Agent-Based Modeling and Simulation (ABMS)on the influence of adjusting medical service fees on patients' choice of medical treatment.

BACKGROUND: We explored the impact of medical service fee adjustments on the choice of medical treatment for hypertensive patients in Beijing. We hope to provide decision-making reference to promote the realization of hierarchical diagnosis and treatment in Beijing. METHODS: According to the framework of modeling simulation research and based on the data of residents and medical institutions in Beijing, we designed three models of residents model, disease model and hospital model respectively. We then constructed a state map of patients' selection of medical treatment and adjusted the medical service fee to observe outpatient selection behaviors of hypertensive patients at different levels of hospitals and to find the optimal decision-making plan. RESULTS: The simulation results show that the adjustment of medical service fees can affect the proportion of patients seeking medical treatment in primary and tertiary hospitals to a certain extent, but has little effect on the proportion of patients receiving medical treatment in secondary hospitals. CONCLUSIONS: Beijing can make adjustments of the current medical service fees by reducing fees in primary hospitals and slightly increasing fees in tertiary hospitals, and in this way could increase the number of patients with hypertension in the primary hospitals.

Mitochondrial C4375T mutation might be a molecular risk factor in a maternal Chinese hypertensive family under haplotype C.

Here, we reported a Han Chinese essential hypertensive pedigree based on clinical hereditary and molecular data. To know the molecular basis on this family, mitochondrial genome of one proband from the family was identified through direct sequencing analysis. The age of onset year and affected degree of patients are different in this family. And matrilineal family members carrying C4375T mutation and belong to Eastern Asian halopgroup C. Phylogenetic analysis shows 4375C is highly conservative in 17 species. It is suggested that these mutations might participate in the development of hypertension in this family. And halopgroup C might play a modifying role on the phenotype in this Chinese hypertensive family.

Knowledge and attitude of mothers regarding infant hearing loss in Changsha, Hunan province, China.

OBJECTIVE: The objective of this study was to explore the knowledge and attitude among mothers of newborns regarding infant hearing loss (HL) in Changsha, Hunan province, China. DESIGN: A questionnaire including 18 items was given to mothers. STUDY SAMPLE: A total of 115 mothers participated in the study. RESULTS: Seven risk factors for hearing loss were identified correctly by above 60% of respondents and the top three were prolonged noise (88.7%), high fever (82.6%) and ear discharge (82.6%). Poor knowledge was demonstrated on risk factors jaundice (20.0%), measles (22.6%), convulsion (33.0%) and traditional Chinese medicine (39.1%). Maternal knowledge scores in identification and intervention (2.68 ± 0.31) was slightly higher than the score in risk factors (2.47 ± 0.34). Ninety-nine per cent of the mothers expressed the willingness to test baby's hearing soon after birth and concern about hearing. CONCLUSIONS: Mothers were concerned about baby's hearing and the attitude was positive. However, the correct recognition rate towards some risk factors for HL was low. Action needs to be taken to raise awareness about ear and hearing care, prevent HL caused by preventable causes and prompt early identification, early diagnosis and intervention of HL.

Deformable liposomes by reverse-phase evaporation method for an enhanced skin delivery of (+)-catechin.

BACKGROUND: (+)-catechin, as the most common catechin isomer, is recognized to be an antioxidant which benefits the skin in many ways. The purpose of the present study was to prepare and evaluate a suitable liposomal delivery systems for (+)-catechin topical application. METHODS: In this study, catechin-loaded conventional liposomal delivery system, deformable conventional liposomal delivery system and deformable liposomes prepared by reverse-phase evaporation (REV) method were compared. The three systems were characterized for liposome particle size, zeta-potential, entrapment efficiency, drug release, permeability across porcine skin and catechin deposition in the skin. RESULTS: It was revealed that the size of deformable conventional liposomes before freeze-drying and deformable REV liposomes after freeze-drying range from 335.6 ± 71.7 nm to 551.1 ± 53.4 nm, respectively, which were considered to be suitable for skin delivery. The deformable REV liposomes had a higher aqueous volume and thus were able to entrap greater amounts of hydrophilic (+)-catechin (50.0 ± 5.9%) compared to conventional (30.0 ± 3.8%) and deformable conventional liposomes (36.1 ± 4.6%). All liposomal formulations exhibited a prolonged catechin release. Compared to deformable liposomes, the REV deformable liposomes showed a significantly better deposition of (+)-catechin while catechin solution did not permeate into the porcine ear skin. CONCLUSION: Among all formulations studied, deformable REV liposomes were considered to be favorable for catechin topical delivery.

