Abstract Icariin has low bioavailability and poor stability, which limits its wide application. The complexation of icariin and whey protein is expected to solve this problem, but there is no research on their interaction mechanism. In view of this, the related mechanism was studied systematically by spectrofluorimetry and molecular docking method in this study. The fluorescence analysis showed that icariin and whey protein could form a non-covalent complex driven by hydrophobic force, which led to the fluorescence quenching of whey protein. In this process, the microenvironment around the tyrosine residue and tryptophan residue of whey protein changed. The molecular docking analysis confirmed the existence of hydrophobic interaction and hydrogen bonding in the complex, which well confirmed fluorescence results. The obtained results can promote the application of icariin in food.

Cell division cycle 42 (CDC42) regulates T helper (Th) cell differentiation and is related to psychological disorders. This study aimed to assess the correlation between blood CDC42 and Th cells, and their association with mental issues in stroke patients. Peripheral blood samples were obtained from 264 stroke patients and 50 controls. Then, serum CDC42 was measured by enzyme-linked immunosorbent assay, and Th1, Th2, and Th17 cells were detected by flow cytometry. Hospital Anxiety and Depression Scale (HADS) and Mini Mental State Examination (MMSE) were applied to patients. CDC42 was decreased (P<0.001), Th1 (P=0.013) and Th17 (P<0.001) cells were elevated, while Th2 cells (P=0.108) showed no difference in stroke patients compared to controls. In addition, CDC42 was negatively associated to Th1 (P=0.013) and Th17 (P<0.001) cells in stroke patients but were not associated with Th2 cells (P=0.223). Interestingly, CDC42 was negatively associated with HADS-anxiety (P<0.001) and HADS-depression scores (P=0.034) and positively associated with MMSE score (P<0.001) in stroke patients. Lower CDC42 was associated to lower occurrence of anxiety (P=0.002), depression (P=0.001), and cognitive impairment (P=0.036) in stroke patients. Furthermore, increased Th17 cells were positively correlated with HADS-anxiety and HADS-depression scores and inversely correlated with MMSE score, which were also associated with higher occurrence of anxiety, depression, and cognitive impairment in stroke patients (all P<0.05). Blood CDC42 and Th17 cells were correlated, and both of them were linked to the risk of anxiety, depression, and cognitive impairment. However, the findings need further large-scale validation, and the implicated mechanism needs more investigation.

ABSTRACT Objective: To investigate the risk factors for predicting atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs). Methods: A total of 140 patients with CIED in our hospital from June 2013 to June 2018 were included and were followed up to observe whether they had AHREs. AHRE are defined as atrial rate ≥ 175 times/minute, lasting > 5 minutes, and reviewed by an experienced electrophysiologist with unclear clinical diagnosis. The patients fasted for 12 hours after implantation, and blood samples were collected for biochemical, lipid, and whole blood count detection. Follow-up was regular after discharge to record follow-up data of each patient and conduct statistical analysis. Results: One hundred and forty patients were implanted with dual-chamber pacemakers, their median age was 70 years old, 44.29% were male, 27 patients had AHRE within one year, and AHRE incidence rate was 19.29%. The microcytic to hypochromic (M/H) ratio was calculated for all AHRE patients and compared with the patients without AHRE; the M/H value of AHRE patients was significantly higher. Throughout the entire follow-up period, a total of 44 patients developed AHRE; when adjusted by multivariate analysis, only M/H ratio ≥ 4.5 vs. < 4.5 had statistical significance, and the adjusted hazard ratio value was 4.313 (1.675-11.105). Conclusion: As an indicator, M/H ratio may play an important role in the occurrence and development of atrial fibrillation and can be used as a predictor of AHRE in patients with CIED.

Abstract Introduction: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. Methods and results: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. Conclusions: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.

