Pollen allergen-induced allergic rhinitis(AR),also known as seasonal allergic rhinitis(SAR),typically manifests during the period of pollen dissemination by anemophilous plants.The prevalence of SAR has more than doubled over the past three decades.The etiology of SAR is multifaceted,involving factors such as pollen allergens,environmental and climatic conditions,genetic predispositions,and the immunological status of the individual.Animal models provide a critical tool for elucidating the mechanisms underlying AR and advancing the development of effective preventive and therapeutic strategies.This review synthesizes the recent pertinent domestic and international literature on pollen-sensitized AR animal experiments.It systematically delineates the factors influencing the efficacy of these models,including the selection of animal strains,the production and associated challenges of sensitizing agents,specifically pollen antigens,the utilization and limitations of adjuvants,the procedural steps involved in model creation,and the method ologies for evaluating model effectiveness.The insights provided are intended to offer guidance and support for the development of appropriate animal models of pollen-induced AR,thereby facilitating both fundamental and applied research in this area.

Objective:To investigate the effects of lipids and lipopolysaccharide (LPS) in Artemisia pollen on the induction of allergic rhinitis in a murine model. Methods:BALB/c mice were randomly divided into seven groups using the random number table method as follows: defatted pollen group (TZ group, n=5), defatted pollen+ LPS group (TZLPS group, n=5), non-defatted pollen group (WTZ group, n=5), non-defatted pollen+ LPS group (WTZLPS group, n=5), PBS group ( n=5), PBS+ LPS group (PBSLPS group, n=5), and blank control group ( n=6). On days 1, 8, and 15, the mice in the TZ and TZLPS groups received a subcutaneous injection in the neck region with 0.1 ml of defatted Artemisia pollen extract (20 μg/ml); the WTZ and WTZLPS groups were administered 0.1 ml of non-defatted Artemisia pollen extract (20 μg/ml), while the PBS and PBSLPS groups were injected with 0.1 ml of PBS (0.1 mol/L). From days 22 to 28, the mice were subjected to intranasal challenge to induce allergic rhinitis symptoms. The TZ, WTZ, and PBS groups received nasal administration of 10 μl per nostril of defatted Artemisia pollen extract (500 μg/ml), non-defatted Artemisia pollen extract (500 μg/ml), and PBS (0.1 mol/L), respectively. For the TZLPS, WTZLPS, and PBSLPS groups, an additional 260 EU (5.2 μl) of LPS was co-administered per nostril alongside the corresponding base solutions. The blank control group received no intervention during this phase. The behaviors of the mice were observed; the levels of specific IgE, IgG1 and IgG2a in serum samples were detected by ELISA; the pathological changes in nasal mucosa and lung tissues were observed by HE staining, and the expression of both IL-4 and IL-5 was observed by immunohistochemistry. One-way analysis of variance and Kruskal-Wallis test were used for statistical analysis. Results:Following Artemisia pollen antigen challenge, the total TZ group (TZLPS group+ TZ group) exhibited significantly higher behavioral scores as compared with the total PBS group (PBSLPS group+ PBS group) and the blank control group (both P<0.001). Serum analysis revealed that the total TZ group showed markedly elevated levels of Artemisia-specific IgE compared with the total WTZ group (WTZLPS group+ WTZ group) and the total PBS group ( P<0.05, P<0.001), along with significantly higher IgG1 levels than the total PBS and blank control groups ( P<0.05, P<0.001), while no significant differences in IgG2a levels were observed among these groups (all P>0.05). In local inflammatory responses, eosinophil infiltration and IL-4/IL-5 expression in both nasal mucosa and lung tissues of mice in the total TZ group were significantly higher than those in the total PBS and blank control groups (all P<0.001). Notably, eosinophil counts in nasal mucosa of mice in the total TZ group surpassed those in the total WTZ group ( P<0.05), whereas no significant differences in IL-4/IL-5 expression in mouse nasal mucosa were detected between the total TZ and total WTZ groups (both P>0.05). LPS supplementation in pollen extracts showed no significant effects on the specific IgE, IgG1, or IgG2a levels in serum across groups (all P>0.05), nor did it alter eosinophil activation or IL-4 expression in mouse nasal mucosa (all P>0.05). However, compared with the TZ group, eosinophil counts and IL-4 expression in lung tissues of mice in the TZLPS group were significantly increased (both P<0.001). Conclusions:This study successfully establishes a mouse model of Artemisia pollen allergy, and finds that the defatting treatment of Artemisia pollen can induce more intense inflammatory response. The presence or absence of LPS in pollen has no significant effect on allergic inflammation in the nasal mucosa, but it can cause different degrees of damage to the lung tissues of mice.

