Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway. Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed. Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK. Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

Objective To study the properties and antimicrobial activity of the novel self-assembled antimicrobial peptide(AMP)CR-16,and to provide experimental evidence for the treatment of bacterial infections.Methods CR-16 was designed and synthesized based on the structure of antimicrobial peptides Buforin Ⅱ and LfcinB.Dynamic light scattering(DLS),transmission electron microscopy(TEM),and X-ray diffraction(XRD)were used to characterize CR-16.Based on the results of critical micelle concentration(CMC),the self-assembled properties of CR-16 were investigated using atomic force microscopy(AFM)and circular dichroism(CD).The minimum inhibitory concentration(MIC)was used to study the inhibitory effect of CR-16 while transmission electron microscopy(TEM)was adopted to observe the interactions between CR-16 and the outer membrane of bacteria.Results AMP CR-16 was prepared as self-assemblies,which were regularly spherical in shape and stable in activity.CR-16 could inhibit both the growth of Escherichia coli and,more importantly,the growth of NDM-1-producing carbapenem-resistant Escherichia coli,promising good prospects in treating infections caused by antibiotic-resistant bacteria.Conclusion CR-16 can be self-assembled and deliver antibacterial effects against Escherichia coli.

Objective To enhance the photostability of colchicine(COL)for sustained-release COL pellets.Methods The degradation was investigated by studying the photochemical degradation kinetics of COL.The impact of such physical properties of the photostabilizers as the type,color,dosage,and position on the photostability of COL in sustained-release pellets was also evaluated.Results The contents of photochemical degradation products did not increase after 10 days of light exposure to sustained-release COL pellets with red iron oxide of 4％(w/w)as the protective layer.Conclusion The findings of this study indicate that use of iron oxide as a photostabilizer in sustained-release COL pellets can significantly reduce the photochemical degradation of COL in the pellets.

Objective:To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene. Methods:Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing.Results:All of the six patients had presented with severe short stature (< 3 s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c. 5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c. 5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c. 5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c. 5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c. 5156G>T was rated as a pathogenic variant (PS2+ PM1+ PM2_Supporting + PM5+ PP3). Conclusion:All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.

Objective To investigate the food allergy situation of children in Changping District of Beijing,and to explore the influence of allergic family history,gender and mode of delivery on food allergy in children,the distribution of food allergy in different age groups,the types of food allergy that are easy to cause in this area,and the comorbidities of food allergy.Methods A total of 515 children aged 0 to 14 years who were admitted to the general pediatric outpatient and emergency department and inpatient of Beijing Changping Hospital from April to November 2023.Using immunoblotting to detect specific immunoglobulin E in the serum of pediatric patients,and using SPSS 26.0 statistical software to perform binomial tests on gender and delivery mode non parameters;Using custom Excel functions to statistically analyze the family history of allergies,the number of people in different age groups,and the frequency of allergic foods in each group;Use a self-made mini program to statistically analyze the combination of comorbid allergic diseases.Results ① The number of male children with food allergies(306 cases)was higher than that of female children(209 cases),and the difference was statistically significant(P＜0.05).(2)There were 109 cases of pediatric patients with parents who had no history of allergic diseases,accounting for 21.17％of the total cases;There were a total of 406 cases where at least one parent had a family history of allergies,accounting for 78.83％of the total cases.Among them,228 cases(44.27％)had one parent with a history of allergies,and 178 cases(34.56％)had both parents with a history of allergies.③ Among 515 children with positive food allergens,there were 10 cases(1.94％)in infancy,37 cases(7.19％)in early childhood,235 cases(45.63％)in preschool,192 cases(37.28％)in school age,and 41 cases(7.96％)in adolescence.The highest positivity rate for food allergens is in milk(444 times),followed by egg white(70 times),cashew nuts(57 times),crab(37 times),beef(26 times),mango(24 times),shrimp(21 times),pineapple(6 times),and shellfish(1 time).Milk protein is the most common allergen in all age groups.(4)Among 515 children with food allergies,399 cases were single food allergies,accounting for 77.47％;116 cases of multiple food allergies(2 or more types of food allergies),accounting for 22.53％.⑤ The most common comorbidity of food allergies is food allergy related gastrointestinal diseases combined with allergic rhinitis,with a total of 267 cases;Secondly,there were 192 cases of allergic rhinitis combined with chronic cough,and 124 cases of food allergy related gastrointestinal diseases combined with chronic cough.Conclusion Milk is the main allergen of food allergy in people of age 14 and under,and gastrointestinal symptoms are the most common in children with food allergy.

