3D hippocampal segmentation based on spatial and frequency domain features adaptive fusion and inter⁃class boundary region enhancement / 解剖学报

Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

The Research about the Emerging Body Enhancement Technique from the Perspective of the Physical Care / 中国医学伦理学

The co-development of the technology pointing to the "external nature" and the technology pointing to the "physical nature" promotes the co-evolution of the man and the machine. The emerging body enhancement technique is derived from the "defective existence" of the man, and it changes the "body nature" from the inside of the man. The emerging body enhancement techniques are rapidly spread out driven by the multiple forces. The emerging body enhancement techniques has led to the weakening of the natural body identity and the strengthening of the symbolic body identity, the class solidification and the rise of "cyberpunk", the mixing of the natural person and the technical person. To consciously guide the development and application of emerging human enhancement surgery used human care theory. The physical care is an important reference to judge the good and the evil of the emerging body enhancement technique. The management about the body ethics is the optimal choice about the management of the emerging body enhancement technique. The physical care is the important content of the education of the emerging body enhancement technique.

Effect of Terpenes on the enhancement of skin permeation of lipophilic drugs: A systematic review

Objectives@#The stratum corneum (SC) remains an obstacle to the passage of drugs applied topically. Several investigations have focused on enhancing the penetration of drugs through the SC by integrating permeation enhancers (PE) into the drug formulation. Terpenes are among the PE utilized in formulations and are categorized by the regulatory bodies as generally recognized as safe (GRAS). This study aimed to comparatively analyze the skin permeation enhancing effect of terpenes on lipophilic drugs. @*Methods@#The present study reviewed the effects of terpenes on the permeation of lipophilic small-molecule drugs through the skin using original research published between 2000 - 2022 retrieved from PubMed®. The search phrase used was (lipophilic drug) AND (terpene) AND (permeation enhancer). @*Results@#Terpenes increase the percutaneous permeation of lipophilic small molecule drugs by 1.06 – 256.80-fold. Linear correlation analysis of terpenes’ cLog P with enhancement ratio (ER) revealed moderate and strong positive correlations in pig skin (r = 0.21) and mouse skin (r = 0.27), and rat skin (r = 0.41) and human skin (r = 0.67), respectively. Drug cLog P is a poor (r = -0.06) predictor of permeation enhancement. Terpenes with cLog P higher than 2.40 had ER greater than 10. Higher ERs (>30) were recorded for nerolidol, carvacrol, borneol, terpineol, limonene, menthone, pulegone, and menthol among the terpene-chemical penetration enhancers. @*Conclusion@#cLog P of terpene-based chemical permeation enhancers (CPE) is strongly correlated with ER of lipophilic drugs across human skin. Non-polar groups in terpenes and hydrogen bond interactions by terpenes with SC lipid enhance cutaneous drug penetration of lipophilic drugs.

Recent Advances in the development of Modified Release Tablets by amalgamating both Solubility Enhancement and Polymer Matrix Sintering Technologies.

Background: The fact that about 90 % of newly discovered API’s or new molecular entity(NME) have little or no aqueous solubility, causes a significant protest to the initialization of development and their scale up of dosage form in the Pharma Industry. Aqueous solubility of API’s has critical role in drug dissolution or availability of drug at the site of action or bioavailability, when a dosage form is administered orally.Objective: The object of this study is to formulate a modified release tablet dosage form of a poorly aqueous soluble drug, which not only have higher aqueous solubility or bioavailability but also have sustained release characteristics with high mechanical strength &their commercial viability. Numerous techniques are available for the solubility enhancement but all individual techniques have its own limitations for commercialization.Method: Aqueous solubility of drugs is improved by the known Solubility enhancement techniques like Micronization &Solid dispersions. After successful solubility enhancement, sustained release or modified release tablets of poorly aqueous soluble drug can be easily formulated into a suitable shape or size by using a known Polymer Matrix Sintering Technology with commercial feasibility. Micronization of poorly water-soluble drugs can be performed by Air Jet Mill or Ball Mill. Whereas Solid dispersion technique involves, molecular dispersion of poorly soluble drug in a suitable inert carrier, to form an amorphous and highly soluble compounds. Sintering Technology is defined as the bonding of adjacent particle surfaces in a mass of powder, or in compact, by the application of heat. Conventional sintering technique involves the heating of compact at a temperature below the melting point of the solid constituents in a controlled environment under atmospheric pressure.Results: Enhanced solubility of poorly soluble API’s by these proposed techniques is due to either conversion of crystalline compound in to amorphous form or reduction of particle size to its molecular level by the application of Micronization or solid dispersion techniques. The developed modified release tablets will show a sustained release characteristic due to Sintering aspect and provides enhanced solubility of BCS class II or IV drugs.Conclusion: Novel modified release tablets have been designed through consolidation of Solubility enhancement and Polymer Matrix Sintering technologies. Simultaneous exploitation of well-known and established approaches- Micronization (optimum particle size reduction) or solid dispersion, optional surfactant and Polymer Matrix Sintering Technique in the recent concept, produces significant enhancement of solubility of poorly water soluble API’s without compromising the content uniformity of dosage form and also provide a modified or sustained release characteristics with high mechanical strength. The release profile of drug can be easily tailored by using combination of both techniques where challenges of low solubility are prominent.

