been shown to be successful in an independent cohort. We aim to develop a machine learning model which could accurately predict death risk of COVID-19 patients at an early stage in other independent cohorts. MethodsWe used a cohort containing 4711 patients whose clinical features associated with patient physiological conditions or lab test data associated with inflammation, hepatorenal function, cardiovascular function and so on to identify key features. To do so, we first developed a novel data preprocessing approach to clean up clinical features and then developed an ensemble machine learning method to identify key features. ResultsFinally, we identified 14 key clinical features whose combination reached a good predictive performance of AUC 0.907. Most importantly, we successfully validated these key features in a large independent cohort containing 15,790 patients. ConclusionsOur study shows that 14 key features are robust and useful in predicting the risk of death in patients confirmed SARS-CoV-2 infection at an early stage, and potentially useful in clinical settings to help in making clinical decisions.

5.
Prostate ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014711

RESUMO

INTRODUCTION: The Wnt proteins play key roles in the development, homeostasis, and disease progression of many organs including the prostate. However, the spatiotemporal expression patterns of Wnt proteins in prostate cell lineages at different developmental stages and in prostate cancer remain inadequately characterized. METHODS: We isolated the epithelial and stromal cells in the developing and mature mouse prostate by flow cytometry and determined the expression levels of Wnt ligands. We used Visium spatial gene expression analysis to determine the spatial distribution of Wnt ligands in the mouse prostatic glands. Using laser-capture microscopy in combination with gene expression analysis, we also determined the expression patterns of Wnt signaling components in stromal and cancer cells in advanced human prostate cancer specimens. To investigate how the stroma-derived Wnt ligands affect prostate development and homeostasis, we used a Col1a2-CreERT2 mouse model to disrupt the Wnt transporter Wntless specifically in prostate stromal cells. RESULTS: We showed that the prostate stromal cells are a major source of several Wnt ligands. Visium spatial gene expression analysis revealed a distinct spatial distribution of Wnt ligands in the prostatic glands. We also showed that Wnt signaling components are highly expressed in the stromal compartment of primary and advanced human prostate cancer. Blocking stromal Wnt secretion attenuated prostate epithelial proliferation and regeneration but did not affect cell survival and lineage maintenance. DISCUSSION: Our study demonstrates a critical role of stroma-derived Wnt ligands in prostate development and homeostasis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34988805

RESUMO

The Belt and Road Initiative (BRI) has attracted widespread attention since its implementation, especially the ecological effect. However, the net environmental impact of the BRI on countries along the route has rarely been directly assessed, though nearly 8 years after the BRI was proposed. This study quantitatively estimates the net effect, impact mechanism, and impact heterogeneity of the BRI on the carbon intensity reduction of countries along the route by adopting the difference-in-differences estimator based on propensity score matching, which enables a more convincing causal relationship between the BRI and the countries' ecological improvement. Research indicates that the BRI has significantly promoted the carbon intensity reduction of countries along the route, which is mainly achieved by boosting the growth of green economy (scale effect), the progress of green technology (technique effect), and the upgrading of industrial structure (composition effect). Moreover, the impact reveals obvious heterogeneity, manifested as the BRI has significantly promoted the carbon intensity reduction of countries with high institutional quality, high-income countries, and countries along the Silk Road Economic Belt, while its impacts on countries with low institutional quality, low-income countries, and countries along the 21st Century Maritime Silk Road are not significant. A series of validity tests further demonstrate the robustness of the estimation.

