Subclinical signs of podocyte injury associated with Circulating Anodic Antigen (CAA) in Schistosoma mansoni-infected patients in Brazil

ABSTRACT Background: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. Methods: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. Results: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. Conclusions: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

Complex benign horizontal canal positional vertigo: new perceptual management

Abstract Objective: Horizontal semicircular canal site pathology of benign paroxysmal positional vertigo demonstrating three types of nystagmi on positional test were studied. We have attempted to design a protocol for its diagnosis and treatment. Methods: 320 patients of HSC-BPPV were subjected to two types of positional tests. Of these, patients with bilateral steady apogeotropic nysatgmus were treated with VAV modification of Semont's maneuver. Patients with unsteady or changing apo/geotropic signs were converted into steady geotropic ones by repetitive positional tests; followed by barbecue maneuver with forced prolong positioning. Results: Overall 88% of patients had a total recovery. 92% of patients with geotropic nystagmus showed no symptoms after second maneuveral sitting. 85% of patients with apogeotropic nystagmus recovered fully after third maneuveral sitting. Conclusion: Correct identification of subtypes of HSC-BPPV is based on provoked nystagmus by positional tests. After locating the site and side on the basis of nystagmic pattern, physician can apply the appropriate PRM. Level of evidence: II a.

Carboplatin-loaded surface modified-PLGA nanoparticles confer sustained inhibitory effect against retinoblastoma cell in vitro / Nanopartículas de PLGA com superfície modificada carregada com carboplatina conferem efeito inibitório sustentado contra células de retinoblastoma in vitro

ABSTRACT Purpose: To investigate the antiproliferative effect of carboplatin-loaded surface-modified poly(lactide-co-glycolide) on retinoblastoma cells. Methods: Carboplatin-loaded poly(lactide-co-glycolide) with or without sodium alginate surface modification was prepared using sodium alginate-poly(lactide-co-glycolide) and poly(lactide-co-glycolide). The zeta potential and carboplatin release behavior were investigated. The cellular uptake of the released drug was observed in the retinoblastoma cell line Y79. The inhibitory effect of carboplatin-loaded nanoparticles against the Y79 cell line was evaluated using methyl thiazolyl tetrazolium assay and western blot. Native carboplatin and void nanoparticles without carboplatin loading were used as controls. Results: The zeta potential was -(26.1 ± 3.1) mV for carboplatin-loaded poly(lactide-co-glycolide) and-(43.1 ± 8.1) mV for carboplatin-loaded sodium alginate-poly(lactide-co-glycolide). The burst release percentages of carboplatin-loaded poly(lactide-co-glycolide) and sodium alginate-poly(lactide-co-glycolide) were (40.0% ± 8.2%) and (18.9% ± 4.3%) at 24 hours, respectively. A significant difference was identified regarding drug release between carboplatin-loaded sodium alginate-poly(lactide-co-glycolide) and carboplatin-loaded poly(lactide-co-glycolide). Fluorescence detection revealed that intense uptake of carboplatin into the cytoplasm of the Y79 cell line that was exposed to carboplatin-loaded sodium alginate-poly(lactide-co-glycolide). Carboplatin-loaded poly(lactide-co-glycolide) or sodium alginate-poly(lactide-co-glycolide) exposure inhibited proliferating cell nuclear antigen expression in Y79 cells on day 3. Extension of exposure to day 5 revealed that the sodium alginate-poly(lactide-co-glycolide) surface modification was superior to that of poly(lactide-co-glycolide) in terms of proliferating cell nuclear antigen inhibition. The cell viability test using methyl thiazolyl tetrazolium revealed a similar inhibitory effect. Furthermore, the carboplatin-loaded nanoparticles of lower concentration inhibited cell viability more strongly than native carboplatin of higher concentration in methyl thiazolyl tetrazolium assay. Conclusions: Carboplatin-loaded sodium alginate-poly(lactide-co-glycolide) inhibited retinoblastoma cell proliferation with superior effect as compared with poly(lactide-co-glycolide) and native carboplatin. Sodium alginate surface modification offers a potential strategy for the sustained carboplatin release system.

