Intervention of muscle strength training combined with neuromuscular electrical stimulation on lower limb function and biomechanical changes in patients with patellofemoral pain / 中国组织工程研究

BACKGROUND:Lower limb peri-knee muscle strength training and neuromuscular electrical stimulation are generally safe and effective rehabilitation methods for patellofemoral joint pain,but the mechanism of their intervention is still unclear. OBJECTIVE:To determine the effect of muscle strength training combined with neuromuscular electrical stimulation on pain,lower extremity function and biomechanical characteristics in patients with patellofemoral pain. METHODS:Thirty-seven patients with patellofemoral pain were randomly divided into muscle strength training combined with electrical stimulation group(trial group,n=19)and muscle strength training group(control group,n=18).Both groups underwent intervention training for 6 weeks,three times a week.The visual analog scale and anterior knee pain scale were used to evaluate the pain level and functional level of the knee.Kinematic and kinetics data during running were collected by using an infrared motion capture system and a three-dimensional force platform simultaneously.A two-way analysis of variance with repeated measures(group*time)was applied to analyze the data. RESULTS AND CONCLUSION:(1)After the intervention,the visual analog scale scores of the trial group and the control group were significantly decreased(P<0.001),and the anterior knee pain scale scores were significantly increased(Ptrial group<0.001,Pcontrol group=0.001)in the trial group and control group.The anterior knee pain scale scores of the trial group were significantly higher compared to the control group after the intervention(P=0.001).(2)The peak knee flexion angle(P=0.011),peak knee extension moment(P<0.001),the peak knee internal rotation moment(P=0.008),the peak patellofemoral stress(P<0.001)and the peak patellofemoral contact force(P<0.001)were significantly decreased in the trial and control groups during running after the intervention compared with those before the intervention.(3)In conclusion,both muscle strength training and muscle strength training combined with electrical stimulation training are helpful to improve the subjective pain and lower limb function of patellofemoral pain patients,enhance the movement pattern during running and reduce the stress of the patellofemoral joint.Compared with muscle strength training alone,muscle strength training combined with electrical stimulation can improve lower limb function more significantly.

Biomechanics characteristics during sitting up in knee osteoarthritis patients of different ages:a systematic review and meta-analysis / 中国组织工程研究

OBJECTIVE:There is no consensus on which sit-up strategy to adopt in knee osteoarthritis patients of different ages.Therefore,this study evaluated the biomechanical characteristics of sit-ups in knee osteoarthritis patients of different ages compared with healthy individuals by meta-analysis system and analyzed the sit-up movement patterns of patients of different ages to provide a reference for improving the sit-up function of patients. METHODS:By March 2023,observational studies of biomechanical characteristics of sitting up in patients with knee osteoarthritis and healthy population were retrieved on PubMed,Web of Science and CNKI.Subjects were required to be patients over 50 years of age with knee osteoarthritis who had Kellgren-Lawrence severity grading≥Ⅰ on knee imaging and who had regular knee pain.Subjects were analyzed by age(50-60 years vs.over 60 years)and severity(mild to moderate patients vs.severe patients)subgroups according to inclusion and exclusion criteria.Quality assessment was performed using the modified Down and black scale.Stata 16.0 software was used to perform subgroup analysis to determine the biomechanical characteristics of sitting up in patients with knee osteoarthritis of different ages and severities. RESULTS:A total of 14 randomized controlled trials(824 subjects)were included in the meta-analysis.The mean quality score of all included literature was 76.2,with a range of 66.7 to 86.7,all of which were of medium to high quality and representative.The included studies were of moderate to high quality and representative.Meta-analysis results found that(1)compared to healthy individuals,patients with knee osteoarthritis had longer total sitting up time(SMD=0.92,95%CI:0.76-1.09),P<0.001)and longer extension phase time(SMD=0.46,95%CI:0.18-0.74,P=0.001).Compared to mild to moderate patients,the total duration increased more significantly in severe patients(P<0.001)and the duration of the extension phase increased more significantly in patients over 60 years of age than in patients 50-60 years of age(P=0.001).(2)Compared to healthy individuals,patients with knee osteoarthritis had greater sitting-up trunk flexion motion range(SMD=0.64,95%CI:0.37-0.91,P<0.001);knee flexion motion range(SMD=-0.47,95%CI:-0.70 to-0.24,P<0.001)and ankle dorsiflexion motion range(SMD=-0.32,95%CI:-0.56 to-0.08,P=0.01)were smaller.And knee flexion motion range decreased more significantly in patients over 60 years of age than in patients 50-60 years of age(P<0.001).(3)The peak hip flexion moment(SMD=-0.57,95%CI:-0.83 to-0.31,P<0.001)and peak knee extension moment(SMD=-0.83,95%CI:-1.08 to-0.59,P<0.001)were smaller in patients with knee osteoarthritis. CONCLUSION:(1)Patients with knee osteoarthritis over the age of 60 years have a longer sit-up cushion and extension phase than patients aged 50 to 60 years.The increase in total sit-up duration was also more pronounced in patients with higher severity grades.The increased length of sitting up in patients with advanced age and knee osteoarthritis severity may increase the duration of cartilage loading,exacerbate knee pain symptoms,and increase the difficulty of sitting up in this population.(2)Patients with knee osteoarthritis exhibit limited knee and ankle flexion motion range.Knee mobility is more limited in patients over 60 years of age.(3)Patients with knee osteoarthritis have reduced peak hip flexion and knee extension moments,which may be a compensatory strategy for pain relief.