7.
Cell Cycle ; : 1-17, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34974804

RESUMO

Intervertebral disc degeneration (IDD) constitutes the pathological foundation of most musculoskeletal disorders of the spine. Previous studies have noted that cell proliferation is a common feature of IDD. Bioinformatics indicated that aberrantly expressed long non-coding RNAs (lncRNAs) were involved in the development of IDD. In this study, we aimed to investigate the function of lncRNA HOTAIR in the proliferation of human nucleus pulposus (NP) cells of IDD in vitro and further clarified its mechanism. The expression of HOTAIR and miR-130b was quantified by qRT-PCR in nucleus pulposus (NP) tissues. Furthermore, NP cells proliferation were assayed by CCK8 and Immunostaining. Dual-luciferase reporter and RIP assay were used to examine the expression of HOTAIR, PTEN, and their co-target gene miR-130b. Western blotting was used to test AKT expression. Our in vitro experiments on human normal NP cells observed that HOTAIR was significantly dysregulated in IDD. Further, HOTAIR can suppress proliferation by directly targeting miR-130b. In addition, Both HOTAIR and PTEN were confirmed to target miR-130b, and miR-130b upregulation reversed the phenomenon of ectopic expression of HOTAIR. More importantly, HOTAIR upregulation significantly reduced CyclinD1 protein expression by PTEN/AKT signaling pathway. Our findings suggest that HOTAIR may bind to miR-130b and subsequently increased CyclinD1 expression via PTEN/Akt pathway. Thereby, HOTAIR could become a potential target for the treatment of IDD.

8.
J Hazard Mater ; 423(Pt A): 127011, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34461532

RESUMO

Residual pesticides in soil may be taken in by plants and thus have a risk for plant growth and food safety. In this study, uptake of triadimefon and its subsequent translocation and accumulation were investigated with wheat as model plants. The results from hydroponics indicated that triadimefon was absorbed by wheat roots mainly through apoplastic pathway and predominantly distributed into the water soluble fractions (66.7-76.0%). After being uptaken by roots, triadimefon was easily translocated upward to wheat shoots and leaves. Interestingly, triadimefon in leaves was mainly distributed in the soluble fraction by 52.5% at the beginning, and gradually transferred into the cell wall by 47.2% at equilibrium. The uptake of triadimefon from soils by wheat plants was similar to that in hydroponics. Its accumulation were mainly governed by adsorption of the fungicide onto soils, and positively correlated with its concentration in in situ pore water (CIPW). Thus, CIPW can be suitable for predicting the uptake of triadimefon by wheat from soils. Accordingly, uptake of triadimefon by wheat was predicted well by using the partition-limited model. Our study provides valuable information for guiding the practical application and safety evaluation of triadimefon.


Assuntos
Poluentes do Solo , Triticum , Hidroponia , Raízes de Plantas , Solo , Triazóis
9.
J Hazard Mater ; 426: 128127, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34953254

RESUMO

Globally distributed earthworms affect compositions of soil compounds, microbial community structures, as well as antibiotic resistance genes (ARGs). Compared to their surroundings, earthworm gut is a simpler environment which could filter out microbes when soil passes through it. However, little is known about how earthworms affect the dissemination of ARGs in soil, and the understanding of the relationship between microbe-microbe interactions and ARGs is still lacking. Here, we designed a microcosm experiment with earthworm addition, and determined bacterial and fungal community compositions based on amplicon sequencing. We also examined mobile genetic elements (MGEs) and ARGs in earthworm gut and soils using high-throughput qPCR. The results showed significant differences of bacterial, fungal and ARG patterns between gut and soil. Earthworms indirectly impacted the patterns of ARGs in soils by affecting bacterial communities and soil properties, which play key roles in the distribution of ARGs and MGEs. The absolute abundances of MGEs in earthworm gut were significantly lower than those in soils, and earthworms reduce the absolute abundance of MGEs in soils. Earthworms changed the microbial co-occurrence patterns, and reduced bacterial connectivity, which were significantly and positively correlated with MGE abundance. These results highlight the importance of earthworm on the distribution and dissemination of ARGs in soils.

