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1.
BMC Public Health ; 24(1): 1120, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654229

RESUMO

BACKGROUND: Dietary rationality and health concept have certain influence on individual health level. This study aims to explore the characteristics and existing problems of Chinese residents' health behaviors from both macro and micro perspectives, and explore the feasibility and realization path of Healthy China strategy. METHODS: We utilized regression models to evaluate the correlation between diet and the risk of disease causes of death. By use of the linear regression analysis model, we distinguished the impact of each dimension on health literacy index at the individual level. Then, we explored the influential factors of the diet health index using the binary logit regression model. RESULTS: Increased consumption of animal-derived foods in China has contributed to the burden of non-communicable diseases. The individuals' health awareness is still weak, and the health literacy index is greatly affected by the diet, while the individual gender and age are positively correlated with the diet health index, and the individual body mass index (BMI) level is negatively correlated with the diet health index. CONCLUSIONS: This study provided a comprehensive understanding of existing problems of Chinese residents' health behaviors. We have proposed a path model for the implementation of the Healthy China strategy from the perspectives of "diet health, physical health, conceptual health and environmental health," which is also a great contribution to the world.


Assuntos
Comportamentos Relacionados com a Saúde , Humanos , China , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Dieta , Letramento em Saúde , Idoso , Dieta Saudável , Adulto Jovem
2.
J Natl Cancer Inst ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637942

RESUMO

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

3.
Plant Mol Biol ; 114(3): 40, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622367

RESUMO

Parasitic lifestyle can often relax the constraint on the plastome, leading to gene pseudogenization and loss, and resulting in diverse genomic structures and rampant genome degradation. Although several plastomes of parasitic Cuscuta have  been reported, the evolution of parasitism in the family Convolvulaceae which is linked to structural variations and reduction of plastome has not been well investigated. In this study, we assembled and collected 40 plastid genomes belonging to 23 species representing four subgenera of Cuscuta and ten species of autotrophic Convolvulaceae. Our findings revealed nine types of structural variations and six types of inverted repeat (IR) boundary variations in the plastome of Convolvulaceae spp. These structural variations were associated with the shift of parasitic lifestyle, and IR boundary shift, as well as the abundance of long repeats. Overall, the degradation of Cuscuta plastome proceeded gradually, with one clade exhibiting an accelerated degradation rate. We observed five stages of gene loss in Cuscuta, including NAD(P)H complex → PEP complex → Photosynthesis-related → Ribosomal protein subunits → ATP synthase complex. Based on our results, we speculated that the shift of parasitic lifestyle in early divergent time promoted relaxed selection on plastomes, leading to the accumulation of microvariations, which ultimately resulted in the plastome reduction. This study provides new evidence towards a better understanding of plastomic evolution, variation, and reduction in the genus Cuscuta.


Assuntos
Convolvulaceae , Cuscuta , Genomas de Plastídeos , Convolvulaceae/genética , Cuscuta/genética , Genes de Plantas , Fotossíntese/genética , Filogenia , Evolução Molecular
4.
Brain Res ; : 148947, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657887

RESUMO

Perceived stress is an acknowledged risk factor for subthreshold depression (StD), and fluctuations in perceived stress are thought to disrupt the harmony of brain networks essential for emotional and cognitive functioning. This study aimed to elucidate the relationship between eye-open (EO) and eye-closed (EC) states, perceived stress, and StD. We recruited 27 individuals with StD and 33 healthy controls, collecting resting state fMRI data under both EC and EO conditions. We combined intrinsic connectivity and seed-based functional connectivity analyses to construct the functional network and explore differences between EC and EO conditions. Graph theory analysis revealed weakened connectivity strength in the right superior frontal gyrus (SFG) and right median cingulate and paracingulate gyrus (MCC) among participants with StD, suggesting an important role for these regions in the stress-related emotions dysregulation. Notably, altered SFG connectivity was observed to significantly relate to perceived stress levels in StD, and the SFG connection emerges as a neural mediator potentially influencing the relationship between perceived stress and StD. These findings highlight the role of SFG and MCC in perceived stress and suggest that understanding EC and EO states in relation to these regions is important in the neurobiological framework of StD. This may offer valuable perspectives for early prevention and intervention strategies in mental health disorders.