Effects of kinesio taping on the biomechanical characteristics of the lower limbs during side-step cutting / 中国组织工程研究

BACKGROUND:Kinesio taping has been widely used as a means of sports protection,but its role as a means to correct abnormal biomechanical changes of the lower limbs during side-step cutting remains unclear. OBJECTIVE:To analyze and compare the changes in lower limb kinematics and dynamics when the subjects complete the side-step cutting of the knee joint under the conditions of kinesio taping,placebo taping and blank control. METHODS:Thirty-nine male college students majoring in basketball were recruited as subjects.Each subject was tested with kinesio taping,placebo taping or no taping.The mechanical correction method was used to patch the dominant knee joint of each subject.The run-up speed of 4.5-5.5 m/s was selected to complete the 45° side-step cutting motion,and the kinematics and kinetics data were collected synchronously by the three-dimensional dynamic capture system and the force measuring platform.The kinematics and kinetics parameters at the moment of initial touchdown and peak ground reaction force were selected for data analysis.SPSS 27.0 software was used for statistical analysis of the test data. RESULTS AND CONCLUSION:Kinematic indexes:compared with no taping and placebo taping,the hip abduction and knee valgus angles at the initial touchdown moment were significantly decreased when kinesio taping was used(P<0.05);at the moment of peak lateral ground reaction force,the angles of hip abduction,knee valgus and ankle plantar flexion decreased significantly(P<0.05),and the knee flexion angle was significantly increased(P<0.05).Kinetic indexes:Compared with no taping,both kinesio taping and placebo taping significantly reduced hip abduction and external rotation torque,knee valgus and external rotation torque at the moment of initial touchdown(P<0.05),and significantly reduced peak vertical ground reaction force and peak horizontal backward ground reaction force(P<0.05);in addition,kinesio taping significantly reduced peak lateral ground reaction force compared with no taping and placebo taping(P<0.05).These results indicate that kinesio taping of the knee joint may improve some kinematic and kinetic indexes associated with lower limb injury risk factors during the completion of the side-step cutting in basketball specialized college students to some extent,and may have a positive effect on the prevention of injury during the side-step cutting.In addition,the trends in the effects of placebo taping and kinesio taping on the knee joint are more consistent in terms of changes in some indexes,suggesting that there may be a placebo effect on the mechanism of action of kinesio taping.

Effects of Different Trunk-Restraint Squatting Postures on Human Lower Limb Kinematics and Dynamics / 医用生物力学

Objective To investigate the effect of trunk control on the biomechanical characteristics of lower limb movements during Asian squats(AS)and Western squats(WS)in young adults to provide empirical support for the application and promotion of deep squat training.Methods Twenty-four healthy young male collegiate students performed AS and WS with and without bar control,and their lower limb kinematic and kinetic characteristics were collected using an infrared light-point motion capture system and a three-dimensional(3D)dynamometer.The 3D angles of the lower limbs were obtained using Cortex-642.6.2 software,based on the calculation of Euler angles,and the 3D moments were obtained by applying the inverse dynamics method.The effects of trunk control and deep squatting posture on the lower limb kinematic characteristics were examined using a two-factor analysis of variance with a 2×2 repeated design.Results There was no significant interaction between trunk control and the deep squatting posture for either kinematic or kinetic parameters(P>0.05).The WS group had a large knee flexion angle,peak patellofemoral contact force,and ratio of peak hip and knee extension moments,and small ankle dorsiflexion and hip flexion angles(P<0.05).The deep squat with a bar had a large ankle dorsiflexion angle,peak patellofemoral contact force,and hip flexion angle as well as a small knee flexion angle and ratio of peak hip and knee extension moments(P<0.05).Conclusions WS is helpful for training hip extension muscle groups,whereas AS is helpful for training knee extension muscle strength.The peak patellofemoral joint contact force of the WS is significantly greater than that of the AS;therefore,it is recommended that patients with patellofemoral joint pain use the AS.A squat with a bar can compensate for the body's balance;thus,people with limited ankle dorsiflexion range of motion or anterior tibial muscle weakness may consider trunk control training,such as a deep squat with a bar.This may help improve lower limb stability during squats.