10.
Exp Neurol ; 347: 113918, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34748756

RESUMO

In temporal lobe epilepsy (TLE), abnormal axon guidance and synapse formation lead to sprouting of mossy fibers in the hippocampus, which is one of the most consistent pathological findings in patients and animal models with TLE. Glypican 4 (Gpc4) belongs to the heparan sulfate proteoglycan family, which play an important role in axon guidance and excitatory synapse formation. However, the role of Gpc4 in the development of mossy fibers sprouting (MFS) and its underlying mechanism remain unknown. Using a pilocarpine-induced mice model of epilepsy, we showed that Gpc4 expression was significantly increased in the stratum granulosum of the dentate gyrus at 1 week after status epilepticus (SE). Using Gpc4 overexpression or Gpc4 shRNA lentivirus to regulate the Gpc4 level in the dentate gyrus, increased or decreased levels of netrin-1, SynI, PSD-95, and Timm score were observed in the dentate gyrus, indicating a crucial role of Gpc4 in modulating the development of functional MFS. The observed effects of Gpc4 on MFS were significantly antagonized when mice were treated with L-leucine or rapamycin, an agonist or antagonist of the mammalian target of rapamycin (mTOR) signal, respectively, demonstrating that mTOR pathway is an essential requirement for Gpc4-regulated MFS. Additionally, the attenuated spontaneous recurrent seizures (SRSs) were observed during chronic stage of the disease by suppressing the Gpc4 expression after SE. Altogether, our findings demonstrate a novel control of neuronal Gpc4 on the development of MFS through the mTOR pathway after pilocarpine-induced SE. Our results also strongly suggest that Gpc4 may serve as a promising target for antiepileptic studies.


Assuntos
Glipicanas/biossíntese , Fibras Musgosas Hipocampais/metabolismo , Pilocarpina/toxicidade , Transdução de Sinais/fisiologia , Estado Epiléptico/metabolismo , Serina-Treonina Quinases TOR/biossíntese , Animais , Células Cultivadas , Glipicanas/antagonistas & inibidores , Masculino , Camundongos , Fibras Musgosas Hipocampais/efeitos dos fármacos , Agonistas Muscarínicos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Estado Epiléptico/induzido quimicamente , Serina-Treonina Quinases TOR/antagonistas & inibidores
11.
World J Psychiatry ; 11(11): 1106-1115, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34888177

RESUMO

BACKGROUND: Studies have indicated that childhood exposure to domestic violence is a common factor in posttraumatic growth (PTG) and posttraumatic stress disorder (PTSD), but it is unclear whether PTG and PTSD share a common/different underlying mechanism. AIM: To explore the common/different underlying mechanism of PTG and PTSD. METHODS: Between February 12 and 17, 2020, a nationwide cross-sectional online survey was conducted in China among 2038 university students, and a self-administered questionnaire was used for the data collection. The data included demographic characteristics, such as age, gender, and subjective social economic status, and childhood exposure to domestic violence scale that was selected from the Chinese version of revised Adverse Childhood Experiences Question, Self-compassion Scale, Connor-Davidson Resilience Scale, Posttraumatic Growth Inventory, and the Abbreviated PTSD Checklist-Civilian version. A structural equation model was used to test the hypotheses. RESULTS: Exposure to domestic violence was significantly associated with PTG and PTSD via a 1-step indirect path of self-compassion (PTG: ß = -0.023, 95%CI: -0.44 to -0.007; PTSD: ß = 0.008, 95%CI: 0.002, 0.014) and via a 2-step indirect path from self-compassion to resilience (PTG: ß = -0.008, 95%CI: -0.018 to -0.002; PTSD: ß = 0.013, 95%CI: 0.004-0.024). However, resilience did not mediate the relationship between exposure to domestic violence and PTG and PTSD. CONCLUSION: PTG and PTSD are common results of childhood exposure to domestic violence, which may be influenced by self-compassion and resilience.

