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1.
Acta Pharm Sin B ; 14(4): 1605-1623, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572102

RESUMO

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine; however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca2+/calmodulin-dependent protein kinasekinase 2 (CaMKKß) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

2.
Int Wound J ; 21(3): e14657, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38472128

RESUMO

To explore the effect of clinical nursing pathway on wound infection in patients undergoing knee or hip replacement surgery. Computerised searches of PubMed, Web of Science, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database, China National Knowledge Infrastructure databases were conducted, from database inception to September 2023, on the randomised controlled trials (RCTs) of application of clinical nursing pathway to patients undergoing knee and hip arthroplasty. Literature was screened and evaluated by two researchers based on inclusion and exclusion criteria, and data were extracted from the final included literature. RevMan 5.4 software was employed for data analysis. Overall, 48 RCTs involving 4139 surgical patients were included, including 2072 and 2067 in the clinical nursing pathway and routine nursing groups, respectively. The results revealed, compared with routine nursing, the use of clinical nursing pathways was effective in reducing the rate of complications (OR = 0.17, 95%CI: 0.14-0.21, p < 0.001) and wound infections (OR = 0.29, 95%CI: 0.16-0.51, p < 0.001), shortens the hospital length of stay (MD = -4.11, 95%CI: -5.40 to -2.83, p < 0.001) and improves wound pain (MD = -1.34, 95%CI: -1.98 to -0.70, p < 0.001); it also improve patient satisfaction (OR = 7.13, 95%CI: 4.69-10.85, p < 0.001). The implementation of clinical nursing pathways in clinical care after knee or hip arthroplasty can effectively reduce the incidence of complications and wound infections, and also improve the wound pain, while also improving treatment satisfaction so that patients can be discharged from the hospital as soon as possible.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Infecção da Ferida Cirúrgica , Humanos , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/enfermagem , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/enfermagem , Dor/complicações , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/enfermagem , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Artigo em Inglês | MEDLINE | ID: mdl-38476123

RESUMO

Background: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade. Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes. Results: From 1990 to 2019, China's age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India's rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China's age-standardized incidence rate is projected to rise. Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Feminino , Estados Unidos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , China/epidemiologia , Material Particulado , Índia/epidemiologia
4.
BMC Urol ; 24(1): 39, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355516

RESUMO

BACKGROUND: This retrospective study was conducted to compare the safety and efficacy of Sun's tip-flexible semirigid ureterorenoscopy (tf-URS), super-mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopy (FURS) in treating upper urinary tract calculi, including upper ureteral or renal calculi. METHODS: We included patients with upper ureteral calculi or renal calculi 1.0-2.0 cm in size, who underwent tf-URS, SMP or FURS, respectively. The indicators reflecting safety and efficacy were compared among the three surgical techniques. RESULTS: SMP presented with higher single stone crushing success rate, but longer operation time and postoperative hospital stay, more blood loss, and higher postoperative pain score compared with FURS and tf-URS (P < 0.05). The hospitalization cost of tf-URS group was lower than that of SMP and FURS groups (P < 0.05). The incidence of postoperative fever in tf-URS group was significantly higher than that in SMP group (P < 0.05). No significant difference was found in mucosal injury, perirenal hematoma, and stone-free rate at 3 months after surgery (P > 0.05). CONCLUSIONS: tf-URS and FURS have the advantages in minimal invasion, hospitalization cost, patient comfort, and hospital stay while SMP has higher stone-free rate. These three surgical techniques are safe, reliable and complementary, which should be selected according to the actual situation.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Ureter , Humanos , Ureteroscopia/métodos , Estudos Retrospectivos , Nefrolitotomia Percutânea/métodos , Resultado do Tratamento , Cálculos Renais/cirurgia , Hemorragia Gastrointestinal
5.
J Perinatol ; 44(2): 273-279, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38087005

