Phage immunoprecipitation sequencing (PhIP-Seq) is a high-throughput and low-cost method for analyzing the specific binding of target proteins to peptide libraries. The method uses oligonucleotide library synthesis (OLS) to encode proteome-scale peptide libraries for display on phages, and then immunoprecipitates these library phages with target proteins (such as antibodies) for subsequent analysis by high-throughput DNA sequencing. PhIP-Seq enables the screening of peptide targets that react specifically with hundreds of proteins or pathogens. PhIP-Seq has been successfully applied in various fields such as disease detection, screening of autoimmune disease biomarkers, vaccine development, and allergen detection, becoming a high-throughput diagnostic technology. This article systematically describes the development, applications, and result evaluation of PhIP-Seq, in order to gain a more comprehensive understanding of the application and future development prospects of this technology in various fields.
Peptide Library ; Humans ; Immunoprecipitation/methods* ; High-Throughput Nucleotide Sequencing/methods* ; Bacteriophages/genetics*

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

Alzheimer's disease(AD)is a typical progressive neurodegenerative disease,mainly manifesting as severe cognitive dysfunction,and involving memory,thought processes,and emotion.The kynurenine pathway(KP)is one of the main metabolic pathways of tryptophan,which can be divided into neurotoxicity and neuroprotective branches.Increasing evidence has suggested that KP is involved in the pathogenesis of AD.This review considers the role of KP in the pathogenesis of AD,with reference to the relevant literature on KP interventions in AD in the PubMed database.The result will provide an important reference for the use of KP as a target for AD drug development.

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

Alzheimer's disease(AD)is a typical progressive neurodegenerative disease,mainly manifesting as severe cognitive dysfunction,and involving memory,thought processes,and emotion.The kynurenine pathway(KP)is one of the main metabolic pathways of tryptophan,which can be divided into neurotoxicity and neuroprotective branches.Increasing evidence has suggested that KP is involved in the pathogenesis of AD.This review considers the role of KP in the pathogenesis of AD,with reference to the relevant literature on KP interventions in AD in the PubMed database.The result will provide an important reference for the use of KP as a target for AD drug development.

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*

Objective:To investigate molecules involved in the occurrence of pruritus in patients with mycosis fungoides (MF) .Methods:Totally, 522 patients with MF were enrolled from Peking University First Hospital from October 2009 to August 2021, and the incidence of pruritus was calculated. The patients were grouped according to whether they suffered from pruritus or not. RNA sequencing data on biopsied skin lesions of 49 patients were analyzed to identify differentially expressed genes between patients with pruritus and those without; enzyme-linked immunosorbent assay and immunohistochemical techniques were performed to determine the protein expression of CC chemokine ligand 17 (CCL17) in serum samples from 88 MF patients, and in tissue samples from 81 MF patients, respectively; flow cytometry was conducted to detect markers for T lymphocyte activation and differentiation in peripheral blood samples from 46 MF patients to identify peripheral blood lymphocyte subsets associated with pruritus. Statistical analysis was carried out by using chi-square test, Mann-Whitney U test, and Spearman correlation analysis. Results:Among the 522 patients with MF, 305 were males and 217 were females; 347 were diagnosed with early-stage MF, and 175 with advanced MF. The incidence of pruritus was 67.2% (351/522) in the patients with MF, and significantly higher in the patients with advanced MF (81.7%, 143/175) than in those with early-stage MF (59.9%, 208/347; χ2 = 25.03, P < 0.001) . RNA sequencing showed that CCL17 mRNA expression was significantly higher in the MF patients with pruritus than in those without (fold change = 10.09, P < 0.001) . The serum CCL17 concentration was significantly elevated in the patients with pruritus (1 017.05[377.12, 4 831.80] pg/ml) compared with those without (361.66 [180.47, 500.08] pg/ml; Z = -4.57, P < 0.001) , and correlated with pruritus scores ( r = 0.57, P = 0.010) . In both early and advanced stages of MF, the serum CCL17 concentration was significantly higher in the patients with pruritus than in those without ( Z = -3.68, P < 0.001; Z = -2.54, P = 0.011, respectively) . Immunohistochemical staining revealed that there was no significant difference in the relative quantification value of CCL17 between the patients with pruritus and those without ( Z = -1.84, P = 0.066) . The percentage of CD3 +CD4 +CD26 -CCR4 + malignant T cells significantly increased in the MF patients with pruritus than in those without ( Z = -2.03, P = 0.043) , and was positively correlated with serum CCL17 concentrations ( r = 0.49, P < 0.001) . Conclusions:Both CCL17 mRNA expression in lesional tissues and serum CCL17 concentrations increased in MF patients with pruritus, and CCL17 was associated with the occurrence of pruritus. CCL17 may be involved in the occurrence of pruritus through the recruitment of CD3 +CD4 +CD26 -CCR4 + malignant T cells.

