Balancing functions of antifouling, nitric oxide release and vascular cell selectivity for enhanced endothelialization of assembled multilayers.

Surface endothelialization is a promising way to improve the hemocompatibility of biomaterials. However, current surface endothelialization strategies have limitations. For example, various surface functions are not well balanced, leading to undesirable results, especially when multiple functional components are introduced. In this work, a multifunctional surface was constructed by balancing the functions of antifouling, nitric oxide (NO) release and endothelial cell promotion via layer-by-layer (LBL) self-assembly. Poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol) methacrylate) (negatively charged) and polyethyleneimine (positively charged) were deposited on silicon substrates to construct multilayers by LBL self-assembly. Then, organic selenium, which has a NO-releasing function, and the cell-adhesive peptide Gly-Arg-Glu-Asp-Val-Tyr, which selectively promotes endothelial cells, were introduced on the assembled multilayers. Poly(oligo(ethylene glycol) methacrylate) is a hydrophilic component for antifouling properties, and poly(sodium p-styrenesulfonate) is a heparin analog that provides negative charges. By modulating the contents of poly(oligo(ethylene glycol) methacrylate) and poly(sodium p-styrenesulfonate) in the copolymers, the NO release rates catalyzed by the modified surfaces were regulated. Moreover, the behaviors of endothelial cells and smooth muscle cells on modified surfaces were well controlled. The optimized surface strongly promoted endothelial cells and inhibited smooth muscle cells to achieve endothelialization effectively.

Endothelium-Inspired Hemocompatible Silicone Surfaces: An Elegant Balance between Antifouling Properties and Endothelial Cell Selectivity.

To address the adverse reactions caused by the implantation of blood-contacting materials, researchers have developed different strategies, of which mimicking multiple key features of endothelial cells is the most effective. However, simultaneously immobilizing multiple chemical components on a single material surface and maintaining the effects of individual components are challenging. In this work, endothelium-mimicking silicone surfaces were developed by incorporating the antifouling polymer poly(oligo(ethylene glycol) methacrylate), the glycosaminoglycan analog poly(sodium 4-vinyl-benzenesulfonate) and a nitric oxide catalyst (selenocystamine dihydrochloride). Through the rational regulation of multiple chemical components, the surfaces harmoniously resisted nonspecific protein adsorption, platelet adhesion and activation and smooth muscle cell hyperproliferation while promoting endothelial cell proliferation and migration. The coculture experiment with HUVECs and HUVSMCs showed that the optimum selectivity of HUVECs/HUVSMCs was ∼1.7. This work contributes insight into the control of antifouling properties and endothelial selectivity, providing a new avenue for the development of blood-contacting materials.

Spatially Confined π-Complexation within Pore-Space-Partitioned Metal-Organic Frameworks for Enhanced Light Hydrocarbon Separation and Purification.

Ultramicroporous metal-organic frameworks (MOFs) are demonstrated to be advantageous for the separation and purification of light hydrocarbons such as C2H2, C2H4, and CH4. The introduction of transition metal sites with strong π-complexation affinity into MOFs is more effective than other adsorption sites for the selective adsorption of π-electron-rich unsaturated hydrocarbon gases from their mixtures. However, lower coordination numbers make it challenging to produce robust MOFs directly utilizing metal ions with π-coordination activity, such as Cu+, Ag+, and Pd2+. Herein, a series of novel π-complexing MOFs (SNNU-33s) with a pore size of 4.6 Å are precisely constructed by cleverly introducing symmetrically matched C3-type [Cu(pyz)3] (pyz = pyrazine) coordinated fragments into 1D hexagonal channels of MIL-88 prototype frameworks. Benifit from the spatial confinement combined with π-complex-active Cu+ of [Cu(pyz)3], pore-space-partitioned SNNU-33 MOFs all present excellent C2H2/CH4, C2H4/CH4, and CO2/CH4 separation ability. Notably, the optimized SNNU-33b adsorbent demonstrates top-level IAST selectivity values for C2H2/CH4 (597.4) and C2H4/CH4 (69.8), as well as excellent breakthrough performance. Theoretical calculations further reveal that such benchmark light hydrocarbon separation and purification ability is mainly ascribed to the extra-strong binding affinity between Cu+ and π-electron donor molecules via a spatially confined π-complexation process.