Visual outcomes of early enhancement following small incision lenticule extraction versus laser in situ keratomileusis

Purpose: To compare visual outcomes of early enhancement following small incision lenticule extraction (SMILE) versus laser in situ keratomileusis (LASIK). Methods: Retrospective analysis of eyes (patients operated in the setting of a tertiary eye care hospital between 2014 and 2020) requiring early enhancement (within one year of primary surgery) was conducted. Stability of refractive error, corneal tomography, and anterior segment Optical Coherence Tomography (AS-OCT) for epithelial thickness was performed. The correction post regression was done using photorefractive keratectomy and flap lift in eyes, wherein the primary procedure was SMILE and LASIK, respectively. Pre- and post enhancement corrected and uncorrected distance visual acuity (CDVA and UDVA), mean refractive spherical equivalent (MRSE), and cylinder were analyzed. IBM SPSS statistical software. Results: In total, 6350 and 8176 eyes post SMILE and LASIK, respectively, were analyzed. Of these, 32 eyes of 26 patients (0.5%) post SMILE and 36 eyes of 32 patients (0.44%) post-LASIK required enhancement. Post enhancement (flap lift in LASIK, and PRK in SMILE group) UDVA was logMAR 0.02 ± 0.05 and 0.09 ± 0.16 (P = 0.009), respectively. There was no significant difference between the refractive sphere (P = 0.33) and MRSE (P = 0.09). In total, 62.5% of the eyes in the SMILE group and 80.5% in the LASIK group had a UDVA of 20/20 or better (P = 0.04). Conclusion: PRK post SMILE demonstrated comparable results to flap lift post LASIK and is a safe and effective approach for early enhancement post SMILE.

Formulation and Evaluation of Orodispersible Tablet Containing Combination of Phosphodiesterase-5 Inhibitor and Herbal Aphrodisiac

Purpose: Sildenafil citrate is widely used drug for the treatment of Erectile Dysfunction (ED) and Ginseng is a natural aphrodisiac reported to benefit this condition. The objective of the present study was to develop orodispersible tablets (ODTs) containing combination of Sildenafil citrate and Ginseng extract to improve the bioavailability, reduce the dosing frequency and thereby maintaining the therapeutic efficacy of the drug. Methods: The ODTs were prepared using superdisintegrants such as Croscarmellose sodium (CCS), povidone, and sodium starch glycolate (SSG) at varying concentrations (2%, 4% and 6%) by direct compression. The bitter taste of Sildenafil citrate was masked by Doshion resin. The optimized formulation based on least disintegration time (DT) was chosen to reformulate using sublimating agents such as camphor, menthol or thymol at varying concentrations (1%, 2%, 3%) to further reduce the DT. The compatibility of drug with excipients was investigated and the prepared formulations were evaluated for pre and post-compression parameters. Results: The post-compression parameters such as weight variation, hardness, friability, DT and in-vitro drug release was found within specified limit. The formulation with camphor (2%) had DT of 12 sec and drug release >90% within 5 min hence was considered as optimized formulation. The accelerated stability study and kinetics modelling was performed for optimized formulation. Conclusion: The formulated Sildenafil citrate and Ginseng ODT’s were found to be promising formulation with quicker DT and drug release which will eventually have higher bioavailability and better efficacy along with averting the issues of swallowing and improving patient compliance.

Perfusion-weighted imaging in vestibular schwannoma: the influence that cystic status and tumor size have on perfusion profiles / Perfusão por ressonância magnética em schwannoma vestibular: influência do tamanho e estádio cístico no perfil da perfusão

Abstract Objective: The perfusion profile of vestibular schwannomas (VSs) and the factors that influence it have yet to be determined. Materials and Methods: Twenty patients with sporadic VS were analyzed by calculating parameters related to the extravascular extracellular space (EES)—the volume transfer constant between a vessel and the EES (Ktrans); the EES volume per unit of tissue volume (Ve); and the rate transfer constant between EES and blood plasma (Kep)—as well as the relative cerebral blood volume (rCBV), and by correlating those parameters with the size of the tumor and its structure (solid, cystic, or heterogeneous). Results: Although Ktrans, Ve, and Kep were measurable in all tumors, rCBV was measurable only in large tumors. We detected a positive correlation between Ktrans and rCBV (r = 0.62, p = 0.031), a negative correlation between Ve and Kep (r = -0.51, p = 0.021), and a positive correlation between Ktrans and Ve only in solid VSs (r = 0.64, p = 0.048). Comparing the means for small and large VSs, we found that the former showed lower Ktrans (0.13 vs. 0.029, p < 0.001), higher Kep (0.68 vs. 0.46, p = 0.037), and lower Ve (0.45 vs. 0.83, p < 0.001). The mean Ktrans was lower in the cystic portions of cystic VSs than in their solid portions (0.14 vs. 0.32, p < 0.001), as was the mean Ve (0.37 vs. 0.78, p < 0.001). There were positive correlations between the solid and cystic portions for Ktrans (r = 0.71, p = 0.048) and Kep (r = 0.74, p = 0.037). Conclusion: In VS, tumor size appears to be consistently associated with perfusion values. In cystic VS, the cystic portions seem to have lower Ktrans and Ve than do the solid portions.