12.
Front Pharmacol ; 12: 753359, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867364

RESUMO

Combinations of two and more drugs with different target sites are being used as a new treatment regimen for resistant clones of bacteria. Though, achieving the right combination of the drugs for optimal dosage regimen is challenging. In our study, we studied the antimicrobial effect of aditoprim, a novel dihydrofolate reductase inhibitor, and its synergistic effect with sulfamethoxazole. Synergy testing was performed by checkerboard micro dilution method and validation of different checkerboard ratios by static and dynamic time-kill analysis and in vitro pharmacokinetic/pharmacodynamics (PK/PD) model, and semi mechanistic PK/PD modeling was used to calculate and validate the synergistic effect of drug combination. Both checkerboard and static time-kill assays demonstrated the greater synergistic effect [fractional inhibitory concentration index (FICI) = 0.37] of the aditoprim [minimum inhibitory concentration (MIC) = 0.25 µg/ml]-sulfamethoxazole (MIC=>64 µg/ml) combination against all T. Pyogenes isolates. In the in vitro PK/PD model, the dosage proportion of sulfamethoxazole 4 mg/ml twice a day in combination with steady-state aditoprim 1 mg/ml efficiently repressed the growth of bacteria in 24 h with the ratio of 2-log10 decrease, related to the early inoculum against three T. Pyogenes isolates. The semi mechanistic PK/PD model projected that a combination of a high dose of aditoprim (2 mg/ml) with sulfamethoxazole (2 mg/day) was necessary to attain the killing of bacteria below the detection limit (limit of detection (LOD); i.e., 1 log10 CFU/ml) at 24 h with an MIC sulfamethoxazole (SMZ) of 64 µg/ml. However, it is anticipated that a combination of high dose of aditoprim with sulfamethoxazole is critical to attain the suppressed bacterial growth to < LOD. This study represents essential PK/PD modeling for optimization of combination of aditoprim and sulfamethoxazole to suppress growth of T. Pyogenens.

13.
BMC Anesthesiol ; 21(1): 305, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861822

RESUMO

BACKGROUND: To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time following brimonidine administration was observed in mice, as was the analgesic activity of brimonidine. METHODS: The median effective dose (ED50) and lethal dose (LD50) of intraperitoneally injected brimonidine were determined in hypnotized mice. In addition, the LD50 of intravenously injected brimonidine, and ED50 of intravenously, intramuscularly, and intrarectally injected brimonidine in hypnotized rabbits were determined. Finally, the synergistic anesthetic effect of brimonidine and chloral hydrate was evaluated in rabbits. RESULTS: Intraperitoneal injection of 10 mg/kg brimonidine enhanced the hypnotic effect of a threshold dose of pentobarbital. Intraperitoneally injected brimonidine produced dose-related analgesic effects in mice. The ED50 of intraperitoneally administered brimonidine in hypnotized mice was 75.7 mg/kg and the LD50 was 379 mg/kg. ED50 values of intravenous, intramuscular, and intrarectal brimonidine for hypnosis in rabbits were 5.2 mg/kg, 8.8 mg/kg, and 8.7 mg/kg, respectively; the LD50 of intravenous brimonidine was 146 mg/kg. Combined intravenous administration of 0.6 mg/kg brimonidine and 0.03 g/kg chloral hydrate had a synergistic anesthetic effect. CONCLUSIONS: Brimonidine elicited hypnotic and analgesic effects after systemic administration and exhibited safety. Moreover, brimonidine enhanced the effects of other types of narcotics when combined.

14.
Ying Yong Sheng Tai Xue Bao ; 32(12): 4212-4222, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951262

RESUMO

There are abundant germplasm resources of drought resistant trees in China. It is difficult for foresters to evaluate and screen excellent germplasm that is suitable for various drought adverse circumstances. In this study, four tree species from different provenances, namely Amygdalus davi-diana, Prunus sibirica, Salix gordejevii, and Caryopteris mongolica, were used as test materials. Four soil regions, namely Dalad Banner, Siziwang Banner, Kouhezi town and Liujiazi town of Kulun Banner in the Central and Eastern Inner Mongolia Autonomous Region were selected as multi-point experiment sites to analyze the growth and physiological status of different tree species and provenances. The additive main effects and multiplicative interaction model was used to evaluate the regional adaptability and stability of the germplasm. The growth and physiological indices of four tree species differed between provenances and locations. Soil conditions (potassium content, nitrogen content, and pH) and climate conditions (annual average temperature, precipitation, and potential evaportranspiration) in different locations all influenced the growth of different provenance species. Concerning tree species, S. gordejevii and C. mongolica are more adapted to the sandy loam and chestnut soil of Dalad Banner and Siziwang Banner. A. davidiana and P. sibirica L. are more adapted to the loess and aeolian sandy soil of Kouhezi town and Liujiazi town. Concerning tree provenances, A. davidiana of Tuzuo, P. sibirica of Ningcheng and Yuanzhou, S. gordejevii of Lanqi, and C. mongolica of Jingbian displayed higher regional stability and better growth adaptability, indicating their suitability for afforestation in similar areas.