METTL4-mediated N6-methyladenine DNA modification regulates thermotolerance in Arabidopsis thaliana.

DNA N6-methyladenine (6 mA) is an evolutionarily conserved DNA modification in procaryotes and eukaryotes. The DNA 6 mA methylation is tightly controlled by 6 mA regulatory proteins. DNA N6-adenine methyltransferase 1 (DAMT-1) has been identified as a DNA 6 mA methyltransferase in animals. In plants, DNA 6 mA methylation has been found, however, the DNA 6 mA methyltransferases and their function in plants are largely unknown. In our study, we find METTL4 is a DNA 6 mA methyltransferase in Arabidopsis thaliana. Both in vitro and in vivo evidences support the DNA 6 mA methyltransferase activity of METTL4. mettl4 mutant is hypersensitive to heat stress, suggesting DNA 6 mA methylation plays important role in heat stress adaption. RNA-seq and 6 mA IP-qPCR analysis show that METTL4 participates in heat stress tolerance by regulating expression of heat responsive genes. Our study find METTL4 is a plant DNA 6 mA methyltransferase and illustrates its function in regulating heat stress response.

Trace Sample Proteome Quantification by Data-Dependent Acquisition without Dynamic Exclusion.

Despite continuous technological improvements in sample preparation, mass-spectrometry-based proteomics for trace samples faces the challenges of sensitivity, quantification accuracy, and reproducibility. Herein, we explored the applicability of turboDDA (a method that uses data-dependent acquisition without dynamic exclusion) for quantitative proteomics of trace samples. After systematic optimization of acquisition parameters, we compared the performance of turboDDA with that of data-dependent acquisition with dynamic exclusion (DEDDA). By benchmarking the analysis of trace unlabeled human cell digests, turboDDA showed substantially better sensitivity in comparison with DEDDA, whether for unfractionated or high pH fractionated samples. Furthermore, through designing an iTRAQ-labeled three-proteome model (i.e., tryptic digest of protein lysates from yeast, human, and E. coli) to document the interference effect, we evaluated the quantification interference, accuracy, reproducibility of iTRAQ labeled trace samples, and the impact of PIF (precursor intensity fraction) cutoff for different approaches (turboDDA and DEDDA). The results showed that improved quantification accuracy and reproducibility could be achieved by turboDDA, while a more stringent PIF cutoff resulted in more accurate quantification but less peptide identification for both approaches. Finally, the turboDDA strategy was applied to the differential analysis of limited amounts of human lung cancer cell samples, showing great promise in trace proteomics sample analysis.

A multifunctional bio-patch crosslinked with glutaraldehyde for enhanced mechanical performance, anti-coagulation properties, and anti-calcification properties.

Bio-patches for the treatment of valvular disease have been evaluated in clinical trials. It has been shown that failure of these devices, occurring within a few years of implantation, may be due to cytotoxicity, immune response, calcification and thrombosis. Some of these effects may be due to the glutaraldehyde crosslinking process used in the preparation of the materials. A number of studies have focused on strategies to control calcification, while others have concentrated on the prevention of micro-thrombus formation. In the present work, we have introduced amino-terminated poly(ethylene glycol) (NH2-PEG-NH2) as an intermolecular bridge, which not only eliminates free aldehyde groups to prevent calcification, but also introduces sites for the attachment of anticoagulant molecules. Furthermore, PEG, itself a hydrophilic polymer with good biocompatibility, may effectively prevent protein adsorption in the early stages of blood contact leading to thrombus formation. After further covalent attachment of heparin, modified bovine pericardium (BP) showed strong anti-calcification (calcium content: 39.3 ± 3.1 µg mg-1) and anti-coagulation properties (partial thromboplastin time: >300 s). The biocompatibility and mechanical properties, important for clinical use, were also improved by modification. The strategy used in this work includes new ideas and technologies for the improvement of valve products used in the clinic.