Assessing the effect of prophylactic ankle taping on ankle and knee biomechanics during landing tasks in healthy individuals: A cross-sectional observational study

ABSTRACT BACKGROUND: Current research supports the fact that prophylactic ankle taping (AT) is effective in preventing ankle injuries in amateur and elite sports athletes. OBJECTIVE: This study aimed to investigate the effect of AT on balance, knee valgus during drop jump and single-leg countermovement jump (SL-CMJ) landings, and ankle range of motion (ROM) restriction in healthy participants. DESIGN AND SETTING: A cross-sectional observational study was conducted at the Universidad Europea de Madrid, Madrid, Spain. METHODS: Participants: Thirty-nine healthy individuals participated in this study and performed the movements under two conditions (with and without tape). Outcome measurements: ankle ROM, balance, SL-CMJ height, flight time, ground time, and knee valgus. Before any intervention, a random process was developed with a 1:1 allocation ratio, and the participants were assigned to groups A (tape-no tape) and B (no tape-tape). RESULTS: Significant differences between tape and no-tape moments were observed for drop jump knee valgus flexion (P = 0.007), with an increase in knee valgus in participants with ankle taping. Similarly, the Y-balance testshowed a significant decrease in all variables (P = 0.001 and), ankle dorsiflexion (P = 0.001) in participants with ankle taping. CONCLUSIONS: AT is effective for immediate ankle ROM restriction. However, an increase in knee valgus during drop jump task and a decrease in lower limb balance were observed during drop jump task. Based on these results, it can be concluded that AT application in healthy individuals should not be recommended as it results in increase in injury risk factors.

Fulcro cardíaco de Trainini en el corazón fetal / Trainini cardiac fulcrum in the fetal heart

RESUMEN Demostrar mediante la disección de piezas anatómicas y de imágenes ultrasonográficas prenatales del corazón fetal la presencia del fulcro cardíaco como estructura de fijación que sirve de soporte a la banda miocárdica helicoidal. Se disecaron 6 corazones de fetos entre las 20 y 24 semanas de edad gestacional productos de abortos espontáneos, logrando encontrar el fulcro cardíaco en la proximidad de la aorta y conexiones con fibras miocárdicas. En 50 embarazos simples con fetos entre las 18 y 37 semanas de gestación, mediante ultrasonografía cardíaca fetal se obtuvieron las modalidades 2D, Doppler, color y tridimensión, STIC, HD Flow y speckle tracking, imágenes, medidas del fulcro y su cinética. Con la estrategia descrita se identificó y demostró la presencia del fulcro cardíaco o palanca miocárdica, estableciendo sus características anatómicas, conexiones con fibras miocárdicas del asa cardíaca y la biometría según la edad gestacional. Se formula una hipótesis sobre la biomecánica o cinética del fulcro durante el ciclo cardíaco. Para que el corazón cumpla su función de bomba aspirante e impelente debe poseer un punto de apoyo, una palanca o fulcro, que constituye una especie de unidad músculo-tendinosa. Dicha palanca presenta desplazamientos mixtos durante la torsión y detorsión del miocardio. Sus diámetros aumentan progresivamente a medida que avanza la gestación.

ABSTRACT To demonstrate by dissection of anatomical specimens and prenatal ultrasonographic images of the fetal heart the presence of the cardiac fulcrum as a fixation structure supporting the helical myocardial band. Six hearts of fetuses between 20-24 weeks of gestational age resulting from spontaneous abortions were dissected, finding the cardiac fulcrum in the proximity of the aorta and connections with myocardial fibers. In 50 singleton pregnancies with fetuses between 18-37 weeks of gestation, fetal cardiac ultrasonography was used to obtain 2D, Doppler, color and three-dimensional modalities, STIC, HD Flow and speckle tracking, images, fulcrum measurements and its kinetics. With the described strategy, the presence of the cardiac fulcrum or myocardial lever was identified and demonstrated, establishing its anatomical characteristics, connections with myocardial fibers of the cardiac loop and the biometry according to gestational age. A hypothesis on the biomechanics or kinetics of the fulcrum during the cardiac cycle is formulated. In order for the heart to fulfill its function as an aspirating and impelling pump, it must have a support point, a lever or fulcrum, which constitutes a sort of muscle-tendon unit. This lever presents mixed displacements during myocardial torsion and detorsion. Its diameters increase progressively as gestation advances.