RESUMO

OBJECTIVE: The primary aim was to evaluate whether the addition of the posterior lung aided in diagnostic accuracy of predicting bronchopulmonary dysplasia (BPD) vs moderate-severe BPD (msBPD); the secondary aim was to explore the diagnostic accuracy of two protocols for BPD vs msBPD. STUDY DESIGN: This was a single-center prospective observational study. Preterm infants with a gestational age ≤ 25 weeks were included. Two LUS score protocols were evaluated on the 14th day of life (DOL): (A) evaluating the anterolateral (LUS score-al) lung and (B) the anterolateral combined with posterior (LUS score-alp) lung. The LUS score range for the two protocols was 0-32 and 0-48, respectively. RESULTS: A total of eighty-nine infants were enrolled. Both the LUS score-al and LUS score-alp were higher in neonates developing BPD and msBPD than in the rest of the cohort (LUS score-al 24 (23,26) vs 22 (20,23); LUS score-alp 36 (34,39) vs 28 (25,32)) (LUS score-al 25 (24,26) vs 23 (21,24); LUS score-alp 40 (39,40) vs 34 (28,36)). The LUS score-al on the 14th DOL showed a moderate diagnostic accuracy to predict BPD and msBPD (AUC 95% CI: 0.797 [0.697-0.896]; 0.811[0.713-0.909]), while the LUS score-alp significantly improved diagnostic accuracy of BPD and msBPD (AUC 95% CI: 0.902 [0.834-0.970]; 0.922 [0.848-0.996]). A cutoff of 25 points in the LUS score-al provided a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 76.9%, 79.4%, 3.7, and 0.3 respectively to predict msBPD. Meanwhile, that of 39 points in the LUS score-alp provided a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 81%, 98.4%, 50.5 and 0.19 to predict msBPD, respectively. CONCLUSIONS: The LUS score on the 14th DOL can predict BPD and msBPD with moderate diagnostic accuracy. Apart from that, scanning posterior enhanced diagnostic accuracy.


Assuntos
Displasia Broncopulmonar , Humanos , Recém-Nascido , Displasia Broncopulmonar/diagnóstico por imagem , Idade Gestacional , Recém-Nascido Prematuro , Pulmão/diagnóstico por imagem , Estudos Prospectivos
6.
J Hand Surg Eur Vol ; 48(11): 1144-1150, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37751489

RESUMO

Congenital muscular hypertrophy is a rare overgrowth disorder in the phosphatidylinositol-3-kinase related spectrum. In the past 3 years, ten patients with 11 limbs involved were treated in our centre. The aim of the study was to describe the clinical and radiological deformities of these patients. We documented the characteristic clinical morphological changes, such as hypertrophy, loss of wrist flexion, thumb hyperabduction, finger deviation and skin crease changes in the palm. Radiologically, the mean first metacarpal radial deviation angle of the affected side measured 55° (range 34 to 67) compared to the normal contralateral side 42° (range 32 to 53). The mean intermetacarpal space ratio was 1.2 (range 1.1 to 1.4) and the mean palm width ratio was 1.2 (range 1.1 to 1.3). In this study, we were able to further characterize the radiological and morphological changes of congenital muscular hypertrophy of upper limbs, which would be helpful for establishing the diagnosis and monitor treatment of this rare condition.Level of evidence: IV.


Assuntos
Anormalidades Musculoesqueléticas , Extremidade Superior , Humanos , Extremidade Superior/diagnóstico por imagem , Radiografia , Dedos/anormalidades , Polegar , Hipertrofia/diagnóstico por imagem
7.
J Am Chem Soc ; 145(34): 18956-18967, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37596711

