Objective This study aims to elucidate the structure-activity domain of LBP1C-2 targeting Kvβ.2 through an exploration of the structure-activity relationship.This study may also provide the scientific basis for the development of drug candidate with anti-early-onset dementia activity.Methods After partial acid hydrolysis,various structural fragments were obtained and subjected to monosaccharide composition and molecular weight analysis.Potential target proteins were selected using a protein chip,followed by validation of the targeting specificity of each structural fragment using surface plasmon resonance(SPR)technology.Results Through high-throughput screening using the HuProtTM human protein array,potential target protein Kvβ.2 was identified for LBP1C-2.SPR experiments revealed a strong binding affinity between LBP1C-2 and Kvβ.2 protein,with a binding constant(KD)of 1.9×10-7 M.The various structural fragments of LBP1C-2 exhibited different binding strengths with the target protein Kvβ.2.Among them,the segment LBP1C-2-1I(18.1 k Da)with a molar ratio of rhamose to galecturonic acid of 1:1 showed a binding strength to Kvβ.2 similar to that of the polysaccharide LBP1C-2,with a KD of approximately 3.3×10-7 M.Structural analysis indicates that the structure of LBP1C-2-1I contains 1,2-linked Rha and 1,4-linked GalA which are alternatively linked.The acid-hydrolyzed extracellular portion corresponding to this segment,LBP1C-2-1O may also bind to Kvβ.2.However,compared to other segments,it demonstrated a higher tendency to dissociate from the protein.Knockdown of the KCNAB2 gene(Kvβ.2)in BV2 cells inhibited the uptake of Aβ in BV2 cells,suggesting that protein Kvβ.2 may be a functional protein in the development of Alzheimer's disease.Conclusion LBP1C-2-1I has been identified as the primary active domain through which LBP1C-2 targets Kvβ.2.This suggests that the active domain of LBP1C-2 predominantly resides on the main chain rather than the side chain.This study provides crucial insights for a deeper understanding of the anti-early-onset dementia activity of LBP1C-2 and lays an experimental foundation for the design and development of targeted drugs for anti-early-onset dementia based on Lycium barbarum polysaccharides.

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases. Methods:The two-sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P＜5×10-8).Causal effect estimates were generated using the inverse-variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed. Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease(OR=1.444,95％CI 1.199 to 1.738,P＜0.001)and ulcerative colitis(OR=1.002,95％CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema. Conclusion:Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

