Allergen immunotherapy（AIT）is currently the etiological treatment for respiratory allergic diseases，which can change the natural course of the disease.However，due to the complexity of patients' autoimmune status，allergy triggers and their complicated relationship with AIT vaccines，there are still about 40% of allergic rhinitis and 10%-20% of asthma patients who respond nonoptimally or even don't show any response to AIT. Thus，searching biomarkers that can evaluate and predict the efficacy of AIT and optimize the AIT strategy has been a major focus and challenge in allergy field.Currently，several serologic biomarkers have been found to be associated with AIT efficacy in vitro，but their value as predictive biomarkers of AIT efficacy needs to be further verified. This article reviews the research progress of serologic candidate biomarkers for AIT efficacy.

Objective To assess the causality between 14 malignant tumors and hypertension.Methods Publicly available datasets from genome-wide association study were used,from which independent genetic variants strongly associated with hypertension and 14 malignant tumors were extracted as instrumental variables for bidirectional Mendelian randomization(MR)analysis,including random effect inverse variance weighted(IVW),simple mode,weighted median,weighted mode and MR-Egger to evaluate the causal effect.Sensitivity analysis was used to test the validity and robustness of the analytical results,and multivariate MR method was used to further control for the effects of confounding factors.Results In the MR analysis of malignant melanoma and hypertension,the study included a total of 11 single nucleotide polymorphisms(SNPs)strongly associated with malignant melanoma.After Bonferroni correction,the IVW-based results showed a causal relationship between malignant melanoma and hypertension(OR=1.67,95％CI:1.27-2.21,P＜0.001).Cochran's Q test,Mendelian randomization pleiotropy residual sum and outlier test and MR-Egger intercept test showed that there were no outliers and no horizontal pleiotropy among the instrumental variables,and the sensitivity analysis of the leave-one-out method showed that there was no single SNP that had a significant impact on the overall results.In the analysis of hypertension and leukemia,the preliminary analysis results showed that there may be a relationship between the two,but after adjusting for confounders,the effect of hypertension on the risk of leukemia was no longer significant.Conclusion Malignant melanoma may be a risk factor in the development of hypertension.

Objective: To investigate the level of maternal and infant health literacy and its influencing factors among lying-in women, so as to provide insights into formulating maternal and infant health education and promotion strategies. Methods: Lying-in women were sampled from Children's Hospital of Shanxi using a cluster sampling method from March to September 2022. Demographic characteristics, maternal and infant health literacy, and health education demands were collected through a questionnaire survey. Factors affecting maternal and infant health literacy among lying-in women were identified using a multivariable logistic regression model. Results: A total of 1 099 questionnaires were allocated, and 1 059 valid questionnaires were recovered, with an effective rate of 96.36%. Participants had a mean age of (30.93±4.01) years, 930 urban residents (87.82%), and 706 pluripara (66.67%). The overall prevalence of maternal and infant health literacy was 35.51% among lying-in women, and the prevalence rates of basic knowledge and concept, healthy lifestyles and behaviors and basic skills were 47.69%, 83.10% and 38.81%, respectively. Multivariable logistic regression analysis showed that educational level (diploma or undergraduate degree, OR=3.916, 95%CI: 1.250-9.031; master degree and above, OR=4.557, 95%CI: 1.498-11.460), occupation (company employees, OR=2.701, 95%CI: 1.385-5.268; medical staff, OR=2.981, 95%CI: 1.289-6.893), pluripara (OR=5.649, 95%CI: 3.919-8.142), participating in health education activities (OR=2.332, 95%CI: 1.524-3.570), and participating in schools for pregnant women (OR=2.252, 95%CI: 1.541-3.291) were promoting factors for maternal and infant health literacy; while gestational hypertension (OR=0.255, 95%CI: 0.133-0.488) and gestational diabetes (OR=0.318, 95%CI: 0.211-0.478) were inhibiting factors for maternal and infant health literacy. Most participants acquired health knowledge through online media (62.42%), and hoped to participate in health education activities through online media publicity (68.18%). Conclusions The maternal and infant health literacy level of lying-in women in this survey is associated with education, occupation, parturition frequency, participation in health education activities, participation in schools for pregnant women, gestational hypertension and gestational diabetes.