RESUMO Objetivo: Investigar o efeito antiproliferativo de poli (lactídeo-coglicolídeo) com superfície modificada carregada com carboplatina contra células de retinoblastoma. Métodos: Preparou-se poli (lactídeo-co-glicolídeo) carregado com carboplatina com ou sem alginato de sódio para modifição da superfície, poli com alginato de sódio (lactídeo-co-glicolídeo) e poli (lactídeo-co-glicolídeo). O potencial zeta e o comportamento de liberação de carboplatina foram investigados. A captação celular do fármaco liberado foi observada na linha celular de retinoblastoma Y79. O efeito inibitório das nanopartículas carregadas com carboplatina contra a linha celular Y79 foi avaliado através do ensaio de metiltiazol tetrazólio e Western-blot. Carboplatina nativa e nanopartículas vazias sem carga de carboplatina serviram como controles. Resultados: O potencial zeta de poli carregado com carboplatina (lactídeo-co-glicolídeo) foi - (26,1 ± 3,1) mV versus - (43,1 ± 8,1) mV em poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo). A percentagem de libertação de explosão de poli carregado com carboplatina (lactídeo-co-glicolídeo) e poli com alginato de sódio (lactídeo-co-glicolídeo) foram (40,0 ± 8,2)% e (18,9 ± 4,3)% às 24 horas, respectivamente. Uma diferença significativa foi identificada em relação à liberação de fármaco entre poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo) e poli carregado com carboplatina (lactídeo-co-glicolídeo). A detecção de fluorescência revelou que a carboplatina foi assimilada intensamente no citoplasma da linha celular Y79 que foi exposta ao poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo). A exposição de poli carregada com carboplatina (lactídeo-co-glicolídeo) ou poli com alginato de sódio (lactídeo-co-glicolídeo) inibiu a expressão de antígeno nuclear de proliferação celular em células Y79 no 3º dia. A extensão da exposição no 5º dia revelou que poli com alginato de sódio (lactídeo-co-glicolídeo) para modificação da superfície foi superior a poli (lactídeo-co-glicolídeo) em termos de inibição do antígeno nuclear de proliferação celular. O teste de viabilidade celular via metiltiazol tetrazólio mostrou um efeito inibitório semelhante. Além disso, as nanopartículas carregadas com carboplatina de concentração mais baixa inibiram a viabilidade celular mais fortemente em comparação com a carboplatina nativa de concentração mais alta no ensaio de metiltiazol tetrazólio. Conclusões: Poli com alginato de sódio carregado com carboplatina (lactídeo-co-glicolídeo) inibiu a proliferação de células de retinoblastoma com efeito superior em contraste com poli (lactídeo-co-glicolídeo) e carboplatina nativa. O alginato de sódio para modificação da superfície oferece uma estratégia potencial para o sistema de liberação de carboplatina sustentada.

Ganoderma applanatum extract mediated synthesis of silver nanoparticles

Abstract Nanotechnology has been used in the field of medicine and pharmacology for its greater efficacy of drug delivery than crude molecules of drugs. In the present study medicinal mushroom Ganoderma applanatum extract mediated silver nanoparticles (AgNPs) were synthesized, characterized by Ultraviolet-visible (UV-Vis.) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction, Dynamic light scattering (DLS) and Furior transform-infrared (FTIR) spectroscopy. Maximum absorbance was recorded at 435nm by UV-Vis. The synthesized nanoparticles of 13.54nm-255nm in size with an average particle size of 58.77nm were analyzed by DLS. FTIR-Spectroscopy provided high transmission at 3606cm-1 corresponds for phenolic capping biochemical. Thus G. applanatum extract can be used for synthesis of silver nanoparticles and the synthesized nanoparticles may be used for development of future therapeutic agent for treatment of diseases.

Effect of particle size on the oral absorption of isoliquiritigenin nanocrystals

Abstract As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have been attracting increasing attention in recent years. Isoliquiritigenin (ISL) is a flavonoid with a chalcone structure, and possesses many biological activities. However, its clinical application is significantly limited mainly due to its low oral bioavailability caused by poor hydrophilicity. To address this, ISL nanocrystals were developed in this study to improve its oral bioavailability. Three types of nanocrystals with differing particle size; R1, R2, and R3, were prepared by anti- solvent precipitation or anti-solvent precipitation combined with sonication, which was optimized by single-factor experiments. These nanocrystals were characterized based on their physical properties, in vitro release, and in vivo absorption performance. The mean particle size of R1, R2, and R3 was 555.7, 271.0, and 46.2, respectively. The dissolution ratio of ISL in the nanocrystals was significantly improved, with the quickest rate recorded in R2. Peak concentration and area under the concentration-time curve of R2 after oral administration in rats was 5.83- and 2.72-fold higher than that of the ISL solution, respectively. These findings indicate that the dissolution and absorption of ISL can be significantly enhanced by nanocrystals, and the dissolution behavior and pharmacokinetic properties of nanocrystals is significantly influenced by particle size.

Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation

Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.