Protective effect of soy isolate protein against streptozotocin induced gestational diabetes mellitus via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Gestational diabetes mellitus (GDM) is a serious complication of pregnancy that is characterized by high blood sugar levels that occur due to insulin resistance and dysfunction in glucose metabolism during pregnancy. It usually develops in the second or third trimester of pregnancy and affects about 7 % of all pregnancies worldwide. In this experimental study, we scrutinized the GDM protective effect of soy isolate protein against streptozotocin (STZ) induced GDM in rats and explore the underlying mechanism. MATERIAL AND METHODS: Sprague-Dawley (SD) rats were used in this experimental study. A 55 mg/kg intraperitoneal injection of streptozotocin (STZ) was administered to induce diabetes in female rats, followed by oral administration of soy isolate protein for 18 days. Body weight, glucose levels, and insulin were measured at different time intervals (0, 9, and 18 days). Lipid profiles, antioxidant levels, inflammatory cytokines, apoptosis parameters, and mRNA expression were also assessed. Pancreatic and liver tissues were collected for histopathological examination during the experimental study. RESULTS: Soy isolate protein significantly (P < 0.001) reduced the glucose level and enhanced the insulin level and body weight. Soy isolate protein remarkably decreased the placental weight and increased the fetal weight. Soy isolate protein significantly (P < 0.001) decreased the HbA1c, hepatic glycogen, serum C-peptide and increased the level of free fatty acid. Soy isolate protein significantly (P < 0.001) altered the level of lipid, antioxidant and inflammatory cytokines. Soy isolate protein significantly (P < 0.001) improved the level of adiponectin, visfatin and suppressed the level of leptin and ICAM-1. Soy isolate protein significantly (P < 0.001) altered the mRNA expression and also restored the alteration of histopathology. CONCLUSION: Based on the result, soy isolate protein exhibited the GDM protective effect against the STZ induced GDM in rats via alteration of TLR4/MyD88/NF-κB signaling pathway.

Regulating cell behavior via regional patterned distribution of heparin-like polymers.

Molecular patterning on biomaterial surfaces is an effective strategy to regulate biomaterial properties. Among the specific molecules, due to their biological functions, such as regulating cell behavior, heparin-like polymers (HLPs) have attracted much attention. In this study, HLP-distributed regional patterned surfaces (300 µm diameter circular array) were prepared by the combination of visible light-induced graft polymerization, transfer imprinting, and self-assembly to regulate the behavior of human umbilical vein endothelial cells (HUVECs) and human umbilical vein smooth muscle cells (HUVSMCs). The introduction of the regional pattern on HLP-modified surfaces enhanced the promotion effect of sulfonate-containing polymer (pSS) and sulfonate-, and glyco-containing copolymer (pS-co-pM), and slightly weakened the inhibition effect of glyco-containing polymer (pMAG) on the growth of HUVECs and HUVSMCs. Compared with flat surfaces, it was found that the unmodified regional patterned surfaces inhibit the spreading of HUVECs and HUVSMCs, while significantly promoting the spreading of HUVECs and HUVSMCs on all the HLP-distributed regional patterned surfaces. The patterned surface modified with pS-co-pM had the highest average spread area of HUVECs (∼10,554 µm2), which was 193 % higher than that of the unmodified flat surface. This trend was somewhat related to surface VEGF adsorption. The combination of regional divisive patterns and different HLP distributions enriched the potential of further exploring the influences of HLP chemical distributions and complex surface environments on cell-material interactions.

Development of a Mixed Multinuclear Cluster Strategy in Metal-Organic Frameworks for Methane Purification and Storage.