Resumo Objetivo: O perfil de perfusão do schwannoma vestibular (SV) não tem sido estudado, nem os fatores que o influenciam. Materiais e Métodos: Vinte pacientes com SV esporádico foram analisados usando Ktrans, Ve, Kep e rCBV e correlacionados com tamanho e estádio cístico. Resultados: Ktrans, Ve e Kep foram medidos em todos os casos. rCBV só foi possível em tumores grandes. Ktrans e rCBV estavam correlacionados positivamente (r = 0,62, p = 0, 0 31 ) . Ve e Kep estavam negativamente correlacionados (r = -0,51, p = 0,021). Ktrans estava correlacionado positivamente com Ve em SVs sólidos (r = 0,64, p = 0,048). Em SVs pequenos, Ktrans foi menor (0,13 vs 0,029, p < 0,001), Kep foi maior (0,68 vs 0,46, p = 0,037) e Ve foi menor (0,45 vs 0,83, p < 0,001) que nos SVs grandes. Ktrans e Ve foram menores dentro dos cistos que nas porções solidas dos SVs císticos (0,14 vs 0,32, p < 0,001; 0,37 vs 0,78, p < 0.001, respectivamente). Foi encontrada correlação positiva em Ktrans (r = 0,71, p = 0,048) e Kep (r = 0,74, p = 0,037) entre as áreas sólidas e císticas. Conclusão: Nos SVs, o tamanho está consistentemente associado com os valores da perfusão. Nos SVs císticos, as porções císticas parecem ter valores menores de Ktrans e Ve do que nas porções sólidas.

Sorting and Elaborating on the Combination Theory of Herb Pairs / 中医杂志

@#As the smallest combination unit of Chinese medicinals， herbal pairs serve as the bridge between medicinals and formulas， whose combination theory reflects the basic characteristics of Chinese medicinals combination and the core essence of prescription composition. Simultaneously， as a key combination of medicinals in clinical treatment of diseases， syndromes， and symptoms， herbal pairs are the main form of clinical medication in traditional Chinese medicine （TCM） as well as the characteristic advantage of treating diseases. This article summarized that “mutual complement of medicinals of same or antagonism flavor and nature” theory is the theoretical origin， and efficacy-enhancement and toxicity-attenuation is the core purpose of the combination of herbal pairs. The property theory of Chinese medicinals and the thought of differentiation and treatment are the main basis of the combination of herbal pairs， and pertinence and flexibility are the key points in clinical application. All mentioned above are expected to provide theoretical guidance for the clinical use and modern research of herbal pairs.

Molecular epidemiology of clinical isolation of carbapenem-resistant Enterobacterales and application of carbapenemase inhibitor enhancement test / 中南大学学报(医学版)

OBJECTIVES@#The prevalence of carbapenem-resistant Enterobacterales (CRE) presents a significant challenge in clinical anti-infective treatment. This study aims to investigate drug resistance and the molecular epidemiological characteristics of CRE in our area. Additionally, we seek to evaluate practicality of utilizing carbapenemase inhibitor enhancement test in clinical laboratory.@*METHODS@#Non-repeated CREs isolated from clinical specimens at Xiangya Hospital, Central South University, were collected. Minimum inhibitory concentration (MIC) combined with Kirby-Bauer (KB) assay was used to detect the drug susceptibility of the strains, and 13 carbapenemase-producing genes were detected by PCR. The phenotype of 126 strains of carbapenemase-producing Enterobacterales identified by PCR was detected by the carbapenemase inhibitor enhancement test to understand the agreement between the method and the gold standard PCR results.@*RESULTS@#Among 704 CRE strains examined, we observed significant drug resistance in 501 strains dentified as carbapenemase-producing Enterobacterales (CPE). Klebsiella pneumoniae was the predominant CPE strain, followed by Enterobacter cloacae and Escherichia coli. A total of 9 carbapenemase types were detected, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron- encoded metallo-β-lactamases (VIM), imipenemase (IMP), oxacillinase-48 (OXA-48), and rare imipenem-hydrolyzing β-lactamase (IMI), adelaide imipenemase (AIM), Bicêtre carbapenemase (BIC), and guiana extended-spectrum β-lactamase (GES). The detection rate of KPC serine carbapenemase was 61.7% (309/501). The carbapenemase inhibitor enhancement test exhibited a 100% consistency rate for the strains producing Class A serine carbapenemase and/or Class B metallo-β-lactamases.@*CONCLUSIONS@#CRE strains in Changsha, Hunan, China, are wide distribution and exhibit carbapenemase production. The main mechanism of carbapenem resistance in these bacterias is predominatly attributed to the production of KPC serine carbapenemase. The presence of GES and IMI genes carried by Enterobacterales has been detected for the first time in this region. The carbapenemase inhibitor enhancement test has been proven to be an accurate method for detecting CRE producing Class A serine carbapenemase and/or Class B metallo-β-lactamases. This method offers simpicity of operation and ease of results interpretation, making it weel-suited meeting the clinical microbiology laboratory's reguirements for the detection of serine carbapenemase and metallo-β-lactamases.

