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1.
J Virol ; : e0073824, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940585

RESUMO

Recently, substantial evidence has demonstrated that pseudogene-derived long noncoding RNAs (lncRNAs) as regulatory RNAs have been implicated in basic physiological processes and disease development through multiple modes of functional interaction with DNA, RNA, and proteins. Here, we report an important role for GBP1P1, the pseudogene of guanylate-binding protein 1, in regulating influenza A virus (IAV) replication in A549 cells. GBP1P1 was dramatically upregulated after IAV infection, which is controlled by JAK/STAT signaling. Functionally, ectopic expression of GBP1P1 in A549 cells resulted in significant suppression of IAV replication. Conversely, silencing GBP1P1 facilitated IAV replication and virus production, suggesting that GBP1P1 is one of the interferon-inducible antiviral effectors. Mechanistically, GBP1P1 is localized in the cytoplasm and functions as a sponge to trap DHX9 (DExH-box helicase 9), which subsequently restricts IAV replication. Together, these studies demonstrate that GBP1P1 plays an important role in antagonizing IAV replication.IMPORTANCELong noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as regulators in various biological processes. A growing body of evidence suggests that host-encoded lncRNAs are important regulators involved in host-virus interactions. Here, we define a novel function of GBP1P1 as a decoy to compete with viral mRNAs for DHX9 binding. We demonstrate that GBP1P1 induction by IAV is mediated by JAK/STAT activation. In addition, GBP1P1 has the ability to inhibit IAV replication. Importantly, we reveal that GBP1P1 acts as a decoy to bind and titrate DHX9 away from viral mRNAs, thereby attenuating virus production. This study provides new insight into the role of a previously uncharacterized GBP1P1, a pseudogene-derived lncRNA, in the host antiviral process and a further understanding of the complex GBP network.

2.
J Virol ; : e0060624, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38809020

RESUMO

Rabies virus (RABV) is highly lethal and triggers severe neurological symptoms. The neuropathogenic mechanism remains poorly understood. Ras-related C3 botulinum toxin substrate 1 (Rac1) is a Rho-GTPase that is involved in actin remodeling and has been reported to be closely associated with neuronal dysfunction. In this study, by means of a combination of pharmacological inhibitors, small interfering RNA, and specific dominant-negatives, we characterize the crucial roles of dynamic actin and the regulatory function of Rac1 in RABV infection, dominantly in the viral entry phase. The data show that the RABV phosphoprotein interacts with Rac1. RABV phosphoprotein suppress Rac1 activity and impedes downstream Pak1-Limk1-Cofilin1 signaling, leading to the disruption of F-actin-based structure formation. In early viral infection, the EGFR-Rac1-signaling pathway undergoes a biphasic change, which is first upregulated and subsequently downregulated, corresponding to the RABV entry-induced remodeling pattern of F-actin. Taken together, our findings demonstrate for the first time the role played by the Rac1 signaling pathway in RABV infection and may provide a clue for an explanation for the etiology of rabies neurological pathogenesis.IMPORTANCEThough neuronal dysfunction is predominant in fatal rabies, the detailed mechanism by which rabies virus (RABV) infection causes neurological symptoms remains in question. The actin cytoskeleton is involved in numerous viruses infection and plays a crucial role in maintaining neurological function. The cytoskeletal disruption is closely associated with abnormal nervous symptoms and induces neurogenic diseases. In this study, we show that RABV infection led to the rearrangement of the cytoskeleton as well as the biphasic kinetics of the Rac1 signal transduction. These results help elucidate the mechanism that causes the aberrant neuronal processes by RABV infection and may shed light on therapeutic development aimed at ameliorating neurological disorders.