Metal-organic frameworks (MOFs) have attracted extensive attention in methane (CH4) purification and storage. Specially, multinuclear cluster-based MOFs usually have prominent performance because of large cluster size and abundant open metal sites. However, compared to diverse combinations of organic linkers, one MOF with two or more multinuclear clusters is difficult to achieve. In this paper, we demonstrate a mixed multinuclear cluster strategy, which successfully led to three new heterometallic MOFs (SNNU-328-330) with the same common H3TATB [2,4,6-tris(4-carboxyphenyl)-1,3,5-triazine] tritopic linker and six types of multinuclear clusters ([YCd(COO)4(µ2-H2O)], [YCd2(COO)8], [In3(COO)6(µ3-OH)], [In3Eu2(COO)9(µ3-OH)3(µ4-O)], [Y9(COO)12(µ3-OH)14] and [Y2Cd8(COO)16(µ2-H2O)4(µ3-OH)8]). Three MOF adsorbents all show great potentials to remove the impurities (CO2 and C2-hydrocarbons) in natural gas and show prominent high-pressure methane storage capacity. Among them, the ideal adsorbed solution theory separation ratios of equimolar C2H2/CH4, C2H4/CH4, C2H6/CH4, and CO2/CH4 at 298 K for SNNU-328 reach to 29.7-16.0, 19.1-8.2, 33.2-10.3, and 74.3-8.5, which have surpassed many famous MOF adsorbents. Dynamic breakthrough experiments conducted at 273 and 298 K showed that SNNU-330 can separate CH4 from C2H2/CH4, C2H4/CH4, C2H6/CH4, and CO2/CH4 mixtures with the breakthrough interval times of about 48.2, 17.9, 37.2, and 17.1 min g-1 (273 K, 1 bar, v/v = 50/50, 2 mL min-1), respectively. Remarkably, SNNU-329 exhibits extremely high methane storage performance at 298 K with the total uptake and working capacity of 192 cm3 cm-3 (95 bar) and 171 cm3 cm-3 (65 bar) due to the synergistic effects of high surface area, suitable pore sizes, and multiple open metal sites.

Effect of Structural Elements of Heparin-Mimicking Polymers on Vascular Cell Distribution and Functions: Chemically Homogeneous or Heterogeneous?

Heparin-mimicking polymers (HMPs) are artificially synthesized alternatives to heparin with comparable regulatory effects on protein adsorption and cell behavior. By introducing two major structural elements of HMPs (sulfonate- and glyco-containing units) to different areas of material surfaces, heterogeneous surfaces patterned with different HMPs and homogeneous surfaces patterned with the same HMPs can be obtained. In this work, heterogeneous HMP-patterned poly(dimethylsiloxane) (PDMS) surfaces with sulfonate-containing polySS (pS) and glyco-containing polyMAG (pM) distributed in circular patterns (with a diameter of 300 µm) were prepared (S-M and M-S). Specifically, pS and pM were distributed inside and outside the circles on S-M, respectively, and exchanged their distribution on M-S. Homogeneous HMP-patterned silicone surfaces (SM-SM) where sulfonate- and glyco-containing poly(SS-co-MAG) (pSM) were distributed uniformly were prepared. Vascular cells showed interestingly different behaviors between chemically homogeneous and heterogeneous surfaces. They tended to grow in the sulfonate-modified area on S-M and M-S and were distributed uniformly on SM-SM. Compared with M-S, S-M showed a better promoting effect on the growth of vascular cells. Among all the samples, SM-SM exhibited the highest proliferation density and an optimum spreading state of vascular cells, as well as the highest human umbilical vein endothelial cell (HUVEC) viability (∼99%) and relatively low human umbilical vein smooth muscle cell (HUVSMC) viability (∼72%). By heterogeneous or homogeneous patterning with different structural elements of HMPs, the modified silicone surfaces spatially guided vascular cell distribution and functions. This strategy provides a new surface engineering approach to the study of cell-HMP interactions.

Auricularia auricular Adsorbs Aflatoxin B1 and Ameliorates Aflatoxin B1-Induced Liver Damage in Sprague Dawley Rats.