Objective To retrospectively analyze the clinical efficacy of Xuanfei Tongqiao Acupuncture for the treatment of allergic rhinitis(AR)based on real world studies.Methods Clinical data in the hospital information system of Acupuncture and Moxibustion Rehabilitation Department of the Affiliated Hospital of Nanjing University of Chinese Medicine from January 2021 to October 2022 and Excel sheet records were extracted.The data were screened according to the criteria.Based on the thresholds of receiver operating characteristic(ROC)curve,the treatment grouping thresholds were clarified.The acupuncture patients was divided into acupuncture group A and acupuncture group B,the treatment was Xuanfei Tongqiao Acupuncture.Groups A and B were compared using propensity score matching(PSM)to make the baseline balance comparable between groups.The efficacy,total effective rate,total nasal symptom score(TNSS),total non nasal symptoms score(TNNSS),adverse events,and recurrence were then compared between the two groups.In stratified analyses,the inverse probability of treatment weighting(IPTW)method was used for between-group comparisons.The efficacy,total effective rate,TNSS and TNNSS,incidence of adverse events,and recurrence were compared between the two groups,respectively.The TNSS and TNNSS before and after treatment within the group were also compared.Results A total of 209 patients'data were collected,including 7 non-acupuncture patients and 202 acupuncture patients,and the acupuncture patients was divided into acupuncture group A(<6 weeks of treatment)and acupuncture group B(≥6 weeks of treatment)according to the ROC curve characteristics,and there was a difference in comparing the conditions of the two groups(P<0.05).66 pairs of patients were successfully matched after PSM,and there was no significant difference between the two groups at baseline(P>0.05).After PSM,the efficacy,total effective rate,post-treatment TNSS and TNNSS and TNSS at the follow-up between the two groups were compared,and the post-treatment TNSS and TNNSS within the groups were also compared,with statistical significance(P<0.01).There was statistical significance in the recurrence rate between the two groups before PSM(P<0.05),while there was no statistical significance in the incidence of adverse events before PSM and in the recurrent rate after PSM between the two groups(P>0.05).Stratified analysis was conducted on patients in the acupuncture patients based on their condition.Mild and moderate to severe patients were divided into acupuncture group A and group B according to the course of treatment.The TNSS and TNNSS before and after treatment were compared within the two groups,with statistical significance(P<0.01).IPTW was performed on two groups to ensure baseline balance and comparability,and there was statistical significance in the distribution of efficacy levels between the two groups(P<0.05),but there was no statistical significance in the total effective rate,TNSS and TNNSS scores after treatment and at follow-up,incidence of adverse events,and recurrence rate between the two groups(P>0.05).The distribution of efficacy levels,total effective rate,TNSS and TNNSS after treatment and at follow-up were compared between the two groups of moderate to severe patients,and the differences were statistically significant(P<0.01).There was no statistical significance in the incidence of adverse events and recurrence rates between the two groups(P>0.05).The TNSS and TNNSS of two groups of moderate to severe patients significantly decreased after treatment compared with before treatment(P<0.01).Conclusion Xuanfei Tongqiao Acupuncture treatment for AR with a duration of 6 weeks or more shows more significant and long-lasting clinical efficacy compared with a duration of less than 6 weeks.Especially for patients with moderate-to-severe AR,this course of treatment can better reflect the advantages of its efficacy.

Ischemic stroke has a high rate of disability and mortality and is often accompanied by white matter injury(WMI).WMI patients often have cognitive disorders,emotional disorders,sensorimotor disorders,urinary incontinence and other symptoms,which seriously affect daily life.WMI can be detected early through imaging techniques,but there is a lack of appropriate intervention and specific treatment.Studying the pathological mechanism of WMI after ischemic stroke is helpful to prevent the occurrence of WMI,delay its progression,and contribute to the development of effective drugs or specific treatments.This article reviewed the research progress of WMI mechanism after ischemic stroke in order to provide scientific basis for clinical prevention and treatment.

Objective:To investigate the intervention effects and influencing factors of family management intervention on parents' disease management ability, family function of children with coronary artery lesions in Kawasaki disease.Methods:This was a quasi experimental study. Conveniently, 88 parents of children with Kawasaki disease coronary artery lesions from the Children's Hospital of Chongqing Medical University from March 2020 to June 2021 were selected for the study, and they were divided into the control group and the intervention group according to the order of the first consultation with 44 cases in each group. In the control group, conventional care and health education were used, while in the intervention group, a 6-month family management intervention was implemented on the basis of the control group. Family Management Measure (FaMM), Family Assessment Device (FAD) were used to assess the parents' disease management ability, family function before and after the intervention, respectively.Results:A total of 88 study subjects completed the pre-intervention survey in this study, and a total of 79 study subjects were surveyed when they returned to the hospital for review at the end of 6 months of intervention, including 40 in the intervention group and 39 in the control group, with a missed rate of 10.23% (9/88). There was no significant difference in the score of FAD, FaMM, Kawasaki disease knowledge questionnaire before the intervention between the two groups ( P>0.05). The scores of FAD in the intervention group was (21.58 ± 4.60) points, which was lower than that in the control group (24.62 ± 5.28) points, and the difference was statistically significant ( t=2.73, P <0.05). The scores of FaMM in the intervention group was (46.83 ± 6.02) points, which was higher than that in the control group (42.72 ± 6.09) points, and the differences was statistically significant ( t=-3.01, P <0.05). The age of the child, and whether the child was an only child were the influencing factors of the difference in disease management ability, and the difference in the family function of the parents of the child, respectively (all P<0.05). Conclusions:Family management intervention can improve the disease management ability of the parents of children with coronary artery lesion, improve family function. In the future, targeted interventions can be conducted according to different ages of children, and different family members' composition in order to obtain better intervention effects.