3.
Nano Lett ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935481

RESUMO

Developing ultrasensitive lateral flow immunoassays (LFIAs) has garnered significant attention in the field of point-of-care testing. In this study, a trimetallic dendritic nanozyme (Pd@Pt-Ru) was synthesized through Ru deposition on a Pd@Pt core and utilized to enhancing the sensitivity of LFIAs. Pd@Pt-Ru exhibited a Km value of 5.23 mM for detecting H2O2, which indicates an H2O2 affinity comparable with that of horseradish peroxidase. The Ru surface layer reduces the activation energy barrier, which increases the maximum reaction rate. As a proof of concept, the proposed Pd@Pt-Ru nanozyme was incorporated into LFIAs (A-Pd@Pt-Ru-LFIAs) for detecting human chorionic gonadotropin (hCG). Compared with conventional gold nanoparticle (AuNP)-LFIAs, A-Pd@Pt-Ru-LFIAs demonstrated 250-fold increased sensitivity, thereby enabling a visible detection limit as low as 0.1 IU/L. True positive and negative rates both reached 100%, which renders the proposed Pd@Pt-Ru nanozyme suitable for detecting hCG in clinical samples.

4.
Ann Hematol ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691144

RESUMO

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.

5.
Langmuir ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326982

RESUMO

In this work, the interaction performance of zwitterionic surfactant [dodecyl dimethyl sulfopropyl betaine (DSB-12) and hexadecyl dimethyl sulfopropyl betaine (DSB-16)] at the n-octadecane oil surface is investigated from experimental and simulation insights. For a macroscopic experiment, interfacial interferometry technology was developed for real-time monitor interaction performances and to obtain the quantitative interfacial thickness and mass results. The Langmuir model was characterized by thermodynamic analysis, deducing the aggregation spontaneity of DSB-16 > DSB-12 with ΔGagg(DSB-16) = -5.94 kJ mol-1 < ΔGagg(DSB-12) = 24.08 kJ mol-1. A three-step dynamic model (adsorption, arrangement, and aggregation) was characterized by kinetic analysis, indicating arrangement process as slow-limiting step with k2(arr) < k1(ads), k3(agg). For microscopic simulation, and molecular dynamic (MD) method was utilized to theoretically investigate interaction performances and obtain the interfacial configuration and energy results. The interaction stability and interaction strength were indicated to be DSB-16 > DSB-12 with differences of final energy ΔEfin = 48-88 kcal mol-1. The interaction mechanism was explained by proposing the model of "response enhancement" and "deposition activity" for DSB-16 interactions, and "response decrease" and "elution activity" for DSB-12 interactions. The different performances can be attributed to the different interaction forms and forces of surfactants. This work provided a platform for performance and mechanism investigation between the surfactant molecule and oil surface, which is of great significance in reservoir exploitation and enhanced oil recovery (EOR).

6.
Scand J Gastroenterol ; 59(1): 39-45, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37622924

RESUMO

BACKGROUND: Few studies have compared endoscopic balloon dilation (EBD) and surgery in the treatment of duodenal stricture in patients with Crohn's disease (CD). METHODS: We performed a retrospective study to compare the efficacy and safety among patients with CD-associated duodenal stricture treated with EBD or surgery from October 2013 to December 2021. Univariate and multivariate analyses were performed to evaluate factors associated with recurrence-free or surgery-free survival. RESULTS: A total of 48 eligible patients were included, including 30 patients treated with EBD only and 18 patients treated with surgery. Patients treated with surgery experienced more symptomatic improvement (100% vs. 63.33%, p = 0.003) and significantly longer recurrence-free survival (6.31 [IQR: 3.00-8.39] years vs. 2.96 [IQR: 1.06-5.42] years, p = 0.01) but suffered more postprocedural adverse events (16.67% vs. 0.74% per procedure, p = 0.001). In patients initially treated with EBD (n = 41), a total of 11 (26.83%) required subsequent surgical intervention. Younger age at CD diagnosis (HR = 0.90, 95% CI: 0.81-1.00, p = 0.04) was associated with a higher risk for subsequent surgery. CONCLUSIONS: Surgery for CD-associated duodenal strictures was associated with a longer recurrence-free survival. EBD was safe and effective with minimal postprocedural adverse events but led to a high frequency of recurrence.