RESUMO

The separation of enantiomers using high-performance chromatography technologies represents great importance and interest. In this aspect, ß-cyclodextrin (ß-CD) and its derivatives have been extensively studied as chiral stationary phases (CSPs). Nevertheless, ß-CD that was immobilized on a traditional matrix often exhibited low stabilities and limited operating ranges. Recently, covalent organic frameworks (COFs) with highly ordered nanopores are emerging as promising CSPs for enantioseparations, but their practical applications are still hampered by the difficulty of monomer and COF synthesis. Herein, two ß-CD-driven COFs are synthesized via a fast and facile plasma-induced polymerization combined postsynthesis modification strategy. The precisely defined COF channels enhanced the accessibility of the accommodated ß-CD to the analytes and acted as robust protective barriers to safeguard the ß-CD from harsh environments. Therefore, the ß-CD-modified COFs can be potentially general CSPs for extensive enantioseparation in both gas chromatography and high-performance liquid chromatography, and a wide range of racemates were separated. Compared to the commonly employed commercial chiral columns, these COF-based columns exhibited comparable resolution capability and superior application versatility. This work integrates the advantages and overcomes the defects of COFs and ß-CD, thus advancing COFs as platforms for chiral selector modification and giving great promise for practical chromatographic enantioseparation.

9.
Pediatr Pulmonol ; 58(9): 2487-2494, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37265422

RESUMO

BACKGROUND: This prospective study aimed to investigate whether lung ultrasound score (LUSs) can predict the patent ductus arteriosus (PDA) ligation. METHODS: Preterm infants ≤25 weeks of gestational age (GA) were enrolled. A lung ultrasound was performed on the 14th day of life. Each lung zone was given a score between 0 and 4. A receiver-operating characteristic (ROC) curve was constructed to evaluate the ability of the LUSs for predicting ligation. RESULTS: A total of 81 infants were eligible with a median GA and birth weight (BW) of 25 weeks (24.1-25.2) and 710 g (645-770), respectively. The median time from birth to ligation was 35 days (32-51). Those who underwent ligation had a longer time of mechanical ventilation (34 [26-39] vs. 19 [12-30], p < 0.001), shorter time of noninvasive respiratory support (39 [32-51] vs. 50 [41.5-57], p < 0.01), higher incidence of the bronchopulmonary dysplasia (BPD) (p < 0.01), and severe BPD (p < 0.001). The LUSs had an area under the ROC of 0.96 (95% confidence interval: 0.93-0.99) for the prediction of ligation. A LUSs cutoff of 36 has a sensitivity and specificity of 96% and 86% and positive and negative predictive values of 82% and 98%, respectively. CONCLUSIONS: LUSs at an early stage of life can predict PDA ligation in extremely preterm infants. It would be helpful to reduce morbidity by reducing the duration and magnitude of respiratory support.


Assuntos
Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Lactente , Recém-Nascido , Humanos , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Lactente Extremamente Prematuro , Pulmão/diagnóstico por imagem , Displasia Broncopulmonar/diagnóstico por imagem
10.
BMC Pulm Med ; 23(1): 229, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365524

RESUMO

BACKGROUND: It is unclear whether Ureaplasma-associated pneumonia and azithromycin treatment affect the risk for bronchopulmonary dysplasia (BPD). METHODS: A retrospective cohort study was performed in very low birth weight (VLBW) infants who tested positive for Ureaplasma within 72 h after birth in a tertiary unit. Chest X-ray (CXR) and laboratory test were performed before and after azithromycin treatment. Multivariate logistic regression analysis was used to identify the independent association between BPD and Ureaplasma-associated pneumonia, as well as BPD and effective azithromycin treatment. RESULTS: A total of 118 infants were included in the current study, of whom 36 developed BPD (defined as supplemental oxygen needed at postmenstrual age 36 weeks or discharge). The rate of BPD was significantly higher in infants with Ureaplasma-associated pneumonia (44.6%) compared to infants with Ureaplasma colonization (17.7%, P = 0.002). After adjusting for confounders, an effective azithromycin treatment was significantly associated with reduced risk of BPD [odd ratio (OR) 0.011; 95% confidence interval (CI): 0.000-0.250), whereas Ureaplasma-associated pneumonia was not significantly associated with BPD (OR 1.835; 95% CI: 0.548-6.147). CONCLUSION: Effective Azithromycin treatment in Ureaplasma positive VLBW infants was associated with a reduced risk of BPD.


