AIM: To observe the preliminary application of fully automatic feedback perimeter based on the eye gaze tracking technique in the college students and to verify its test performance.METHODS: Home computer, monitor and eye tracker were used to complete the new automatic feedback perimeter meter. Based on the two characteristic eye movements of fixation and pulsation, the abnormal visual field is determined by analyzing whether the participant perceives the visual target, line-of-sight scan path and the fixation towards the visual target. RESULTS: A total of 63 participants(119 eyes)were collected with valid eye movement data. The average time for all participants was 82.46±14.68 s, the average time for right eyes was 88.21±15.30 s, and average time for the left eyes was 76.42±11.29 s(P<0.05).CONCLUSION: The fully automatic feedback perimeter based on eye gaze tracking technique can realize automatic human-computer interaction, and the detection method is simple and easy, which shortens the time of perimetry and improves the experience of participants.

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

Objective:To investigate the risk factors of acute respiratory distress syndrome(ARDS)after traumatic hemorrhagic shock.Methods:This was a retrospective cohort study of 314 patients with traumatic hemorrhagic shock at Trauma Medicine Center,Peking University People's Hospital from De-cember 2012 to August 2021,including 152 male patients and 162 female patients,with a median age of 63.00(49.75-82.00)years.The demographic data,past medical history,injury assessment,vital signs,laboratory examination and other indicators of these patients during hospitalization were recorded.These patients were divided into two groups,ARDS group(n=89)and non-ARDS group(n=225)ac-cording to whether there was ARDS within 7 d of admission.Risk factors for ARDS were identified using Logistic regression.The C-statistic expressed as a percentage[area under curve(AUC)of the receiver operating characteristic(ROC)curve]was used to assess the discrimination of the model.Results:The incidence of ARDS after traumatic hemorrhagic shock was 28.34％.Finally,Logistic regression model showed that the independent risk factors of ARDS after traumatic hemorrhagic shock included male,histo-ry of coronary heart disease,high acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,road traffic accident and elevated troponin Ⅰ.The OR and 95％confidence intervals(CI)were 4.01(95％CI:1.75-9.20),5.22(95％CI:1.29-21.08),1.07(95％CI:1.02-1.57),2.53(95％CI:1.21-5.28),and 1.26(95％CI:1.02-1.57),respectively;the P values were 0.001,0.020,0.009,0.014,and 0.034,respectively.The ROC curve was used to analyze the value of each risk factor in predicting ARDS.It was found that the AUC for predicting ARDS after traumatic hemor-rhagic shock was 0.59(95％CI:0.51-0.68)formale,0.55(95％CI:0.46-0.64)for history of coronary heart disease,0.65(95％CI:0.57-0.73)for APACHE Ⅱ score,0.58(95％CI:0.50-0.67)for road traffic accident,and 0.73(95％CI:0.66-0.80)for elevated troponin Ⅰ,with an overall predictive value of 0.81(95％CI:0.74-0.88).Conclusion:The incidence of ARDS in pa-tients with traumatic hemorrhagic shock is high,and male,history of coronary heart disease,high APACHE Ⅱ score,road traffic accident and elevated troponin Ⅰ are independent risk factors for ARDS after traumatic hemorrhagic shock.Timely monitoring these indicators is conducive to early detection and treatment of ARDS after traumatic hemorrhagic shock.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To analyze the status and influencing factors of empathy fatigue in hospice nurses based on ABC-X model (A: stressor event; B:resources available to a family; C: family sperceptions of the stressor; X: likelihood of crisis), so as to provide a reliable basis for developing comprehensive intervention strategies.Methods:A total of 325 nurses engaged in hospice care in China from April 2022 to June 2022 were selected by convenient sampling method. The influencing factors of empathy fatigue of hospice care nurses were analyzed by ABC-X model (working environment, resilience and coping style). The hospice care nurses were investigated by self-made general questionnaire, Chinese version of Empathy Fatigue Scale, Simplified Coping Style Questionnaire, Coping Style Resilience Scale and Nursing Work Environment Scale. The statistical analysis was performed by SPSS.26.0 statistical software.Results:There were 316 females and 9 males with age of (33.0 ± 7.9) years old. The total score of empathy fatigue in 325 hospice nurses was (91.16 ± 9.60) points, the scores of empathy satisfaction, ocupational burnout and secondary traumatic stress were (31.35 ± 6.01), (28.43 ± 5.86), (31.38 ± 5.76) points respectively. The scores of positive coping style, negative coping style, psychological resilience and nursing working environment were (37.46 ± 5.69), (21.28 ± 6.90), (89.84 ± 16.46), (117.13 ± 19.95) points respectively. The negative predictive factor for empathy satisfaction among nurses with the professional title of palliative care ( t=-4.22, P<0.05), and the positive predictive factors for simple coping strategies, psychological resilience, and nursing work environment ( t=4.52, 3.05, 9.03, all P<0.05), could explain 56.7% of the total variation. Psychological resilience, simplified coping strategies, nursing work environment were negative predictive factors for occupational burnout among hospice nurses ( t=-6.93, -3.54, -2.51, all P<0.05), while work nature was a positive predictive factor ( t=2.36, P<0.05), which could explain 49.4% of the total variation. Simplified coping strategies, psychological resilience, and nursing work environment were all negative predictors of secondary traumatic stress in hospice nurses ( t=-5.40, -3.25, -5.95, all P<0.05), which could explain 48.8% of the total variation. Conclusions:Based on the ABC-X model, it is found that the empathic fatigue of hospice nurses is mainly affected by the nursing work environment, mental resilience and coping styles. It is necessary for nursing managers to actively take measures to improve the working environment and coping styles of nurses, enhance their mental resilience and reduce their empathic fatigue.