Assuntos
Doença de Crohn , Obstrução Intestinal , Humanos , Doença de Crohn/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Estudos Retrospectivos , Dilatação/efeitos adversos , Obstrução Intestinal/etiologia , Resultado do Tratamento , Endoscopia Gastrointestinal/métodos
7.
J Vet Pharmacol Ther ; 47(2): 114-120, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37950414

RESUMO

This study aimed to examine the depletion of tilmicosin residues in Gushi chickens following the administration at a concentration of 75 mg/L in their drinking water for three consecutive days. Plasma, liver, kidney, lung, muscle, and skin + fat samples were collected from 6 chickens at 6 h, 1, 3, 5, and 7 days after the treatment. Tilmicosin concentrations in the samples were determined using a high-performance liquid chromatography (HPLC) method. The findings revealed that the highest tilmicosin residues were detected in the liver, followed by the kidney, lung, skin + fat, muscle, and plasma. Notably, at 7 days post-treatment, no drug residue was detected in all samples except for the liver and kidney. The non-compartmental model was employed to calculate relevant pharmacokinetic parameters. The elimination half-lives (t1/2λz ) of tilmicosin were as follows, ranked from long to short: skin + fat (45.42 h), liver (44.17 h), kidney (40.06 h), plasma (37.64 h), lung (31.39 h), and muscle (30.05 h). Considering the current residue depletion and the maximum residue limits (MRLs) set by Chinese regulatory authorities, the withdrawal times for tilmicosin were estimated as 18.91, 10.81, and 8.58 days in the kidney, liver, and skin + fat, respectively. A rounded-up value of 19 days was selected as the conclusive withdrawal time. Furthermore, based on the observed tilmicosin concentrations in plasma and lung, combined with previously reported minimum inhibitory concentration (MIC) values against Mycoplasma gallisepticum, the current dosing regimen was deemed adequate for treating Mycoplasma gallisepticum infections in Gushi chickens.


Assuntos
Antibacterianos , Água Potável , Tilosina/análogos & derivados , Animais , Galinhas , Administração Oral
8.
Surg Innov ; 31(2): 157-166, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38339842

RESUMO

BACKGROUND: Prophylactic intraoperative drains have been shown not superior for patients underwent intestinal surgery. However, for patients with Crohn's disease (CD), this needs further exploration. METHODS: In this pilot study, CD patients were randomly assigned to drain (n = 50) and no-drain (n = 50) groups. The primary endpoint was the rate of postoperative prolonged ileus (PPOI). The secondary endpoints were postoperative abdominal ascites, postoperative systemic inflammatory response syndrome (SIRS) and C-reactive protein (CRP) levels. RESULTS: The incidences of PPOI and postoperative abdominal ascites were significantly lower in the drain group (12% vs 44%; 0% vs 24%, both P < .05). Postoperative SIRS incidence and CRP levels were significantly increased in the no-drain group [36% vs 10%; 54.9 vs 34.3 mg/L, both P < .05]. In multivariate analysis, prophylactic drainage was the independent protective factor for PPOI and postoperative LOS. CONCLUSIONS: Prophylactic drainage may be associated with improved clinical outcomes in CD patients.


Assuntos
Ascite , Doença de Crohn , Humanos , Ascite/complicações , Doença de Crohn/cirurgia , Doença de Crohn/complicações , Projetos Piloto , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Drenagem , Síndrome de Resposta Inflamatória Sistêmica/complicações
9.
Small ; 19(46): e2303678, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37475508