SUMMARY: This study aims to extract teeth and alveolar bone structures in CBCT images automatically, which is a key step in CBCT image analysis in the field of stomatology. In this study, semantic segmentation was used for automatic segmentation. Five marked classes of CBCT images were input for U-net neural network training. Tooth hard tissue (including enamel, dentin, and cementum), dental pulp cavity, cortical bone, cancellous bone, and other tissues were marked manually in each class. The output data were from different regions of interest. The network configuration and training parameters were optimized and adjusted according to the prediction effect. This method can be used to segment teeth and peripheral bone structures using CBCT. The time of the automatic segmentation process for each CBCT was less than 13 min. The Dice of the evaluation reference image was 98 %. The U-net model combined with the watershed method can effectively segment the teeth, pulp cavity, and cortical bone in CBCT images. It can provide morphological information for clinical treatment.

RESUMEN: El objetivo del presente estudio fue extraer estructuras dentarias y óseas alveolares desde imágenes CBCT automáticamente, lo cual es un paso clave en el análisis de imágenes CBCT en el campo de la estomatología. En este estudio, se utilizó la segmentación de tipo emántica para la segmentación automática. Se ingresaron cinco clases de imágenes CBCT marcadas, para el entrenamiento de la red neuronal U-net. El tejido duro del diente (incluidos esmalte, dentina y cemento), la cavidad de la pulpa dentaria, hueso cortical, hueso esponjoso y otros tejidos se marcaron manualmente en cada clase. Los datos se obtuvieron de diferentes regiones de interés. La configuración de la red y los parámetros de entrenamiento se optimizaron y ajustaron de acuerdo con un análisis predictivo. Este método se puede utilizar para segmentar dientes y estructuras óseas periféricas mediante CBCT. El tiempo del proceso de segmentación automática para cada CBCT fue menor a 13 min. El “Dice” de evaluación de la imagen de referencia fue de 98 %. El modelo U-net combinado con el método “watershed”puede segmentar eficazmente los dientes, la cavidad pulpar y el hueso cortical en imágenes CBCT. Puede proporcionar información morfológica para el tratamiento clínico.

RESUMO: Globalmente, todos os setores ambientais estão ameaçados pelas mudanças climáticas, principalmente para os setores de alimentos e agricultura. O Paquistão é um país em desenvolvimento mais vulnerável a condições climáticas extremas e adversas, especialmente no sudeste da Ásia. As mudanças climáticas costumam ter efeitos adversos no Paquistão, porque muitas vezes é afetado por condições climáticas severas. Embora alguns estudos relatem a percepção dos agricultores em relação à adaptação e mitigação das mudanças climáticas, ainda há consciência insuficiente entre os agricultores paquistaneses. O conhecimento chave é muito importante para os agricultores superarem as duras condições climáticas para a colheita e economia de safras. Para preencher essa lacuna, esta pesquisa pretende descobrir o nível de consciência das mudanças e condições climáticas e fatores relacionados entre os agricultores paquistaneses. Por meio de uma técnica de amostragem aleatória estratificada, 500 questionários estruturados foram distribuídos entre os agricultores em quatro distritos de Punjab Paquistão para análise do estudo. O modelo probit foi usado para analisar a percepção do agricultor em relação às mudanças climáticas, variáveis sócio-demográficas e econômicas. Os resultados desta pesquisa mostram que 75% dos agricultores estão cientes das mudanças climáticas. A percepção da mudança climática entre os agricultores foi diretamente associada à experiência agrícola, idade dos agricultores, situação de propriedade da terra, nível de educação, fontes de informação e acesso à extensão. Além disso, nossa pesquisa mostrou que a avaliação dos agricultores sobre o comportamento adaptativo mostra que eles estão implementando ativamente a diversificação de culturas, irrigação e outras estratégias de adaptação. Os resultados deste estudo ajudarão agências governamentais e formuladores de políticas no Paquistão e em outras regiões a desenvolver medidas de adaptação sustentáveis no contexto das mudanças climáticas.