Pollen allergen-induced allergic rhinitis(AR),also known as seasonal allergic rhinitis(SAR),typically manifests during the period of pollen dissemination by anemophilous plants.The prevalence of SAR has more than doubled over the past three decades.The etiology of SAR is multifaceted,involving factors such as pollen allergens,environmental and climatic conditions,genetic predispositions,and the immunological status of the individual.Animal models provide a critical tool for elucidating the mechanisms underlying AR and advancing the development of effective preventive and therapeutic strategies.This review synthesizes the recent pertinent domestic and international literature on pollen-sensitized AR animal experiments.It systematically delineates the factors influencing the efficacy of these models,including the selection of animal strains,the production and associated challenges of sensitizing agents,specifically pollen antigens,the utilization and limitations of adjuvants,the procedural steps involved in model creation,and the method ologies for evaluating model effectiveness.The insights provided are intended to offer guidance and support for the development of appropriate animal models of pollen-induced AR,thereby facilitating both fundamental and applied research in this area.

Objective:To investigate the effects of lipids and lipopolysaccharide (LPS) in Artemisia pollen on the induction of allergic rhinitis in a murine model. Methods:BALB/c mice were randomly divided into seven groups using the random number table method as follows: defatted pollen group (TZ group, n=5), defatted pollen+ LPS group (TZLPS group, n=5), non-defatted pollen group (WTZ group, n=5), non-defatted pollen+ LPS group (WTZLPS group, n=5), PBS group ( n=5), PBS+ LPS group (PBSLPS group, n=5), and blank control group ( n=6). On days 1, 8, and 15, the mice in the TZ and TZLPS groups received a subcutaneous injection in the neck region with 0.1 ml of defatted Artemisia pollen extract (20 μg/ml); the WTZ and WTZLPS groups were administered 0.1 ml of non-defatted Artemisia pollen extract (20 μg/ml), while the PBS and PBSLPS groups were injected with 0.1 ml of PBS (0.1 mol/L). From days 22 to 28, the mice were subjected to intranasal challenge to induce allergic rhinitis symptoms. The TZ, WTZ, and PBS groups received nasal administration of 10 μl per nostril of defatted Artemisia pollen extract (500 μg/ml), non-defatted Artemisia pollen extract (500 μg/ml), and PBS (0.1 mol/L), respectively. For the TZLPS, WTZLPS, and PBSLPS groups, an additional 260 EU (5.2 μl) of LPS was co-administered per nostril alongside the corresponding base solutions. The blank control group received no intervention during this phase. The behaviors of the mice were observed; the levels of specific IgE, IgG1 and IgG2a in serum samples were detected by ELISA; the pathological changes in nasal mucosa and lung tissues were observed by HE staining, and the expression of both IL-4 and IL-5 was observed by immunohistochemistry. One-way analysis of variance and Kruskal-Wallis test were used for statistical analysis. Results:Following Artemisia pollen antigen challenge, the total TZ group (TZLPS group+ TZ group) exhibited significantly higher behavioral scores as compared with the total PBS group (PBSLPS group+ PBS group) and the blank control group (both P<0.001). Serum analysis revealed that the total TZ group showed markedly elevated levels of Artemisia-specific IgE compared with the total WTZ group (WTZLPS group+ WTZ group) and the total PBS group ( P<0.05, P<0.001), along with significantly higher IgG1 levels than the total PBS and blank control groups ( P<0.05, P<0.001), while no significant differences in IgG2a levels were observed among these groups (all P>0.05). In local inflammatory responses, eosinophil infiltration and IL-4/IL-5 expression in both nasal mucosa and lung tissues of mice in the