Biodegradación de polietilenglicol 400 con consorcio de Pseudomonas sp. y Rhizobium trifolii

Se evaluó la biodegradación de polietilenglicol de peso molecular 400 - PEG 400 con el consorcio Pseudomonas sp. y Rhizobium trifolii en reactores en Batch; para determinar las condiciones óptimas de operación del reactor se preparó medio con sales mínimas esenciales suplementado con peptonaCSMEP; en estos medios se estimó el comportamiento del consorcio con condiciones de temperatura entre 15-37°C, pH en un rango de 5-9 y concentración de PEG 400 del .1-2%. Con los resultados obtenidos en estos ensayos previos se ensamblaron tres reactores en Batch - BK. Se analizaron 14 muestras del contenido de cada uno de los reactores durante 20 días para medir la biodegradación del PEG 400 usando demanda química de oxígeno - DQO en sistema de digestión cerrado. Se obtuvo una disminución de hasta el 98.5% del poliéter, lo que mostró que la simbiosis fue efectiva para alcanzar una remoción importante del contaminante.

The biodegradation of polyethylene glycol of molecular weight 400 - PEG 400 was evaluated with the consortium Pseudomonas sp. and Rhizobium trifolii in Batch reactors. To determine the optimal operating conditions of the reactor, a medium with minimum essential salts supplemented with CSMEP peptone was prepared; In these media, the behavior of the consortium was estimated with temperature conditions between 15-37°C, pH in a range of 5-9 and PEG 400 concentration of .1-2%. With the results obtained in these previous tests, three Batch - BK reactors were assembled. 14 samples of the contents of each one of the reactors were analyzed during 20 days to measure the biodegradation of PEG 400 using chemical oxygen demand - COD in a closed digestion system. A decrease of up to 98.5% of the polyether was obtained, which showed that the symbiosis was effective to achieve an important removal of the contaminant.

Avaliação da cinética on da frequência cardíaca em pacientes asmáticos e em indivíduos saudáveis durante o Endurance Shuttle Walk Test / Evaluation of heart rate on kinetics in asthmatic patients and in healthy individuals during the endurance shuttle walk test

Introdução: O comportamento cinético da frequência cardíaca (FC) na transição do repouso para o exercício nos informa sobre a integridade do sistema nervoso autônomo. Recuperações mais lentas associam-se ao risco de mortalidade por eventos cardiovasculares, tornando-se imprescindível sua avaliação. Objetivo: Avaliar e comparar a resposta da cinética on da FC em pacientes asmáticos e indivíduos saudáveis durante o Endurance Shuttle Walk Test (ESWT). Métodos: Trata-se de um estudo prospectivo, transversal e controlado, com 14 adultos asmáticos e 8 controles saudáveis. Os indivíduos realizaram as seguintes avaliações: Teste de função pulmonar, Variabilidade da Frequência Cardíaca (VFC) e Incremental Shuttle Walk Test e ESWT. Resultados: O grupo asmático apresentou um atraso da cinética on da FC na transição do repouso para o teste, e uma correlação negativa moderada (r=-0,60; p<0,05) entre a distância percorrida (m) e o tempo de resposta (TRM) cinética on da FC. Conclusão: Os pacientes asmáticos apresentaram um atraso da cinética "on", quando comparados ao grupo de indivíduos saudáveis, demonstrando ser um importante marcador na avaliação da performance física.

Introduction: The kinetic behavior of heart rate (HR) in the transition from rest to exercise, as this assessment informs us about the integrity of the autonomic nervous system. Slower recoveries are associated with the risk of mortality from cardiovascular events, making their evaluation, essential. Objective: To evaluate and compare the HR on kinetics response in asthmatic patients and healthy individuals during the Endurance Shuttle Walk Test (ESWT). Methods: This is a prospective, cross-sectional, controlled study with 14 asthmatic adults and 8 healthy controls. Subjects performed the following assessments: Pulmonary Function Test, Heart Rate Variability (HRV) and Incremental Shuttle Walk Test and ESWT. Results: The asthmatic group showed a delay in the HR on kinetics in the transition from rest to the test, and a moderate negative correlation (r=-0.60; p<0.05) between the distance covered (m) and the response time (TRM) kinetics on from FC. Conclusion: Asthmatic patients showed a delay in "on" kinetics, in comparison to the group of healthy individuals, proving to be an important marker in physical performance assessments.