RESUMO

Photosensitive materials, such as energetic complexes, usually have high sensitivity and cause heavy-metal pollution, whereas others, like carbon black and dye, do not contain energy, which affects energy output and mechanical properties. In this work, donor-acceptor π-conjugated energetic catalysts, denoted as D-n, are designed and synthesized. Nonmetallic hybrid energetic composites are prepared by assembling the as-synthesized catalysts into multiscale ammonium perchlorate (AP). Composites containing catalysts and APs can be successfully ignited without the involvement of metals. The new ignition mechanism is further analyzed using experimental and theoretical analyses such as UV-vis-near-infrared (NIR) spectra, electron-spin resonance spectroscopy, and energy-gap analysis. The shortest ignition delay time is 56 ms under the experimental condition of a NIR wavelength of 1064 nm and a laser power of 10 W. At the voltage of 1 kV and the electric field of 500 V mm-1 , the laser-ignition delay time of D-2/AP hybrid composite decreases from 56 to 35 ms because D-2 also exhibits organic semiconductor-like properties. D-2/AP and D-12/AP can also be used to successfully laser ignite other common energetic materials. This study can guide the development of advanced metal-free laser-ignitable energetic composites to address challenges in the field of aerospace engineering.

10.
Langmuir ; 39(4): 1694-1708, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36649094

RESUMO

Experiment evaluation and mechanism analysis of separation performance are crucial for oily wastewater treatment. In this work, a fluorinated superhydrophobic/superoleophilic (F-SHPB/SOPL) surface was fabricated on a steel mesh substrate by double depositions of SiO2-TiO2 nanoparticles for high-roughness improvement and composite modification of fluorine-alkyl groups for low-energy achievement. Measurements of SEM, XPS, FTIR, laser scanning confocal microscope (LSCM), and excitation-emission matrix (EEM) were carried out for surface property characterization. The oil-water separation performances at the prepared F-SHPB/SOPL surface were investigated from experimental and simulation aspects. Separation tests, flux tests, and anti-contamination tests were performed by experimental methods. The results indicated that the surface showed excellent separation efficiencies (>99.2%) for oil-water mixture and oil-in-water emulsion, high permeate flux (>3000 L·m-2·h-1) for organic oils, and perfect anti-pollution/self-cleaning capacity for liquid and solid contaminations. The interaction energies and interaction distances were measured by ab initio molecular dynamics simulation (AIMD) simulations. With lower interaction energy (Eoil = -456.52∼-1044.22 eV) than that of water molecules (Ewater = -172.73 eV) and shorter distance (Doil = 4.42∼5.13 Å) than that of water molecules (Dwater = 11.49 Å), oil molecules showed higher interaction stability than water molecules on the F-SHPB/SOPL surface. The calculation revealed the essence of the oil-water separation phenomenon. This work not only proposes the fabrication methodology of the SHPB/SOPL material but also elucidates the intermolecular interaction for oil-water separation. The results can provide a fundamental basis for separation operation and removal treatment in industrial and domestic applications.

11.
Dis Colon Rectum ; 66(1): e4-e9, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36515520

RESUMO

BACKGROUND: Anastomotic recurrence after bowel resection is problematic in patients with Crohn's disease. Antimesenteric functional end-to-end handsewn (Kono-S) anastomosis is associated with a low risk of anastomotic recurrence in patients with Crohn's disease. IMPACT OF INNOVATION: Kono-S anastomosis is effective but may be time-consuming. This study aimed to describe stapled antimesenteric functional end-to-end anastomosis for patients with Crohn's disease. TECHNOLOGY MATERIALS AND METHODS: The mesentery of the affected bowel segment was divided. A 5-cm-wide stapled functional end-to-end anastomosis was performed approximately 6 cm from the affected segment. The bowel was divided transversely exactly 90° to the intestinal lumen and the mesentery, and a supporting column was then constructed. PRELIMINARY RESULTS: From January 2018 to June 2021, 17 stapled antimesenteric functional end-to-end anastomoses were performed. The mean operative time was 106 (range, 80-135) minutes, and the time to construct the stapled antimesenteric functional end-to-end anastomosis was 21 (range, 18-28) minutes. The mean follow-up time was 8.9 (range, 1-15) months. In total, 10 patients underwent surveillance endoscopy. The average Rutgeerts score was 0.8 (range, 0-4), and the incidence of endoscopic recurrence was 11.8%. No postoperative mortality or anastomotic leakage was observed. CONCLUSION: Stapled antimesenteric functional end-to-end anastomosis may be a safe and time-saving procedure for patients with Crohn's disease. FUTURE DIRECTIONS: Further prospective studies with a large sample size are warranted.