total TZ group were significantly higher than those in the total PBS and blank control groups (all P<0.001). Notably, eosinophil counts in nasal mucosa of mice in the total TZ group surpassed those in the total WTZ group ( P<0.05), whereas no significant differences in IL-4/IL-5 expression in mouse nasal mucosa were detected between the total TZ and total WTZ groups (both P>0.05). LPS supplementation in pollen extracts showed no significant effects on the specific IgE, IgG1, or IgG2a levels in serum across groups (all P>0.05), nor did it alter eosinophil activation or IL-4 expression in mouse nasal mucosa (all P>0.05). However, compared with the TZ group, eosinophil counts and IL-4 expression in lung tissues of mice in the TZLPS group were significantly increased (both P<0.001). Conclusions:This study successfully establishes a mouse model of Artemisia pollen allergy, and finds that the defatting treatment of Artemisia pollen can induce more intense inflammatory response. The presence or absence of LPS in pollen has no significant effect on allergic inflammation in the nasal mucosa, but it can cause different degrees of damage to the lung tissues of mice.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Objective:To explore the influencing factors of efficacy of glucocorticoids in the treatment of moderate to severe ulcerative colitis (UC) in children.Methods:A retrospective case-control study was conducted. The clinical data of 38 children with moderate to severe UC treated with glucocorticoids in Beijing Children's Hospital of Capital Medical University from January 2016 to December 2021 were analyzed. According to the response to glucocorticoids therapy, the patients were divided into steroid-intractable group and steroid-effective group. Kaplan-Meier method was used to calculate the cumulative recurrence rate. Univariate analysis was performed to analyze the differences of clinical data between the two groups, and Logistic regression was used to analyze the risk factors of steroid-intractable UC in children.Results:A total of 38 children with moderate to severe UC were enrolled, including 22 males and 16 females. The median onset age was 10.7 (8.5, 12.7) years old, and the median disease duration was 4.3 (1.1, 13.6) months. The cumulative recurrence rates of 38 UC patients at 3 months, 6 months, 1 year and 2 years after glucocorticoids treatment were 26.3%, 52.6%, 63.7% and 69.5%, respectively. There were 17 patients (44.7%) in steroid-effective group. There were 21 patients (55.3%) in steroid-intractable group, including 16 (42.1%) of steroid dependence and 5 (13.2%) of steroid resistance. In the steroid-intractable group, the PUCAI scores at baseline, on the 3rd day and 5th day of glucocorticoids treatment [65.0 (50.0, 70.0) points vs. 50.0 (37.5, 60.0) points, 25.0 (10.0, 37.5) points vs. 10.0 (10.0, 20.0) points, 25.0 (10.0, 37.5) points vs. 10.0 (5.0, 12.5) points] and early recurrence rate (85.7% vs. 35.3%) were higher than those in steroid-effective group, the recurrence time [4.0 (2.0, 5.0) months vs. 19.0 (7.5, 46.5) months] was shorter than that in steroid-effective group, albumin level at baseline [ (33.3 ± 5.5) g/L vs. (37.6 ± 5.9) g/L] was lower than that in steroid-effective group, and the differences were statistically significant (all P<0.05) . Multivariate Logistic regression analysis showed that the PUCAI score at baseline was an independent risk factor for steroid-intractable UC ( OR = 1.070, 95% CI: 1.011-1.132, P = 0.020) . Conclusions:The rates of steroid dependence and the steroid resistance are high in moderate to severe UC children. Children in the steroid-intractable group have an earlier recurrence time, a higher rate of early recurrence, and a lower albumin level at baseline. The steroid dependence and resistance are more likely to occur in children with moderate to severe UC when PUCAI score at baseline is high.