Objective:To investigate the impact of non-high-density lipoprotein cholesterol (non-HDL-C) level on major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality in the Kailuan Study cohort undergoing revascularization.Methods:This is a prospective cohort study, with participants from the Kailuan Study cohort who participated in physical examinations from 2006 to 2020 and received revascularization therapy for the first time. According to the level of non-HDL-C, the study subjects were divided into 3 groups:<2.6 mmol/L group, 2.6-<3.4 mmol/L group, and≥3.4 mmol/L group. Annual follow-up was performed, and the endpoint events were MACCE and all-cause mortality. Cox proportional regression model was implemented to estimate the impact on MACCE and all-cause mortality associated with the different non-HDL-C groups. The partial distributed risk model was used to analyze the impact of different non-HDL-C levels on MACCE event subtypes, and death was regarded as a competitive event. The restricted cubic spline regression model was used to explore the dose-response relationship between non-HDL-C level and all-cause mortality, MACCE and its subtypes.Results:A total of 2 252 subjects were enrolled in the study, including 2 019 males (89.65%), aged (62.8±8.3) years, the follow-up time was 5.72 (3.18, 8.46) years. There were 384 cases(17.05%) of MACCE and 157 cases(6.97%) of all-cause mortality. Compared with patients with non-HDL-C≥3.4 mmol/L, patients with non-HDL-C<2.6 mmol/L were associated with a 38% reduced risk of MACCE after revascularization [ HR=0.62(95% CI: 0.48-0.80)]. Every 1 mmol/L decrease in non-HDL-C was associated with a 20% reduction in the risk of MACCE [ HR=0.80(95% CI: 0.73-0.88)]. The results of restricted cubic spline also showed that non-HDL-C levels after revascularization therapy were positively correlated with MACCE events (overall association P<0.001, non-linear association P=0.808). For all-cause mortality, compared to the non-HDL-C≥3.4 mmol/L group, the HR for all-cause mortality after revascularization in non-HDL-C<2.6 mmol/L group was 0.67(95% CI: 0.46-1.01). Every 1 mmol/L decrease in non-HDL-C was associated with a 15% reduction in the risk of all-cause mortality [ HR=0.85(95% CI: 0.73-0.99)]. The restricted cubic spline results showed a linear association between non-HDL-C levels after revascularization therapy and the risk of all-cause mortality (overall association P=0.039, non-linear association P=0.174). Conclusion:The decrease in non-HDL-C levels after revascularization were significantly associated with a reduced risk of MACCE and all-cause mortality.