Study on noninvasive blood glucose detection method using the near-infrared light based on particle swarm optimization and back propagation neural network / 生物医学工程学杂志

Most of the existing near-infrared noninvasive blood glucose detection models focus on the relationship between near-infrared absorbance and blood glucose concentration, but do not consider the impact of human physiological state on blood glucose concentration. In order to improve the performance of prediction model, particle swarm optimization (PSO) algorithm was used to train the structure paramters of back propagation (BP) neural network. Moreover, systolic blood pressure, pulse rate, body temperature and 1 550 nm absorbance were introduced as input variables of blood glucose concentration prediction model, and BP neural network was used as prediction model. In order to solve the problem that traditional BP neural network is easy to fall into local optimization, a hybrid model based on PSO-BP was introduced in this paper. The results showed that the prediction effect of PSO-BP model was better than that of traditional BP neural network. The prediction root mean square error and correlation coefficient of ten-fold cross-validation were 0.95 mmol/L and 0.74, respectively. The Clarke error grid analysis results showed that the proportion of model prediction results falling into region A was 84.39%, and the proportion falling into region B was 15.61%, which met the clinical requirements. The model can quickly measure the blood glucose concentration of the subject, and has relatively high accuracy.

Research on gait recognition and prediction based on optimized machine learning algorithm / 生物医学工程学杂志

Aiming at the problems of individual differences in the asynchrony process of human lower limbs and random changes in stride during walking, this paper proposes a method for gait recognition and prediction using motion posture signals. The research adopts an optimized gated recurrent unit (GRU) network algorithm based on immune particle swarm optimization (IPSO) to establish a network model that takes human body posture change data as the input, and the posture change data and accuracy of the next stage as the output, to realize the prediction of human body posture changes. This paper first clearly outlines the process of IPSO's optimization of the GRU algorithm. It collects human body posture change data of multiple subjects performing flat-land walking, squatting, and sitting leg flexion and extension movements. Then, through comparative analysis of IPSO optimized recurrent neural network (RNN), long short-term memory (LSTM) network, GRU network classification and prediction, the effectiveness of the built model is verified. The test results show that the optimized algorithm can better predict the changes in human posture. Among them, the root mean square error (RMSE) of flat-land walking and squatting can reach the accuracy of 10 -3, and the RMSE of sitting leg flexion and extension can reach the accuracy of 10 -2. The R 2 value of various actions can reach above 0.966. The above research results show that the optimized algorithm can be applied to realize human gait movement evaluation and gait trend prediction in rehabilitation treatment, as well as in the design of artificial limbs and lower limb rehabilitation equipment, which provide a reference for future research to improve patients' limb function, activity level, and life independence ability.

Soybean meal particle size for pigs during the nursery phase / Tamanho da partícula do farelo de soja em suínos no período de creche

This study evaluated the effect of soybean meal (SBM) particle size on nutrient digestibility and the growth performance of nursery piglets. Sixty-three piglets (BW = 6.86 kg ± 0.56; 23 d of age) were distributed in a randomized block design (by initial weight and sex) with 3 dietary treatments: diets with 1,017 µm (unground); 585 µm; and 411µm SBM, with 7 replicates of 3 piglets each. All diets were offered ad libitum in mash form, formulated differently according to three growing phases: (1) with 20% of SBM, from 23 to 32 d of age; (2) with 25% of SBM, from 32 to 44 d of age, and (3) with 30% of SBM, from 44 to 63 d of age. For the first 21 d, pigs fed diets with a medium particle size of SBM (585mm) had better average weight gain and feed/gain ratio (P<0.05). The average feed intake, average body weight gain, and feed/gain ratio from 44 to 63 d improved (P<0.05) with increasing SBM particle sizes, and the average live weight for the overall period increased with coarser SBM (P<0.05). There was a marginally improvement (P < 0.1) on digestible energy as particle size of SBM decreased; although, no differences (P > 0.05) in the coefficients of apparent digestibility of dry matter and crude protein for the assessed SBM particle sizes were observed. It was concluded that the grinding of dietary SBM is not required for piglets during the nursery phase.