Assuntos
Displasia Broncopulmonar , Infecções por Ureaplasma , Recém-Nascido , Humanos , Lactente , Azitromicina/uso terapêutico , Displasia Broncopulmonar/epidemiologia , Recém-Nascido Prematuro , Ureaplasma , Estudos de Coortes , Estudos Retrospectivos , Infecções por Ureaplasma/complicações , Infecções por Ureaplasma/tratamento farmacológico
11.
Cell Metab ; 35(6): 1022-1037.e6, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37167965

RESUMO

Type 2 diabetes (T2D) is a major health and economic burden worldwide. Despite the availability of multiple drugs for short-term management, sustained remission of T2D is currently not achievable pharmacologically. Intracerebroventricular administration of fibroblast growth factor 1 (icvFGF1) induces sustained remission in T2D rodents, propelling intense research efforts to understand its mechanism of action. Whether other FGFs possess similar therapeutic benefits is currently unknown. Here, we show that icvFGF4 also elicits a sustained antidiabetic effect in both male db/db mice and diet-induced obese mice by activating FGF receptor 1 (FGFR1) expressed in glucose-sensing neurons within the mediobasal hypothalamus. Specifically, FGF4 excites glucose-excited (GE) neurons while inhibiting glucose-inhibited (GI) neurons. Moreover, icvFGF4 restores the percentage of GI neurons in db/db mice. Importantly, intranasal delivery of FGF4 alleviates hyperglycemia in db/db mice, paving the way for non-invasive therapy. We conclude that icvFGF4 holds significant therapeutic potential for achieving sustained remission of T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Camundongos , Animais , Masculino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Fator 4 de Crescimento de Fibroblastos/uso terapêutico , Roedores/metabolismo , Glucose/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia , Fatores de Crescimento de Fibroblastos/uso terapêutico , Fatores de Crescimento de Fibroblastos/metabolismo
12.
J Asthma Allergy ; 16: 501-513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181452

RESUMO

Purpose: To investigate the lifestyle and stress of mothers during pregnancy to analyze the risk factors for the disease in early childhood. Patients and Methods: A cross-sectional survey was conducted from January 2022 to June 2022 in a sub-district in Guangzhou, China. A total of 3437 valid questionnaires were eventually collected. The questionnaire consisted of 56 questions in three sections included questions on child's birth conditions and early life environment, questions on mother's lifestyle during pregnancy, and questions about father. Results: 49.75% of the children were likely to have allergic diseases (suspected allergy group). There were more boys in the suspected allergy group (58% vs 50%), and the percentage of children born at first birth was also higher in the suspected allergy group (61% vs 51%). 67% to 69% of children had suspicious allergies when one parent claimed an allergy, and 80.1% when both parents reported an allergy. The results of the multifactorial logistic model showed that male had 1.49 (1.28 to 1.73) times the risk of allergic diseases than female, and preterm births increased the risk of allergic diseases by 1.53 (1.13-2.07) times compared to full-term births. Both unplanned pregnancies and pregnancy complications increased the risk of allergic diseases in children before school age [1.34 (1.15-1.55) and 1.82 (1.46-2.26)]. Among pregnant women who reported regular passive smoking, the risk of the disease was increased 2.43 (1.71 to 3.50) times in preschool children. Reported allergies in all family members were significant risk factors for allergic diseases in children, especially mother [2.88 (2.41~3.46)]. In the prenatal period, maternal negative emotions are more common in children with suspected allergies. Conclusion: Nearly half of the children in the region suffer from allergic diseases. Sex, birth order and full-term delivery all contributed to early childhood allergy. Family history of allergy, especially maternal, was the most important risk factor, and the number of family members with allergy was significantly associated with the allergy in children. Maternal effects are also reflected in prenatal conditions such as unplanned pregnancy, smoke exposure, pregnancy complications, and prenatal stress.