Objective:To investigate the effect of macrophage-derived exosomes on the morphological transformation of Candida albicans (CA), and to explore the underlying mechanisms.Methods:In vitro cultured human acute monocytic leukemia cell line THP-1 was induced and differentiated into M0 macrophages using the phorbol ester PMA. CA was activated and prepared as the fungal suspension. M0 macrophages were infected with the CA suspension, and the process of cell phagocytosis was observed under a high-content imaging analysis system. M0 macrophage-derived exosomes (exosome group) and CA-infected M0 macrophage-derived exosomes (CA exosome group) were extracted by differential centrifugation; transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis were performed to identify and compare exosomes in the two groups. The exosomes from the two groups were separately co-cultured with CA (exosome-treated group and CA exosome-treated group), and independently cultured CA served as the blank control group; the morphological changes of CA were observed under an inverted microscope, the intracellular cyclic adenosine monophosphate (cAMP) contents were detected by the enzyme-linked immunosorbent assay (ELISA), and the expression levels of cAMP-related genes, RAS1 and CDC35 (also known as Cyr1), were detected by real-time quantitative PCR (RT-qPCR) . Results:Western blot analysis showed that exosomes from the exosome group and CA exosome group both expressed the tumor susceptibility gene 101 protein (TSG101, an exosome marker), and did not express calnexin (a negative marker) ; transmission electron microscopy and nanoparticle tracking analysis showed no significant differences in the morphology or size of the exosomes between the two groups. Compared with the blank control group, the exosome-treated group and CA exosome-treated group both showed obvious inhibition of the yeast-to-mycelial phase transition of CA, with a noticeable reduction in the length of the hyphae under the inverted microscope. ELISA revealed that the intracellular cAMP content in CA significantly decreased in the exosome-treated group and CA exosome-treated group (16.70 ± 0.84 pmol/ml, 16.82 ± 0.87 pmol/ml, respectively) compared with the blank control group (21.82 ± 1.08 pmol/ml; t = 6.45, 6.23, respectively, both P = 0.003). RT-qPCR revealed that the expression of the cAMP-related genes, RAS1 and CDC35, was down-regulated in the exosome-treated group and CA exosome-treated group compared with the blank control group (all P < 0.01), and the RAS1 mRNA expression was significantly lower in the CA exosome-treated group than in the exosome-treated group ( t = 7.43, P = 0.002) . Conclusion:Both M0 macrophage-derived exosomes and CA-infected M0 macrophage-derived exosomes could effectively inhibit the mycelial growth of CA, and the latter one exhibited a stronger inhibitory effect, possibly by down-regulating cAMP in the cAMP/protein kinase A pathway.

Objective To investigate the correlation between exposure of uric acid accumulation and the risks of acute pancreatitis(AP)in the population in Kailuan Group.Methods A prospective study was performed based on thesubjects receiving annual physical examination during 2006 to 2010 in Kailuan Group.All of them had no AP history but had complete data on UA.The starting point of follow-up was when the subjects completed the health examination in 2010,and the end point was new AP events,deaths or the end of follow-up(2021-12-31).Exposure of uric acid accumulation(cumUA)was calculated according to the average values of uric acid measured in each two consecutive physical examinations and the intervalbetween these two consecutive physical examinations.The cumulative incidences of AP indifferent subgroups(determined by the quartile of cumUA)were described using Kaplan-Meier product limit-method and compared by log-rank test.Multivariate Cox proportional hazards regression model was used to analyze the impacts of different cumUA subgroups on new occurrence of AP events.Results A total of 55,799 subjects were included in this study.The subjects were divided into four groups according to the quartile of cumUA.Sex ratio,average age,BMI,systolic blood pressure(SBP),diastolic blood pressure(DBP),FPG,TC,TG,LDL-C,HDL-C,smoking,alcohol consumption,education≥9 years,physical exercise,history of hypertension,and history of cholelithiasis differed significantly among the groups(P<0.05),there was no difference in diabetes history among the 4 groups(P=0.30).153 patients developed AP during an average follow-up of(10.52±1.75)years,the incidence rates were 1.65,2.76,2.13 and 3.96 per 10 000 person-year in the Q1,Q2,Q3and Q4,respectively(P<0.01).After adjusting sex,age,TC,TG,eGFR,smoking,alcohol consumption,education,physical activity,and history of hypertension,diabetes,or cholelithiasis,Multivariate analysis showed a significantly increased risk in Q4(HR=1.77,95%CI:1.07～2.92)as comparing with Q1.After excluding deaths during the follow-up period,Multivariate Cox regression analysis was performed again in Q4 HR=1.75(95%CI:1.04～2.95).Conclusions With the increase of cumUA exposure,both morbidity and risk of AP occur-rence have the tendency of rising.