Motor imagery therapy improved upper limb motor function in stroke patients with hemiplegia by increasing functional connectivity of sensorimotor and cognitive networks.

Background: Motor imagery therapy (MIT) showed positive effects on upper limbs motor function. However, the mechanism by which MIT improves upper limb motor function is not fully understood. Therefore, our purpose was to investigate the changes in functional connectivity (FC) within and outside the sensorimotor network (SMN) induced by MIT associated with improvement in upper limb motor function in stroke patients. Methods: A total of 26 hemiplegic stroke patients were randomly divided into MIT (n = 13) and control (n = 13) groups. Fugl-Meyer Assessment Upper Extremity Scale (FMA-UL), Modified Barthel Index (MBI) and resting-state functional magnetic resonance imaging (rs-fMRI) were evaluated in the two groups before treatment and 4 weeks after treatment. The efficacy of MIT on motor function improvement in stroke patients with hemiplegia was evaluated by comparing the FMA-UL and MBI scores before and after treatment in the two groups. Furthermore, the FC within the SMN and between the SMN and the whole brain was measured and compared before and after different treatment methods in stroke patients. The correlation analysis between the improvement of upper limbs motor function and changes in FC within the SMN and between the SMN and the whole brain was examined. Results: The FCs between ipsilesional primary motor cortex (M1.I) and contralateral supplementary motor area (SMA.C), M1.I and ipsilesional SMA (SMA.I), and SMA.C and contralateral dorsolateral premotor cortex (DLPM.C) significantly increased in the control group but decreased in the MIT group; while the FC between SMA.C and contralateral primary somatosensory cortex (S1.C) significantly increased in the control group but showed no significant difference in the MIT group. The FCs between M1.I and the ipsilesional hippocampal gyrus and ipsilesional middle frontal gyrus significantly decreased in the control group but increased in the MIT group; while the FC in the contralateral anterior cingulate cortex significantly increased in the MIT group but there was no significant difference in the control group. The results of the correlation analysis showed that the differences in abnormal intra-FCs within the SMN negatively correlated with the differences in FMA and MBI, and the difference in abnormal inter-FCs of the SMN positively correlated with the differences in FMA and MBI. Conclusions: MIT can improve upper limb motor function and daily activities of stroke patients, and the improvement effect of conventional rehabilitation therapy (CRT) combined with MIT is significantly higher than that of CRT alone. CRT may improve the upper limb motor function of stroke patients with hemiplegia mainly through the functional reorganization between SMN, while MIT may mainly increase the interaction between SMN and other brain networks.

Development of water-in-oil microemulsions with the potential of prolonged release for oral delivery of L-glutathione.

Oral delivery of L-L-glutathione is quite a challenge due to the enzymatic and physical barriers in the gastrointestinal tract (GIT). Colloidal delivery systems such as microemulsions (ME) can be valuable for oral delivery of L-glutathione, because they may protect L-glutathione from enzymatic degradation and enhance its permeability across the intestinal epithelium. The aim of this study was to identify ME systems capable of accommodating maximum amounts of L-glutathione in internal aqueous phase intended for oral delivery. Pseudoternary phase diagrams for the systems based on a single or a blend of two oily components, one or two nonionic surfactants and an aqueous phase loaded with L-glutathione were constructed, identified and characterized in terms of morphological, rheological and in vitro release studies. Among the tested formulations, the coarse emulsions resulted in the highest release rate, while the ME and liquid crystal systems provided sustained release of L-glutathione in vitro. There was a linear relationship between the cumulative amount of L-glutathione released from the ME and the liquid crystals, and the square root of time indicting a diffusion controlled process. The release of L-glutathione from the ME and the liquid crystal was related to the concentration of L-glutathione remaining in the formulations. In conclusion, two novel delivery colloidal systems of L-glutathione loaded water-in-oil ME and liquid crystal systems were developed and characterized. In addition, a simple isocratic HPLC analytic method was developed and validated, and was used for the qualitative and quantitative analysis of L-glutathione released from the selected formulations.

Development and Validation of Pretreatment Serum Total Bilirubin as a Biomarker to Predict the Clinical Outcomes in Primary Central Nervous System Lymphoma: A Multicenter Cohort Study.

