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1.
Protein Expr Purif ; 189: 105978, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34562586

RESUMO

Urate oxidase is a promising biological medicine for hyperuricemia treatment, but immunogenicity obstructs the development of its clinical application. The recombinant porcine-human chimeric uricase mutant named dHU-wPU is a humanized chimeric uricase based on wild porcine uricase (wPU), which can effectively reduce the limitation of potential immunogenicity with a high homology (92.76%) to deduced human uricase (dHU). Unfortunately, the insoluble expression form of dHU-wPU in E. coli increases the difficulty of production. In this study, we described a more convenient method to efficiently obtain recombinant dHU-wPU protein from E. coli. Combination small ubiquitin-related modifier protein (SUMO) and maltose-binding protein (MBP) was employed to achieve the soluble expression of dHU-wPU. MBP-SUMO-dHU-wPU fusion protein was not only overexpressed in a soluble form, but also showed high purification and cleavage efficiency. Subsequently, we optimized the culture conditions of shake flasks and expanded the production of MBP-SUMO-dHU-wPU fusion protein in a 5 L bioreactor. Finally, about 15 mg of recombinant dHU-wPU was obtained from 1 L M9 fermentation culture by using two-step affinity chromatography, with a SDS-PAGE purity over 90%. In vitro activity analysis showed that dHU-wPU had better ability to catalyze uric acid than wPU.

2.
Glia ; 70(1): 106-122, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34498776

RESUMO

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory-inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD. Here, we report that increasing hippocampal astrogenesis during development induces autistic-like behavior in mice and a concurrent decreased E/I ratio in the hippocampus that results from enhanced GABAergic transmission in CA1 pyramidal neurons. Suppressing the aberrantly elevated GABAergic synaptic transmission in hippocampal CA1 area rescues autistic-like behavior and restores the E/I balance. Thus, we provide direct evidence for a developmental role of astrocytes in driving the behavioral phenotypes of ASD, and our results support that targeting the altered GABAergic neurotransmission may represent a promising therapeutic strategy for ASD.

3.
Talanta ; 237: 122896, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736712

RESUMO

Noroviruses are the leading cause of acute gastroenteritis and food-borne diseases worldwide. Thus, a rapid, accurate, and easy-to-implement detection method for controlling infection and monitoring progression is urgently needed. In this study, we constructed a novel sandwich-type electrochemical biosensor integrated with two specific recognition elements (aptamer and peptide) for human norovirus (HuNoV). The electrochemical biosensor was fabricated using magnetic covalent organic framework/pillararene heterosupramolecular nanocomposites (MB@Apt@WP5A@Au@COF@Fe3O4) as the signal probes. The sensor showed high accuracy and selectivity. The detection method does not need the extraction and amplification of virus nucleic acid and has a short turn-around time. Intriguingly, the proposed biosensor had a limit of detection of 0.84 copy mL-1 for HuNoV, which was the highest sensitivity among published assays. The proposed biosensor showed higher sensitivity and accuracy compared with immunochromatographic assay in the detection of 98 clinical specimens. The biosensor was capable of determining the predominant infection strain of GII.4 and also GII.3 and achieved 74% selectivity for HuNoV GII group. This study provides a potential method for point-of-care testing and highlights the integrated utilization of Apt and peptide in sensor construction.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Nanocompostos , Norovirus , Humanos , Imunoensaio
4.
Phytomedicine ; 94: 153805, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34749177