Objective To analyze levels of pan-immune-inflammation value(PIV),interleukin-6(IL-6),heparin-binding protein(HBP)and prealbumin(PAB)in patients with severe community-acquired pneumonia(CAP),and their values in evaluating the therapeutic effect at 72 h after admission.Methods According to the initial(72 h)treatment outcome,120 patients with severe CAP(the severe group)were divided into the effective group(n=87)and the failed group(n=33).Meanwhile,120 patients with non-severe CAP admitted in the same period were selected as the non-severe group.PIV,IL-6,HBP and PAB levels on the day after admission were compared between the severe group,the non-severe group,the failed group and the effective group.The value of above indicators in evaluating the condition of CAP and the therapeutic effect at 72 h after admission separately and in combination were analyzed using receiver operating characteristic(ROC)curves.Results Compared with the non-severe group,there were higher PIV,IL-6 and HBP levels,and lower PAB levels in the servere grouop(P＜0.05).ROC curves indicated that for evaluating severe CAP using a single indicator,the area under the curve(AUC)of PIV was the highest[0.830(95%CI:0.780-0.881)].The AUC of PIV combined with IL-6,HBP and PAB for evaluating severe CAP was 0.929(95%CI:0.892-0.967),which was higher than that of evaluation using a single indicator(P＜0.05).Compared with the effective group,there were higher PIV,IL-6 and HBP levels,and lower PAB level in the failed group(P＜0.05).ROC curves indicated that for evaluating the therapeutic effect on severe CAP at 72 h after admission using a single indicator the AUC of PIV was the highest[0.777(95%CI:0.692-0.862)].The AUC of PIV combined with IL-6,HBP and PAB for evaluating the therapeutic effect on severe CAP at 72 h after admission was 0.916(95%CI:0.846-0.986),which was higher than that of evaluation using a single indicator(P＜0.05).Conclusion Detection of PIV combined with IL-6,HBP and PAB has a good value in evaluating the condition of patients with CAP and the therapeutic effect on severe CAP at 72 h after admission.

Objective To investigate the association between asthma and IL-9 level,to provide reference for early prevention of asthma occurrence and improvement of asthma condition.Methods The data of single nucleotide polymorphism (SNP) were collected from two genome-wide association studies (GWAS) related to asthma and IL-9.Forty-three SNP instrumental variables associated with IL-9 were screened to conduct the forward direction Mendelian randomization (MR) analysis with asthma as the outcome.The three SNP associ-ated with asthma served as the instrumental variables,the IL-9 level change served as the study outcome to conduct the reverse MR analysis.Heterogeneity was detected by using Cochran's Q test,and the pleiotropy was detected by using the MR-Egger regression method.The robustness of the results was tested by the a leave-one-out method.Results The Q-test showed that no heterogeneity existed (P=0.383,0.883),and the MR analysis of fixed-effects model was used.The IL-9 level increase led to that the asthma occurrence risk was increased by 17％ (OR=1.17,95％CI:1.02-1.34).The asthma occurrence led to the IL-9 level increase by 0.09 standard deviation (OR=1.09,95％CI:1.01-1.19).After removing SNP one by one,the MR analy-sis results were steady.The MR-Egger regression method did not find the pleiotropy of instrumental variables (P=0.995,0.129).Conclusion There are bidirectional gene association between the IL-9 level change and asthma occurrence risk.