Primary central nervous system lymphoma (PCNSL) is a predominantly aggressive neoplasm isolated to the central nervous system or vitreoretinal space. Bilirubin is an important biomarker reflecting hepatic function and oxidative stress status that is associated with the occurrence and development of various tumors. However, its prognostic role in PCNSL has yet to be evaluated. Therefore, we conducted a prospective-retrospective study to analyze the predictive value of serum total bilirubin (STB) in PCNSL patients. The association between the pretreatment STB and clinical outcomes in PCNSL was developed in the discovery cohort (retrospective [n = 44] and prospective [n = 45]) and validated in an independent retrospective cohort (n = 69). A generalized additive model, Kaplan-Meier curve, and Cox analysis were applied. In the discovery cohort, the STB showed a linear relationship with overall survival (OS, p = 0.011) and progression-free survival (PFS, p = 0.0476). The median STB level of 12.0 µmol/L was determined as the cutoff value to predict the clinical outcomes with area under the receiver operating characteristic curve (AUROC) values of 0.9205 and 0.8464 for OS and PFS, respectively. The median STB level resulted in similar accuracy for predicting the clinical outcomes in the validation cohort with AUROC values of 0.8857 and 0.8589 for OS and PFS, respectively. In both the discovery and validation cohorts, the Kaplan-Meier survival curve and Cox regression analysis showed that the upper median STB groups showed significantly worse OS than the lower median STB groups. In conclusion, the pretreatment STB could be considered a novel biomarker to predict the clinical outcomes in patients with PCNSL receiving high-dose methotrexate-based combination immunochemotherapy.

Association Between Exposure to Ozone (O3) and the Short-Term Effect on Tuberculosis Outpatient Visits: A Time-Series Study in 16 Cities of Anhui Province, China.

Introduction: Evidence has shown that air pollutant exposure plays a vital role in the progression of tuberculosis (TB). The aim of this research was to assess the short-term effects of ozone (O3) exposure and TB outpatient visits in 16 prefecture-level cities of Anhui, China, 2015-2020. Methods: Distributed lag nonlinear model (DLNM), Poisson generalized linear regression model and random effects model were applied in this study. The effects of different age and gender on TB were investigated by stratified analysis, and then we performed sensitivity analyses to verify the stability of the results. Results: A total of 186,623 active TB cases were registered from January 1, 2015 to December 31,2020 in Anhui. The average concentration of ozone is 92.77 ± 42.95 µg/m3. The maximum lag-specific and cumulative relative risk (RR) of TB outpatient visits was 1.0240 (95% CI: 1.0170-1.0310, lag 28 days) for each 10 µg/m³ increase in O3 in the single-pollutant model. Estimation for 16 prefecture-level cities indicated that the strong association between O3 and the risk of TB outpatient visits was in tongling (RR = 1.0555, 95% CI: 1.0089-1.1042), Suzhou (RR = 1.0475, 95% CI: 1.0268-1.0687), wuhu (RR = 1.0358, 95% CI: 1.0023-1.0704). Stratified analysis showed that the health effects of ozone exposure remained significant in male and older adults, and there was no significant association between exposure to ozone in children and adolescents and the risk of tuberculosis. Discussion: We found that ozone exposure increases the risk of TB infection in outpatient patients, with males and the elderly being more susceptible, and it is necessary for government departments to develop targeted publicity and prevention measures in response to the local air quality conditions.

[Significance of identification of fungi in gastric juice of patients with artificial airway in intensive care unit].