Aflatoxin B1 (AFB1), as a class I carcinogen, poses a substantial health risk to individuals. Contamination of food sources, particularly grains and nuts, with Aspergillus flavus (A. flavus) contributes to the prevalence of AFB1. The impact of global warming has spurred research into the development of AFB1 prevention technologies. While edible fungi have shown potential in detoxifying AFB1, there is a scarcity of literature on the application of Auricularia auricular (A. auricular) in this context. This study aimed to investigate the ability and underlying mechanism of A. auricular mycelia to adsorb aflatoxin B1, as well as evaluate its protective effects on the AFB1-induced liver damage in SD rats. Additionally, the effects of temperature, time, pH, and reaction ratio on the adsorption rate were examined. Combining thermodynamic and kinetic data, the adsorption process was characterized as a complex mechanism primarily driven by chemical adsorption. In SD rats, the A. auricular mycelia exhibited alleviation of AFB1-induced liver damage. The protective effects on the liver attributed to A. auricular mycelia may involve a reduction in AFB1 adsorption in the intestine, mitigation of oxidative stress, and augmentation of second-phase detoxification enzyme activity. The adsorption method for AFB1 not only ensures safety and non-toxicity, but also represents a dietary regulation strategy for achieving effective defense against AFB1.

PERK/ATF3-Reduced ER Stress on high potassium environment in the suppression of tumor ferroptosis.

Potassium (K+) is a vital intracellular cation. In the human body, it regulates membrane potential, electrical excitation, protein synthesis, and cell death. Recent studies revealed that dying cancer cells release potassium into the tumor microenvironment (TME), thereby influencing cell survival-related events. Several investigations reported that potassium channels and high potassium levels influence apoptosis. Increasing extracellular potassium and inhibiting K+ efflux channels significantly block the apoptotic machinery. However, it is unknown whether a high-potassium environment also affects other types of cell death such as ferroptosis. In the present study, cell counting kit (CCK-8), colony formation ability, and 5-ethynyl-2'-deoxyuridine (EdU) assays demonstrated that a high-potassium environment reverses erastin-induced ferroptosis. RNA sequencing (RNA-Seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses indicated that high potassium levels attenuated the unfolded protein response that is characteristic of endoplasmic reticulum (ER) stress. The ER transmembrane proteins PRKR-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6) are recognized as ER stress sensors. Here, the PERK blocker GSK2606414 significantly rescued ferroptosis. The present work also disclosed that the ER-related gene activating transcription factor 3 (ATF3) played a vital role in regulating ferroptosis in a high-potassium environment. The foregoing results revealed the roles of potassium and the TME in cancer cell ferroptosis and provided a potential clinical therapeutic strategy for cancer.

A Phase III Clinical Trial Evaluating the Efficacy of Yinghua Tablet in the Treatment of Sequelae of Pelvic Inflammatory Disease.

Objective: To evaluate the efficacy and safety of the Yinghua tablet in treating sequelae of pelvic inflammatory diseases (PID) that manifest as the syndrome of dampness-heat stasis. Methods: The experimental group enrolled 360 cases, while the control group enrolled 120 cases. The experimental group took Yinghua tablets three times a day, three tablets each time, and the control group took Fuyankang tablets three times a day, three tablets each time. The treatment course was six weeks. Before treatment, at three weeks and six weeks of treatment, the patients were scored for TCM syndrome, clinical symptoms and, signs, and adverse events during treatment were recorded. Results: The experimental group included 340 cases, and the control group finally included 114 cases. After six weeks of treatment, statistically significant differences were observed between the two groups in the treatment effect, recovery rate, markedly effective rate, and total effective rate (P < .05). The two groups had no significant difference in the effective rate of local signs (P > .05). However, the two groups had a significant difference in the total effective rate (P < .05). Before and after treatment, traditional Chinese medicine (TCM) symptoms score, symptom sign score, and local sign score were statistically significant (P < .05). The incidence of adverse events (AEs) after taking Yinghua Tablets was 3.61% (13 times), of which the incidence of adverse events related to study drugs was 0.28% (1 case). The AEs of Fuyankang Tablets were 1.67% (2 times), of which the incidence of adverse events related to study drugs was 1.67% (2 cases). There was no significant difference in the incidence of AEs between the two groups as compared to Fisher (P = .3767), indicating that no serious AEs occurred in either group. Conclusions: Yinghua tablet was effective and safe in treating sequelae of pelvic inflammatory diseases.

