Objective To investigate the changes of CD4 + CD25 + Foxp3 + regulatory T cell (Treg) and relative cell factors in peripheral blood of steroid-resistant allergic rhinitis (AR) patients,and to study their functions in occurrence of steroid-resistant AR.Methods The CD4 + CD25 + Foxp3 + Treg cell in 30 cases general physical examination (The control group),30 cases steroid-sensitive AR patients (steroidsensitive group) and 30 cases steroid-resistant AR patients (steroid-resistant group) were detected by flow cytometry.The levels of serum interleukin 10 (IL-10) and transforming growth factor β1 (TGF-β1) in the three groups were detected by enzyme-linked immunoadsorbent assay (ELISA).Results Compare to the control group,proportion of CD4 + CD25 + Foxp3 + Treg cell and the levels of serum IL-10,TGF-β1 in steroid-sensitive group and steroid-resistant group were significantly reduced (P ＜ 0.01).The proportion of CD4 + CD25 + Foxp3 + Treg cell and the levels of serum IL-10,TGF-β1 in steroid-resistant group were decreased significantly than steroid-sensitive group (P ＜ 0.01).The proportion of CD4 + CD25 + Foxp3 + Treg cell were positively correlated with the serum IL-10,and TGF-β1 (P ＜ 0.01).Conclusions The reduced proportion of CD4 + CD25 + Foxp3 + Treg cell and lower serum IL-10,TGF-β1 play an important role in the occurrence of steroid-resistant AR patients.

Objective To investigate the function of activator protein-1(AP-1)and nuclear factor-κB(NF-κB)on the treatment of montelukast sodium tables for patients with steroid-resistant allergic rhinitis (AR). Methods A random-ized study was carried out in 50 patients with steroid-resistant AR. 25 cases were treated with montelukast sodium ta-bles(montelukast sodium group), and the others by ATP tables(placebo group). Score system was used to compare the therapeutic effect of these two drugs on clinical symptoms and signs on 21th day after therapy. The DNA binding activ-ities of Ap-1 and NF-κB were measured by electrophoretic mobility shift assay(EMSA). The expression of IL-4, IL-5 and IL-10 were determined by enzyme-linked immunoadsorbent assay (ELISA). Results The therapeutic effect rate in montelukast sodium group was significantly higher than that in placebo group at 21 days after treatment begining (P<0.01). Compared with placebo group, the DNA binding activities of Ap-1 and NF-κB were significantly reduced in montelukast sodium group (P<0.01). The score reduce index (SRI)of the clinical symptoms and signs was negatively correlated with the DNA binding activities in montelukast sodium group (P<0.05), but there was any correlation be-tween them in placebo group(P>0.05).The expression of IL-4 and IL-5 in montelukast sodium group were significantly lower and IL-10 was higher than those in placebo group (P<0.01). Conclusion The treatment effect of montelukast sodium tables for steroid-resistant AR may be aroused by suppressing the Ap-1 and NF-κB DNA binding activities, and effecting the expression of IL-4, IL-5 and IL-10.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.