OBJECTIVE: To investigate the direct relationship and significance between the pH value of gastric juice and positive fungi in culture critical patients with artificial airway in intensive care unit (ICU) by analyzing and identifying the type of fungi and their sensitivity to antifungal therapy. METHODS: A prospective study was conducted.One hundred and sixty patients (between December, 2008 and October, 2011) with artificial airway lasting longer than 48 hours were studied in the ICU at the First Affiliated Hospital of Shenzhen University. The gastric juice specimens were collected through a nasogastric tube, their pH values were measured using precise litmus paper. These samples were divided into six groups according to their pH values: pH ≤ 2.0, pH 2.1-3.0, pH 3.1-4.0, pH 4.1-5.0, pH 5.1-6.0 and pH 6.1-7.0, and then fungi were cultured in these specimens with different pH values. Susceptibility of different fungicide drugs were also investigated. The susceptibility of fungi to gastric juice with different pH values was also investigated. The relationship between 28-day survival rate and the presence of fungi in gastric juice was analyzed in order to analyze the relationship of the presence of fungi in gastric juice and clinical outcome. RESULTS: (1) No fungal growth was found in the gastric juice with pH value lower than 4.0, and the positive rate of fungal culture was significantly increased when the pH value of gastric juice raised. (2) The positive rate of fungal growth was 27.9% (55/197), in which, the positive rate of Candida and non-Candida fungi was 38.2% (21/55) and 61.8% (34/55) respectively, and the difference was significant statistically [χ(2) = 4.16, P < 0.05]. (3) The fungal positive rate was 40.0% (22/55) and 60.0% (33/55) respectively, in survivors (102 cases) and non-survivors (58 cases). The percentage of Candida infection and non-Candida infection was 54.5% (12/22) and 45.5% (10/22) respectively, in survivors, and it was 27.3% (9/33) and 72.7% (24/33), respectively, in non-survivors. The rate of resistance of Candida and non-Candida fungi was 4.7%-14.3% (mean 10.1%) and 0-60% (mean 28.5%) respectively. CONCLUSIONS: Positive fungus culture rate was higher in critical patients with artificial airway and higher gastric juice pH values. Non-Candida fungi were mainly found in gastric juice with increasing resistance rate. Candida was more commonly found in survivors, and non-Candida fungi were more commonly found in non-survivors.

MiR-361-5p Inhibits the Wnt Axis via Targeting Lgr4 and Promotes Sepsis-induced Myocardial Injury.

OBJECTIVE: A growing body of evidence demonstrated that microRNAs (miRNAs) play a key role in sepsis-induced organ dysfunction. However, the mechanism of miR-361-5p in sepsis-induced myocardial injury remains to be clarified. METHODS: A mouse model of sepsis-induced myocardial injury was established using lipopolysaccharide (LPS). MiR-361-5p expression level was determined by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). G protein-coupled receptor-4 (Lgr4), apoptosis-related proteins, and the Wnt signaling pathway-related proteins were determined by Western blotting. The relationship between miR-361-5p and Lgr4 was determined using dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays. RESULTS: MiR-361-5p expression level was upregulated in the mouse model of sepsis-induced myocardial injury, while an opposite result was found for Lgr4 expression level. Knockdown of miR-361-5p protected the mouse model of sepsis-induced myocardial injury against inflammation and oxidative stress, and reduced cardiomyocyte (CM) apoptosis, which could be reversed by knockdown of Lgr4. The analysis of underlying mechanism revealed that miR-361-5p could target Lgr4 to modulate the activity of Wnt axis in CM apoptosis. CONCLUSION: MiR-361-5p could aggravate myocardial injury in LPS-induced septic mice by targeting Lgr4 to inhibit the Wnt axis.

Identification of hub genes and pathways in bladder cancer using bioinformatics analysis.

Bladder cancer (BC) is the most common malignant tumor of urinary tract system. The aim of this study was to investigate the genetic signatures of bladder cancer (BC) and identify its potential molecular mechanisms. The gene expression profiles of GSE3167 (50 samples, including 41BC and 9 non-cancerous urothelial cells) was downloaded from the GEO database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) were performed to identify enriched pathways, and a protein-protein interaction (PPI) network was used to identify hub genes and for module analysis. Moreover, we conducted expression and survival analyses to screen and validate hub genes. In total, 1528 DEGs were identified in bladder cancer (BC), including 1212 up-regulated genes and 316 down-regulated genes. Up-regulated differentially expressed genes (DEGs) were significantly enriched in negative regulation of macromolecule metabolic process, macromolecule catabolic process, proteolysis and regulation of cell death, while the down-regulated differentially expressed genes (DEGs) were mainly involved in cell surface receptor linked signal transduction, ion transport, cell-cell signaling and defense response. The top 10 hub genes with the highest degrees were selected from the PPI network. These genes included HSP90AA1, MYH11, MYL9, CNN1, ACTC1, RAN, ENO1, HNRNPC, ACTG2 and YWHAZ. From sub-networks, we found these genes were involved in the proteasome, pathways in cancer and cell cycle. Hence, the identified DEGs and hub genes may be beneficial to elucidate the mechanisms underlying BC.