Assuntos
Doença de Crohn , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Doença de Crohn/cirurgia , Estudos Prospectivos , Anastomose Cirúrgica/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Intestinos/cirurgia , Íleo/cirurgia
12.
BMC Med ; 20(1): 7, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35022060

RESUMO

BACKGROUND: The overall consumption of ultra-processed food (UPF) has previously been associated with type 2 diabetes. However, due to the substantial heterogeneity of this food category, in terms of their nutritional composition and product type, it remains unclear whether previous results apply to all underlying consumption patterns of UPF. METHODS: Of 70,421 participants (35-70 years, 58.6% women) from the Lifelines cohort study, dietary intake was assessed with a food frequency questionnaire. UPF was identified according to the NOVA classification. Principal component analysis (PCA) was performed to derive UPF consumption patterns. The associations of UPF and adherence to UPF consumption patterns with incidence of type 2 diabetes were studied with logistic regression analyses adjusted for age, sex, diet quality, energy intake, alcohol intake, physical activity, TV watching time, smoking status, and educational level. RESULTS: During a median follow-up of 41 months, a 10% increment in UPF consumption was associated with a 25% higher risk of developing type 2 diabetes (1128 cases; OR 1.25 [95% CI 1.16, 1.34]). PCA revealed four habitual UPF consumption patterns. A pattern high in cold savory snacks (OR 1.16 [95% CI 1.09, 1.22]) and a pattern high in warm savory snacks (OR 1.15 [95% CI 1.08, 1.21]) were associated with an increased risk of incident type 2 diabetes; a pattern high in traditional Dutch cuisine was not associated with type 2 diabetes incidence (OR 1.05 [95% CI 0.97, 1.14]), while a pattern high in sweet snacks and pastries was inversely associated with type 2 diabetes incidence (OR 0.82 [95% CI 0.76, 0.89]). CONCLUSIONS: The heterogeneity of UPF as a general food category is reflected by the discrepancy in associations between four distinct UPF consumption patterns and incident type 2 diabetes. For better public health prevention, research is encouraged to further clarify how different UPF consumption patterns are related to type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Fast Foods , Feminino , Manipulação de Alimentos , Humanos , Masculino , Estudos Prospectivos
13.
J Med Virol ; 94(2): 557-566, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-30968963

RESUMO

Although the expression of thousands of host long noncoding RNAs (lncRNAs) can be regulated by viral infection, the number of lncRNAs with experimentally verified function is limited. In this study, the expression of host lncRNA TSPOAP1-AS1 was significantly induced by influenza A virus (IAV) infection in a dose- and time-dependent manner. Polyinosine-polycytidylic acid (poly (I:C)), a synthetic analog of double-stranded RNA, also increased TSPOAP1-AS1 expression. RNA fractionation revealed that TSPOAP1-AS1 was a nucleocytoplasmic lncRNA, and an increased nuclear/cytoplasmic ratio was detected after IAV infection. The nuclear factor-κB signaling acting as a critical factor in the transcription of TSPOAP1-AS1 was determined through the use of pharmacological and genetic approaches. Functionally, overexpression of TSPOAP1-AS1 resulted in a significant increase in IAV replication. In contrast, the abolition of TSPOAP1-AS1 by RNA interference restricted viral replication. Furthermore, we demonstrated that TSPOAP1-AS1 negatively modulated the IAV-induced Ifnb1 transcription, interferon-sensitive response element (ISRE) activation, and downstream interferon-stimulated genes expression. Collectively, our data provides evidence for the host lncRNA utilized by viruses to support its replication.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Vírus da Influenza A/fisiologia , Interferon Tipo I/metabolismo , RNA Longo não Codificante/genética , Replicação Viral/efeitos dos fármacos , Células A549 , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Influenza Humana/genética , Influenza Humana/virologia , Interferons , NF-kappa B/metabolismo , Poli I-C/farmacologia , Interferência de RNA , RNA Antissenso/farmacologia , Transdução de Sinais/efeitos dos fármacos
14.
J Gen Intern Med ; 37(15): 3907-3916, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35419742