13.
J Hand Surg Eur Vol ; 48(11): 1191-1200, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37211793

RESUMO

We proposed a modification of the Rotterdam classification for thumb triplication and tetraplication. Twenty-one patients were included (24 cases of thumb triplication and four cases of tetraplication). These were analysed and classified according to a modification of the Rotterdam classification involving three steps; from the radial to ulnar side, we first identified each thumb on radiographs and gross appearance to divide into triplication or tetraplication. Second, we define the levels of duplication and established the nomenclature. Third, the aberrant features and their location were assigned for each thumb, again from radial to ulnar side. A surgical algorithm was also proposed. This modified classification may be helpful for characterizing the rare conditions of thumb triplication and tetraplication for use in patient and management and communication between surgeons.Level of evidence: III.


Assuntos
Procedimentos de Cirurgia Plástica , Polidactilia , Cirurgiões , Humanos , Polegar/diagnóstico por imagem , Polegar/cirurgia , Polidactilia/cirurgia , Radiografia
14.
Eur J Orthop Surg Traumatol ; 33(7): 3197-3205, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36947312

RESUMO

PURPOSE: This systematic review and meta-analysis aimed to identify whether posterior tilt increases the risk of treatment failure in nondisplaced femoral neck fractures. METHODS: We searched the databases of the PubMed, Embase, and Cochrane Library from 1980 to 2022. The search strategy was based on the combination of keywords "nondisplaced," "hip fracture," "femoral neck fracture," and "internal fixation." Cohort studies enrolled patients with nondisplaced (Garden I and Garden II) femoral neck fractures were included. Two investigators independently extracted data and the other two assessed the methodological quality. Data were analyzed using Review Manager software. RESULTS: We analyzed 13 cohort trials with a pooled sample of 4818 patients, with posterior tilt ≥ 20° in 698 patients and < 20° in 3578 patients in 11 trials, and posterior tilt ≥ 10° in 483 patients and < 10° in 496 patients in 4 trials. All studies were of high quality based on Newcastle-Ottawa Scale evaluation. Treatment failure was reported in 24.4% (170/698) of patients with posterior tilt ≥ 20° and 10.9% (392/3578) of patients with posterior tilt < 20°, indicating that posterior tilt ≥ 20° was significantly associated with a higher risk of treatment failure (Risk ratio, 2.73; 95% confidence interval [CI], 1.77-4.21). Posterior tilt ≥ 10° was not found to be a risk factor for fixation failure (risk ratio, 1.92; 95% CI 0.76-4.83). CONCLUSION: Nondisplaced femoral neck fractures with posterior tilt ≥ 20° were associated with an increasing rate of failure when treated with internal fixation. LEVEL OF EVIDENCE : III, Systematic review and meta-analysis.


Assuntos
Fraturas do Colo Femoral , Humanos , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fatores de Risco , Estudos de Coortes , Reoperação , Estudos Retrospectivos
15.
ACS Appl Mater Interfaces ; 15(5): 6397-6410, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36625595

RESUMO

Drugs for metabolic diseases usually require systemic administration and act on multiple tissues, which may produce some unpredictable side effects. There have been many successful studies on targeted drugs, especially antitumor drugs. However, there is still little research on metabolic disease drugs targeting specific tissues. Fibroblast growth factor 1 (FGF1) is a potential therapy for type 2 diabetes (T2D) without the risk of hypoglycemia. However, the major impediment to the clinical application of FGF1 is its mitogenic potential. We previously engineered an FGF1 variant (named FGF1ΔHBS) to tune down its mitogenic activity via reducing the heparin-binding ability. However, other notable side effects still remained, including severe appetite inhibition, pathogenic loss of body weight, and increase in fatality rate. In this study, we used AlphaFold2 and PyMOL visualization tools to construct a novel FGF1ΔHBS conjugate fused with skeletal muscle-targeted (MT) peptide through a flexible peptide linker termed MT-FGF1ΔHBS. We found that MT-FGF1ΔHBS specifically homed to skeletal muscle tissue after systemic administration and induced a potent glucose-lowering effect in T2D mice without hypoglycemia. Mechanistically, MT-FGF1ΔHBS elicits the glucose-lowering effect via AMPK activation to promote the GLUT4 expression and translocation in skeletal muscle cells. Notably, compared with native FGF1ΔHBS, MT-FGF1ΔHBS had minimal effects on food intake and body weight and did not induce any hyperplasia in major tissues of both T2D and normal mice, indicating that this muscle-homing protein may be a promising candidate for T2D treatment. Our targeted peptide strategy based on computer-aided structure prediction in this study could be effectively applied for delivering agents to functional tissues to treat metabolic or other diseases, offering enhanced efficacy and reducing systemic off-target side effects.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Camundongos , Animais , Fator 1 de Crescimento de Fibroblastos/metabolismo , Fator 1 de Crescimento de Fibroblastos/farmacologia , Fator 1 de Crescimento de Fibroblastos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Músculo Esquelético , Peptídeos/metabolismo , Glucose/metabolismo , Hipoglicemia/metabolismo , Peso Corporal
16.
Front Oncol ; 12: 1013770, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439458