Analysis of drying kinetic of brewer ́s spent grains: effect of the temperature on the physical properties and the content of bioactive compounds / Análisis de la cinética de secado del bagazo residual de malta: efecto de la temperatura sobre las propiedades físicas y el contenido de compuestos bioactivos

Background: Brewer ́s spent grain (BSG) is a biomass by-product generated in large volumes during industrial beer production. BSG has become a growing environmental problem, as most breweries discard it inappropriately, negatively impacting the environment. Alternatives for the exploitation of this by-product have consisted of elaborating food supplements for farm animals, obtaining biofuels, developing adsorbents, and obtaining substances for the food industry. However, the high moisture content in BSG (approximately 70%), poses a significant challenge in exploring various reuse alternatives. Therefore, the implementation of a pre-drying process becomes essential. Objective: This study aimed to analyze the BSG drying kinetics at different temperatures and the effect of the drying temperature on the physical properties and the content of bioactive compounds. Methods: BSG samples were dried at different temperatures (50, 60, 70, 80, 90, and 105°C) and analyzed for their moisture ratio, water activity, total polyphenol content (TPC), and DPPH (1,1-diphenyl-2-picrylhydrazil) radical scavenging activity. Also, four kinetics models were fitted to the drying data. Results:It was determined that the effective diffusivity was between 5.23x10

Antecedentes: El Bagazo residual de malta (BSG por sus siglas en inglés) es un subproducto biomásico generado en grandes volúmenes durante la producción industrial de cerveza. El BSG se ha convertido en un creciente problema para el medio ambiente, debido a que la mayoría de las cervecerías descartan inapropiadamente este residuo generando un impacto negativo al ambiente. Las alternativas para el aprovechamiento de este subproducto han consistido especialmente en la elaboración de suplementos alimenticios para animales de granja, obtención de biocombustibles, desarrollo de adsorbentes y obtención de productos para la industria alimentaria. Sin embargo, el alto contenido de humedad (~70%) del BSG representa un reto para el desarrollo de diferentes alternativas de reutilización, por lo que se hace necesario un proceso de secado previo. Objetivos: En este estudio se analizó la cinética de secado del BSG a diferentes temperaturas y el efecto de la temperatura de secado sobre sus propiedades físicas y contenido de compuestos bioactivos. Métodos: Las muestras de BSG fueron secadas a diferentes temperaturas (50, 60, 70, 80, 90 y 105°C) y analizadas en términos de razón de humedad, actividad acuosa, contenido de polifenoles totales (TPC) y actividad secuestradora del radical DPPH. Además, se ajustaron 4 modelos cinéticos a los datos de secado. Resultados: Se determinó que la difusividad efectiva del BSG varió entre 5.23x10

A Novel Approach for the Treatment of Hypertension: Gastroretentive Microballoons of Atenolol

The formulation of atenolol-loaded microballoons involved the use of Eudragit RS 100, HPMC K4 M as a polymer, and span 80 as a surfactant. The microballoons were prepared by an emulsion solvent diffusion (non-aqueous) using liquid paraffin, methanol, and dichloromethane as a processing medium. The Box-Behnken design was utilized to get optimized formulation using a concentration of HPMC K4 M (A), Concentration of Eudragit RS 100 (B), Concentration of surfactant (C), and stirring speed (D) as an independent parameter while, Particle size (Y1), entrapment efficiency (Y2) and %buoyancy (Y3) using as a dependent parameter. For the optimised formulation, the mean particle size was 85.878 ± 1.063 ?m, entrapment efficiency was 92.26 ± 1.65%, and buoyancy was 89.19 ± 1.48% found. An image of the formulation taken using a scanning electron microscope (SEM) reveals discrete particles with a smooth surface texture, a hollow interior, a spherical shape, and a particle size of less than 200 ?m. The FTIR study confirms there was no interaction between the drug and excipients. The in-vitro drug release study found that atenolol-loaded microballoons released the drug for up to 12 hours as compared to the pure drug. This was due to increasing the gastric residence time and absorption area in the stomach. The drug release kinetic study reveals that it follows the Higuchi model and the drug release mechanism was type II transport which was obtained from the Korsmeyer Peppas model. The stability study shows that there is no significant change in the optimized microballoons for 30 days as per ICH guidelines.