Entre o medo e a esperança: um estudo sobre os usos e sentidos do treinamento cerebral no Brasil / Between fear and hope: a study on the uses and meanings of brain training in Brazil

O presente trabalho tem como objeto de análise os usos e sentidos das práticas de treinamento cerebral na realidade brasileira. Este tipo de treinamento, também chamado de treinamento cognitivo e ginástica cerebral, diz respeito à prática guiada de determinados exercícios e jogos com o objetivo de preservar ou melhorar as habilidades cognitivas e/ou a cognição como um todo. O objetivo central deste trabalho é mapear e analisar os sentidos atribuídos pelas empresas de treinamento cerebral e seus clientes às próprias atividades de treinamento cerebral. Para atingir tal objetivo realizamos a análise de conteúdo de dois conjuntos de dados: a) informações textuais dos sites oficiais das três franquias de treinamento cerebral existentes no Brasil (Supera, Super Cérebro e Ginástica do Cérebro) assim como das principais plataformas virtuais brasileiras (Supera Online, NeuroForma, Afinando o Cérebro e Mente Turbinada); b) transcrições de entrevistas semiestruturadas com dez clientes destas empresas, com idades entre 22 e 87 anos, e que praticavam regulamente tais atividades. Após analisarmos o conteúdo dos sites e das entrevistas pudemos observar que os sentidos do treinamento cerebral se relacionam, para os clientes, a uma série de medos e esperanças ­ e também à busca por diversão e sociabilidade. Dentre os medos destaca-se aquele relacionado à possibilidade de desenvolver a doença de Alzheimer ou algum outro quadro demencial que prejudique suas funções cognitivas e os levem a perder a autonomia e se tornarem dependentes de outras pessoas. Por outro lado, a busca por atividades de treinamento cerebral se relaciona também à esperança de reverter ou interromper o "declínio cognitivo" e de evitar, assim, o desenvolvimento de uma demência. As empresas, por sua vez, fomentam em seus clientes e potenciais clientes, através dos seus sites publicitários, diferentes formas de esperança, em especial a esperança de um futuro com capacidade cognitiva nas diversas etapas da vida. É possível dizer que o que há em comum entre aquilo que é vendido pelas empresas e aquilo que é comprado por seus clientes é a esperança. Apontamos, por fim, para as técnicas de treinamento cerebral como tecnologias da esperança, devido ao fato de serem utilizadas pelas empresas do ramo para fomentarem em seus clientes e potenciais clientes a crença de que é possível agir no presente de forma a preservar e aprimorar as habilidades cognitivas, a prevenir doenças como o Alzheimer e a prolongar o tempo de vida com saúde, autonomia e independência... (AU)

The main goal of the present doctoral thesis is to analyze the uses and meanings of the practices of cerebral training in Brazil. This type of training, also known as cognitive training and cerebral gymnastics, is related to the guided practice of specific exercises and games to preserve or improve cognitive skills and/or cognition in general. The main objective of this work is to map and analyze the definitions attributed to cerebral training companies and their clients to their brain training activities. To achieve this goal, we analyzed two groups of data: a) textual information available on the official websites of three Brazilian franchises focused on brain training (Super, Super Cérebro e Ginástica do Cérebro), as well the leading Brazilian virtual platforms (Supera Online, NeuroForma, Afinando o Cérebro e Mente Turbinada); b) transcriptions of semi-structured interviews with ten regular consumers of these companies, ages from 22 to 87 years. After analyzing the contents available on the websites and interviews, we could observe that the aims of brain training are connected. Besides the search for fun and sociability on the client's side, there are a series of fears and hopes. Among fears, we could stand out as the ones connected to the possibility of developing a future Alzheimer's disease or any other type of dementia state that could harm their cognitive functions and, consequently, lead them to lose their autonomy and become dependent on others. On the other hand, the search for brain gymnastic activities is related to the hope to revert or interrupt the "cognitive decline" and avoid the development of dementia. However, on their side, the companies encourage their clients and potential clients, through their advertising websites, different ways to trigger their hopes, especially the hope of a future when they develop cognitive capacities in different parts of their lives. We could claim that what connects the message released and these types of products, bought and sold, is hope. We finally point out that the techniques of brain training are technologies of hope since the companies of the field use them to foment their clients and potential clients the belief that it is possible to achieve, in the present, some preservation and improvement of cognitive skills, to prevent some diseases as Alzheimer and to lengthen their life expectancy healthily, enjoying autonomy and independence...(AU)