RESUMO

BACKGROUND: Education and income, as two primary socioeconomic indicators, are often used interchangeably in health research. However, there is a lack of clear distinction between these two indicators concerning their associations with health. OBJECTIVE: This study aimed to investigate the separate and combined effects of education and income in relation to incident type 2 diabetes and cardiovascular diseases in the general population. DESIGN AND PARTICIPANTS: Participants aged between 30 and 65 years from the prospective Dutch Lifelines cohort study were included. Two sub-cohorts were subsequently created, including 83,759 and 91,083 participants for a type 2 diabetes cohort and a cardiovascular diseases cohort, respectively. MAIN MEASURES: Education and income level were assessed by self-report questionnaires. The outcomes were incident type 2 diabetes and cardiovascular diseases (defined as the earliest non-fatal cardiovascular event). KEY RESULTS: A total of 1228 new cases of type 2 diabetes (incidence 1.5%) and 3286 (incidence 3.6%) new cases of cardiovascular diseases were identified, after a median follow-up of 43 and 44 months, respectively. Low education and low income (<1000 euro/month) were both positively associated with a higher risk of incident type 2 diabetes (OR 1.24 [95%CI 1.04-1.48] and OR 1.71 [95%CI 1.30-2.26], respectively); and with a higher risk of incident cardiovascular diseases (OR 1.15 [95%CI 1.04-1.28] and OR 1.24 [95%CI 1.02-1.52], respectively); independent of age, sex, lifestyle factors, BMI, clinical biomarkers, comorbid conditions at baseline, and each other. Results from the combined associations of education and income showed that within each education group, a higher income was associated with better health; and similarly, a higher education was associated with better health within each income group, except for the low-income group. CONCLUSIONS: Education and income were both independently associated with incident type 2 diabetes and cardiovascular diseases. The combined associations of these two socioeconomic indicators revealed that within each education or income level, substantial health disparities existed across strata of the other socioeconomic indicator. Education and income are two equally important socioeconomic indicators in health, and should be considered simultaneously in health research and policymaking.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos de Coortes , Renda , Incidência , Fatores de Risco
15.
Ann Hematol ; 101(9): 1925-1929, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35779117

RESUMO

The present study aims to evaluate the characteristics and treatment outcomes of adult Langerhans cell histiocytosis (LCH) patients with thyroid involvement. We retrospectively described the clinical, biological, and genomic characteristics of a series of 36 LCH patients with thyroid involvement in our center between January 2001 and December 2021. At the time of diagnosis, only one patient was classified as having single-system LCH, and 35 patients were classified as having multisystem (MS) LCH. Three patients had coexisting papillary thyroid carcinoma. Patients with thyroid gland involvement had higher frequencies of pituitary (88.6% vs. 53.4%, P < 0.001), liver (45.7% vs. 20.7%, P = 0.003), and lymph node (54.3% vs. 31.6%, P = 0.012) involvement and a lower frequency of bone (45.7% vs. 72.0%, P = 0.003) involvement than patients without thyroid gland involvement. Sixteen patients had abnormal thyroid function, including nine patients with primary hypothyroidism, one patient with central hypothyroidism, and six patients with subclinical hypothyroidism. BRAFV600E, BRAF N486_P490, and MAP2K1 mutations were detected in 14.3%, 57.1%, and 7.1% of patients, respectively. After a 43-month median follow-up, none of the patients died, and 15 patients experienced reactivation. The median event-free survival was 37.5 months. Two of 6 patients with subclinical hypothyroidism had normal thyroid function, and 12 patients still had hypothyroidism after treatment. As the largest adult LCH cohort with thyroid gland involvement to date, we found that patients with thyroid gland involvement had different clinical characteristics, genetic profiles, and outcomes than patients without thyroid gland involvement.