RESUMO

Background: There are few studies on the application of radiomics in the risk prediction of early recurrence (ER) after radiofrequency ablation (RFA). This study evaluated the value of a multi-parametric magnetic resonance imaging (MRI, mpMRI)-based radiomics nomogram in predicting ER of small hepatocellular carcinoma (HCC) after RFA. Materials and methods: A retrospective analysis was performed on 90 patients with small HCC who were treated with RFA. Patients were divided into two groups according to recurrence within 2 years: the ER group (n=38) and the non-ER group (n=52). Preoperative T1WI, T2WI, and contrast-enhanced MRI (CE-MRI) were used for radiomic analysis. Tumor segmentation was performed on the images and applied to extract 1316 radiomics features. The most predictive features were selected using analysis of variance + Mann-Whitney, Spearman's rank correlation test, random forest (importance), and least absolute shrinkage and selection operator analysis. Radiomics models based on each sequence or combined sequences were established using logistic regression analysis. A predictive nomogram was constructed based on the radiomics score (rad-score) and clinical predictors. The predictive efficiency of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC). Decision curve analysis (DCA) was used to evaluate the clinical efficacy of the nomogram. Results: The radiomics model mpMRI, which is based on T1WI, T2WI, and CE-MRI sequences, showed the best predictive performance, with an AUC of 0.812 for the validation cohort. Combined with the clinical risk factors of albumin level, number of tumors, and rad-score of mpMRI, the AUC of the preoperative predictive nomogram in the training and validation cohorts were 0.869 and 0.812, respectively. DCA demonstrated that the combined nomogram is clinically useful. Conclusions: The multi-parametric MRI-based radiomics nomogram has a high predictive value for ER of small HCC after RFA, which could be helpful for personalized risk stratification and further treatment decision-making for patients with small HCC.

17.
Nat Metab ; 4(9): 1202-1213, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36131205

RESUMO

Insulin signaling is essential for glucose metabolism, and insulin decreases insulin receptor (InsR) levels in a dose-dependent and time-dependent manner. However, the regulatory mechanisms of InsR reduction upon insulin stimulation remain poorly understood. Here, we show that Eph receptor B4 (EphB4), a tyrosine kinase receptor that modulates cell adhesion and migration, can bind directly to InsR, and this interaction is markedly enhanced by insulin. Due to the adaptor protein 2 (Ap2) complex binding motif in EphB4, the interaction of EphB4 and InsR facilitates clathrin-mediated InsR endocytosis and degradation in lysosomes. Hepatic overexpression of EphB4 decreases InsR and increases hepatic and systemic insulin resistance in chow-fed mice, whereas genetic or pharmacological inhibition of EphB4 improve insulin resistance and glucose intolerance in obese mice. These observations elucidate a role for EphB4 in insulin signaling, suggesting that EphB4 might represent a therapeutic target for the treatment of insulin resistance and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Receptor EphB4 , Receptor de Insulina , Animais , Clatrina , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Resistência à Insulina/genética , Fígado/metabolismo , Camundongos , Receptor EphB4/metabolismo , Receptor de Insulina/metabolismo
18.
Front Pediatr ; 10: 919879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958170