ABSTRACT: Globally, all environmental sectors are threatened by climate change, most especially to the food and agriculture sectors. Pakistan is a developing country that is most vulnerable to extreme and harsh climatic conditions, especially in Southeast Asia. Climate change has often adverse effects on Pakistan because it is often affected by severe weather conditions. Although, some studies have reported on farmers’ perceptiveness regarding climate change adaptation and mitigation, there is still insufficient awareness among Pakistanis’ farmers. Key knowledge is very important for farmers to overcome the harsh climatic conditions for harvesting and saving crops. To bridge this gap, this research discovered the awareness level of climate change, weather conditions, and related factors among Pakistani farmers. Through a stratified random sampling technique, 500 structured questionnaires were distributed among the farmers in four districts of Punjab Pakistan for study analysis. The probit model was used to analyze the farmer’s perception regarding climate change, socio-demographic and economic variables. The findings of this research showed that 75% of farmers are aware of climate change. Perception of climate change between farmers was directly associated with agriculture experience, farmers’ age, land ownership status, level of education, information sources, and access to extension. Also, our research showed that farmers’ assessment of adaptive behavior showed that farmers are actively implementing crop diversification, irrigation, and other adaptation strategies. Results of this study will help government agencies and policymakers in Pakistan and other regions to develop sustainable adaptation measures in the framework of climate change.

Abstract A number of complications have been ascribed to shoulder arthroscopy, but pulmonary edema is rarely reported. A 64-year-old female underwent right shoulder arthroscopic repair for supraspinatus and subscapular tears under intermuscular sulcus brachial plexus block (ISBPB) and general anesthesia. Finishing suture of torn tendon, and acromion and distal clavicle plasty, the patient represented the symptoms of dyspnea, and oxygen saturation quickly dropped to 80% without oxygen supply. After inhaled oxygen, the oxygen saturation quickly returned to 95%, while dyspnea didn’t improve. Noticing swelling in neck and chest, left movement of the trachea, low breath sounds and wet rales during auscultation, ultrasound examination was performed and found the obvious pleural slip, and a large number of b-lines in the lung, indicating pulmonary edema. After injection of furosemide and dexamethasone (i.v.), the outcome of patient was satisfactory. This is the first report of pulmonary edema as a complication of shoulder arthroscopy, which also reviews the relevant factors of fluid extravasation, and highlights the good use of the equipment at hand to quickly judge the patient's condition.

Abstract Danzhi Jiangtang capsule (DJC), a traditional medicinal formula composed of cortex moutan, heterophylly falsestarwort root, unprocessed rehmannia root, oriental waterplantain rhizome, dodder seed and leech, has been used to treat type 2 diabetes in clinic for almost 10 years. In addition, DJC was also confirmed that it could relieved oxidative stress of vascular endothelium in diabetic macroangiopathy. Based on the fact that the DJC could regulated the level of free fatty acids in diabetes patients and the constituents of DJC also possess potential anti-hyperlipidemic effect, thus, the present work aimed to evaluate the anti-hyperlipidemic effect of DJC and further investigated potential molecular mechanism of this action. As in vivo results revealed, DJC could reduced the levels of TC, TG, LDL, increased HDL level as well as decreased the level of ALT and AST of model rats. In addition, DJC also showed significant antioxidant effect by decreasing the level of MDA and increasing the level of SOD and GSH-Px. Furthermore, western blot analysis showed that DJC could up-regulated the expression of phosphorylated JAK2 and STAT3, and down-regulated the expression of SCOC3 protein, which indicated that DJC could regulate the metabolism of lipid via JAK2/STAT3 pathway.