Breaking up sedentary time to improve glucose control in a population at risk for developing type 2 diabetes (BURST2D study): a randomized controlled trial

Background: To compare the acute and chronic effects of frequent, short physical activity (PA) bouts spread throughout the day to a time-matched intervention consisting in a single continuous daily bout of PA on glucose control and potential underlying mechanisms in adults at risk of developing type 2 diabetes (T2D). Methods: BURST2D is a single-center, parallel-group, randomized controlled trial, in which sedentary adults with overweight/obesity and pre-diabetes (18-45 y, BMI: 25-40 kg/m2, fasting glucose: 100-125 mg/dL or 2h glucose: 140-199 mg/dL or HbA1c: 5.7-6.4%) will be randomly assigned to one of two 3-month PA interventions: BREAK, nine bouts of 5-min brisk walking performed every hour for nine consecutive hours (45-min/d total), 5 days/wk; ONE, one continuous 45-min bout of brisk walking, 5 days/wk. Primary outcomes will be daily glycemic mean and variability, fasting glucose and HbA1c, postprandial plasma glucose and insulin, glucose kinetics, and content of skeletal muscle proteins related to insulin signaling and glucose uptake. Secondary outcomes will be whole-body insulin sensitivity, 24-h total substrate oxidation, postprandial triglycerides, daily PA and sedentary behavior (SB) patterns, knowledge and attitude towards PA and SB, barriers and facilitators to intervention compliance, self-perceived appetite, mood, and sleep. Outcomes will be assessed at baseline and after one month and/or three months of intervention. Conclusions: This study will establish the acute and chronic effects of breaking up SB, independent of increases in PA, on glucose control and underlying mechanisms in adults with pre-diabetes. Results will advance the science of T2D prevention. Trial registration: This study is registered with the ClinicalTrials.gov, registry number NTC05041491

Formulation and evaluation of Buccal mucoadhesive tablets of diclofenac sodium using 23 factorial designs

Buccal tablets

Diclofenac sodium

Drug release

Mucoadhesion

Mucoadhesive tablets

Release kinetics

Content determination of 5-HMF in glucosamine hydrochloride tablets and formation kinetics study / 中国药房

OBJECTIVE To establish the method for the content determination of 5-hydroxymethylfurfural （5-HMF） in glucosamine hydrochloride tablets， and to analyze its regularity and influential factors. METHODS Quantitative analysis of 5-HMF was performed using high-performance liquid chromatography. The analysis was conducted on Shim-pack GIST C18-AQ column with mobile phase consisted of 0.1% phosphoric acid solution-methanol （90∶10， V/V） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃， and detection wavelength was 284 nm. The injection volume was 20 μL. Reaction kinetics test of different temperatures was adopted to analyze the relationship of 5-HMF content with reaction temperature and reaction time， and utilized to build its formation kinetic model. RESULTS The linger range of 5-HMF was 0.057-5.698 μg/mL （r＝0.999 9）. The limits of detection and quantitation were 5.70 and 17.09 ng/mL； RSDs of precision， repeatability and stability （24 h） tests were all lower than 1.0% （n＝6）. The average recoveries ranged from 99.38% to 99.73%（RSD＝0.53%， n＝9）. The contents of the 5-HMF in 8 batches of samples ranged 4.10-35.13 μg/g. Results of data fitting in reaction kinetics test showed that the higher reaction temperature and the longer reaction time， the higher 5-HMF content in the sample. At 50， 60， 70 and 80 ℃ ， the relationship between the content of 5-HMF and the reaction time was linear， in accordance with a zero-order kinetic model. The reaction rate constants were 6.789， 7.715， 8.815 and 11.430， respectively. CONCLUSIONS The established method has strong specificity， high sensitivity， and good accuracy； the reaction temperature and reaction time are important influential factors for the formation of 5-HMF in glucosamine hydrochloride tables. The change rule of its content conforms to the zero-order kinetic model.

Inhibition of total flavonoids from Abelmoschus Manihot on cytochrome P450 / 中国药科大学学报

@#To investigate the influential mechanism of total flavonoids from Abelmoschus Manihot (HKZ) on cytochrome P450 (CYP450) isoforms in human liver microsomes and to verify its effect on the most significantly inhibited subtype CYP2C9 in rats.The inhibitory effects of HKZ on human CYP3A4, CYP2C9, CYP2C19, CYP2E1, CYP1A2 and CYP2D6 were evaluated through the cocktail method using ultra-performance liquid chromatography tandem mass spectrometry, then its inhibitory mechanism was investigated and kinetic parameters of enzyme inhibition were calculated By comparing the pharmacokinetic behaviors of tolbutamide after single or multiple administration of 200 mg/kg HKZ and equal dose of CMC-Na in rats, the effects of HKZ on CYP2C11 enzyme (CYP2C9 isoenzyme) was estimated.The results indicated the significant inhibitory effect of HKZ on CYP2C9 and CYP2E1 with IC50 of 3.22 and 8.64 μg/mL, respectively. Also, it showed certain inhibitory ability on other isoforms with IC50 of 20-30 μg/mL.As demonstrated, HKZ may not be a time-dependent inhibitor which competitively inhibited CYP2E1 and CYP2C9 with Ki of 3.84 and 6.33 μg/mL.In contrast, it showed noncompetitive inhibition on CYP3A4 mediated testosterone-6β-hydroxylation and midazolam-4-hydroxylation reaction with Ki of 7.37 and 3.32 μg/mL.It was also a noncompetitive inhibitor of CYP1A2, CYP2D6 and CYPC219 with Ki values of 8.66, 11.49 and 21.94 μg/mL. HKZ did not change the pharmacokinetic parameters of CYP2C11 probe substrate tolbutamide in rat, but it affected the AUC0-t, cmax of 4-hydroxytolubutamide (P < 0.05). Therefore, drug-drug interaction mediated by CYP450 should be considered in clinical study.