Advance on anti-tumor theranostics and biosafety of bismuth-based nanomedicine / 药学学报

Nanomedicine is one of the most promising fields in biomedicine. Inorganic nanomaterials stand out among many nanomaterials due to their excellent physicochemical properties, stable chemical properties and high biocompatibility. As an inorganic nanomaterial, bismuth-based nanomaterials have the advantages of adjustable band gap, low toxicity, easy functionalization, large X-ray attenuation coefficient, high photothermal conversion efficiency and long cycle half-life, so they have good promising application in cancer diagnosis and treatment. This review summarizes the recent research progress of bismuth-based nanomaterials in tumor diagnosis, treatment and biosafety, which provides a theoretical basis for the design and exploitation of a new generation of bismuth-based nanomedicine systems.

Efficacy of daily use of a test emollient combined with topical glucocorticoids applied at the weekend for delaying the recurrence of atopic dermatitis in children during the maintenance period: a randomized, blank-controlled, multicenter clinical study / 中华皮肤科杂志

Objective:To evaluate the efficacy of daily use of a test emollient combined with topical glucocorticoids applied at the weekend for delaying the recurrence of atopic dermatitis (AD) in children during the maintenance period.Methods:A randomized, blank-controlled, multicenter clinical study was conducted in children with moderate AD from Beijing Children′s Hospital, Capital Medical University, Children′s Hospital of Chongqing Medical University and Shenzhen Children′s Hospital from March 2021 to February 2022. A total of 127 children aged 0 - 12 years with moderate AD were treated with topical glucocorticoids combined with emollients during the run-in period, 112 out of them achieved the investigator′s global assessment (IGA) score ≤ 1 point, and then the 112 patients were randomly divided into a test group (56 cases) and a control group (56 cases) at a ratio of 1∶1. Patients in the test group received treatment with a test emollient twice a day in combination with topical glucocorticoids applied at the weekend, and those in the control group were only treated with topical glucocorticoids at the weekend. Patients in the two groups were followed up at baseline, week 2 (± 3 d), week 4 (± 5 d), and week 12 (±7 d), as well as at the time of AD relapse, and the effect of the test emollient on the remission rate of AD in children during the maintenance period was evaluated, so were its effects on the dosage of topical glucocorticoids, pruritus, sleep, and skin pH. The occurrence of treatment-related adverse events was evaluated and recorded at the same time. Study endpoints were defined as AD relapse during the maintenance period, end of 12-week follow-up, or occurrence of serious adverse events. Comparisons of efficacy indicators between groups were conducted by using chi-square test, Kaplan-Meier survival analysis, Satterthwaite t′ test and Mann-Whitney U test. Results:In the full-analysis set, 45 (80.36%) patients with AD maintained remission in the test group (56 cases) and 30 (53.57%) in the control group (56 cases), and the remission rate difference between the two groups was 26.79% (95% confidence interval [ CI]: 10.09%, 43.49%; χ2 = 9.11, P = 0.003) ; the 12-week follow-up during the maintenance period showed that the time to first relapse was 75.05 ± 25.07 days in the test group, which was significantly longer than that in the control group (49.55 ± 33.92 days, t′ = 4.52, P < 0.001). At the study endpoint, the test group showed significantly decreased AD disease severity score (eczema area and severity index [EASI] score: 0.00 [0.00, 1.20] points vs. 0.60 [0.00, 4.00] points), pruritus visual analog scale (VAS) score (0.00 [0.00, 2.00] points vs. 2. 00 [0.00, 10.00] points), and sleep VAS score (0.00 [0.00, 0.00] points vs. 1.00 [0.00, 4.00] points) compared with the control group ( Z = -2.77, 2.43, 3.48, P = 0.006, = 0.015, < 0.001, respectively), while there was no significant difference in the pH value at the lesional sites between the test group and control group ( t = 0.97, P = 0.335). For the group aged 0 - 2 years, the average daily glucocorticoid dosage at the weekend in AD children during the maintenance period was significantly lower in the test group than in the control group ( Z = -1.97, P = 0.049) ; for the group aged >2 - 12 years, there was no significant difference in the average daily glucocorticoid dosage at the weekend between the two groups ( Z = -0.25, P = 0.802). During the study period, no significant difference was observed in the incidence of treatment-related adverse events between the test group (2/56, 3.57%) and control group (3/56, 5.36%; P = 1.000), and no serious adverse events occurred. Conclusion:Compared with the weekend treatment with topical glucocorticoids alone, the daily use of the test emollient combined with topical glucocorticoids at the weekend could markedly improve the remission rate of AD, prolong the time to relapse, and reduce the disease severity at relapse in children with AD during the maintenance period, which provides a new option for maintenance treatment of children with AD.