RESUMO Objetivo: O VEGF-D é um potencial biomarcador para linfangioleiomiomatose (LAM); entretanto, seu desempenho diagnóstico ainda não foi sistematicamente estudado. Métodos: Foram realizadas buscas nos bancos de dados PubMed, EMBASE, Scopus, Web of Science e Cochrane Library para identificar estudos primários sobre o VEGF-D com relação ao diagnóstico de LAM. A qualidade dos estudos foi avaliada por meio da ferramenta Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). As estimativas sumárias de acurácia diagnóstica foram combinadas utilizando um modelo bivariado de efeitos aleatórios. Análises de subgrupo e de sensibilidade foram realizadas para explorar possíveis heterogeneidades. O sistema Grading of Recommendations Assessment, Development, and Evaluation (GRADE) foi aplicado para avaliar a qualidade das evidências e indicar a força das recomendações. Resultados: Dez estudos envolvendo 945 pacientes eram de alto risco em qualidade, segundo a ferramenta QUADAS-2. Os parâmetros diagnósticos combinados foram indicados da seguinte forma: sensibilidade = 0,82 (IC95%: 0,71-0,90); especificidade = 0,98 (IC95%: 0,94-0,99); e OR diagnóstica = 197 (IC95%: 66-587). A ASC da análise summary ROC foi de 0,98. As análises de subgrupo e de sensibilidade revelaram que o desempenho global não foi substancialmente afetado pela composição do grupo controle, valor de corte pré-especificado, país de origem ou diferentes valores de corte (p > 0,05 para todos). Uma forte recomendação para a dosagem de VEGF-D sérico para auxiliar no diagnóstico de LAM foi feita de acordo com o sistema GRADE. Conclusões: O VEGF-D parece ter grandes implicações potenciais para o diagnóstico de LAM na prática clínica em virtude da excelente especificidade e sensibilidade subótima.

ABSTRACT Objective: VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. Methods: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. Results: Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. Conclusions: VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.

Abstract Quinoa starch microparticles (QSMs) fabricated with unhydrolyzed quinoa starch (QS) by inverse microemulsion technology could be used as medicine delivery and cosmetic accessories. The size distribution of QSMs was uniform at 28.5 μM, and the adsorption capacity of methylene blue was 0.82 mg/ g. The optimum preparation process was as follows: a QS mass fraction of 9%, an epoxy chloropropane content of 1%, an amount of oil phase of 100 mL, a span 80 of 3 mg/mL, and a stirring speed of 400 r/min for 3 h at room temperature and pressure. The QSMs were spherical, ellipsoidal in shape with the specific surface area of 1.676 m2/g. The crystallinity of the QSMs increased from 1.24% to 16.8% after crosslinking. The maximum thermal degradation temperature of the QSMs rose slightly than QS. It will be a promising material for application as a drug carrier and in cosmetics.

Abstract Evidences showed that Prognostic Nutritional Index (PNI) is one important predictive factor for some cancers. However, the association between PNI and colorectal cancer is still unclear. In this study, we aim to explore the association between PNI and death in patients with locally advanced colorectal cancer. We enrolled 400 patients with colorectal cancer. The pathological results was used to confirm it. The patients received radical resection. The PNI at baseline was set as the exposure variable, death was the outcome variable, and other potential confounders were also analyzed. There was no association between PNI and the deaths of local advanced colorectal cancer and radical resection of colorectal cancer (HR=0.88; 95% CI, 0.78-1.00).Applying the cubic spline function, we found that it is not linear between PNI and death. Two-piecewise cox model showed that there was 68% decrease of risk of deaths when PNI change per 1 (HR=0.32; 95% CI, 0.13-0.79) on the left side of the inflection point (41.35). On the right of the inflection point, there was no association between PNI and death. PNI and deaths are linear correlation. Within a certain range (PNI=26-41), PNI is an independent protective factor for death risk.