RESUMO

BACKGROUND: Shikonin is one of the major phytochemical components of Lithospermum erythrorhizon (Purple Cromwell), which is a type of medicinal herb broadly utilized in traditional Chinese medicine. It is well established that shikonin possesses remarkable therapeutic actions on various diseases, with the underlying mechanisms, pharmacokinetics and toxicological effects elusive. Also, the clinical trial and pharmaceutical study of shikonin remain to be comprehensively delineated. PURPOSE: The present review aimed to systematically summarize the updated knowledge regarding the therapeutic actions, pharmacokinetics, toxicological effects, clinical trial and pharmaceutical study of shikonin. METHODS: The information contained in this review article were retrieved from some authoritative databases including Web of Science, PubMed, Google scholar, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database and so on, till August 2021. RESULTS: Shikonin exerts multiple therapeutic efficacies, such as anti-inflammation, anti-cancer, cardiovascular protection, anti-microbiomes, analgesia, anti-obesity, brain protection, and so on, mainly by regulating the NF-κB, PI3K/Akt/MAPKs, Akt/mTOR, TGF-ß, GSK3ß, TLR4/Akt signaling pathways, NLRP3 inflammasome, reactive oxygen stress, Bax/Bcl-2, etc. In terms of pharmacokinetics, shikonin has an unfavorable oral bioavailability, 64.6% of the binding rate of plasma protein, and enhances some metabolic enzymes, particularly including cytochrome P450. In regard to the toxicological effects, shikonin may potentially cause nephrotoxicity and skin allergy. The above pharmacodynamics and pharmacokinetics of shikonin have been validated by few clinical trials. In addition, pharmaceutical innovation of shikonin with novel drug delivery system such as nanoparticles, liposomes, microemulsions, nanogel, cyclodextrin complexes, micelles and polymers are beneficial to the development of shikonin-based drugs. CONCLUSIONS: Shikonin is a promising phytochemical for drug candidates. Extensive and intensive explorations on shikonin are warranted to expedite the utilization of shikonin-based drugs in the clinical setting.

5.
Ultrasonics ; 119: 106632, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34717143

RESUMO

Since the temperature has a great effect on the service behavior of the ultrasonic motor, high temperature will affect its mechanical characteristics and service life. This article is on a model of a piezoelectric driven three-stator multi-degree-of-freedom ultrasonic motor. Firstly, the motion mechanism is analyzed, and the main causes of temperature rise are determined to be friction heat generation and vibration heat generation. Then, the theoretical model of temperature rise is built, and the temperature rise characteristics of the ultrasonic motor are simulated and analyzed by establishing a three-dimensional transient temperature field model. Finally, it is verified by temperature test experiment. The results show that the simulation analyses are consistent with the experimental results, and this analysis can correctly reflect the temperature rise characteristics of the motor. It provides a reference for further seeking the effect of the body temperature rise on the service behavior of the ultrasonic motor and improving the operating characteristics of the ultrasonic motor.

6.
Adv Radiat Oncol ; 7(1): 100812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34805621

RESUMO

Purpose: A modern radiation oncology electronic medical record (RO-EMR) system represents a sophisticated human-computer interface with the potential to reduce human driven errors and improve patient safety. As the RO-EMR becomes an integral part of clinical processes, it may be advantageous to analyze learning opportunities (LO) based on their relationship with the RO-EMR. This work reviews one institution's documented LO to: (1) study their relationship with the RO-EMR workflow, (2) identify best opportunities to improve RO-EMR workflow design, and (3) identify current RO-EMR workflow challenges. Methods and Materials: Internal LO reports for an 11-year contiguous period were categorized by their relationship to the RO-EMR. We also identify the specific components of the RO-EMR used or involved in each LO. Additionally, contributing factor categories from the ASTRO/AAPM sponsored Radiation Oncology Incident Learning System's (RO-ILS) nomenclature was used to characterize LO directly linked to the RO-EMR. Results: A total of 163 LO from the 11-year period were reviewed and analyzed. Most (77.2%) LO involved the RO-EMR in some way. The majority of the LO were the results of human/manual operations. The most common RO-EMR components involved in the studied LO were documentation related to patient setup, treatment session schedule functionality, RO-EMR used as a communication/note-delivery tool, and issues with treatment accessories. Most of the LO had staff lack of attention and policy not followed as 2 of the highest occurring contributing factors. Conclusions: We found that the majority of LO were related to RO-EMR workflow processes. The high-risk areas were related to manual data entry or manual treatment execution. An evaluation of LO as a function of their relationship with the RO-EMR allowed for opportunities for improvement. In addition to regular radiation oncology quality improvement review and policy update, automated functions in RO-EMR remain highly desirable.