Objective:To investigate the efficacy of acidified aliphatic ester in the treatment of atopic dermatitis (AD) in mouse models, and to preliminarily explore its mechanisms of action.Methods:Twenty female BALB/c mice aged 6 to 8 weeks were randomly divided into 2 groups: 5 mice in the blank control group were topically treated with absolute ethanol on both ears (14.3 μl per ear) every day, and 15 mice in the model group were topically treated with calcipotriol liniment (14.3 μl per ear) and 20 g/L ovalbumin (25 μl per ear) on both ears every day for 10 consecutive days to establish AD-like mouse models. From day 11, 15 mice in the model group were randomly divided into 3 groups (5 mice in each group), including AD model group, aliphatic ester group, and acidified aliphatic ester group; in the forenoon, all the 3 groups continued to be topically treated with calcipotriol liniment and ovalbumin to maintain AD-like models; in the afternoon, the aliphatic ester group and acidified aliphatic ester group were topically treated with aliphatic ester and acidified aliphatic ester respectively (10 μl per ear), and no treatment was given to the AD model group. Changes in body weight, ear thickness, ear skin lesion scores, and scratching frequency were observed. Ear skin swabs were obtained from the mice on days 10 and 14 for 16S rRNA gene - based microbial diversity tests. On day 14, mice were sacrificed after reflectance confocal microscopy examinations of the ear skin, ear tissues were resected for hematoxylin and eosin staining, mast cell staining, and real-time fluorescence-based quantitative PCR (RT-qPCR), and blood samples were collected for detection of serum IgE levels. One-way analysis of variance was used for analysis of data that met homogeneity of variance criteria, and least significant difference- t test for multiple comparisons. Results:On day 14, the severity of mouse ear lesions was the highest in the AD model group, followed in turn by the aliphatic ester group, acidified aliphatic ester group, and blank control group; compared with the AD model group, the acidified aliphatic ester group showed significantly decreased mouse ear thickness ( F = 897.50, P < 0.001), skin lesion scores ( F = 268.80, P < 0.001), scratching frequency ( F = 64.36, P < 0.001), and epidermal thickness ( F = 256.20, P < 0.001). In addition, RT-qPCR indicated that the expression of inflammatory factors such as interleukin (IL) -33, thymic stromal lymphopoietin, IL-4, and tumor necrosis factor-α in lesional areas, and the degree of mast-cell infiltration were all significantly lower in the acidified aliphatic ester group than in the AD model group ( F = 3.38, 8.70, 41.73, 44.30, 134.30, P = 0.049, = 0.001, < 0.001, < 0.001, <0.001, respectively). Microbial diversity tests showed that the acidified aliphatic ester treatment could inhibit the colonization of Staphylococcus spp. in the ears of AD-like mouse models, and the Shannon index and Simpson index significantly differed among the 4 groups ( F = 9.00, 7.92, P = 0.001, 0.002, respectively) . Conclusion:Acidified aliphatic ester could improve skin lesions of AD-like mouse models, possibly by regulating immunity, suppressing inflammation, and restoring skin microecological diversity.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a severe global burden in terms of both health and the economy. Few studies, however, have thoroughly assessed the influence of air pollution on COPD-related mortality among elderly people in developing areas in the hinterland of southwestern China. This study is the first to examine the association between short-term exposure to ambient airborne pollutants and COPD-related mortality among elderly people in the central Sichuan Basin of southwestern China. METHODS: Data on COPD-related mortality among elderly people aged 60 and older were obtained from the Population Death Information Registration and Management System (PDIRMS). Data on airborne pollutants comprised of particulate matter < 2.5 μm in aerodynamic diameter (PM RESULTS: A total of 61,058 COPD-related deaths of people aged 60 and older were obtained. Controlling the influences of daily temperature and relative humidity, interquartile range (IQR) concentration increases of PM CONCLUSIONS Increased concentrations of ambient airborne pollutants composed of PM
Aged ; Aged, 80 and over ; Air Pollutants/adverse effects* ; China/epidemiology* ; Cities/epidemiology* ; Environmental Exposure/adverse effects* ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/mortality* ; Time Factors