Effect of smoking habit on cardiopulmonary function in patients with myocardial infarction -A study based on cardiopulmonary exercise testing- / 体力科学

The purpose of this study was to examine the relationship between smoking and cardiopulmonary function, and the effect of smoking habit on exercise tolerance after discharge from the hospital, focusing on CPX test data of patients hospitalized for acute myocardial infarction, and on CPX test data at 6 months after discharge. A total of 123 male patients hospitalized for acute myocardial infarction between April 2014 and December 2020 were included. Laboratory and CPX data were compared between smokers and non-smokers. CPX data of smokers, ex-smokers and non-smokers were also compared in 24 patients who underwent CPX examination 6 months after discharge. HDL-C was significantly decreased (p < 0.05) and τON was significantly prolonged (p < 0.05) during hospitalization in smokers. τON was significantly shorter only in ex-smokers (p < 0.05) 6 months after discharge compared to during hospitalization. These results suggest that τON, which reflects the oxygen uptake kinetics of peripheral tissues, is shortened by smoking cessation.

The UGT74L2 of Andrographis paniculata catalyzes phloretin to produce trilobatin and its enzymatic study / 药学学报

The last essential enzyme in the biosynthetic pathway of trilobatin, phloretin-4'-O glycosyltransferase (P4'-OGT), catalyzes the conversion of trilobatin to phloretin in vitro. However, only a few P4'-OGTs have been found in plants. This study used Malus domestica phloretin-4'-O glycosyltransferase (MdPh-4'-OGT) as a query to identify and clone two UDP-glucuronosyltransferase (UGT) genes, designated UGT74L2 and UGT74L3, from the transcriptome of Andrographis paniculata. According to a phylogenetic tree analysis, UGT74L2 and UGT74L3 belonged to the UGT74 family, which has been linked to several activities in other species. The in vitro enzymatic reaction demonstrated that UGT74L2 could particularly catalyze the formation of trilobatin from phloretin, but UGT74L3 had no effects. By using Ni-NTA affinity chromatography to extract the soluble UGT74L2 recombinant protein, the enzymatic kinetics of the activity was investigated using phloretin as the substrate. The results showed that the optimal temperature and pH for UGT74L2 enzymatic reaction were 40 ℃ and 8.0 (Tris-HCl system), respectively. Three metal ions (Ca2+, Mn2+ and Co2+) showed inhibitory effect on the activity of UGT74L2, while Mg2+ could improve the activity of UGT74L2. Other tested metal ions have no significant effect on UGT74L2. The results of enzymatic kinetic parameters that the Km value was 29.84 μmol·L-1, the kcat was 0.02 s-1, and the kcat·Km-1 was 572.6 mol-1·s-1. By homology modeling, molecular docking and mutation experiments, we found that multiple amino acids residues around the substrate binding pocket play quite an important role during catalytic process, In summary, we identified a novel P4'-OGT gene from medicinal plant Andrographis paniculata and provided a new efficient catalyst to synthesize trilobatin. Meanwhile, this study provides a reference for mining new efficient glycosylation modules from plants.

Study on the kinetic model of the clearance of protein-bound uremic toxins in maintenance hemodialysis patients / 中华肾脏病杂志