UNC-51-like kinase 1 (ULK1), as a serine/threonine kinase, is an autophagic initiator in mammals and a homologous protein of autophagy related protein (Atg) 1 in yeast and of UNC-51 in Caenorhabditis elegans. ULK1 is well-known for autophagy activation, which is evolutionarily conserved in protein transport and indispensable to maintain cell homeostasis. As the direct target of energy and nutrition-sensing kinase, ULK1 may contribute to the distribution and utilization of cellular resources in response to metabolism and is closely associated with multiple pathophysiological processes. Moreover, ULK1 has been widely reported to play a crucial role in human diseases, including cancer, neurodegenerative diseases, cardiovascular disease, and infections, and subsequently targeted small-molecule inhibitors or activators are also demonstrated. Interestingly, the non-autophagy function of ULK1 has been emerging, indicating that non-autophagy-relevant ULK1 signaling network is also linked with diseases under some specific contexts. Therefore, in this review, we summarized the structure and functions of ULK1 as an autophagic initiator, with a focus on some new approaches, and further elucidated the key roles of ULK1 in autophagy and non-autophagy. Additionally, we also discussed the relationships between ULK1 and human diseases, as well as illustrated a rapid progress for better understanding of the discovery of more candidate small-molecule drugs targeting ULK1, which will provide a clue on novel ULK1-targeted therapeutics in the future.

To evaluate the psychological symptoms of patients with Crohn disease (CD), and to explore the risk factors affecting quality of life (QOL) in CD patients, 50 adult patients with CD, and 50 healthy controls were enrolled. Psychological questionnaires including self-rating anxiety scale (SAS), self-rating depression scale (SDS), the inflammatory bowel disease questionnaire (IBDQ) and the short form-36 health survey (SF-36) were completed. The results showed both the SAS (40.3±8.5 VS 37.6±7.0) and the SDS (47.1±11.1 VS 41.8±9.6) in CD patients were significantly higher than those in the healthy controls ( t=5.4, P<0.05; t=10.6, P<0.05). The IBDQ scores revealed the physical symptoms scores were 49.50±7.62, systemic symptoms scores 23.92±5.07, emotional functions scores 57.13±15.62, and social function scores 22.15±9.08 in CD active phase. However, the above scores were 60.12±4.01, 26.24±3.97, 67.34±15.17, and 25.44±2.03 respectively in the remission phase. Four subscale items of IBDQ in CD active phase were significant lower than those in the remission phase (all P<0.05). The subscale items of SF-36 scores (PF, RP, BP, GH, VT, SF, RE, MH) in CD patients were significant lower than those in healthy controls (all P<0.05). The SF-36 items scores of PF,RP and MH in the remission phase were significant higher than those in the active phase (all P<0.05). The SF-36 items scores of GH and VT in patients with malnutrition were significant lower than those with nutrition (both P<0.05). Multivariate regression analysis showed that disease status and nutritional risk ( P<0.05) significantly affected the patients' IBDQ scores. Factors including sex, age, marital status, education background, medical insurance, use of biologicals, surgery treatment had little influence on the total score of IBDQ ( P>0.05). Psychological conseling and treatment in the active phase may improve QOL of CD patients.

AlM: To analyze the prescribing of different antiplatelet drugs and clinical conditions of patients with coronary heart disease in department of Geriatrics. METHODS: This study was a single center and cross-sectional study. Patients with coronary heart disease were recruited when hospitalized in the department of Geriatrics department, Xiangya Hospital, Central South University between December 2021 and June 2022. We investigated and analyzed the clinical conditions of patients including the prescribing of the antiplatelet drugs. RESULTS: A total of 347 coronary heart disease patients with a mean age of (65.2 ± 10.1) years were included. The antiplatelet drug clopidogrel was the most commonly prescribed. Among the different dual antiplatelet therapy (DAPT), aspirin combined with clopidogrel was the most widely used. With the increasing of the numbers of target coronary lesions, the prescribing rate of clopidogrel increased significantly (P < 0.05). In three groups with different degrees of target coronary lesions, the prescribing rate of aspirin was higher than that of indobufene (P < 0.05). Compared with patients taking aspirin, the patients taking indobufene were older with a higher blood creatinine level, a higher proportion of chronic gastropathy and the higher level of platelet aggregation rates (P < 0.05). CONCLUSlON: Clopidogrel is the most commonly prescribed antiplatelet drugs in patients with coronary heart disease. Aspirin combined with clopidogrel is the most widely used in DAPT. Compared with aspirin, indobufene is more commonly used in elderly patients with the chronic gastritis and a higher serum creatinine level.

Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing disease-causing mutations in patients. However, problems such as mosaicism and low mutagenesis efficiency continue to pose challenges to clinical application of such approaches. Recently, a base editor (BE) system built on cytidine (C) deaminase and CRISPR/Cas9 technology was developed as an alternative method for targeted point mutagenesis in plant, yeast, and human cells. Base editors convert C in the deamination window to thymidine (T) efficiently, however, it remains unclear whether targeted base editing in mouse embryos is feasible. In this report, we generated a modified high-fidelity version of base editor 2 (HF2-BE2), and investigated its base editing efficacy in mouse embryos. We found that HF2-BE2 could convert C to T efficiently, with up to 100% biallelic mutation efficiency in mouse embryos. Unlike BE3, HF2-BE2 could convert C to T on both the target and non-target strand, expanding the editing scope of base editors. Surprisingly, we found HF2-BE2 could also deaminate C that was proximal to the gRNA-binding region. Taken together, our work demonstrates the feasibility of generating point mutations in mouse by base editing, and underscores the need to carefully optimize base editing systems in order to eliminate proximal-site deamination.
APOBEC-1 Deaminase ; genetics ; metabolism ; Animals ; Bacterial Proteins ; genetics ; metabolism ; Base Sequence ; CRISPR-Associated Protein 9 ; CRISPR-Cas Systems ; Cytidine ; genetics ; metabolism ; Embryo Transfer ; Embryo, Mammalian ; Endonucleases ; genetics ; metabolism ; Gene Editing ; methods ; HEK293 Cells ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Mice, Inbred C57BL ; Microinjections ; Plasmids ; chemistry ; metabolism ; Point Mutation ; RNA, Guide ; genetics ; metabolism ; Thymidine ; genetics ; metabolism ; Zygote ; growth & development ; metabolism ; transplantation

Objective To investigate the influence factors for quality of life in functional dyspepsia (FD) outpatients.Methods Based on purposive sampling,268 FD outpatients from a grade III class A hospital were selected from January to June 2014. The participants were assessed by using the functional dyspepsia-related quality of life (FDDQL) scale,FD self-efficacy scale,Zung self-rating anxiety scale (SAS),and depression self-rating scale (SDS).Results The total score for FDDQL was (57.78±7.45) in the participants. FDDQL was significantly different in people with different genders or SAS scores (P<0.05) but seemed less different in people with different BMI (P>0.05). FDDQL had a positive association with gender,self-efficacy,and BMI,but had a negative association with SAS,SDS,and symptom severity (P<0.05). Thus,the risk factors appeared to include anxiety,symptom severity,course of disease,self-efficacy,and depression in FD outpatients.Conclusions FD outpatients tend to have a low quality of life and need more concerns and management. During the nursing intervention,nurses should pay more attention to the mental status such as anxiety in patients with a short course of disease,severe symptom,and/or less self-efficacy. Patients should improve their ability of self-management to achieve a higher quality of life.

Objective To explore the influence of application of health management strategy on quality of life in outpatients with functional dyspepsia (FD). Methods A total of 140 FD patients were divided into the intervention group and the control group by random digits table method with 70 cases in each. The patients in the intervention group received the researchers on the implementation of health management strategy, and the patients in the control group were given routine outpatient health education and telephone follow- up. Before and after the intervention in one month or three, the FD patients Quality of Life Scale (FDDQL) was used to evaluate the quality condition of the patient's life. Results Eventually 65 cases in the intervention group and 61 cases in the control group completed the research. 1 months after intervention in the intervention group, total score of life quality and score of each dimension rose faster, in addition to the dimension of pressure, total score and daily activities, anxiety, diet, sleep, feeling unwell, health, disease control dimension scores were 73.84 ± 3.45, 81.22±4.55, 71.58±6.19, 73.05±5.14, 74.74± 5.58, 74.72±3.91, 79.26±5.85, 73.75±6.32, higher than 60.59 ±5.06, 76.04±6.06, 68.41±9.78, 69.52±6.68,66.63±9.87, 64.37±6.24, 54.50±7.96, 50.76±7.54, the difference was statistically significant (t =2.160-20.590, P < 0.01 or < 0.05). Three months after intervention, the intervention group the total score of life quality and score of daily activities, anxiety, diet, sleep, feeling unwell, health, disease control, pressure dimension scores were 76.35±3.74, 85.21±5.34, 80.15±5.86, 73.21±4.99, 75.49±6.81, 75.46±3.80, 79.35± 6.39, 74.06±6.74, 70.86±7.00, significantly higher than 58.60±5.22, 72.02±6.53, 59.26±7.81, 60.90±6.36, 61.19±9.08, 62.24±6.02, 54.15±8.25, 50.13±7.67, 60.02±5.67 in the control group, the difference of two groups was statistically significant (t = 5.726-19.946, P < 0.01). Conclusions Using health management strategy intervention for FD outpatients will improve FD patient′s quality of life.

Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.
Blastocyst ; CRISPR-Cas Systems ; Hemoglobins, Abnormal ; genetics ; metabolism ; Humans ; Zygote