OBJECTIVE: To explore the effect of chromosomal translocations on the composition of embryonic chromosomes and its mechanism. METHODS: For 52 couples with one partner carrying a chromosomal translocation, results of next generation sequencing of all embryos derived from 61 cycles were divided into different groups based on the type of translocations, gender of the carrier, and maternal age. Effect of parental chromosomal translocations on the composition of embryonic chromosomes of each group was analyzed. RESULTS: A significant difference was found between carriers of reciprocal and Robertsonian translocations in terms of proportion of abnormal embryos and structurally normal chromosomes (63.3% vs. 27.5%, and 1.1% vs. 0.3%, respectively). Compared with male carriers, there was an increase in the rate of abnormalities for female carriers (67.2% vs. 58.3% for reciprocal translocations, and 45.5% vs. 13.8% for Robertsonian translocations). The risk for chromosomal abnormality also increased with the maternal age. No significant difference was found in the proportion of abnormal embryos between carriers divided by involvement of acrocentric chromosomes or terminal chromosomal breakpoints. CONCLUSION The types of parental translocation, gender of carrier, maternal age, and interchromosomal effect have certain effect on the composition of embryonic chromosomes.
Chromosomes, Human ; genetics ; Female ; Genetic Carrier Screening ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Maternal Age ; Pregnancy ; Preimplantation Diagnosis ; Translocation, Genetic

OBJECTIVETo observe the clinical effects on analgesia, tranquilization and prevention of abortion syndrome of artificial abortion operation treated with transcutaneous electrical acupoint stimulation (TEAS) with different acupoint combination and explore the optimal acupoint combination of TEAS in artificial abortion operation.

METHODSTwo hundred patients intended to artificial operation were randomized into No.1 group[Sanyinjiao (SP 6) + Zusanli (ST 36)], No.2 group[Sanyinjiao (SP 6) + Diji (SP 8)], No.3 group[Sanyinjiao (SP 6) + Taichong (LR 3)], No.4 group (cervical blockage anesthesia with lidocaine) and No.5 group (blank group, without any analgesia measure applied), 40 cases in each one. In the No.1, No.2 and No.3 groups, Sanyinjiao (SP 6) was the main acupoint, combined with Zusanli (ST 36), Dijin (SP 8) and Taichong (LR 3) respectively. TEAS was given 30 min before the operation till the end of operation. Mean arterial pressure, heart rate and oxygen saturation during operation, as well as bleeding amount were observed in the five groups. The visual analogue scale (VAS) score was observed during and 30 min after operation, and Ramsay score was observed during operation. Cervical relaxation degree and the incidence of artificial abortion syndrome were recorded.

RESULTSFor VAS score during and 30 min after operation and Ramsay score during operation, the differences were significant statistically in the No. 1, No.2, No.3 and No.4 groups as compared with the No.5 group (<0.01,<0.05). The results in the No.2 group were better than those in the No.1, No.3 and No.4 groups (all<0.05). For cervical relaxationdegree, the result in the No.2 group was better than that in each of the rest groups (<0.01,<0.05). For artificial abortion syndrome, the incidences in the No.2 and No.3 groups were lower than those in the No.4 and No.5 groups (all<0.05). For bleeding amount and hemodynamic changes, the differences were not significant statistically among the five groups (all>0.05).

CONCLUSIONSTEAS apparently reduces pain score during and 30 min after artificial abortion operation and achieves the satisfactory tranguilization effects. The combination of Sanyinjiao (SP 6) and Diji (SP 8) achieves the optimal effect of analgesia, tranquilization, dilating cervix and preventing from artificial abortion syndrome in the operation.