Objective:A kinetic model of the clearance of protein-bound uremic toxins (PBUTs) in maintenance hemodialysis patients is established to evaluate the effects of adding sorbents with different sorption efficiency to dialysate on the clearance rate of PBUTs, and to predict the sorption efficiency of sorbents using the model.Methods:The kinetic model was established by integrating the parameters of plasma flow rate ( Qp), dialysate flow rate ( Qd), free plasma fraction of PBUTs ( f1), free dialysate fraction of PBUTs ( f2), mass transfer coefficient of dialyzer ( K) and surface area of dialysis membrane ( A), and using the mass balance equation and Fick's first law. The model was also used to evaluate the relationship between the clearance rate of different PBUTs and the parameters of dialyzer and the sorption efficiency of sorbents. Results:The kinetic model of PBUTs clearance (CL): ?CL=Qp1-f1-f2γφf1-f2γ,?γ=QpQd,?φ=eKAf1Qp-f2Qd. The model was used to analyze the dialysis parameters of indoxyl sulfate and p-cresol sulfate dialysis.The clearance rate of PBUTs increased with the decrease of its binding capacity to albumin in plasma and the increase of plasma flow rate in dialyzer, dialysate flow rate, mass transfer coefficient of dialyzer, surface area of dialysis membrane, and sorption capacity of sorbents in dialysate. The increasing trend of PBUTs clearance rate was particularly obvious after applying sorbents. Further analysis of the dialysate flow rate and the sorption efficiency of sorbents in the dialysate showed that the increase of the dialysate flow rate could make up for the difference of the sorption efficiency of sorbents. When the dialysate flow rate tended to be infinite, the sorption efficiency of sorbents in the dialysate had no effect on the clearance rate of PBUTs. Conclusion:Adding sorbents of PBUTs to the dialysate during dialysis can significantly improve the clearance rate of PBUTs, suggesting a promising clinical application value.

Establishment and application of activity determining methods for different subtypes of xanthine oxidoreductase / 药学学报

Xanthine oxidoreductase (XOR), the key enzyme catalyzing purine to produce uric acid, including two subtypes, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), respectively, in vivo. Usually, XDH and XO can transform to each other. In this study, based on the principle that the subtype XO or XDH uses different electron acceptors, the methods for the measuring the activities of bovine milk XOR (pure enzyme) and its subtypes were established. The optimal concentrations of substrate xanthine (50 μmol·L-1) and electron acceptor NAD+ (50 μmol·L-1), pH value (7.80) were investigated. The ranges of the XOR, XO, XDH activity which could be determined were 0.97-17.5 U·L-1, 1-9 U·L-1, and 66-1 191 mU·L-1, respectively. Furthermore, the methods for determining the activities of XOR and its subtypes in mouse liver were established. The preparation of liver samples, the optimal concentrations of xanthine (100 μmol·L-1) and NAD+ (100 μmol·L-1) were researched. And the activity ranges of XOR, XO and XDH in mouse liver which could be determined were 0.67-3.98, 0.19-1.08, and 0.52-3.55 U·gprot-1, respectively. With the methods above, the effects of classic XOR inhibitor allopurinal (Allo) on XOR, XO and XDH from both milk and mouse liver were determined. All animal experiments have been approved by the Animal Experimental Center, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College (00003346). This study established new methods for the determination of XOR and its subtypes activity in pure enzyme system and in mouse liver, respectively, which were accurate and convenient. It laid the experimental foundation for exploring the different pathophysiological effects of XOR in the body and developing new XOR inhibitors.

Advanced subunit vaccine delivery technologies: From vaccine cascade obstacles to design strategies

Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

Fabrication of 1,4-alpha-D-glucan glucanohydrolase holding Gel-Scaffolds using Agar-Agar, a natural polysaccharide and Polyacrylamide, a synthetic organic polymer for continuous liquefaction of starch

1,4-alpha-D-glucan glucanohydrolase is among the most widely used commercial hydrolytic enzymes acting randomly on the glycosidic linkages of starch resulting in its saccharification and liquefaction. Its applicability in different industries can be improved by enhancing its stability and reusability. Therefore, in the present study attempts have been made to enhance the industrial applicability of 1,4-alpha-D-glucan glucanohydrolase from Bacillus subtilis KIBGE-HAR by adapting immobilization technology. The study developed mechanically stable, enzyme containing gel-frameworks using two support matrices including agar-agar, a natural polysaccharide and polyacrylamide gel, a synthetic organic polymer. These catalytic gel-scaffolds were compared with each other in terms of kinetics and stability of entrapped 1,4-α-D-glucan glucanohydrolase. In case of polyacrylamide gel, Km value for immobilized enzyme increased to 7.95 mg/mL, while immobilization in agar-agar resulted in decreased Km value i.e 0.277 mg/mL as compared to free enzyme. It was found that immobilized enzyme showed maximum activity at 70 °C in both the supports as compared to free enzyme having maximum activity at 60 °C. Immobilized 1,4-α-D-glucan glucanohydrolase exhibited no change in optimal pH 7.0 before and after entrapment in polyacrylamide gel and agar-agar. The enzyme containing gel-scaffold was found suitable for repeated batches of starch liquefaction in industrial processes. Agar-agar entrapped 1,4-α-D-glucanglucanohydrolase was capable to degrade starch up to seven repeated operational cycles whereas polyacrylamide entrapped enzyme conserved its activity up to sixth operational cycle.