Abstract In this study, rice protein was used as raw material to explore the effects of γ-irradiation treatment doses (0, 0.5, 1, 2, 3, 5 kGy) on the physicochemical properties of rice protein (particle size, zeta potential, secondary structure, scanning electron microscope microstructure), surface hydrophobicity (H0), thermal stability), functional properties (solubility, water and oil retention, emulsification) and sensory quality. The results show that when the γ-irradiation dose is 2 kGy, the average particle size of rice protein is the smallest, the absolute value of the potential is the highest 33.58 mV, the content of β-sheets in the secondary structure is at least 31.16 ± 0.16, and the content of random curl is at most 14.56 ± 0.06, the surface of the microstructure is rough and the degree of pore depression is the deepest, the highest H0 is 160.45 ± 2.98, the minimum denaturation temperature (Td) and enthalpy (△H) are 70.49 ± 0.05 °C and 1.30 ± 0.01 J/g, which shows that γ-irradiation treatment can be significant affect the physicochemical properties of rice protein. When the irradiation dose is 2 kGy, the highest solubility of rice protein is 69.18 ± 1.07%, and the highest water and oil holding capacity are 5.89 ± 0.08 g/g and 3.45 ± 0.04 g/g, respectively. The highest emulsification activity and emulsification stability are 45.65 ± 1.26 m2/g and 208.33 ± 4.79 min, which shows that γ-irradiation treatment can improve the functional properties of protein. When the irradiation dose was less than 5 kGy, the sensory quality of rice protein was not significantly affected. The research results provide a theoretical basis for the deep processing and value-added utilization of rice protein by γ-irradiation technology.

Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.

Abstract Frailty is a geriatric syndrome that predicts the onset of disability, morbidity and mortality in elderly people; it is a state of pre-disability and is reversible. This review aimed to assess the impact of dietary supplementation interventions in frail older adults. A systematic search of PubMed, Web of Science, Embase, and the Cochrane Library databases was performed to collect randomized controlled trials of dietary supplements for the treatment of frailty in the elderly published before March 2022. The frailty score, muscle mass, muscle strength and physical performance of the frail elderly were extracted for analysis. Meta-analysis was performed using Review Manager Version 5.4 and Stata version 15.0. Totally, 18 studies met the inclusion criteria, with 1204 participants (603 experiment group vs. 601 control group). Compared to control group, multi-nutrient nutrition intervention can significantly improve the frailty score of the elderly (MD = -0.19, 95% CI: -0.38 to -0.01, P = 0.04, I2 = 0). Protein supplementation intervention significantly improved body weight (MD = 4.86, 95% CI: 1.21 to 8.52, P = 0.009), muscle mass [lean mass (MD = 2.73, 95% CI:1.26 to 4.20, P = 0.0003)], muscle strength (MD = 1.90, 95% CI: 0.68 to 3.12, P = 0.002), and physical performance [chair stand test (MD = -2.15, 95% CI: -3.21 to -1.10, P < 0.0001)] in frail older adults compared to control. This meta-analysis and systematic review suggests that dietary supplements interventions positively influence in older people with frailty.

Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine, demonstrating an increasing incidence every year. TongXieYaoFang (TXYF) has been used widely in China as a complementary therapy to relieve the symptoms of IBD for hundreds of years. In the present research, a network pharmacology-based approach was used to systematically explore the intrinsic mechanisms of TXYF in IBD at the molecular level. Network pharmacology-based methods, which mainly included database mining, screening of bioactive compounds, target prediction, collection of IBD-related targets, gene enrichment analysis, network construction, and molecular docking, were employed in the present study. Network analysis revealed a total of 108 potential targets derived from 22 component compounds of TXYF, among which 34 targets were common with the IBD-related targets. In the protein-protein interaction (PPI) network, 10 key targets were identified. The gene enrichment analysis suggested that anti-inflammatory processes, such as NF-kappa B signaling pathway and Toll-like receptor signaling pathway, could be the core processes involved in the action of TXYF in IBD. Molecular docking results revealed that three compounds present in TXYF exhibited strong binding affinity for PTGS2. The present study provides novel insights into the molecular mechanisms and network approaches of TXYF action in IBD from a systemic perspective. The potential targets and pathways identified in the present study would assist in further research on the clinical application of TXYF in IBD therapy.