O objetivo deste estudo foi avaliar o efeito do tamanho da partícula do farelo de soja (FS) sobre o desempenho e digestibilidade de leitões no período de creche. 63 leitões (6,86 kg ± 0,56; 23 dias de idade) foram distribuídos aleatoriamente em um delineamento de blocos casualizados (peso inicial e sexo) entre os tratamentos. As dietas experimentais foram produzidas a partir de diferentes tamanhos médios de partículas do FS moídos ou não: 1,017 µm (sem moer), 585 µm (moído em peneira de 10 mm), e 411µm (moído em peneira de 3 mm), totalizando três tratamentos com sete repetições de três animais cada. Todas as dietas foram fornecidas na forma farelada e ad libitum, sendo divididas em três fases: 1) com 20% de FS, dos 23 a 32 dias de idade; 2) com 25% de FS, dos 32 a 44 dias de idade; e 3) com 30% de FS, dos 44 a 62 dias de idade. Nos primeiros 21 dias de experimento, os animais consumindo a dieta com o tamanho médio (585 µm) das partículas do FS apresentaram melhores resultados para o ganho de peso médio e conversão alimentar. No período seguinte (44 a 63 d), houve (P<0.05) aumento do consumo de ração médio, do ganho do peso médio e melhor conversão alimentar dos leitões conforme o aumento do tamanho da partícula de FS incluída na ração. Consequentemente, ao final do experimento houve melhora linear do peso vivo médio dos animais com o aumento do tamanho do FS consumido. Foi observado melhora marginalmente significativa (P < 0.1) da energia digestível conforme a redução no tamanho do FS, entretanto, não houve diferença (P > 0.05) no coeficiente de digestibilidade aparente da matéria seca e da proteína bruta dos animais entre os diferentes tamanhos do FS. Em conclusão, de acordo com as condições deste estudo, não se faz necessária a moagem do farelo de soja para leitões no período de creche.

Particle size of oyster shell meal and calcium: phosphorus ratios in broiler diets / Efeito do tamanho de partícula da farinha de ostras e relações cálcio: fósforo em dietas para frangos de corte

The effects of Ca:P total ratio and particle size of oyster shell meal (OSM) were evaluated in broiler diets. In Experiment 1, 800 broilers (22-42 days old) were distributed in a 2×2 factorial design, with two Ca:P ratios (1.7 and 2.0:1) and two OSM particle sizes (coarse = 1,354 µm and fine = 428 µm), totaling four treatments with 10 repetitions with 20 broilers. Feed intake, weight gain, and feed conversion ratio were calculated. In Experiment 2, 1,280 broilers were distributed in a 2×2×2 factorial design (1.7 and 2.0:1 Ca:P ratios; coarse and fine OSM; male and female broilers), with eight treatments and 16 repetitions with 10 broilers. Apparent metabolizability of dry matter, Ca, P, and apparent metabolizable energy (AME), as well as bone resistance, bone weight, ash, Ca, and P content in the tibia were assessed. Growth performance was not affected (P > 0.05). Coarse OSM increased tibia Ca content in male broilers (P < 0.001), and higher Ca:P ratio improved bone ash and bone resistance in both sexes (P < 0.001), but reduced P content in male broilers (P < 0.05); male broilers displayed heavier bones with higher ash content than females (P < 0.05). Metabolizability of Ca was improved with coarse OSM (P < 0.05); whereas metabolizability of DM, P, and AME was not affected (P > 0.05). In conclusion, diets with a Ca:P total ratio of 2.0:1 containing coarser OSM improved bone mineral composition, particularly in male broilers, and coarse OSM improved the metabolizability of Ca in broilers regardless of the Ca:P total ratio or broiler sex.

Dois experimentos foram conduzidos para avaliar os efeitos do tamanho de partícula da farinha de ostras (FO) e relação Ca:P total em dietas para frangos de corte. No primeiro experimento, 800 frangos (22 a 42 dias) foram distribuídos em um delineamento fatorial 2x2: 2 relações Ca:P (1,7 e 2,0:1) e dois tamanhos de partícula da FO (grossa = 1354 µm e fina = 428 µm), totalizando quatro tratamentos com 10 repetições de 20 aves. O consumo de ração, o ganho de peso e a conversão alimentar foram calculados. No segundo experimento, 1.280 frangos foram distribuídos em um fatorial 2x2x2 (relações Ca:P 1,7 e 2,0:1; FO grossa e fina; aves machos e fêmeas) com oito tratamentos e 16 repetições de 10 aves. Foram avaliados: metabolizabilidade aparente da matéria seca, Ca e P, energia metabolizável aparente (EMA), peso e resistência óssea, conteúdo de cinzas, Ca e P na tíbia. As variáveis de desempenho não foram afetadas (P > 0,05). O uso de FO grossa aumentou o conteúdo de Ca na tíbia de frangos machos (P < 0,001), e a relação Ca:P de 2,0:1 aumentou o conteúdo de cinzas e aprimorou resistência óssea em ambos os sexos (P < 0,001), porém reduziu P na tíbia dos machos (P < 0,05); frangos machos também tiveram ossos mais pesados e maior conteúdo de cinzas do que fêmeas (P < 0,05). A metabolizabilidade de Ca foi melhorada com FO grossa, enquanto a metabolizabilidade da matéria seca, P, e EMA não foram afetadas (P > 0,05). Conclui-se que as dietas com relação Ca:P de 2,0:1 e com FO grossa resultaram em melhor composição mineral óssea - particularmente em frangos machos - e a FO grossa melhorou a metabolizabilidade de Ca independentemente da relação Ca:P ou do gênero das aves.