7.
J Affect Disord ; 296: 408-417, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34638025

RESUMO

BACKGROUND: Studies show that disturbances of the fronto-striato-thalamic-cerebellar circuit could be correlated to facial emotion processing (FEP) biases in major depressive disorder (MDD). Nevertheless, the underlying mechanism of natural metabolism-emotion relationships in adolescent MDD remains unclear. METHODS: Thirty-seven adolescent patients with MDD and 30 healthy controls completed FEP tasks using the Chinese Facial Affective Picture System (CAFPS). Proton magnetic resonance spectroscopy (1H-MRS) was also used to obtain ratios of N-acetylaspartate (NAA) /creatine (Cr) and choline (Cho) /Cr ratios in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), putamen, thalamus and cerebellum. Correlations between abnormal neurometabolic ratios and FEP were also computed. RESULTS: Compared with the control group, the MDD group had significantly lower accuracy and perception intensity of happiness, and significantly higher accuracy of disgust and perception intensity of sad and fearful faces in FEP tasks. Compared to healthy controls, adolescent patients with MDD showed significantly lower NAA/Cr ratios in the left PFC, higher NAA/Cr ratios in the right thalamus, and higher Cho/Cr ratios in the right putamen, although there were no significant differences in metabolites in the ACC and cerebellum between two groups. In the MDD group, NAA/Cr ratios of the right thalamus were negatively correlated with happy reaction time and positively correlated with sad, anger, and fear intensity; Cho/Cr ratios in the right putamen were positively correlated with fear reaction time. CONCLUSIONS: Our findings suggest that FEP bias may exist in adolescents with MDD, while the impairment of FEP may be associated with abnormal metabolites in the fronto-striato-thalamic circuit.

8.
Chemosphere ; 287(Pt 1): 131946, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34438212

RESUMO

The degradation reactions of propylamino and dipropylamino radicals in the presence of NO, NO2 and O2 were investigated at the CCSD(T)/6-311++G (2d, 2p)//B3LYP/6-311++G (d,p) levels of theory. Result indicates that nitrosamines, nitramines, nitroso-oxy compounds and imines can be formed at atmosphere. Time dependent density functional theory (TDDFT) calculation shows that nitrosamines and nitroso-oxy compounds can photolyze under sunlight, while nitramines cannot undergo photolysis in the daytime. Moreover, the ecotoxicity assessment result implies that the degradation of propyl-substituted amines by OH radicals, NO and NO2 will reduce their toxicity to fish, daphnia and green algae in the aquatic environment.


Assuntos
Dióxido de Nitrogênio , Nitrosaminas , Aminas , Animais , Atmosfera , Fotólise
9.
Chemosphere ; 287(Pt 1): 132061, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34523448

RESUMO

The photo-Fenton system exhibits great potential in environmental remediation. However, photo-Fenton process suffers from slow reaction kinetics, which is caused by the low yield of available charge carriers and active radicals. In this work, the 2D/2D FeNi-layered double hydroxide/bimetal-organic frameworks nanosheets (FeNi-LDH/BMNSs) photocatalyst was fabricated via an in-situ semi-sacrificial template strategy. The optimized FeNi-LDH/BMNSs + H2O2+Vis system showed excellent tetracycline hydrochloride (TC-HCl) removal rate of 95.76% in 60 min. Besides, the high TC-HCl degradation rates (above 80%) are obtained in a wide pH range and the total organic carbon (TOC) removal rate of 48.98% was remained after four cycles. Experiments and characterizations identified the fast catalysis process were ascribed to the synergetic effect between 2D/2D heterojunctions and Lewis acid sites with mixed-valence (Fe (III)/Ni (II)) in FeNi-LDH/BMNSs. As a result, the catalysis of H2O2 and the reduction of O2 was accelerated by the continuous generation of Fe (II) and available photogenerated electrons, respectively, producing abundant active radicals including OH and O2-. Finally, this photo-Fenton system exhibited high removal rate to oxycycline, levofloxacin, norfloxacin and doxycycline and showed excellent performance for TC-HCl removal in different composed wastewater. The findings provide a new strategy towards creating 2D/2D active heterogeneous catalysts for photo-Fenton catalytic application.