RESUMO

Introduction: Ibuprofen is one of the most common non-steroidal anti-inflammatory drugs used to close patent ductus arteriosus (PDA) in preterm infants. PDA is associated with bronchopulmonary dysplasia (BPD), while PDA closure by ibuprofen did not reduce the incidence of BPD or death. Previous studies have indicated an anti-angiogenesis effect of ibuprofen. This study investigated the change of angiogenic factors after ibuprofen treatment in preterm infants. Methods: Preterm infants with hemodynamically significant PDA (hsPDA) were included. After confirmed hsPDA by color doppler ultrasonography within 1 week after birth, infants received oral ibuprofen for three continuous days. Paired plasma before and after the ibuprofen treatment was collected and measured by ELISA to determine the concentrations of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A), and hypoxia-inducible factor-2α (HIF-2α). Results: 17 paired plasma from infants with hsPDA were collected. The concentration of PDGF-BB and VEGF-A significantly decreased after ibuprofen treatment (1,908 vs. 442 pg/mL for PDGF-BB, 379 vs. 174 pg/mL for VEGF-A). HIF-2α level showed a tendency to decrease after ibuprofen treatment, although the reduction was not statistically significant (p = 0.077). Conclusion: This study demonstrated decreased vascular growth factors after ibuprofen exposure in hsPDA infants.

19.
Front Pediatr ; 10: 899785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712615

RESUMO

Background: Nutrition is an essential factor in preventing and managing bronchopulmonary dysplasia (BPD), a multifactorial chronic respiratory disease in premature infants. This study examined the association between nutritional intakes during the first 2 weeks of life and BPD in extremely preterm infants. Methods: A retrospective single-center cohort study was performed in infants born <28 weeks' gestational age or with a birth weight <1,000 g. Intake of energy and ratio of enteral feeding/ total fluid intake during the first 2 weeks of life and association with outcome of BPD were examined. Results: 134 infants were included in our study, and 43 infants (32.1%) developed BPD. During the first 2 weeks of life, the average of total caloric intake and the ratio of enteral feeding/ total fluid intake were significantly lower in the BPD group (total caloric intake:91.90 vs. 95.72 kcal/kg/d, p < 0.05, ratio of enteral feeding/total fluid intake: 0.14 vs. 0.18, p < 0.05), while the average of total fluid intake, caloric and protein intake from parenteral nutrition did not differ between the groups. The ratio of enteral feeding/ total fluid intake during the second week were significantly lower in the BPD group (0.21 vs. 0.28, p < 0.05), while this ratio during the first week did not differ between the groups. An increase of 10% in the ratio of enteral feeding/ total fluid intake during the second week of life significantly reduced the risk of BPD (OR 0.444, 95% CI: 0.270-0.731). Conclusions: A higher ratio of enteral feeding/ total fluid intake was associated with a lower risk for BPD. Early and rapidly progressive enteral nutrition should be encouraged in extremely preterm infants in the absence of feeding intolerance.

20.
Front Pediatr ; 10: 791664, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35633958

RESUMO

Point-of-care lung ultrasound (LUS) is increasingly applied in the neonatal intensive care unit (NICU). Diagnostic applications for LUS in the NICU contain the diagnosis of many common neonatal pulmonary diseases (such as Respiratory distress syndrome, Transient tachypnea of the newborn, Meconium aspiration syndrome, Pneumonia, Pneumothorax, and Pleural effusion) which have been validated. In addition to being employed as a diagnostic tool in the classical sense of the term, recent studies have shown that the number and type of artifacts are associated with lung aeration. Based on this theory, over the last few years, LUS has also been used as a semi-quantitative method or as a "functional" tool. Scores have been proposed to monitor the progress of neonatal lung diseases and to decide whether or not to perform a specific treatment. The semi-quantitative LUS scores (LUSs) have been developed to predict the demand for surfactant therapy, the need of respiratory support and the progress of bronchopulmonary dysplasia. Given their ease of use, accuracy and lack of invasiveness, the use of LUSs is increasing in clinical practice. Therefore, this manuscript will review the application of LUSs in neonatal lung diseases.

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