Research Progress of Micro-PIV in Biomedical Engineering Field / 医用生物力学

Blood is an important component of living organism which is responsible for material transportation. The microenvironment of blood flow plays an important role in physiological and pathological processes of angiogenesis and cardiac development, erythrocytes aggregation and blood viscosity, tumor metastasis and atherosclerosis. Besides, micro-fluid environment significantly affects drug delivery, cell screening, and artificial organ design. Thus, the measurement and quantitative analysis of micro-fluid contribute to the biomedical engineering filed. Micro-particle imaging velocimetry (Micro-PIV) combines conventional PIV with microscopy technique. Correlation analysis is conducted in two groups of images captured by high speed camera at different time intervals, and the velocity profiles in micro-fluid environment are successfully measured. Compared with other velocity measurement methods, Micro-PIV has high temporal resolution and spatial resolution. The main setup of Micro-PIV and its principle analysis method were introduced in this review. Recent studies of Micro-PIV applications in biomedical engineering field were then summarized. Moreover, the drawbacks of Micro-PIV technique and prospect of its applications were discussed.

Population bioequivalence statistical method based on earth mover′s distance for evaluation of particle size distribution consistency of ophthalmic emulsion / 中国药科大学学报

@#Population bioequivalence (PBE) is a statistical approach recommended by FDA to evaluate the consistency of particle size distribution of numerous nanoparticle products.However, when particle size distribution (PSD) profile exhibits multiple peaks or other complex distributions, the traditional descriptors D50 and SPAN are no longer suitable to describe PSD.Earth mover''s distance (EMD) is a new statistical metric for assessing the difference between distributions.In this study, we used EMD to measure the discrepancy between PSD and then PBE was applied to perform statistical test to establish equivalence.Our results showed that the proposed method can effectively reject an unequivalent product and pass an equivalent product, thus indicating its helpfulness in guiding the optimization of formulation and preparation process.

Clinical value of remnant lipoproteins and low density lipoprotein cholesterol particle concentration detected by vertical auto profile on the diagnosis of carotid plaque / 中华检验医学杂志

Objective:To explore the clinical value of peripheral remnant lipoproteins (RLP), low density lipoprotein cholesterol particle (LDL-P) and sdLDL particle (sdLDL-P) measurement in the diagnosis of carotid plaque, so as to provide practical basis for the accurate diagnosis of carotid plaque and the control of carotid plaque related cardiovascular and cerebrovascular diseases.Methods:People who underwent carotid plaque ultrasound examination in Xingtai Third Hospital , from January 2020 to June 2021 were selected as the research object. According to the ultrasound results, they were divided into carotid plaque group ( n=146) and control group without carotid plaque ( n=149). The fasting RLP, LDL-P and sdLDL-P of the two groups were measured by vertical auto profile (VAP) centrifugal separation phase, and the fasting TG and LDL-C were detected by routine mixed phase method. The indexes were compared between the two groups and the true positive rate, true negative rate, false positive rate and false negative rate of the diagnosis of carotid plaque were analyzed. The receiver operating characteristic curve of each test index was drawn, and AUC was used to evaluate the clinical diagnostic value of each test index for carotid plaque. Results:The levels of RLP, LDL-P and sdLDL-P in carotid plaque group were significantly higher than those in non-carotid plaque group ([1.07±0.36] mmol/L vs [0.59±0.17] mmol/L,[1 300±370] nmol/L vs [781±215] nmol/L,[435±139] nmol/L vs [156±59] nmol/L, all P<0.01). The true positive rate (78.08% [114/146],81.51% [119/146]) and true negative rate (84.56% [126/149], 86.58%[129/149]) of serum RLP and LDL-P for the diagnosis of carotid plaque were significantly higher than TG (58.90%[86/146], 43.62%[65/149]) and LDL-C (59.59% [87/146], 46.98% [70/149]), and the false positive rate (15.44% [23/149], 13.42% [20/149]) and false negative rate (21.92% [32/146], 18.49% [27/146]) were significantly lower than TG (56.38% [84/149], 41.10% [60/146]) and LDL-C (53.02% [79/149], 40.41% [59/146], all P<0.01). The AUC of the ROC curve of RLP (0.890), LDL-P (0.902) and sdLDL-P (0.973) for the diagnosis of carotid plaque was higher than TG (0.682) and LDL-C (0.712). The AUC of ROC curve of the RLP combined with sdLDL-P (0.977) for the diagnosis of carotid plaque was higher than the RLP and sdLDL-P (all P<0.01). Conclusion:The serum RLP, LDL-P and sdLDL-P can be used as indicators of carotid plaque, and their clinical diagnostic value are superior to TG and LDL-C; the combined diagnostic effect of lipoprotein subclass is better than that of single index alone.