Assuntos
Antibacterianos , Peróxido de Hidrogênio , Catálise , Hidróxidos , Tetraciclina
10.
Cereb Cortex ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34849643

RESUMO

Previous studies on dual-brain social interaction have shown different patterns of interpersonal neural synchronization (INS) between conflictual and supportive interactions, but the role of emotion in the dual-brain mechanisms of such interactions is not well understood. Furthermore, little is known about how the dual-brain mechanisms are affected by relationship type (e.g., romantic relationship vs. friendship) and interaction mode (e.g., verbal vs. nonverbal). To elaborate on these issues, this study used functional near-infrared spectroscopy to collect hemodynamic signals from romantic couples and cross-sex friends while they were discussing conflictual, neutral, or supportive topics. For the couples but not the friends, INS between the sensorimotor cortex of both participants was greater when discussing the conflictual topic than when discussing the supportive topic. INS was positively correlated with the arousal level but not the valence level of communication contents. INS was also positively correlated with interpersonal physiological synchronization based on galvanic skin response, a physiological measure of arousal. Furthermore, the differences in INS between the conflictual and supportive topics were closely associated with verbal rather than nonverbal behaviors. Together, these findings suggest that it is the arousal level induced by verbal interactions during interpersonal conflicts that increases romantic couples' INS.

11.
Front Pharmacol ; 12: 675350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737693

RESUMO

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.

12.
Front Pharmacol ; 12: 739749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744722

RESUMO

Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH). Methods: A total of 356 patients with pregnancy-induced hypertension (PIH) were randomly divided into three groups: DXM, TMD and DXM + TMD groups. These patients were treated with different doses of DXM, TMD or combination of DXM and TMD by a patient-controlled intravenous injection device. The scores of static pain and dynamic pain, sedation degree, and adverse reaction were recorded. The plasma levels of inflammatory mediators IL-10 and C-reactive protein (CRP), and the serum level of p-p38-MAPK were evaluated. Results: It was found that administration with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg result in stronger sedative effect than single administration with DXM or TMD. The mean arterial pressure (MAP) and heart rate (HR) of patients with PIH were decreased with the combinational treatment of DXM and TMD. Interestingly, the PIH patients injected with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg showed stronger sedative effect. In addition, the plasma level of level of IL-10 was increased and CRP decreased. The serum level of p-p38/MAPK was decreased. Conclusion: Taken together, our study indicates that combination of DXM and TMD effectively lowers blood pressure and reduces inflammation through increasing the level of IL-10, reducing CRP and inhibiting p-p38/MAPK in patients with PIH. This study suggests that the combination of DXM and TMD could be an anesthetic choice in the management of PIH.

13.
Oral Dis ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741375

RESUMO

OBJECTIVE: Cancer-associated fibroblasts (CAFs) are abundantly infiltrated in oral squamous cell carcinoma (OSCC), but the contact-dependent mechanisms that regulate CAFs phenotype in precursor cells, such as paracancerous fibroblasts (PFs), remain unclear. Here, a fibroblast-attached organoid (FAO) model was initiated to determine phenotype transition of fibroblasts triggered by contact with OSCC. MATERIAL AND METHODS: Organoids and fibroblasts were generated using OSCC and adjacent tissues. Cell-clusters containing fibroblasts and tumour cells were aggregated to allow for FAOs expansion. Immunoblotting assay was performed to compare expression of Notch intracellular domain (NICD) in CAFs and PFs. Colony formation assay was employed to evaluate morphological activation of fibroblasts. RESULTS: Compared to traditional 3D co-culture, FAOs better modulated the spatial distribution of fibroblasts with tumour nests. The presence of CAFs with multiple branches was stably observed in FAOs during serial passage. Incorporation with organoids promoted the ability of PFs to form multiple branches. Immunoblotting assay confirmed higher NICD level in CAFs than PFs. Treatment with Notch inhibitor, N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (i.e. DAPT) blocked morphological activation of fibroblasts incorporated into FAO. CONCLUSION: We developed a robust strategy to study contact-dependent mechanisms underlying tumour-stromal interaction, and suggested that Notch activity contributes to biogenesis of OSCC-associated fibroblasts.