Advances in the diagnosis of primary solid small bowel tumors by contrast-enhanced multislice spiral CT / 中国辐射卫生

@#Primary small bowel tumors have low incidence and contain predominantly solid components, and the lesions are similar and difficult to be detected and distinguished with multislice spiral CT (MSCT) plain scans. In this article we describe contrast-enhanced MSCT technique and imaging characteristics for solid small bowel tumors or small bowel tumors containing predominantly solid components, including the type and use of contrast agents. In contrast-enhanced MSCT, small bowel imaging with CT has the advantages of determining the true extent of intestinal wall lesions, the possible extent of wall penetration, the degree of mesenteric involvement, and distant metastases, as well as easiness to detect and identify the blood supply vessels of small bowel tumors and assessment of the corresponding complications. Contrast-enhanced MSCT has become the best noninvasive imaging technique for the diagnosis, evaluation, and staging of solid small bowel tumors or small bowel tumors containing predominantly solid components. CT texture analysis (CTTA) is a new research hotspot and can be useful for the correct diagnosis of primary small bowel tumors containing predominantly solid components.

Research on phase modulation to enhance the feature of high-frequency steady-state asymmetric visual evoked potentials / 生物医学工程学杂志

High-frequency steady-state asymmetric visual evoked potential (SSaVEP) provides a new paradigm for designing comfortable and practical brain-computer interface (BCI) systems. However, due to the weak amplitude and strong noise of high-frequency signals, it is of great significance to study how to enhance their signal features. In this study, a 30 Hz high-frequency visual stimulus was used, and the peripheral visual field was equally divided into eight annular sectors. Eight kinds of annular sector pairs were selected based on the mapping relationship of visual space onto the primary visual cortex (V1), and three phases (in-phase[0º, 0º], anti-phase [0º, 180º], and anti-phase [180º, 0º]) were designed for each annular sector pair to explore response intensity and signal-to-noise ratio under phase modulation. A total of 8 healthy subjects were recruited in the experiment. The results showed that three annular sector pairs exhibited significant differences in SSaVEP features under phase modulation at 30 Hz high-frequency stimulation. And the spatial feature analysis showed that the two types of features of the annular sector pair in the lower visual field were significantly higher than those in the upper visual field. This study further used the filter bank and ensemble task-related component analysis to calculate the classification accuracy of annular sector pairs under three-phase modulations, and the average accuracy was up to 91.5%, which proved that the phase-modulated SSaVEP features could be used to encode high- frequency SSaVEP. In summary, the results of this study provide new ideas for enhancing the features of high-frequency SSaVEP signals and expanding the instruction set of the traditional steady state visual evoked potential paradigm.

CT and MRI fusion based on generative adversarial network and convolutional neural networks under image enhancement / 生物医学工程学杂志

Aiming at the problems of missing important features, inconspicuous details and unclear textures in the fusion of multimodal medical images, this paper proposes a method of computed tomography (CT) image and magnetic resonance imaging (MRI) image fusion using generative adversarial network (GAN) and convolutional neural network (CNN) under image enhancement. The generator aimed at high-frequency feature images and used double discriminators to target the fusion images after inverse transform; Then high-frequency feature images were fused by trained GAN model, and low-frequency feature images were fused by CNN pre-training model based on transfer learning. Experimental results showed that, compared with the current advanced fusion algorithm, the proposed method had more abundant texture details and clearer contour edge information in subjective representation. In the evaluation of objective indicators, Q AB/F, information entropy (IE), spatial frequency (SF), structural similarity (SSIM), mutual information (MI) and visual information fidelity for fusion (VIFF) were 2.0%, 6.3%, 7.0%, 5.5%, 9.0% and 3.3% higher than the best test results, respectively. The fused image can be effectively applied to medical diagnosis to further improve the diagnostic efficiency.