Efficacy of crisaborole ointment in clinical symptom relief in the early stage of childhood atopic dermatitis and in symptom improvement in the remission stage: a multicenter clinical study / 中华皮肤科杂志

Objective:To evaluate the efficacy and tolerability of crisaborole 2% ointment in the treatment of childhood atopic dermatitis (AD) at the early stage, and to compare the efficacy of every-other-day (Qod) regimen versus twice-a-week (Biw) regimen against recurrence in the remission stage of AD.Methods:A multicenter, randomized, open-label clinical trial was conducted. Totally, 150 children with mild to moderate AD aged 2 - < 18 years were enrolled from 6 hospitals (including Beijing Children′s Hospital, Capital Medical University, etc), and randomly divided into the Qod group (76 cases) and the Biw group (74 cases). In the acute stage of AD, both groups were treated with topical crisaborole 2% ointment on skin lesions twice a day for 2 - 4 weeks, as well as with emollients throughout the whole body. The improvement of early clinical symptoms was evaluated, and the occurrence of adverse reactions was recorded in the follow up. Once the investigator′s static global assessment (ISGA) scores decreased to 1 point or less, the patient would be enrolled into the remission stage. In the remission stage of AD, patients in the Qod group and Biw group were treated with crisaborole ointment every other day and twice a week respectively; the recurrence rate of AD in the remission stage was evaluated, as well as the severity of skin lesions, itching, life quality, and the occurrence of adverse reactions at weeks 4, 8, and 12. Statistical analysis was carried out with SPSS 23.0 software by using t test for comparisons of normally distributed continuous data between two groups, Mann-Whitney U test for non-normally distributed data, chi-square test for enumeration data, and Kaplan-Meier method for analysis of survival rates. Results:A total of 142 patients were enrolled in the modified intention-to-treat population, including 71 in the Qod group and 71 in the Biw group. In the acute stage of AD, the improvement of itching and skin lesions self-reported by the children or their family members occurred on days 1.9 (1.0, 3.0) and 2.0 (1.0, 4.1) after the application of crisaborole ointment, respectively. At the end of treatment in the acute stage, 89 children (62.7%) achieved ISGA 0/1 and successfully transferred into the remission stage. The follow-up in the remission stage was completed in 83 patients (44 in the Qod group and 39 in the Biw group). In addition, recurrence occurred in 19 (43.2%) and 12 (30.8%) patients in the Qod group and Biw group respectively, and there was no significant difference in the recurrence rate between the two groups ( χ2 = 1.36, P = 0.243) ; the average time to recurrence was 64.25 (95% CI: 53.33 - 75.17) days and 75.78 (95% CI: 65.46 - 86.10) days in the Qod group and Biw group respectively. Among the patients who were in the remission stage and had not yet experienced relapse at weeks 4, 8, and 12, there were no significant differences in the eczema area and severity index (EASI) scores, ISGA scores, pruritus numerical rating scale (NRS) scores, or quality-of-life scores between the two groups (all P > 0.05) at any time points, except for the ISGA scores at week 12 (Biw group: 0 [0, 1] point vs. Qod group: 1 [0, 1] point; Z = -2.31, P = 0.021). A total of 146 patients were enrolled in the safety set. During the study period, 70 adverse events occurred in 65 patients, with an incidence rate of 44.5%, and all were mild or moderate adverse events; 55 (37.7%) patients experienced discomfort at the medication site, which mainly referred to pain (45 cases, 30.8%) and mostly occurred in the tender and skinfold areas. Conclusions:Crisaborole 2% ointment could effectively relieve clinical symptoms in children with mild to moderate AD in the early stage, and intermittent treatment could continuously relieve clinical symptoms in the remission stage. The common adverse reaction was discomfort at the application site in the early stage of AD. There was no significant difference in the impact on AD recurrence in the remission stage between the Qod regimen and Biw regimen.