5.
Small Methods ; : e2301645, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607956

RESUMO

Bimetallic phosphides are considered as promising electrocatalysts for zinc-air batteries toward oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). To address the semi-conductor inherent low electronic conductivity and catalytic activity, a polymetal-chelated strategy is employed to in situ fabricate bimetallic nanophosphides within carbon matrix anchoring by chemical bonding. The employment of biomolecule polydopamine (PDA) efficiently anchors various transition metal ions due to its strong chelating capability via inherent functional groups. Furthermore, the chelation of multi-metal ion is proved to promote the formation of graphitic nitrogen. The bimetallic FexCoyP phosphides nanoparticles are intimately encapsulated in carbon matrix through in situ carbonization and phosphatization processes. When utilized in Zinc-air batteries, Fe0.20Co0.80P anchored within N, P co-doped sub-microsphere (Fe0.20Co0.80P /PNC) exhibit a maximum power density of 167 mW cm-2 and cycle life up to 270 cycles, with a round-trip voltage of 0.955 V. The mechanisms for catalytic activity passivation are ascribed to the etching of nitrogen and oxidation of phosphorus in carbon matrix, as well as the oxidation of the surface phosphide on the sub-microspheres. This study presents a promising candidate for advancing the further development of energy conversation catalysis.

6.
Technol Cancer Res Treat ; 23: 15330338241242637, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584417

RESUMO

Background: Endometrial cancer (EC) is the leading gynecological cancer worldwide, yet current EC screening approaches are not satisfying. The purpose of this retrospective study was to evaluate the feasibility and capability of DNA methylation analysis in cervical Papanicolaou (Pap) brush samples for EC detection. Methods: We used quantitative methylation-sensitive PCR (qMS-PCR) to determine the methylation status of candidate genes in EC tissue samples, as well as cervical Pap brushes. The ability of RASSF1A and HIST1H4F to serve as diagnostic markers for EC was then examined in cervical Pap brush samples from women with endometrial lesions of varying degrees of severity. Results: Methylated RASSF1A and HIST1H4F were found in EC tissues. Further, methylation of the two genes was also observed in cervical Pap smear samples from EC patients. Methylation levels of RASSF1A and HIST1H4F increased as endometrial lesions progressed, and cervical Pap brush samples from women affected by EC exhibited significantly higher levels of methylated RASSF1A and HIST1H4F compared to noncancerous controls (P < .001). Receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses revealed RASSF1A and HIST1H4F methylation with a combined AUC of 0.938 and 0.951 for EC/pre-EC detection in cervical Pap brush samples, respectively. Conclusion: These findings demonstrate that DNA methylation analysis in cervical Pap brush samples may be helpful for EC detection, broadening the scope of the commonly used cytological screening. Our proof-of-concept study provides new insights into the field of clinical EC diagnosis.


Assuntos
Neoplasias do Endométrio , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Metilação de DNA , Estudos Retrospectivos , Colo do Útero/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia
7.
Biomed Environ Sci ; 37(2): 196-203, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582982

RESUMO

Objective: Cognitive impairment (CI) in older individuals has a high morbidity rate worldwide, with poor diagnostic methods and susceptible population identification. This study aimed to investigate the relationship between different retinal metrics and CI in a particular population, emphasizing polyvascular status. Methods: We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers, retinal nerve fiber layer (RNFL) thickness, and cognitive function of 3,785 participants, aged 40 years or older. Logistic regression was used to analyze the relationship between retinal metrics and cognitive function. Subgroups stratified by different vascular statuses were also analyzed. Results: RNFL thickness was significantly thinner in the CI group (odds ratio: 0.973, 95% confidence interval: 0.953-0.994). In the subgroup analysis, the difference still existed in the non-intracranial arterial stenosis, non-extracranial carotid arterial stenosis, and peripheral arterial disease subgroups ( P < 0.05). Conclusion: A thin RNFL is associated with CI, especially in people with non-large vessel stenosis. The underlying small vessel change in RNFL and CI should be investigated in the future.