Prognostic Value of MRI Arterial-phase Enhancement Pattern in Intrahepatic Cholangiocarcinoma Patients / 中山大学学报(医学科学版)

ObjectiveTo investigate the prognostic value of the enhancement pattern in arterial phase of preoperative Gd-EOB-DTPA enhanced magnetic resonance imaging （MRI） in evaluating the disease-free survival （DFS） and overall survival （OS） in patients undergoing curative resection for intrahepatic cholangiocarcinoma （ICC）. MethodsA retrospective analysis was done on the clinical， preoperative MRI findings and postoperative follow-up results of 93 pathologically confirmed ICC patients undergoing surgery in our hospital between January 2018 and December 2021. Kaplan-Meier survival curves and log-rank test were used to compare the DFS and OS of three groups with different arterial enhancement patterns. Cox regression analysis was used to identify the factors affecting DFS and OS. ResultsThere were significant differences in DFS and OS among the 3 groups （log-rank test， P < 0.05）. The arterial enhancement pattern was an independent predictive factor for DFS （using diffuse hyperenhancement as a reference， peripheral rim enhancement： HR = 3.550； 95%CI： 1.16 ~ 10.8； P = 0.026；diffuse hypoenhancement： HR = 3.430； 95%CI： 1.04 ~ 11.3； P = 0.042）. The arterial enhancement pattern and tumor location were predictive factors for OS （（using diffuse hyperenhancement as a reference， diffuse hypoenhancement， HR = 8.500； 95%CI： 1.09-66.3； P = 0.041； using tumor distal location as a reference， tumor perihilar location HR=2.583，95%CI： 1.14-5.83， P =0.022）. The AUC of arterial enhancement patterns in predicting 1-， 2-， and 3- year DFS were 0.722， 0.748， and 0.617， respectively； in OS， 0.720， 0.704， and 0.730， respectively， which showed better prognostic efficacy than AJCC-TNM staging system. ConclusionArterial-phase enhancement pattern of preoperative Gd-EOB-DTPA enhanced MRI is an independent predictive factor for DFS and OS of ICC patients， with a better prognostic value than AJCC-TNM staging system， and can be used for the clinical management of ICC patients.

Construction of CeRNA network of differential LncRNAs in THP-1 cells infected by Dengue virus type Ⅲ and its antibody dependent enhancement / 中国生物制品学杂志

@#ObjectiveTo establish models of Dengue virus type Ⅲ（DENV-3,DV-3）infection and antibody dependent enhancement(ADE)infection at the acute monocytic leukemia cells(THP-1),investigate the differential expression of long non-coding RNAs(LncRNAs),map the competitive endogenous RNA(CeRNA)regulatory network and predict the translation function of LncRNAs.MethodsThe culture supernatant was harvested 6 d after C6/36 cells were infected with DENV-3,the virus titer was determined by CCID50,and the type and full-length genome amplification were identified by PCR;The DENV-3 standard plasmid was amplified,identified by PCR,and the standard curve was drawn;THP-1 cells were divided into negative control group(THP-1),direct infection group(DV-3),ADE group and blank control group[1640(-)]. After 48 h of infection,the total RNA was extracted and the copy number of intracellular virus nucleic acid was measured;Through the whole transcriptome sequencing technology,the CeRNA regulatory network was constructed for the top five up-regulated and down-regulated LncRNAs in THP-1 vs DENV3,THP-1 vs ADE,DENV3 vs ADE groups,and the functions of their coding proteins were analyzed.ResultsC6/36 cells infected with DENV-3 for 3 d showed obvious cell fusion,vacuoles and abscission;The virus had a titer of about 1. 0 × 104. 64PFU/mL and was identified as DENV-3 by PCR specific primers,of which the complete gene sequence was obtained;The number of viral nucleic acid copies in ADE group was significantly higher than those in DV-3 group and blank control group;In THP-1 vs DENV-3,the expression of cytohesin interacting protein(CYTIP)was predicted to be up-regulated;In THP-1 vs ADE,the expression of kinesin family5A(KIF5A)was predicted to be down-regulated;In DENV-3 vs ADE,the expression of cluster differentiation antigen 9(CD9)and insulin like growth factor 2(IGF2)was predicted to be up-regulated. All of these differential LncRNAs had open reading frames(ORFs). Except Lnc-SH3BP1 and Lnc-RPL41,all of the other LncRNAs had internal ribosome binding site(IRES).ConclusionIn DENV-3 infection of THP-1 cells and ADE infection mediated by DENV-3,the expression of LncRNAs has changed significantly,and may regulate the process of infection through a variety of biological functions,which is helpful for a deeper understanding of the mechanism of ADE infection.

Research progress in optimization of therapeutic effect of antibodies against flavivirus / 中华微生物学和免疫学杂志

Flaviviruses are a class of positive-strand RNA viruses mainly transmitted by arthropods, which can cause high mortality and morbidity worldwide. At present, there is no specific therapy. Therapeutic antibodies bring hope for the treatment of flavivirus infection, but the antibody-dependent enhancement (ADE) effect induced by flavivirus infection can lead to disease progression. The ideal therapeutic antibodies against flaviviruses should not only treat flavivirus infection, but also avoid the harm caused by ADE. Therefore, researchers have optimized some of the antibodies to seek the best therapeutic antibodies. This review briefly described the research progress and mechanism of therapeutic antibodies against flaviviruses as well as some strategies to reduce the ADE effect induced by the therapeutic antibodies.