Assuntos
Histiocitose de Células de Langerhans , Hipotireoidismo , Adulto , Genômica , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/genética , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos
16.
Ann Hematol ; 101(4): 831-836, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35039900

RESUMO

Idarubicin 12 mg/m2 has been recommended as a standard induction therapy for acute myeloid leukemia (AML). It is unknown whether a higher dose of idarubicin can improve the remission rate. This phase 2 prospective single-arm study enrolled 45 adults with newly diagnosed AML between September 2019 and May 2021 (NCT 04,069,208). Induction therapy included administration of idarubicin 14 mg/m2 for 3 days and cytarabine 100 mg/m2 every 12 h subcutaneously for 7 days. The primary endpoint was the composite complete response rate (complete response (CR) plus complete response with incomplete blood count recovery (CRi)). The median age was 45 years (range 14-60 years). Forty (88.9%) patients had CR or CRi, including 39 patients with CR and 1 patient with CRi after one course of induction therapy. The median times to recovery of absolute neutrophil and platelet counts were 21 days. Only 1 patient died of intracranial hemorrhage during induction therapy. After a median follow-up of 14 months (range 3.5-24 months), the estimated 18-month overall survival and disease-free survival (DFS) were 66.9% and 57.5%, respectively. In conclusion, idarubicin 14 mg/m2 plus cytarabine was a safe and efficient intensive regimen for younger and fit patients with newly diagnosed AML.


Assuntos
Idarubicina , Leucemia Mieloide Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Adulto Jovem
17.
Langmuir ; 38(31): 9532-9545, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35905457

RESUMO

A novel Bi4Ti3O12/g-C3N4/BiOBr(BTO/CN/BOB) composite was synthesized by a solvothermal-mechanical mixed thermal method. The composition, structure, and micromorphology of the samples were analyzed. The BTO/CN/BOB composite photocatalyst shows better photocatalytic performance for tetracycline hydrochloride (TC) degradation compared to Bi4Ti3O12 and binary composite photocatalysts. The highest degradation rate of TC can reach 89.84% using the BTO/CN/BOB photocatalyst under the optimal conditions, and BTO/CN/BOB still exhibits good photocatalytic properties after recycling. Moreover, it also shows good photodegradation activity for different kinds of antibiotics, implying its wide application prospect. The photocatalytic performance and reuse stability of BTO/CN/BOB were significantly improved, which may be because of the enhanced spectral absorption range and efficient electron transfer capability by the synergistic effect and interaction among Bi4Ti3O12, BiOBr, and g-C3N4. Finally, the possible degradation pathway and electron transfer mechanism of the dual Z-scheme heterojunction are proposed.


Assuntos
Antibacterianos , Titânio , Bismuto , Catálise , Luz
18.
Am J Hematol ; 97(2): 203-208, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34797941

RESUMO

Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had multiple lesions within a single system (SS-m), and 182 patients had multisystem disease (MS). The most common organ involved in MS patients was the bone (69.8%), followed by the pituitary (61.5%) and lung (61.0%). BRAFV600E , BRAF deletion, and MAP2K1 mutation were detected in 38.8%, 25.4%, and 19.4% patients, respectively. BRAF deletion was found more common in patients with MS LCH compared to single-system LCH (38.5% vs 7.1%, p = .004), also in patients with liver involvement (69.2% vs 14.3%, p < .001). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 94.4% and 54.7%, respectively, in SS-m and MS LCH. Multivariate Cox regression showed that involvement of the liver or spleen at baseline predicted poor EFS and receiving cytarabine-based therapy as a first-line treatment and age older than 30 years at diagnosis predicted favorable EFS. The involvement of risk organs and age older than 50 years predicted poor OS, and receiving cytarabine-based therapy predicted favorable OS. Therefore, BRAF deletion was correlated with MS LCH, particularly those with liver involvement. Liver or spleen involvement at baseline indicates a poor prognosis, and a cytarabine-based regimen could be considered as first-line treatment for adult LCH patients.