Association between clinical factors and orofacial dyskinesias in anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND AND PURPOSE: We aimed to determine whether demographic information, clinical characteristics, laboratory tests, and imaging features are associated with orofacial dyskinesias (OFLD) in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: In this retrospective study, patients who were diagnosed with anti-NMDAR encephalitis were enrolled. All patients' factors, including demographic information, clinical characteristics, laboratory tests, and imaging features, were obtained at the time of hospitalization. The neurological function was assessed using the modified Rankin scale (mRS). Univariate and multivariate logistic regressions were used to examine the associations between clinical factors and OFLD. RESULTS: In total, 119 patients (median age: 28.0 [19.0-41.0] years; 67 females) were recruited. Of 119 patients, 44 (37.0%) had OFLD. OFLD was associated with increased mRS at admission, serum sodium, lumbar puncture pressure, female biologic sex, fever, psychiatric symptoms, seizures, impaired consciousness, autonomic dysfunction, and central hypoventilation in univariate logistic regression, respectively. Multivariate regression analysis revealed that female biologic sex (odds ratios [OR], 4.73; 95% confidence interval [CI], 1.27-17.64; p = .021), increased mRS at admission (OR, 2.09; 95% CI, 1.18-3.71; p = .011), psychiatric symptoms (OR, 7.27; 95% CI, 1.20-43.91; p = .031), and seizures (OR, 5.11; 95% CI, 1.22-21.43; p = .026) were associated with OFLD, after adjusting for confounding factors. CONCLUSIONS: Our analysis suggests that the following clinical factors are associated with OFLD: female biologic sex, increased mRS at admission, psychiatric symptoms, and seizures.

Niosomal Nanocarriers for Enhanced Dermal Delivery of Epigallocatechin Gallate for Protection against Oxidative Stress of the Skin.

Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of -45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival after UVA-irradiation, reduced lipid peroxidation, and increased the antioxidant enzymes' activities in human dermal fibroblasts (Fbs) compared to free EGCG. Finally, the uptake of niosomes was via energy-dependent endocytosis. The optimised niosomes have the potential to be used as a dermal carrier for antioxidants and other therapeutic compounds in the pharmaceutical and cosmetic industries.

Prognostic significance of pretreatment red blood cell distribution width in primary diffuse large B-cell lymphoma of the central nervous system for 3P medical approaches in multiple cohorts.

Background/aims: Predicting the clinical outcomes of primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) to methotrexate-based combination immunochemotherapy treatment in advance and therefore administering the tailored treatment to the individual is consistent with the principle of predictive, preventive, and personalized medicine (PPPM/3PM). The red blood cell distribution width (RDW) has been reported to be associated with the clinical outcomes of multiple cancer. However, its prognostic role in PCNS-DLBCL is yet to be evaluated. Therefore, we aimed to effectively stratify PCNS-DLBCL patients with different prognosis in advance and early identify the patients who were appropriate to methotrexate-based combination immunochemotherapy based on the pretreatment level of RDW and a clinical prognostic model. Methods: A prospective-retrospective, multi-cohort study was conducted from 2010 to 2020. We evaluated RDW in 179 patients (retrospective discovery cohorts of Huashan Center and Renji Center and prospective validation cohort of Cancer Center) with PCNS-DLBCL treated with methotrexate-based combination immunochemotherapy. A generalized additive model with locally estimated scatterplot smoothing was used to identify the relationship between pretreatment RDW levels and clinical outcomes. The high vs low risk of RDW combined with MSKCC score was determined by a minimal P-value approach. The clinical outcomes in different groups were then investigated. Results: The pretreatment RDW showed a U-shaped relationship with the risk of overall survival (OS, P = 0.047). The low RDW (< 12.6) and high RDW (> 13.4) groups showed significantly worse OS (P < 0.05) and progression-free survival (PFS; P < 0.05) than the median group (13.4 > RDW > 12.6) in the discovery and validation cohort, respectively. RDW could predict the clinical outcomes successfully. In the discovery cohort, RDW achieved the area under the receiver operating characteristic curve (AUC) of 0.9206 in predicting the clinical outcomes, and the predictive value (AUC = 0.7177) of RDW was verified in the validation cohort. In addition, RDW combined with MSKCC predictive model can distinguish clinical outcomes with the AUC of 0.8348 for OS and 0.8125 for PFS. Compared with the RDW and MSKCC prognosis variables, the RDW combined with MSKCC scores better identified a subgroup of patients with favorable long-term survival in the validation cohort (P < 0.001). RDW combined MSKCC score remained to be independently associated with clinical outcomes by multivariable analysis. Conclusions: Based on the pretreatment RDW and MSKCC scores, a novel predictive tool was established to stratify PCNS-DLBCL patients with different prognosis effectively. The predictive model developed accordingly is promising to judge the response of PCNS-DLBCL to methotrexate-based combination immunochemotherapy treatment. Thus, hematologists and oncologists could tailor and adjust therapeutic modalities by monitoring RDW in a prospective rather than the reactive manner, which could save medical expenditures and is a key concept in 3PM. In brief, RDW combined with MSKCC model could serve as an important tool for predicting the response to different treatment and the clinical outcomes for PCNS-DLBCL, which could conform with the principles of predictive, preventive, and personalized medicine. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00290-5.