Particle size and size distribution of mRNA vaccines under different testing conditions / 中华微生物学和免疫学杂志

Objective:To investigate the factors that could influence the particle size and size distribution of mRNA vaccines.Methods:The influences of several factors including the ionic strength and pH values of buffers, solutions, dilution folds and testing equipments on the particle size and size distribution of three batches of mRNA vaccines were analyzed by dynamic light scattering.Results:The particle size increased with increasing ionic strength, but no significant change in size distribution was observed. The particle size also increased with increasing pH values and the size distribution showed significant change when the buffer solution was weakly alkaline. Solution types could affect the particle size, but had no influence on size distribution. There was no significant change in the particle size or size distribution when the dilution was limited to 100 folds. Moreover, the particle size and size distribution detected by different equipments showed no significance difference.Conclusions:The particle size and size distribution of mRNA vaccines could be affected by solution, dilution fold and testing equipment, which should be concerned during the vaccine production and quality control.

Retrospective study on clinical manifestation, thigh MRI and electrophysiology characteristics of immune-mediated necrotizing myopathy / 中华内科杂志

Objective:To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM).Methods:A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP +) group, anti-HMGCR antibody positive (HMGCR +) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result:(1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP +, 8 (25.0%) with HMGCR +, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP +group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb ( P<0.01). The axial muscle score was lower than the distal limb score ( P<0.05).(3) Extramuscular manifestations of HMGCR + group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups ( P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP + group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR + group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion:IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP + group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR +group were more prone to myotonia potential and CRDs.

Research progress of powder modification of TCM based on particle design theory / 药学学报

Particle design, based on the concept of "quality by design", combines the elements of microbiology, formulation science, heat and mass transfer, solid state physics, powder science, and nanotechnology. It is widely used to develop particles with excellent functional properties. Without affecting the active ingredients, the modification technology of traditional Chinese medicine (TCM) powder based on particle design theory, could improve the flowability, tabletability, disintegration and dissolution behavior, hygroscopicity, wettability, and other functional properties at the physical structure level. This greatly promotes the development of solid preparations of TCM. The present review aims to summarize and discuss the research progress of powder modification of TCM from the perspective of the theory of particle design, powder modification technology, equipment used for powder modification, application in TCM and modification mechanism mainly based on researches published in recent ten years. This review could provide ideas and theory basis for the development of particle design.

Preparation, in vitro characterization and pharmacokinetics of paclitaxel thermosensitive gel / 药学学报

Local drug delivery is a new strategy to prevent postoperative recurrence of cancer, thermosensitive gel is a typical topical drug delivery system. In this study, a novel paclitaxel thermosensitive gel (PTG) was prepared to prevent recurrence after chemotherapy for cancer, the effects of drug particle size on release and absorption rate in vivo were investigated. Paclitaxel suspensions with different particle sizes were prepared by medium grinding, high pressure homogenization, air crushing and screening. Using poloxamer as the gel matrix and carbomer as the biological adhesive, Box-Behnen was used to optimize the formulation of PTG. The morphology, viscosity, rheological properties and biological adhesion of thermosensitive gel were characterized. The relationship between dissolution and release of thermosensitive gel was investigated by weight loss method, pharmacokinetics was studied in rats. The paclitaxel suspensions with the particle sizes of 350 nm, 800 nm, 3 μm and 9 μm were prepared, 19% poloxamer 407, 4% poloxamer 188 and 0.1% carbomer were used to prepare PTG. The phase transition temperature of thermosensitive gel was 30 to 35 ℃, there was a good linear relationship between in vitro release and gel dissolution. In the pharmacokinetic study, area under the curve (AUC0-t) increased with the decrease of particle size. In general, the PTG prepared in this study can rapidly change into gel under human body temperature, provided with good adhesion. The release rate in vitro is closely related to the particle size, the release rate increased with the decrease of particle size. This study provides data support for preventing postoperative recurrence of cancer. The animal welfare and experimental process in this paper follow the regulations of the Animal Ethics Committee of the Academy of Military Medical Sciences.