The effect of vitamin D supplementation on individuals with autism spectrum disorder (ASD) is inconclusive. We aimed to conduct a meta-analysis of the available randomized controlled trials (RCTs) to explore whether vitamin D supplementation can improve core symptoms and coexisting conditions in children with ASD. Data were obtained by searching the PubMed, Embase, Web of Science, CINAHL and Cochrane Library databases up to February 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a random-effects model, mean differences with 95% confidence intervals (CIs) were calculated through a meta-analysis. There were eight RCTs with 266 children with ASD in the present review, among which six RCTs were included in the meta-analysis.Children who received vitamin D supplementation showed a significant improvement in stereotypical behavior scores (pooled mean difference (MD): −1.39; 95% CI: −2.7, −0.07; p = 0.04) with low heterogeneity (I2 = 34%), and there was a trend toward decreased total scores on the Social Responsiveness Scale (SRS) and Childhood Autism Rating Scale (CARS, p = 0.05); however, there were no other significant differences in the core symptoms of ASD and coexisting conditions between groups as measured by the Aberrant Behavior Checklist (ABC). Vitamin D supplementation appears to improve stereotypical behaviors but does not improve other core symptoms and coexisting conditions. Further randomized controlled trials with large sample sizes and individualized doses are needed.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Objective:To analyze the epidemiological characteristics and track probable imported sources of the local dengue outbreak in Zhangzhou city, Fujian province, 2019.Methods:Serum samples of patients with suspected dengue fever at acute phases were collected for virus detecting and serotyping by real-time fluorescence quantitative RT-PCR. For the positive specimens of local cases, full-length fragments of E gene were amplified by RT-PCR, and were sequenced and analyzed.Result:In 2019, there were 98 local cases of dengue fever in Zhangzhou city, which were concentrated in Zhao’an county, Longhai district and Yunxiao county. In this study, fourteen dengue virus E gene sequences representing different sources in different districts and counties were selected. The amino acid sequence virulence site analysis showed that the local epidemic strains were relatively virulent strains. The gene sequence alignment and phylogenetic analysis showed that all the local strains were classified as DENV-I subgenotype genotype I, divided into a, b and c three different branches. The evolutionary branch a contained all Zhao’an and Longhai sequences and was divided into three sub-branches, the b and c evolutionary branches were both the sequences of Yunxiao. There was a high correlation between the Shenqiao Town in Zhao’an and the Haicheng Town in Longhai. The other areas of the strains were limited to the towns, and the evolutionary branches were close to the other areas in China and countries in Southeast Asia.Conclusions:The indigenous dengue outbreaks in Zhangzhou, 2019 were caused by multiple sources of introduction and originated from other areas in China or from Southeast Asian countries and there was also the possibility of local cross-county transmission.

Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs that can control caspase-11 activation. We report here that scutellarin, a flavonoid from Erigeron breviscapus, acted as an inhibitor for caspase-11 activation in macrophages. Scutellarin dose-dependently inhibited intracellular LPS-induced release of caspase-11p26 (indicative of caspase-11 activation) and generation of N-terminal fragment of gasdermin D (GSDMD-NT), leading to reduced pyroptosis. It also suppressed the activation of non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as evidenced by reduced apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and decreased interleukin-1 beta (IL-1β) and caspase-1p10 secretion, whereas the NLRP3-specific inhibitor MCC950 only inhibited IL-1β and caspase-1p10 release and ASC speck formation but not pyroptosis. Scutellarin also suppressed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells lacking ASC expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway.

Objective: To study the preventive effect of Timosaponin BⅡ (T-BⅡ) -loaded temperature/ion-sensitive nasal in situ hydrogels (ISGs) on Alzheimer's disease (AD), its preparation technology, characteristics and in vivo effects were evaluated.Methods: The morphological and rheological properties were evaluated. The preventive effects of T-BⅡ ISG on scopolamine-induced AD in mice were determined with the index of muscarinicreceptor 1 (M1) expression and pathological changes. Results: Results revealed that T-BⅡ ISG significantly increased the content of M1 choline receptors in the hippocampus of mice and ameliorated the damage incurred to the hippocampal cornu ammonis 1 (CA1) area. Conclusion: T-BⅡ ISGs is a reasonable and convenient method of exerting an obvious preventive effect on mice with AD induced by scopolamine. This, thereby, lays forth a new treatment option for preventing AD.