Objective:To explore the influencing factors of efficacy of glucocorticoids in the treatment of moderate to severe ulcerative colitis (UC) in children.Methods:A retrospective case-control study was conducted. The clinical data of 38 children with moderate to severe UC treated with glucocorticoids in Beijing Children's Hospital of Capital Medical University from January 2016 to December 2021 were analyzed. According to the response to glucocorticoids therapy, the patients were divided into steroid-intractable group and steroid-effective group. Kaplan-Meier method was used to calculate the cumulative recurrence rate. Univariate analysis was performed to analyze the differences of clinical data between the two groups, and Logistic regression was used to analyze the risk factors of steroid-intractable UC in children.Results:A total of 38 children with moderate to severe UC were enrolled, including 22 males and 16 females. The median onset age was 10.7 (8.5, 12.7) years old, and the median disease duration was 4.3 (1.1, 13.6) months. The cumulative recurrence rates of 38 UC patients at 3 months, 6 months, 1 year and 2 years after glucocorticoids treatment were 26.3%, 52.6%, 63.7% and 69.5%, respectively. There were 17 patients (44.7%) in steroid-effective group. There were 21 patients (55.3%) in steroid-intractable group, including 16 (42.1%) of steroid dependence and 5 (13.2%) of steroid resistance. In the steroid-intractable group, the PUCAI scores at baseline, on the 3rd day and 5th day of glucocorticoids treatment [65.0 (50.0, 70.0) points vs. 50.0 (37.5, 60.0) points, 25.0 (10.0, 37.5) points vs. 10.0 (10.0, 20.0) points, 25.0 (10.0, 37.5) points vs. 10.0 (5.0, 12.5) points] and early recurrence rate (85.7% vs. 35.3%) were higher than those in steroid-effective group, the recurrence time [4.0 (2.0, 5.0) months vs. 19.0 (7.5, 46.5) months] was shorter than that in steroid-effective group, albumin level at baseline [ (33.3 ± 5.5) g/L vs. (37.6 ± 5.9) g/L] was lower than that in steroid-effective group, and the differences were statistically significant (all P<0.05) . Multivariate Logistic regression analysis showed that the PUCAI score at baseline was an independent risk factor for steroid-intractable UC ( OR = 1.070, 95% CI: 1.011-1.132, P = 0.020) . Conclusions:The rates of steroid dependence and the steroid resistance are high in moderate to severe UC children. Children in the steroid-intractable group have an earlier recurrence time, a higher rate of early recurrence, and a lower albumin level at baseline. The steroid dependence and resistance are more likely to occur in children with moderate to severe UC when PUCAI score at baseline is high.

Objective:To evaluate the efficacy and safety of infliximab(IFX)in pediatric patients with ulcerative colitis(UC).Methods:The clinical data of 17 UC patients who received IFX treatment at Beijing Children′s Hospital, Capital Medical University from January 2017 to December 2021 were retrospectively analyzed, and the pediatric ulcerative colitis activity index(PUCAI)and laboratory data were compared before and after treatment to evaluate the efficacy and safety of IFX.Results:A total of 17 UC patients were included, and among them there were 9 boys and 8 girls.The age of onset was 12.1(10.7, 12.8)years old, and median age at IFX initiation was 12.5(11.8, 13.6)years old.The duration of IFX medication was 46.1(17.4, 56.9)weeks, and the times of IFX injections was 8.0(4.5, 10.5). The mean PUCAI score of the 17 UC patients at start of IFX treatment was (50.6±21.2) points, and the Mayo endoscopic score showed: ten severe activity, six moderate activity, and one mild activity.IFX efficacy analysis: the clinical response rate was 87.5%(14/16), and the clinical remission rate was 56.3%(9/16) at the 14th week.The sustained response rate was 81.8%(9/11), and the sustained remission rate was 36.4%(4/11) at the 30th week.At the 14th week of IFX treatment, PUCAI score[2.5(0, 10.0)points vs.50.0(41.3, 70.0)points] and white blood cell count[5.7(4.8, 8.6)×10 9/L vs.8.7(6.4, 13.5)×10 9/L] significantly decreased(all P<0.05), hemoglobin[(113.8±20.4)g/L vs.(99.3 ± 19.4)g/L] and albumin level[42.2(40.0, 44.4)g/L vs.36.6(28.6, 40.2)g/L] significantly increased compared with those before IFX treatment, and the differences were statistically significant(all P<0.05). The Mayo endoscopic scores at 14 weeks of IFX treatment in 12 active UC patients showed: only 2 patients achieved mucosal healing, 5 patients had reduced from severe to moderate mucosal inflammation, and 5 patients had no improvement.Seven patients had 10 adverse events, 2 cases had 4 times acute infusion reactions, and 5 cases had 6 times infections. Conclusion:IFX is effective and relatively safe in inducing and maintaining clinical remission in pediatric UC patients.