Assuntos
Secas , Árvores , Adaptação Fisiológica , China , Clima , Solo
15.
JCI Insight ; 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34905509

RESUMO

The anatomical routes for the clearance of cerebrospinal fluid (CSF) remain incompletely understood. However, recent evidence has given strong support for routes leading to lymphatic vessels. A current debate centers upon the routes through which CSF can access lymphatics, with evidence emerging for either direct routes to meningeal lymphatics or along cranial nerves to reach lymphatics outside the skull. Here, a method was established to infuse contrast agent into the ventricles using indwelling cannulae during imaging of mice at 2 and 12 months of age by magnetic resonance imaging. As expected, a significant decline in overall CSF turnover was found with aging. Quantifications demonstrated that the bulk of the contrast agent flowed from the ventricles to the subarachnoid space in the basal cisterns. Comparatively little contrast agent signal was found at the dorsal aspect of the skull. The imaging dynamics from the two cohorts revealed that the contrast agent cleared from the cranium through the cribriform plate to the nasopharyngeal lymphatics. On decalcified sections, we confirmed that fluorescentlylabeled ovalbumin drains through the cribriform plate and can be found within lymphatics surrounding the nasopharynx. In conclusion, routes leading to nasopharyngeal lymphatics appear to be a major efflux pathway for cranial CSF.

16.
Stem Cells Int ; 2021: 5513309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824587

RESUMO

Liver disease is a severe health problem that endangers human health worldwide. Mesenchymal stem cell (MSC) therapy is a novel treatment for patients with different liver diseases due to its vast expansion potential and distinctive immunomodulatory properties. Despite several preclinical trials having confirmed the considerable efficacy of MSC therapy in liver diseases, the questionable safety and efficacy still limit its application. As a precursor cell, MSCs can adjust their characteristics in response to the surrounding microenvironment. The microenvironment provides physical and chemical factors essential for stem cell survival, proliferation, and differentiation. However, the mechanisms are still not completely understood. We, therefore, summarized the mechanisms underlying the MSC immune response, especially the interaction between MSCs and the liver microenvironment, discussing how to achieve better therapeutic effects.

17.
J Mol Model ; 27(12): 363, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34825997

RESUMO

The study of the reaction between plutonium and nitrogen is helpful in further understanding the interaction between plutonium and air molecules. Currently, there is no research on the microscopic reaction mechanism of plutonium nitridation reactions. Therefore, the microscopic mechanism of the Pu with N2 gas phase reaction is explored in this study, based on density functional theory (DFT) using different basis functions. In this paper, the geometry of stationary points on the potential energy surface is optimized. In addition, the transition states are verified by frequency analysis and intrinsic reaction coordination (IRC). Finally, we obtained the reaction potential energy curve and micro reaction pathways. Analysis of the reaction mechanism shows that the reaction of Pu with N2 has two pathways. Pathway 1 (Pu + N2 → R1 → TS1 → PuN2) has a T-shaped transition state and pathway 2 (Pu + N2 → R2 → TS2 → PuN + N) has an L-shaped transition state. Both transition states have only one imaginary frequency. According to the comparison of the energy at each stagnation point along the two pathways, and the heat energy emitted by the two reaction paths, we found that pathway 1 is the main reaction pathway. The nature of Pu-N bonding evolution along the pathways was studied by atoms in molecules (AIM) and electron localization function (ELF) topological approaches. In order to analyze the role of the plutonium atom 5f orbital in the reaction, the variation in density state along the pathways was measured. Results show that the 5f orbital mainly contributes to the formation of Pu-N bonds, and the influence of temperature on the reaction rate is revealed by calculating the rate constants of the two reaction pathways.