Feasibility and accuracy of dual-energy CT multiparameter technique in evaluating myocardial scar in patients with heart failure / 中华放射学杂志

Objective:To evaluate the reliability of cardiac late iodine enhancement dual-energy CT (LIE-DECT) multiparameter post-processing technique for evaluating the presence, location, and extent of cardiac scars in patients with heart failure (HF), using cardiac MR (CMR) late gadolinium enhancement (LGE) as a reference standard.Methods:Thirty-nine HF patients who underwent cardiac LIE-DECT and LGE-CMR examinations in the Second Affiliated Hospital of Nantong University from November 2019 to November 2021 were prospectively collected, all enrolled HF patients underwent LIE-DECT post-processing to reconstruct monoenergetic plus (Mono+) map (40 keV), iodine map and Rho/Z map, to evaluate the enhancement degree, location and extent of left ventricular myocardial LIE on the left ventricular short-axis map, respectively, and compared with LGE-CMR. Cohen′s Kappa test was used to assess the intra-and inter-observer consistency of LIE by DECT multiparameter technique and the consistency of LIE presence and location by DECT multiparameter technique and by CMR. The diagnostic efficacy of DECT multiparameter technique in diagnosing myocardial scar was calculated.Results:Of the 39 patients included, 32 patients were detected by CMR with LGE in 147 segments, including 37 subendocardial patterns, 19 transmural patterns, 74 mid-wall patterns, and 17 epicardial patterns. The intra-observer consistency Kappa values of 40 keV Mono+map, iodine map and Rho/Z map were 0.878, 0.930 and 0.835 ( P all<0.001), respectively. The inter-observer consistency Kappa values were 0.838, 0.892 and 0.808 ( P all<0.001), respectively. The LIE of 40 keV Mono+map, iodine map and Rho/Z map were in good agreement with CMR, Kappa values were 0.903, 0.883 and 0.810 ( P all<0.001), respectively. For the per-patient analysis, the accuracies of 40 keV Mono+map, iodine map and Rho/Z map were 92.3% (36/39), 92.3% (36/39) and 82.1% (32/39), respectively. For the segment-based analysis, the accuracies of 40 keV Mono+map, iodine map and Rho/Z map accuracy were 96.1% (492/512), 95.3% (488/512) and 92.6% (474/512), respectively. In Bland-Altman analysis, the consistency bias between scar extent measured by 40 keV Mono+map, iodine map, Rho/Z map and that measured by LGE-CMR were -2.03%, -2.21%, -2.65%, and the 95% limit of agreement were -12.20%-8.14%, -12.69%-8.28% and -14.85%-9.58%, respectively. Conclusion:LIE-DECT multiparameter technique can detect myocardial scar in HF patients well, which is consistent with LGE-CMR.

Tumor perfusion enhancement effect combined with programmed cell death-Ligand 1 antibody improves the immune microenvironment of solid tumors / 中华超声影像学杂志

Objective:To investigate the tumor perfusion enhancement induced by low intensity ultrasound stimulated microbubble cavitation (USMC) combined with programmed cell death-Ligand 1(PD-L1) antibody on improving the immune microenvironment of solid tumors.Methods:Tumor-bearing mice were divided into 4 groups: Control ( n=26) group, USMC ( n=27) group, anti-PD-L1 ( n=27) group and USMC+ anti-PD-L1 ( n=27) group. USMC treatment was performed with a VINNO 70 ultrasound theranostics system. Tumor perfusion was evaluated by contrast-enhanced ultrasound (CEUS). The anti-tumor efficacy was assessed by the tumor growth curve and the survival time of mice. The number and function of CD8 + T cells, the differentiation of CD4 + T cells, the proportion of MDSC and the phenotype distribution of TAM in tumors were analyzed by flow cytometry. The content of CXCL9, CXCL10 and HIF-1α in tumor were detected by ELISA. The expression of VEGF in tumor tissues was analyzed by immunofluorescence. Results:CEUS showed that the values of PI and AUC of tumors were significantly increased after USMC compared with before USMC (all P<0.05). USMC combined with anti-PD-L1 therapy did suppress the tumor progression. FCM showed the number, the expression of proliferation antigen Ki67, the secretion of IFN-γ and Granzyme B of CD8 + T cells in tumors were higher in combined group than those in other three groups after therapy (all P<0.05). Meantime, the proportion of Th1 was rose while Tregs and MDSC were declined and the polarization of TAM was toward M1 type by combined therapy. ELISA analysis showed that the combined therapy also increased the concentration of CXCL9, CXCL10 and decreased the content of HIF-1α in tumors (all P<0.05). Meanwhile, the immunofluorescence expression of VEGF was significantly lower in combined group than that in the control group after treatment ( P<0.05). Conclusions:Tumor perfusion enhancement by USMC combined with PD-L1 antibody therapy could improve tumor immune microenvironment and USMC might be a novel effective method for potentiating PD-L1 antibody immunotherapy.