Susceptibility of Alabama argillacea and Chrysodeixis includens (Lepidoptera: Noctuidae) larvae to Beauveria bassiana associated with kaolin / Susceptibilidade de larvas de Alabama argillacea e Chrysodeixis includens (Lepidoptera: Noctuidae) a Beauveria bassiana associada com caulim

Abstract The mortality of the Alabama argillacea and Chrysodeixis includens (Lepidoptera: Noctuidae) larvae caused by the kaolin inert powder and the entomopathogenic fungus Beauveria bassiana were determined under laboratory conditions. Using the caterpillar submersion method, the CG 138 B. bassiana isolate was more pathogenic to A. argillacea than the CG 70, GC 82, ESALQ 634, and ESALQ 645. All five tested isolates caused similar mortality of C. includens. The mortality of first-instar larvae of A. argillacea and C. includens by feeding on leaf-disc impregnated with B. bassiana (CG 138) and kaolin was also determined. Higher A. argillacea mortalities were observed in the B. bassiana (CG 138) treatments, regardless of the presence of kaolin. However, the activity of kaolin + B. bassiana (CG 138) against C. includens was higher than each ingredient alone, indicating an additive action against C. includes larvae. The mortality of A. argillacea and C. includens larvae treated with kaolin + B. bassiana (CG 138) was similar, and the A. argillacea mortality was higher than that of C. includens with kaolin and B. bassiana (GC 138) separated. The treatment kaolin + B. bassiana (CG 138) is promising for the simultaneous management of these two defoliator pests, mainly A. includes. In addition, the monophagous A. argillacea is more susceptible to both kaolin and B. bassiana (GC 138) than the polyphagous C. includens, suggesting that the nutritional ecology plays an important role in the susceptibility of these defoliator species to alternative insecticides.

Resumo A mortalidade de larvas de Alabama argillacea e Chrysodeixis includens (Lepidoptera: Noctuidae), causada pelo pó inerte do caulim e pelo fungo entomopatogênico Beauveria bassiana, foi determinada em condições de laboratório. Usando o método de submersão da lagarta, o isolado CG 138 de B. bassiana foi mais patogênico para A. argillacea que os CG 70, GC 82, ESALQ 634 e ESALQ 645 desse fungo. Os cinco isolados testados causaram mortalidade semelhante de C. includens. A mortalidade de larvas de primeiro ínstar de A. argillacea e C. includens pelo método de alimentação em discos foliares impregnados com B. bassiana (CG 138) e caulim foi, também, determinada. A mortalidade de A. argillacea foi maior nos tratamentos com B. bassiana (CG 138), independentemente da presença do caulim. A atividade do caulim + B. bassiana (CG 138) contra C. includens foi maior que cada ingrediente isolado, indicando ação aditiva contra larvas desse Lepidoptera. A mortalidade de larvas de A. argillacea e C. includens, com caulim + B. bassiana (CG 138), foi semelhante e as de A. argillacea maiores que as de C. includens com caulim e B. bassiana (GC 138) isoladamente. O tratamento caulin + B. bassiana (CG 138) é promissor para o manejo simultâneo dessas duas pragas desfolhadoras, principalmente A. includens. Além disso, a monófaga, A. argilacea, é mais suscetível ao caulim e à B. bassiana (GC 138) que a polífaga, C. includens, sugerindo que a ecologia nutricional desempenha papel importante na suscetibilidade dessas espécies desfolhadoras a inseticidas alternativos.

Nutritional value, total dry matter losses, effluent production and pollutant potential in Brachiaria brizantha cv. Paiaguás grass / [Valor nutricional, perdas totais de matéria seca, produção e potencial poluidor de efluentes em silagem de Brachiaria brizantha cv. Paiaguás]