Proposed new prognostic model using the systemic immune-inflammation index for primary central nervous system lymphoma: A prospective-retrospective multicohort analysis.

Purpose: The systemic immune-inflammation index (SII) has been considered a novel prognostic biomarker in several types of lymphoma. Our aims were to determine the best statistical relationship between pretreatment SII and survival and to combination of SII and the Memorial Sloan Kettering Cancer Center model (MSKCC) to derive the best prognostic mode in primary central nervous system lymphoma (PCNSL). Methods: Pretreatment SII and clinical data in 174 newly diagnosed PCNSL patients were included from two retrospective discovery cohorts (n = 128) and one prospective validation cohort (n = 46). A generalized additive model, Kaplan-Meier curve, and Cox analysis were performed. The high risk versus low risk of SII-MSKCC for the PCNSL cutoff point (0-1 vs. 2-4) was determined by the minimum P-value approach. Results: The SII showed a U-shaped relationship with the risk of overall survival (OS; P = 0.006). The patients with low SII or high SII had poorer OS and progression-free survival (PFS) than those with median SII. For PFS and OS, SII-MSKCC was a better predictor than MSKCC alone. The area under the receiver operating characteristic curve of the SII-MSKCC score was 0.84 for OS and 0.78 for PFS in the discovery cohorts. The predictive value of the SII-MSKCC score (OS, 0.88; PFS, 0.95) was verified through the validation cohort. Multivariable Cox analysis and Kaplan-Meier curve showed excellent performance for SII-MSKCC, with significant separation of two groups and better performance than MSKCC alone. Conclusions: We propose a new prognostic model using SII, age, and Karnofsky score that outperforms MSKCC alone and enables individualized estimates of patient outcome.

Advanced carrier systems in cosmetics and cosmeceuticals: a review.

Carrier systems refer to carrier vesicles such as liposomes, nano/microparticles, emulsions, etc., that are coupled with active agents and applied to products to achieve the promoted effects of the active ingredients. This article reviews the recent research on carrier systems, focusing on cosmetic and cosmeceutical applications; the pros and cons of each carrier system and products on the market utilizing the technologies are discussed.

Bioinformatic analysis of key pathways and genes involved in pediatric atopic dermatitis.

The initiation of atopic dermatitis (AD) typically happens very early in life, but most of our understanding of AD is derived from studies on AD patients in adult. The aim of the present study was to identify gene signature speficic to pediatric AD comapred with adult AD. The gene expression profiles of four datasets (GSE32924, GSE36842, GSE58558, and GSE107361) were downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network was constructed by Cytoscape software. Total 654 differentially expressed genes (DEGs) (394 up-regulated and 260 down-regulated) were identified in pediatric AD samples with adult AD samples as control. The up-regulated DEGs were significantly enriched in the migration and chemotaxis of granulocyte and neutrophil, while down-regulated DEGs were significantly enriched in biological adhesion. KEGG pathway analysis showed that up-regulated DEGs participated in chemokine signaling pathway while down-regulated DEGs participated in adherens junction, focal adhesion, and regulation of actin cytoskeleton. The top 10 hub genes GAPDH, EGFR, ACTB, ESR1, CDK1, CXCL8, CD44, KRAS, PTGS2, and SMC3 were involved in chemokine signaling pathway, cytokine-cytokine receptor interaction, interleukin-17 signaling pathway, and regulation of actin cytoskeleton. In conclusion, we identified DEGs and hub genes involved in pediatric AD, which might be used as therapeutic targets and diagnostic biomarkers for pediatric AD.