Assuntos
Estenose das Carótidas , Disfunção Cognitiva , Humanos , Idoso , Constrição Patológica , Tomografia de Coerência Óptica , Vasos Retinianos , Fibras Nervosas
8.
Artigo em Inglês | MEDLINE | ID: mdl-38606549

RESUMO

PtRu alloys have been recognized as the state-of-the-art catalysts for the methanol oxidation reaction (MOR) in direct methanol fuel cells (DMFCs). However, their applications in DMFCs are still less efficient in terms of both catalytic activity and durability. Rare earth (RE) metals have been recognized as attractive elements to tune the catalytic activity, while it is still a world-class challenge to synthesize well-dispersed Pt-RE alloys. Herein, we developed a novel hydrogen-assisted magnesiothermic reduction strategy to prepare a highly dispersed carbon-supported lutetium-doped PtRu catalyst with ultrafine nanoclusters and atomically dispersed Ru sites. The PtRuLu catalyst shows an outstanding high electrochemical surface area (ECSA) of 239.0 m2 gPt-1 and delivers an optimized MOR mass activity and specific activity of 632.5 mA mgPt-1 and 26 A cmPt-2 at 0.4 V vs saturated calomel electrode (SCE), which are 3.6 and 3.5 times of commercial PtRu-JM and an order higher than PtLu, respectively. These novel catalysts have been demonstrated in a high-temperature direct methanol fuel cell running in a temperature range of 180-240 °C, achieving a maximum power density of 314.3 mW cm-2. The AC-STEM imaging, in situ ATR-IR spectroscopy, and DFT calculations disclose that the high performance is resulted from the highly dispersed PtRuLu nanoclusters and the synergistic effect of the atomically dispersed Ru sites with PtRuLu nanoclusters, which significantly reduces the CO* intermediates coverage due to the promoted water activation to form the OH* to facilitate the CO* removal.

9.
Chin Med ; 19(1): 60, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589903

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. METHODS: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-ß to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-ß with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. RESULTS: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. CONCLUSION: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.

10.
Small ; : e2400252, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461522

RESUMO

Owing to the high economic efficiency and energy density potential, manganese-based layer-structured oxides have attracted great interests as cathode materials for potassium ion batteries. In order to alleviate the continuous phase transition and K+ re-embedding from Jahn-Teller distortion, the [Mn-Co-Mo]O6 octahedra are introduced into P3-K0.45 MnO2 herein to optimize the local electron structure. Based on the experimental and computational results, the octahedral center metal molybdenum in [MoO6 ] octahedra proposes a smaller ionic radius and higher oxidation state to induce second-order JTE (pseudo-JTE) distortion in the adjacent [MnO6 ] octahedra. This distortion compresses the [MnO6 ] octahedra along the c-axis, leading to an increased interlayer spacing in the K+ layer. Meanwhile, the Mn3+ /Mn4+ is balanced by [CoO6 ] octahedra and the K+ diffusion pathway is optimized as well. The proposed P3-K0.45 Mn0.9 Co0.05 Mo0.05 O2 cathode material shows an enhanced cycling stability and rate performance. It demonstrates a high capacity of 80.2 mAh g-1 at 100 mAh g-1 and 77.3 mAh g-1 at 500 mAh g-1 . Furthermore, it showcases a 2000 cycles stability with a 59.6% capacity retention. This work presents a promising solution to the challenges faced by manganese-based layered oxide cathodes and offers a deep mechanism understanding and improved electrochemical performance.

11.
Liver Int ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436551

RESUMO

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

13.
Neurosurg Rev ; 47(1): 115, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38480550

RESUMO

OBJECTIVE: The study aimed to evaluate the short-term clinical efficacy of percutaneous full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) for lumbar degenerative diseases (LDD). METHODS: From July 2020 to July 2021, 93 patients who underwent single-level lumbar fusion procedure were retrospective analysis. The patients were divided into Endo-TLIF group and transforaminal lumbar interbody fusion (TLIF) group. General demographic and perioperative data were recorded, the clinical outcomes were evaluated using visual analogue scale (VAS) and oswestry disability index (ODI). The disk height (DH) was compared between the two groups. RESULTS: All of the surgical procedures were successfully completed, and the patients were followed for a minimum of 2 years. Intraoperative blood loss, drainage volume, time to independent ambulation and hospital length of stay in the Endo-TLIF group were significantly decreased in comparison with the open TLIF group (p < 0.05). The VAS for back pain on postoperative 7 day and ODI on postoperative 1 month were lower in the Endo-TLIF group than in the open TLIF group (P < 0.05), but no significant difference at 1 year and 2 years postoperatively (P > 0.05). The VAS score of leg pain had no demographic statistically significant differences between the groups (P > 0.05). The DH were significantly heightened after surgery compared to the preoperative height (p < 0.05). CONCLUSION: Endo-TLIF is a minimally invasive, safety surgery which can achieve comparable short-term effects as open TLIF. It may be a promising option for the treatment of LDD.