Objective: The use and effect of nitrous oxide sedation techniques in oral clinics were analyzed retrospectively. Methods: Patients who were treated with nitrous oxide inhalation sedation in the clinic of the Affiliated Stomatological Hospital of Guangzhou Medical University from January 1, 2016, to December 30, 2018, were examined. Age and gender of the patients, dental treatments involved, reasons for nitrous oxide inhalation, sedative effects and adverse reactions were compiled. Results : A total of 1 429 cases were examined, comprising 587 males and 842 females, and the average age was 32.64±16.34 years old. Among the patients who underwent nitrous oxide inhalation sedation in the oral clinic, 79.98% needed tooth extraction, and 79.50% had a dental fear of procedures. The patients were divided into following 7 age groups: 5-15 years old, 16-25 years old, 26-35 years old, 36-45 years old, 46-55 years old, 56-65 years old and > 65 years old. The sedation satisfaction rate of the 5-15-year-old group was 45.71%, and the sedation satisfaction rate of the other 6 age groups was 90.83%- 96.20% (P < 0.001). The incidence of total adverse reactions was 5.39%; the incidence was higher in females than in males, and the incidence was higher in the 16-25 age group than in the other age groups (P < 0.05). The most frequent adverse reaction was vertigo (81.82%). Conclusion Among the four common oral outpatient treatment programs including the extraction of teeth, dental implants, pulp treatment and periodontal treatment, patients undergoing inhalation sedation of nitrous oxide in the dental extraction most. The most common reason for requiring sedation is dental fear, and the sedative effect of the 5-15-year-old group was significantly worse than that of the other age groups. The incidence of adverse reactions of nitrous oxide sedation was low and manageable.

Objective:To observe the changes of cognitive function, subcortical nuclei volumes, and diffusion kurtosis imaging (DKI) parameters (values of fractional anisotropy [FA], mean diffusivity [MD] and mean kurtosis [MK]) after surgery in patients with aneurysmal subarachnoid hemorrhage (aSAH), and analyze the correlations of cognitive dysfunction with subcortical nuclei volumes and DKI parameters.Methods:A prospective sutdy was conducted;17 patients with aSAH confirmed by surgery in our hospital from September 2019 to June 2020 were selected as patient group, and 16 healthy volunteers whose age, gender, and education level were matched with the patient group were recruited as control group. Neuropsychological tests and MR imaging were performed in the patients 3 months after surgery and the controls right after enrollment. The structural image data of all subjects were post-processed. Bilateral subcortical nuclei volumes and DKI parameters were analyzed. The differences of general clinical data, subcortical nuclei volumes and DKI parameters were compared between the two groups. The correlations of mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores with subcortical nuclei volumes and DKI parameters were analyzed.Results:As compared with the control group, the patient group had significantly lower MMSE and MoCA scores, and statistically decreased volumes of ipsilateral hippocampus, ipsilateral thalamus and ipsilateral lentiform nucleus ( P<0.05). The FA values of the contralateral caudate nucleus, bilateral thalamus and bilateral lentiform nucleus and MK values of the ipsilateral hippocampus in the patient group were significantly decreased as compared with those in the control group ( P<0.05); while the MD values of the ipsilateral caudate nucleus in the patient group were significantly increased as compared with those in the control group ( P<0.05). The volume of ipsilateral hippocampus was positively with MoCA scores ( r=0.604, P=0.038); the FA values of contralateral caudate nucleus were negatively correlated with MMSE scores ( r=-0.579, P=0.049). Conclusions:Cognitive dysfunction, atrophy of ipsilateral hippocampus, thalamus and lenticular nucleus, and changes of DKI parameters exist in patients with aSAH after surgery. The changes in ipsilateral hippocampus volume and FA values of caudate nucleus may be related to the postoperative cognitive dysfunction in these patients.

Objective:To explore the effect of time-sensitive incentive nursing on psychological resilience, quality of life, nursing satisfaction and disease cognition of postoperative patients with chronic sinusitis (CS) .Methods:From January 2019 to July 2020, the convenience sampling method was used to select 60 postoperative patients with CS who were admitted to Fuyang Hospital of Anhui Medical University as the research objects. Patients were randomly divided into the observation group and the control group, with 30 cases in each group. The control group carried out conventional nursing, and the observation group was given conventional nursing combined with time-sensitive incentive nursing. The Connor-Davidson Resilience Scale (CD-RISC) , the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) dimensions of mental health, general health, physical functioning and role emotional were used to compare the psychological resilience and quality of life of the two groups of patients before and after nursing. Disease cognition and nursing satisfaction of the two groups of patients after nursing were compared.Results:The scores of the CD-RISC dimensions, disease cognition, four dimensions of the SF-36, and nursing satisfaction of patients in the observation group after nursing were higher than those of the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The application of time-sensitive incentive nursing in postoperative patients with CS can improve their psychological resilience, disease cognition, quality of life and nursing satisfaction.