Assuntos
Histiocitose de Células de Langerhans/diagnóstico , Adulto , Idoso , Citarabina/uso terapêutico , Feminino , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/terapia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
19.
BMC Gastroenterol ; 22(1): 302, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729495

RESUMO

BACKGROUND: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by infiltration of lipid-laden foamy macrophages within different tissues. Clinical manifestations of ECD are highly heterogeneous. Bone lesions are found in 80%-95% of patients, while extraosseous lesions usually involve the cardiovascular system, retroperitoneum, central nervous system (CNS), and skin. Pancreatic involvement in ECD has barely been reported. CASE PRESENTATION: A 29-year-old female initially presented with menoxenia, diabetes insipidus and diabetes mellitus. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) revealed hypermetabolic foci in the bilateral frontal lobe, saddle area, and pancreas. A 99mTc-MDP bone scrintigraphy scan revealed symmetrical increased uptake in distal femoral and proximal tibial metaphysis, which was confirmed to be osteosclerosis by high-resolution peripheral quantitative computed tomography. The patient underwent incomplete resection of the sellar mass. Histological examination of biopsies showed histiocytic aggregates, which were positive for S100 and negative for CD1a and CD207 on immunohistochemistry. Enhanced abdominal CT scan showed hypointense nodules within the body and tail of the pancreas. Endoscopic ultrasonography guided fine-needle aspiration (EUS-FNA) found no evidence of malignancy. She was diagnosed with ECD and treated with high-dose IFN-α. Repeated examinations at three-and eight-months post treatment revealed markedly reduction of both intracranial and pancreatic lesions. CONCLUSIONS: ECD is a rare histiocytic neoplasm that can involve almost every organ, whereas pancreatic involvement has barely been reported to date. Here, we present the rare case of pancreatic lesions in ECD that responded well to interferon-α. We further reviewed reports of pancreatic involvement in histiocytic disorders and concluded the characteristics of such lesions to help diagnosis and treatment, in which these lesions mimicked pancreatic adenocarcinoma and caused unnecessary invasive surgeries.


Assuntos
Adenocarcinoma , Doença de Erdheim-Chester , Neoplasias Pancreáticas , Adulto , Doença de Erdheim-Chester/diagnóstico por imagem , Doença de Erdheim-Chester/tratamento farmacológico , Feminino , Humanos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
20.
Int J Colorectal Dis ; 37(4): 949-956, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35315507

RESUMO

PURPOSE: We aim to identify the risk factors of PPOI in patients with CD and create a nomogram for prediction of PPOI for CD. METHODS: Data on 462 patients who underwent partial intestinal resection for CD in Jin-ling Hospital between January 2019 and June 2021 were retrospectively collected. Univariate and multivariate analyses were performed to determine the risk factors for PPOI and we used the risk factors to create a nomogram. Then we used the Bootstrap-Concordance index and calibration diagrams to evaluate the performance of the Nomogram. Decision curve analysis was performed to evaluate clinical practicability of the model. RESULTS: The incidence of PPOI was 27.7% (n of N). Course of CD ≥ 10 years, operation time ≥ 154 min, the lowest mean arterial pressure ≤ 76.2 mmHg, in-out balance per body weight ≥ 22.90 ml/kg, post-op day 1 infusion ≥ 2847 ml, post-op lowest K+ ≤ 3.75 mmol/L, and post-op day 1 procalcitonin ≥ 2.445 ng/ml were identified as the independent risk factors of PPOI in patients with CD. The nomogram we created by these risk factors presented with good discriminative ability (concordance index 0.723) and was moderately calibrated (bootstrapped concordance index 0.704). The results of decision curve analysis showed that the nomogram was clinically effective within probability thresholds in the 8 to 66% range. CONCLUSION: The nomogram we developed is helpful to evaluate the risk of developing PPOI after partial intestinal resection for CD. Clinicians can take more necessary measures to prevent PPOI in CD's patients or at least minimize the incidence.


Assuntos
Doença de Crohn , Íleus , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Humanos , Íleus/epidemiologia , Íleus/etiologia , Nomogramas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
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