18.
Regen Ther ; 18: 441-446, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34754889

RESUMO

Backgroud and study aims: Esophageal stricture is a serious adverse event occurring after circular endoscopic submucosal dissection (ESD) involving the whole esophagus. However, there is still a lack of effectively preventive methods. The main purpose of this study is to evaluate the efficacy of application of acellularized dermis matrix (ADM) for the prevention of post-ESD esophageal stricture. The main objective of this study was to evaluate the use of decellularized dermal matrix (ADM) in the prevention of post-esophageal ESD strictures. Patients and methods: A pilot, single-center, prospective study was conducted. The study enrolled seven patients who had high-risks with extended resection of developing post-ESD esophageal stricture. After undergoing ESD, we attached different size of ADM patches to the mucosal defects using titanium clips then fixed with a metal mesh stent. The stent covered with metal mesh was removed at the median time of 27 days after the endoscopic procedure. Follow-up and repeated outpatient endoscopic screening were performed at appropriate scheduled times. Results: The average longitudinal diameter of the resected specimens was 58.3 mm (range 38-90 mm). There were three patients developing strictures postoperatively at a mean time of 87 days (range 42-140). The median number of postoperative endoscopic balloon dilatation (EBD) in patients with stenosis was 2 (range 2-9). There were no deaths during a median follow-up period of 6 moths (range 1-12). Conclusions: This study was performed to assess the efficacy and safe method of relieving the severity of esophageal stricture after ESD through transplantation of ADM.

19.
Front Cell Dev Biol ; 9: 779123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805183

RESUMO

Background: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive B-cell non-Hodgkin lymphoma (B-NHL). While combined chemotherapy has improved the outcomes of DLBCL, it remains a highly detrimental disease. Pyroptosis, an inflammatory programmed cell death, is considered to have both tumor-promoting and tumor-suppressing effects. The role of pyroptosis in DLBCL has been gradually appreciated, but its value needs further investigation. Methods: We analyzed mutations and copy number variation (CNV) alterations of pyroptosis-related genes (PRGs) from The Cancer Genome Atlas (TCGA) cohort and evaluated the differences in expression in normal B cells and DLBCL patients in two Gene Expression Omnibus (GEO) datasets (GSE12195 and GSE56315). Based on the expression of 52 PRGs, we divided 421 DLBCL patients from the GSE31312 dataset into distinct clusters using consensus clustering. The Kaplan-Meier method was used to prognosis among the three clusters, and GSVA was used to explore differences in the biological functions. ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) were used to analyze the tumor immune microenvironment (TME) in different clusters. A risk score signature was developed using a univariate survival analysis and multivariate regression analysis, and the reliability and validity of the signature were verified. By combining the signature with clinical factors, a nomogram was established to predict the prognosis of DLBCL patients. The alluvial diagram and correlation matrix were used to explore the relationship between pyroptosis risk score, clinical features and TME. Results: A large proportion of PRGs are dysregulated in DLBCL and associated with the prognosis. We found three distinct pyroptosis-related clusters (cluster A, B, and C) that differed significantly with regard to the prognosis, biological process, clinical characteristics, chemotherapeutic drug sensitivity, and TME. Furthermore, we developed a risk score signature that effectively differentiates high and low-risk patients. The nomogram combining this signature with several clinical indicators showed an excellent ability to predict the prognosis of DCBCL patients. Conclusions: This work demonstrates that pyroptosis plays an important role in the diversity and complexity of the TME in DLBCL. The risk signature of pyroptosis is a promising predictive tool. A correct and comprehensive assessment of the mode of action of pyroptosis in individuals will help guide more effective treatment.

20.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5278-5283, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738430

RESUMO

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 µm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) µg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.


Assuntos
Diterpenos , Fenantrenos , Administração Cutânea , Sistemas de Liberação de Medicamentos , Compostos de Epóxi , Agulhas , Pele
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