Assuntos
Vértebras Lombares , Fusão Vertebral , Humanos , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Endoscopia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento
15.
J Nat Prod ; 87(4): 810-819, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38427823

RESUMO

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.


Assuntos
Alcaloides , Antibacterianos , Testes de Sensibilidade Microbiana , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Estrutura Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Relação Estrutura-Atividade , Biologia Marinha , Ascomicetos/química , Fluorenos/farmacologia , Fluorenos/química , Fluorenos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores
16.
18.
Brain Res ; 1833: 148885, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38531465

RESUMO

BACKGROUND: Immune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core factors in immune-inflammatory responses, interleukin (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also play an important role in OD induced by diseases, such as Sjögren's syndrome and coronavirus disease 2019. However, there is no study has reported its role in OD in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, in an attempt to discover a new target for the prevention and treatment of OD in patients with AR. METHODS: Differential expression analysis was performed using the public datasets GSE52804 and GSE140454 for AR, and differentially expressed genes (DEGs) were obtained by obtaining the intersection points between these two datasets. IL-6, a common differential factor, was obtained by intersecting the DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the reliability of IL-6 as a key factor of OD in AR and explore the potential mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 was established to identify the cellular and molecular mechanisms of IL-6-mediated OD in AR. RESULTS: The level of IL-6 in the nasal mucosa and olfactory bulb of AR mice with OD significantly increased and showed a positive correlation with the expression of olfactory bulb microglia marker Iba-1 and the severity of OD. In-vitro experiments showed that the level of IL-6 significantly increased in the supernatant after the nasal mucosa epithelial cells were stimulated by Derp1, along with significantly decreased barrier function of the nasal mucosa. The expression levels of neuroinflammatory markers IL-1ß and INOS increased after a conditioned culture of microglia with the supernatant including IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the expression of IL-1ß and INOS significantly diminished. CONCLUSION: IL-6 plays a key role in the occurrence and development of OD in AR, which may be related to its effect on olfactory bulb microglia-mediated neuroinflammation.

19.
Gut ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553043

RESUMO

OBJECTIVE: Currently, there is no cure for chronic pancreatitis (CP). Germline loss-of-function variants in SPINK1 (encoding trypsin inhibitor) are common in patients with CP and are associated with acute attacks and progression of the disease. This preclinical study was conducted to explore the potential of adeno-associated virus type 8 (AAV8)-mediated overexpression of human SPINK1 (hSPINK1) for pancreatitis therapy in mice. DESIGN: A capsid-optimised AAV8-mediated hSPINK1 expression vector (AAV8-hSPINK1) to target the pancreas was constructed. Mice were treated with AAV8-hSPINK1 by intraperitoneal injection. Pancreatic transduction efficiency and safety of AAV8-hSPINK1 were dynamically evaluated in infected mice. The effectiveness of AAV8-hSPINK1 on pancreatitis prevention and treatment was studied in three mouse models (caerulein-induced pancreatitis, pancreatic duct ligation and Spink1 c.194+2T>C mouse models). RESULTS: The constructed AAV8-hSPINK1 vector specifically and safely targeted the pancreas, had low organ tropism for the heart, lungs, spleen, liver and kidneys and had a high transduction efficiency (the optimal expression dose was 2×1011 vg/animal). The expression and efficacy of hSPINK1 peaked at 4 weeks after injection and remained at significant level for up to at least 8 weeks. In all three mouse models, a single dose of AAV8-hSPINK1 before disease onset significantly alleviated the severity of pancreatitis, reduced the progression of fibrosis, decreased the levels of apoptosis and autophagy in the pancreas and accelerated the pancreatitis recovery process. CONCLUSION: One-time injection of AAV8-hSPINK1 safely targets the pancreas with high transduction efficiency and effectively ameliorates pancreatitis phenotypes in mice. This approach is promising for the prevention and treatment of CP.

20.
BMJ ; 384: e078581, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443074

RESUMO

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.


Assuntos
Endoscopia por Cápsula , Varizes Esofágicas e Gástricas , Varizes , Adulto , Humanos , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Cirrose Hepática/complicações , Estudos Prospectivos
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