Non-ionic surfactant vesicles as a carrier system for dermal delivery of (+)-Catechin and their antioxidant effects.

Numerous skin disorders and diseases are related to oxidative stress. The application of an antioxidant, serving as a strong defense agent against oxidation, is of great interest in dermatology yet remains challenging for delivery. This paper aimed to develop a niosome carrier system to deliver the antioxidant (+) Catechin into the skin. (+) Catechin-loaded niosomes were prepared using film hydration technique and the physicochemical properties of drug-loaded niosomes were characterised and investigated by a series of in vitro and ex vivo studies. The optimised formulation displayed an acceptable size in nanoscale (204 nm), high drug entrapment efficiency (49%) and amorphous state of drug in niosomes. It was found that (+) Catechin-loaded niosomes could effectively prolong the drug release. Drug deposition in the viable layers of human skin was significantly enhanced when niosomal carriers were applied (p < 0.05). Compared to the pure drug, the niosomal formulation had a greater protective effect on the human skin fibroblasts (Fbs). This is consistent with the observation of internalisation of niosomes by Fbs which was concentration-, time- and temperature-dependent, via an energy-dependent process of endocytosis. The research highlighted that niosomes are potential topical carriers for dermal delivery of antioxidants in skin-care and pharmaceutical products.

The Prevalence of Symptomatic Knee Osteoarthritis in Relation to Age, Sex, Area, Region, and Body Mass Index in China: A Systematic Review and Meta-Analysis.

Purpose: This study aimed to investigate the overall prevalence of symptomatic knee osteoarthritis (OA) in China by conducting a meta-analysis. Methods: Six databases were searched for articles published from the date of inception to October 1, 2017, based on the Population, Intervention, Comparator, Outcomes (PICO) framework. The review was in line with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The χ2-based Q statistic and I 2 metrics were used for exploring the sources of heterogeneity. Random models were utilized to obtain prevalence estimates due to the heterogeneity that was observed. Comprehensive Meta-Analysis version 2.0 was used for assessing publication bias by inspecting funnel plots and Egger's tests. Results: Twenty-one eligible studies (74,908 participants in total) were identified. The overall pooled prevalence of symptomatic knee OA in China was 14.6%. The prevalence of symptomatic knee OA presented a rapid growth trend between the periods of 1990-2008 and 2008-2013 (9.1 vs. 20.1%, p = 0.005). However, after 2013, the prevalence dropped to 14.9% (p = 0.01). The prevalence rates of symptomatic knee OA increased with age and presented an almost linear growth after 40 years of age. Compared with males (10.9%), females (19.1%) exhibited a higher prevalence of symptomatic knee OA (p = 0.015). The symptomatic knee OA prevalence was significantly higher in rural than it was in urban areas (16.9 vs. 11.1%, p = 0.037). Conclusion: For symptomatic knee OA intervention, more attention should be paid to females, people in rural areas, and people aged over 40 years.

Comparison of auditory steady-state response and click-evoked auditory brain response in infants with different types and degrees of hearing loss.

Background: Auditory steady-state response (ASSR) and click-evoked auditory brain response (c-ABR) have been used for hearing assessment for decades years, the correlation of the two methods and the effects of type and degree of hearing loss (HL) to the correlation in infants younger than 6 months of age are unclear.Objectives: To compare the correlation of ASSR and c-ABR and then to analyse the effects of type and degree of HL on the correlation in infants younger than 6 months of age.Material and methods: Retrospective study comparing ASSR thresholds at various frequencies with c-ABR thresholds. 182 ears from 96 infants were assessed and classified according to types and degrees of HL.Results: The correlation coefficients were: 0.823, 0.864, 0.891, 0.871, 0.908, 0.915 and 0.913 between ASSR thresholds at 0.5, 1, 2, 4, 2-4, 1-2-4, 0.5-1-2-4 kHz and c-ABR thresholds respectively. The correlation coefficients in the group of sensorineural HL (SHL) (r = 0.763-0.900) were higher than conductive HL (r = 0.309-0.619) across all frequencies. The coefficients of severe-profound SHL (r = 0.595-0.790) were higher than mild-moderate SHL (r = 0.434-0.687) across all frequencies.Conclusions and significance: ASSR was one valuable cross-check measure by providing frequency specific information in auditory assessment.