Diagnostic value of cardiac magnetic resonance contrast medium perfusion and delayed contrast enhancement for early myocardial ischemia / 中国基层医药

Objective:To investigate the diagnostic value of cardiac magnetic resonance (CMR) contrast medium perfusion and delayed contrast enhancement for early myocardial ischemia.Methods:Ninety-one patients with coronary artery stenosis diagnosed by coronary angiography (CAG) between March 2020 and March 2022 in Yiwu Central Hospital were included in this study. These patients underwent first-pass perfusion cardiac magnetic resonance imaging and delayed enhancement examination. Arrival time ( t0), accumulative signal intensity (ASI), relative peak enhancement rate (SI%), maximum intensity of signal enhancement (SIp), and maximum curve slope (α) were statistically analyzed in the CMR contrast agent normal-dose perfusion and low-dose perfusion segments. The diagnostic value of CMR contrast agent perfusion versus CAG for early myocardial ischemia was determined. The signal intensity was compared between enhanced and non-enhanced areas of CMR contrast agent perfusion. Results:There were significant differences in ASI, SI%, SIp, and Slope (α) between normal perfusion and low perfusion segments ( t = 9.62, 10.65, 8.67, 6.93, all P < 0.05). There was no significant difference in the detection rate of lesioned vessels in early myocardial ischemia between CMR contrast agent perfusion and CAG [50.42% (120/238) vs. 51.68% (123/238), χ2 = 1.32, P = 0.163). There was a significant difference in the detection rate of lesioned vessels in myocardial ischemia between CMR contrast agent perfusion and CAG ( χ2 = 15.31, P < 0.001, r = 0.71). The signal intensity value in the delayed enhancement segment was significantly higher than that in the non-delayed enhancement segment [(598.43 ± 40.19) vs. (298.64 ± 70.58), t =19.85, P = 0.001). Conclusion:CMR contrast agent perfusion can effectively evaluate the severity of early myocardial ischemia and locate the diseased blood vessels. Delayed enhancement can determine the location and area of early myocardial ischemia, and can objectively reflect the severity of myocardial ischemia.

Value of endoscopic ultrasound elastography versus contrast-enhanced computed tomography in the diagnosis of gastrointestinal stromal tumors / 中国基层医药

Objective:To investigate the clinical value of endoscopic ultrasound elastography versus contrast-enhanced computed tomography in the risk stratification of gastrointestinal stromal tumors (GISTs). Methods:Clinical and imaging data were obtained from 77 patients who were confirmed to have GISTs and underwent endoscopic or surgical treatment at Wenzhou Central Hospital between May 2019 and April 2021. Endoscopic ultrasound elastography based on a five-point scoring system and hypotonic gastrointestinal contrast-enhanced computed tomography were performed for preoperative risk stratification of GISTs. The two techniques were compared in terms of the accuracy of preoperative risk stratification of GISTs. The imaging features of the two techniques were summarized.Results:According to the postoperative pathological results, 13 patients were at high risk, 13 patients were at medium risk, 35 patients were at low risk, and 16 patients were at extremely low risk. These patients were divided into two groups according to postoperative pathological results: a low-risk group (low risk + extremely low risk) and a medium- and high-risk group (high + medium risk). In the low-risk group ( n = 51), 42 patients were identified by endoscopic ultrasound elastography to have low-risk GISTs and were recommended to receive endoscopic treatment, while the rest 9 patients were identified to have medium-risk GISTs. Contrast-enhanced computed tomography findings revealed that 30 patients had low-risk GISTs and were recommended to receive endoscopic treatment, and 21 patients had medium-risk GISTs. In the medium- and high-risk group ( n = 26), 4 patients were identified by endoscopic ultrasound elastography to have low-risk GISTs, and 22 patients had medium- or high-risk GISTs. Contrast-enhanced computed tomography findings revealed that 9 patients were identified to have low-risk GISTs, and 17 patients had medium- or high-risk GISTs. Endoscopic ultrasound elastography yielded an overall diagnostic accuracy of 83.11% (64/77), while contrast-enhanced computed tomography had an overall diagnostic accuracy of 61.04% (47/77). Endoscopic ultrasound elastography outperformed contrast-enhanced computed tomography in accurate risk stratification of GISTs ( χ2 = 4.66, P < 0.05). In terms of predicting high-risk GISTs, endoscopic ultrasound elastography had a sensitivity of 84.62% and a specificity of 82.35%, both were higher than those of contrast-enhanced computed tomography (sensitivity: 65.38%; specificity: 58.82%), but the differences in sensitivity and specificity between the two techniques were not significant (sensitivity: Fisher's exact test P = 0.590, specificity: χ2 = 0.93, P > 0.05). Conclusion:Endoscopic ultrasound elastography appears to have a better overall diagnostic accuracy in the risk stratification of GISTs compared with contrast-enhanced computed tomography. The combined use of these two techniques may offer a better comprehensive understanding of the perilesional structure and organ involvements and distant metastasis than a single technique, thereby providing a reliable reference for the choice of treatment for GISTs.