The objective of the present study was to evaluate losses, production and polluting potential of the effluent, nutritional value and aerobic stability of silages of Brachiaria brizantha cv. Paiaguás grass, in different particle sizes and compaction density in silage. Three theoretical particle sizes (TTP 5; 8 and 12mm) and three compaction densities (DC 550; 600 and 650kg/m3) were evaluated, distributed in a factorial design (3 x 3), with four repetitions. The highest volume of effluent was found in silages with higher compaction densities (600 and 650kg/m3) and lower TTP (5 and 8mm). The highest chemical oxygen demand and biochemical oxygen demand were registered in the treatment with TTP of 5mm and higher DC (600 and 650kg/m3). Greater in vitro digestibility of DM was verified in the silage chopped at 5 and 8mm. There was no break in aerobic stability for 216 hours. Silage with a low compaction density 550kg/m3 and processing with a theoretical particle size of 12mm reduces effluent losses. In general, the nutritional value of Paiaguás grass was not influenced by the treatments. Different particle sizes and compaction density did not change the aerobic stability of silages.(AU)

Objetivou-se avaliar perdas, produção e potencial poluidor do efluente, valor nutricional e estabilidade aeróbia de silagens do capim Brachiaria brizantha cv. Paiaguás, em diferentes tamanhos de partícula e densidade de compactação na ensilagem. Foram avaliados três tamanhos teóricos de partícula (TTP 5; 8 e 12mm) e três densidades de compactação (DC 550; 600 e 650kg/m3), distribuídos em arranjo fatorial (3 x 3), com quatro repetições. O maior volume de efluente foi verificado nas silagens com maiores densidades de compactação (600 e 650kg/m3) e menores TTP (5 e 8mm). As maiores demanda química de oxigênio e demanda bioquímica de oxigênio foram registradas no tratamento com TTP de 5mm e nas maiores DC (600 e 650kg/m3). Maior digestibilidade in vitro da MS (média de 57,2%) foi verificada na silagem picada a 5 e 8mm. Não houve quebra da estabilidade aeróbia durante 216 horas. A ensilagem com baixa densidade de compactação (550kg/m3) e o processamento com tamanho teórico de partículas 12mm reduzem as perdas por efluente. O valor nutricional da silagem de capim-paiaguás, em geral, não foi influenciado pelos tratamentos. Diferentes tamanhos de partícula e densidade de compactação não alteraram a estabilidade aeróbia das silagens.(AU)

Physically effective fiber changes nutrient levels of total mixed ration and fecal parameters in beef feedlots / A fibra fisicamente efetiva altera os nutrientes da dieta e parâmetros fecais em confinamentos de bovinos de corte

ABSTRACT: This study evaluated the effects of the physically effective fiber (peNDF) content on nutrient composition of the total mixed ration (TMR), orts and fecal parameters in 15 commercial beef feedlots. The particle size distribution of TMR was measured adopting Penn State Particle Size Separator (PSPS). Samples were evaluated for dry matter (DM), ash, ether extract (EE), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and starch content. Fecal samples were also evaluated for pH and score. The feedlots were categorized into peNDF<20% and peNDF ≥ 20%. Data were analyzed by a model that included fixed effects of treatment and covariates (sex and genetic groups). Levels of DM, CP, EE and starch were lower in TMR with peNDF ≥ 20% (P<0.05). Fecal dry matter was higher and morning fecal pH was lower for TMR with peNDF<20% (P<0.05). Physically effective fiber changed nutrient levels in TMR, orts, fecal pH and DM. So, using PSPS and fecal parameters are practical and indirect tools for measuring fecal starch and assessing the effectiveness of the diet supplied to ruminants.

RESUMO: O objetivo desse estudo foi avaliar o teor de fibra fisicamente efetiva (FDNfe) de dietas totais e seus efeitos nos nutrientes da dieta, das sobras e nos parâmetros fecais de bovinos de corte em 15 confinamentos comerciais. As amostras da dieta foram separadas utilizando a peneira Penn State Particle Size Separator (PSPS). As amostras foram analisadas quanto aos teores de matéria seca (MS), matéria mineral (MM), extrato etéreo (EE), proteína bruta (PB), fibra em detergente neutro (FDN), fibra em detergente ácido (FDA) e amido. Nas amostras de fezes também foram avaliadas o escore e pH fecal. Os confinamentos foram categorizados em dois tratamentos: FDNfe<20% e FDNfe≥20%. Os dados foram analisados ​​ por um modelo que incluiu os efeitos de grupo e covariável (sexo e grupo genético). Os teores de MS, PB, EE e amido foram menores nas dietas com FDNfe≥20%(P<0,05). A MS fecal foi maior e pH fecal matinal foi menor nas dietas com FDNfe<20% (P<0,05). Sendo assim a efetividade da fibra alterou os nutrientes da dieta total e sobras, bem como as variáveis pH e MS fecal. Com isso, o uso de PSPS e parâmetros fecais são ferramentas práticas e indiretas para medir o amido fecal e a efetividade da dieta em confinamentos de bovinos comerciais.