14.
PeerJ ; 9: e12337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760365

RESUMO

The jack mackerel (Trachurus japonicus) is both a dominant pelagic fish species and an important fishing target in the Beibu Gulf, South China Sea. However, the resource status of this species fluctuates dramatically, and it has recently been added to a "red list" of threatened species of the International Union for Conservation of Nature (IUCN). Despite its economic importance and decreasing population status, limited research on its spatiotemporal distribution has been undertaken over the last decades. In order to evaluate the most crucial factors that influence the spatiotemporal variability of T. japonicus and to determine GAM performance and predictability, we analyze catch per unit effort (CPUE) of T. japonicus from Beibu Gulf over four seasons (months) from 2013 to 2014. A generalized additive model (GAMs) is populated with water depth and remotely sensed sea surface temperature (SST), sea surface salinity (SSS), sea surface chlorophyll-a concentration (Chl-a) and sea level anomaly (SLA). The CPUE of T. japonicus varies seasonally, with higher CPUE in summer and autumn than in spring and winter, and the highest CPUE in summer. GAM results explain 57% of the deviation explained in CPUE, with the most important variables being SLA, Month, Depth, SSS, and SST , each explaining 21.2%, 18.7%, 10.7%, 5.1%, and 1.3% of the variation in CPUE, respectively. This species occurs mainly between 50 and 75 m depth, SSS values 32.3-33.5 PSU and SST 25-30.5 °C. High CPUE sites occur near SLA ≤ 0 m, on the edge of cold eddies, and there is a certain catch near the sea surface with SLA ≥ 0 m. The spatial and temporal distribution of T. japonicus is affected by the season and the marine hydrological environment. This study might contribute to a better understanding of the distributional patterns of T. japonicus as well as provide a basis for sustainable management in the Beibu Gulf.

15.
Chem Commun (Camb) ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766614

RESUMO

Two functionalized pillar[5]arenes (H1 and H2) with significant AIE properties were synthesized. H2 is an excellent probe to selectively detect specific alkanediamines owing to its multiple binding sites, which result in the enhancement of emission based on the AIE mechanism and the induced-fit mechanism, and provides a new strategy to develop probes with high selectivity and sensitivity.

16.
Front Oncol ; 11: 785394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722323

RESUMO

[This corrects the article DOI: 10.3389/fonc.2021.650173.].

17.
Front Pharmacol ; 12: 657047, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759816

RESUMO

Background: Cyclophosphamide is a common tumor chemotherapy drug used to treat various cancers. However, the resulting immunosuppression leads to leukopenia, which is a serious limiting factor in clinical application. Therefore, the introduction of immunomodulators as adjuvant therapy may help to reduce the hematological side effects of cyclophosphamide. Lvjiaobuxue granule has been widely used in the clinical treatment of gynecological diseases such as anemia and irregular menstruation. Recently, it has been found to increase the function of white blood cells, but its mechanism of action is still unclear. We aimed to reveal the mechanisms of Lvjiaobuxue granule against acute leukopenia by an integrated strategy combining metabolomics with network pharmacology. Methods: Subcutaneously inoculated 4T1 breast cancer cells to prepare tumor-bearing mice, intraperitoneal injection of cyclophosphamide to establish a 4T1 tumor-bearing mice leukopenia animal model, using pharmacodynamic indicators, metabolomics, network pharmacology and molecular biology and other technical methods. To comprehensively and systematically elucidate the effect and mechanism of Lvjiaobuxue granule in improving cyclophosphamide-induced leukopenia in 4T1 tumor-bearing mice. Results: Lvjiaobuxue granule can improve the blood routine parameters and organ index levels of the leukopenia model of 4T1 tumor-bearing mice. Metabolomics studies revealed that 15 endogenous metabolites in the spleen of mice were considered as potential biomarkers of Lvjiaobuxue granule for their protective effect. Metabonomics and network pharmacology integrated analysis indicated that Lvjiaobuxue granule exerted the leukocyte elevation activity by inhibiting the branched-chain amino acids (BCAAs) degradation pathway and increasing the levels of valine, leucine and isoleucine. The results of molecular biology also showed that Lvjiaobuxue granule can significantly regulate the key enzymes in the catabolism of BCAAs, which further illustrates the importance of BCAAs in improving leukopenia. Conclusion: Lvjiaobuxue granule exerts obvious pharmacological effects on the leukopenia model of 4T1 tumor-bearing mice induced by cyclophosphamide, which could be mediated by regulating the branched-chain amino acid degradation pathway and the levels of valine, leucine and isoleucine.

18.
Toxicol Res (Camb) ; 10(5): 1013-1021, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34733486

RESUMO

Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO4-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO4-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO4 toxicity by acting as a sponge for the miR-663b through JAK-STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.