Objective:To compare the efficacy of combination therapy on cyclic vomiting syndrome(CVS)in children, and improve the efficacy of CVS treatment in the future.Methods:This study retrospectively analyzed patients′ medical records of CVS, which were admitted to Digestive Department of Beijing Children′s Hospital from 2012 to 2019.The treatment regimen was A(Cyproheptadine+ Doxepin+ Valproate), B(Propranolol+ Cyproheptadine), or C(Propranolol+ Amitriptyline). Meanwhile, the patients should take drugs more than three months.The clinical data of 42 cases were analyzed retrospectively, and the treatment effect after discharge was followed up by telephone until October, 2020.Results:Among the 42 cases, 17 were male and 25 were female, whose mean age of onset was (4.65±3.23) years, and the age of diagnosis was (6.79±3.58) years.The main accompanied symptoms were abdominal pain and upper gastrointestinal bleeding.Forty-two patients were moderate/severe CVS.The regimens A, B and C were observed in 7, 11, and 24 patients, respectively.The age at improvement was(8.17±4.12)years.The course of treatment was(1.37±0.96)years.The age at follow-up was(10.32±4.03)years.During the 1-year follow-up, 35 cases were effective, and the efficiency was 83.3%.Among them, 23 cases had no paroxysmal vomiting and 7 cases had no effect.There was no significant difference in therapy effects among group A, B and C. Between the effective group and non-effective group, there were statistical differences in the personal history of hiatus hernia( P=0.024), the weight at follow-up ( P=0.042), and the course of medication( P=0.020). Conclusion:The combination regimen has a higher effective rate in the treatment of CVS.There was no significant difference among the three regimens in the treatment of CVS.For children with refractory CVS, who can not be treated with combination therapy, individualized therapy should be further developed.

Objective:To investigate the clinical features of pediatric ulcerative colitis (UC) and analyze the risk factors of disease relapse.Methods:The clinical data of 79 children with UC diagnosed in Beijing Children′s Hospital, Capital Medical University from January 2016 to February 2021 were retrospectively analyzed. They were divided into early relapse group and non-early relapse group according to the clinical relapse within 12 months after diagnosis. T-test, rank sum test, χ 2 test or Fisher′s exact test were used to compare the variables between the 2 groups, including the clinical features, laboratory examination results and treatments. The Logistic regression was used to analyze the risk factors of early relapse. The cumulative relapse rate during follow-up was calculated by Kaplan-Meier method. Results:Among the 79 UC children, 46 were males and 33 were females, and the age of onset was 10.6 (6.4, 12.7) years. The children were mainly characterized by extensive disease (E3) and pancolitis (E4) (51/79, 65%), moderate to severe activity (48/79, 61%) and moderate to severe inflammation of colonic mucosa (71/79, 90%). Thirty-eight (48%) patients had atypical phenotype and 17 (22%) had extraintestinal manifestations. The follow-up period was 43.9 (22.8, 61.3) months, and of the 41 patients rechecked with colonoscopy, 7 (17%) had disease progression. According to Kaplan-Meier analysis, the cumulative relapse rate of the 79 cases at 3 months, 6 months, 1 year and 2 years after diagnosis were 27% (21/79), 47% (37/79), 57% (45/79) and 73% (53/73), respectively. There were 45 children (57%) in early relapse group and 34 (43%) in non-early relapse group. In early relapse group, hemoglobin and mucosal healing rate were both significantly lower (105 (87, 122) vs. 120 (104, 131) g/L, 28% (7/25) vs. 7/9, Z=-2.38, χ2=4.87, both P<0.05). The rate of steroid-dependent, E3 and step-up therapy during the induction period were all significantly higher than those in non-early relapse group (11/19 vs. 1/12, 24% (11/45) vs. 6% (2/34), 29% (13/45) vs. 6% (2/34), χ2=5.67, 4.85, 6.66, all P<0.05). Multivariate Logistic regression analysis showed that extraintestinal manifestations ( OR=4.33, 95% CI 1.05-17.83), E3 ( OR=8.27, 95% CI 1.47-46.46) and step-up therapy during the induction period ( OR=5.58, 95% CI 1.01-30.77) were independent risk factors for early relapse. Conclusions:Pediatric UC is usually extensive and severe, with atypical phenotype, a high rate of relapse and a risk of disease progression. Extraintestinal manifestations, E3 and step-up therapy during the induction period are independent risk factors for early relapse.