Analysis of clinical characteristics and treatment status of atopic dermatitis in a children's hospital in Beijing from 2015 to 2019 / 中华预防医学杂志

To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ2=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ2=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.

Analysis of clinical characteristics and treatment status of atopic dermatitis in a children's hospital in Beijing from 2015 to 2019 / 中华预防医学杂志

To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ2=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ2=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.

The effects of high concentration electrolyte on fat emulsion stability in multi-chambered bag parenteral nutrition / 中华临床营养杂志

Objective:To investigate the effect of high concentration electrolyte on fat emulsion stability in multi-chambered bag parenteral nutrition, and to protect clinical drug safety.Methods:Multi-chambered bag parenteral nutrition with the same composition containing high concentration electrolyte were used, except for that water-soluble vitamins, fat-soluble vitamins, sodium glycerophosphate and trace elements were supplemented in the experimental group only. The appearance, pH, osmolality and average particle size were examined at 0, 12, 24, 36, 48, 60, 72, and 168 hours after preparation under room temperature.Results:There was no flocculation or oil-water separation in both groups. The pH value was 5.73 to 5.83 for the experimental group, while that was 5.52 to 5.57 for the control group ( P<0.001). For both groups, the comparison between 0 and 168 hours showed significant differences ( P<0.001). The osmolality was significantly different between the experimental group (1 076-1 117 mOsmol/kg) and the control group (1 072-1 104 mOsmol/kg, P=0.012), but showed no statistical significant difference across examined time points within each group ( P>0.05). The average particle size was 296.1 to 310.9 nm for the experimental group, and 296.6 to 334.9 nm for the control group, showing no statistical significant difference ( P=0.096). The particle size showed no profound changes over time in both groups ( P>0.05). Conclusions:The average particle size of fat emulsion in multi-chambered bag parenteral nutrition were basically stable over 168 hours after preparation under room temperature. The addition of water-soluble vitamins, fat-soluble vitamins, sodium glycerophosphate and trace elements had no significant impact on the stability of fat emulsion.

High-Performance Turn-On Fluorescent Metal-Organic Framework for Detecting Trace Water in Organic Solvents Based on the Excited-State Intramolecular Proton Transfer Mechanism.

Simple, fast, and sensitive detection of trace water in organic solvents is an urgent requirement for chemical industries. Herein, combining the unusual excited-state intramolecular proton transfer (ESIPT) mechanism with the effective strategy of pore space partition, for the first time, we construct a powerful fluorescent metal-organic framework (SNNU-301) probe with excellent water stability. The SNNU-301 probe shows a remarkable performance for turn-on ESIPT-based fluorescence response to water in nine common organic solvents, exhibiting wide linear ranges, low limit of detection values, and ultrafast response, especially in dimethyl sulfoxide (0-5.2%; 0.011%, v/v; 110 s). The typical ESIPT-sensitive linker 2,5-dihydroxyterephthalate (DHBDC) imparts it with discriminative detection properties via enol-keto tautomerism, and light-responsive triangular tri(pyridin-4-yl)-amine (TPA) realizes pore space partition. The theoretical calculation gives an in-depth explanation about the proton transfer mechanism. Comparative experiments and GCMC simulation provide evidence that the synergy of the ESIPT process and TPA of the framework further boosts its performance effectively. Definitely, this work not only offers a promising candidate with fast detection speed, high sensitivity, excellent universality, and visual observation for the determination of water in organic solvents but also provides valuable guidance for the design of high-performance fluorescent probes.