19.
BMC Pulm Med ; 21(1): 367, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34775948

RESUMO

BACKGROUND: Hypoxemia frequently occurs during bronchoscopy. High-flow nasal cannula (HFNC) oxygen therapy may be a feasible alternative to prevent the deterioration of gas exchange during bronchoscopy. With the convenience of clinical use in mind, we modified an HFNC using a single cannula. This clinical trial was designed to test the hypothesis that a modified HFNC would decrease the proportion of patients with a single moment of peripheral arterial oxygen saturation (SpO2) < 90% during bronchoscopy. METHODS: In this single-center, prospective randomized controlled trial, hospitalized patients in the respiratory department in need of diagnostic bronchoscopy were randomly assigned to a modified HFNC oxygen therapy group or a conventional oxygen therapy (COT) group. The primary outcome was the proportion of patients with a single moment of SpO2 < 90% during bronchoscopy. RESULTS: Eight hundred and twelve patients were randomized to the modified HFNC (n = 406) or COT (n = 406) group. Twenty-four patients were unable to cooperate or comply with bronchoscopy. Thus, 788 patients were included in the analysis. The proportion of patients with a single moment of SpO2 < 90% during bronchoscopy in the modified HFNC group was significantly lower than that in the COT group (12.5% vs. 28.8%, p < 0.001). There were no significant differences in the fraction of inspired oxygen between the two groups. The lowest SpO2 during bronchoscopy and 5 min after bronchoscopy in the modified HFNC group was significantly higher than that in the COT group. Multivariate analysis showed that a baseline forced vital capacity (FVC) < 2.7 L (OR, 0.276; 95% CI, 0.083-0.919, p = 0.036) and a volume of fluid instilled > 60 ml (OR, 1.034; 95% CI, 1.002-1.067, p = 0.036) were independent risk factors for hypoxemia during bronchoscopy in the modified HFNC group. CONCLUSIONS: A modified HFNC could decrease the proportion of patients with a single moment of SpO2 < 90% during bronchoscopy. A lower baseline FVC and large-volume bronchoalveolar lavage may predict desaturation during bronchoscopy when using a modified HFNC. Trial registration ClinicalTrials. Gov: NCT02606188. Registered 17 November 2015.

20.
Int J Gen Med ; 14: 7925-7931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795510

RESUMO

Purpose: There are limited clinical studies aimed at solving the problem of the efficiency of conventional treatment with oral phosphate and calcitriol in adults with hypophosphatemic osteomalacia (HO). In addition, there still had no good non-hazardous markers to evaluate the severity of bone loss of osteomalacia before and after treatment. Therefore, the purpose of this study was to assess the efficacy of conventional treatment with a self-blended phosphate supplementation and calcitriol on patients with HO and whether bone mineral density (BMD) can be helpful for monitoring the efficacy. Patients and Methods: A total of 21 HO patients and 105 healthy controls were enrolled. All patients were tested for serum biomarkers and BMD of the lumbar spine (L1-L4), femoral neck, and total left hip. After three years of treatment, 11 of 21 HO patients were recalled for BMD measurement. According to the administration of drugs, HO patients with calcium and calcitriol were divided into three phosphate treatment groups: patients in group A (n = 3) received continuous phosphate supplementation, patients in group B (n = 5) received intermittent phosphate supplementation and patients in group C (n = 3) received no phosphate supplementation. Results: The diagnoses of 21 HO patients were 5 cases of hereditary hypophosphatemic rickets, 4 cases of Fanconi syndrome with the features of renal tubular acidosis and vitamin D deficiency, and 12 cases of hereditary vitamin D abnormality. The average initial serum phosphorus level of the patient group was approximately 50% lower than that of the control group. Lower BMD was significantly observed in the HO group than the control group at the lumbar spine and total hip. Continuous treatment with the phosphate supplement could increase BMD in the lumbar spine and total hip by 33.4-52.3% and in the femoral neck increased by 43.2-79.3% compared with baseline, and the effect appears to be continued once treatment is discontinued. Conclusion: These findings suggest that conventional therapy can improve bone mineral defects in patients with HO, especially in the femoral neck. Detection of BMD in HO patients is a good tool to assess the extent of bone defects and the therapeutic effect. Trial Registration: Chinese Clinical Trial Registry, ChiCTR-OOC-16010095. Registered 7 December 2016. Retrospectively registered.

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