[Appropriate protocol of treatment modulation for seasonal allergic rhinitis caused by cypress pollens].

Objective: To investigate appropriate protocol of treatment modulation for seasonal allergic rhinitis (AR) patients, in order to promote the implementation of personalized medicine. Methods: Total of 124 AR patients allergic to cypress pollens were recruited from January to February 2020 in Department of Allergy in Peking Union Medical College Hospital, 43 males and 81 females with an average age of (41±9) years. The patients were divided into two groups with block randomization method. In the first group, treatment was modulated every two days according to the average daily rhinoconjunctivitis symptom score of the last two days (short-term symptom-score group); while in the second group, therapy regimen was adjusted every week based on the Allergic Rhinitis Control Test (ARCT) score of the last week (long-term ARCT group). The treatment level was up-regulated when the cypress pollen count increased and stayed at a high level (step-up pharmacotherapy stage); and treatment was down-regulated while the pollen count decreased (step-down pharmacotherapy stage). Daily symptom scores, medicine scores, and ARCT scores of the two groups were recorded and compared. Results: During the whole cypress pollen season, the daily rhinoconjunctivitis symptom score of short-term symptom-score group was significantly lower than that in long-term ARCT group(2.4±1.0 vs 2.7±1.0, P<0.01), and the difference between the two groups was more pronounced in the step-up pharmacotherapy stage than that in the step-down pharmacotherapy stage, while there was no statistical difference between the daily medicine scores of the two groups (P>0.05). During the pollen rising period, the ARCT score of short-term symptom-score group was significantly better than that of long-term ARCT group (21(19, 22) vs 20 (17, 21), P=0.049); while in the pollen peak period and decreasing period, the ARCT scores of the two groups showed no statistical difference (P>0.05). The proportion of incompliance with doctor's advice was higher in long-term ARCT group compared to that in short-term symptom-score group (30.1% vs 6.7%, P<0.001). Conclusion: The protocol of treatment modulation for seasonal AR patients allergic to pollens should be developed flexibly according to the variation trend of pollen allergen exposure, so as to implement the idea of personalized medicine.

[The effect on patient life quality of prophylactic treatment to seasonal allergic rhinitis and related transcriptomics research].

Objective: The preseason prophylactic treatment of seasonal allergic rhinitis (AR) caused by pollens could alleviate AR symptoms during the pollen season. This study aimed to evaluate the effect of prophylaxis usage of suplatast tosilate on the life quality of AR patients in the pollen season, and investigate the potential mechanism of action through transcriptomic analysis. Methods: This is a randomized controlled study. AR patients allergic to weed pollens were recruited from Allergy Clinic of Peking Union Medical College Hospital from January 2020 to June 2020, and divided into prophylactic group who started to take suplatast tosilate as prophylaxis 2 weeks before the spread of weed pollens[n=10, 4 men and 6 women with age range of (34±6) years old] and control group who did not use any prophylactic treatment[n=24, 12 men and 12 women with age range of (33±9) years old]. The differences of age (t=0.381, P=0.706) and gender (χ²=0.595, P=0.715) distribution between the patients of two groups were not statistically significant. All the subjects filled in the rhinoconjunctivitis quality of life questionnaire (RQLQ) while onset of AR symptoms, and peripheral blood was drawn for transcriptomic analysis 1 month before and during the pollen season. Differences between groups were statistically analyzed through chi-square test and t test. Results: There was no significant difference in visual analogue scale of rhinitis symptom in the last pollen season between prophylactic group and control group[ 8.0 (6.4, 9.3) vs 7.3 (6.1, 8.0), Z=1.180, P=0.254]. The RQLQ score of prophylactic group was superior to that of control group in the weed pollen season (2.9±0.9 vs 3.7±0.9, t=-2.438, P=0.026). 210 differentially expressed genes of fold change ≥2 were identified, with 147 genes upregulated and 63 genes downregulated in the prophylactic group compared to the control group. Gene Ontology annotation showed that IL-12 and IL-23 related pathways were downregulated in prophylactic group (P=0.006 48). Polymerase Chain Reaction (PCR) verification of differentially expressed genes indicated that the relative expression level of HLA-G in prophylactic group was significantly lower than that in control group (0.23±0.19 vs 1.00±0.49,t=4.016, P=0.006). Conclusion: The prophylactic treatment of suplatast tosilate showed some benefit to the life quality of seasonal AR patients during the pollen season, and the potential mechanism might be related with the downregulation of IL-12 and IL-23 pathways and decreased expression of HLA-G.

[The comparison of step-down pharmacotherapy and maintaining dose therapy for seasonal allergic rhinitis].

Objective:There is no standard algorithm for the modulation of pharmacologic treatment of allergic rhinitis. This study aimed to recruited allergic rhinitis patients caused by cypress pollens, and compare the step-down pharmacotherapy guided by pollen count and the maintaining therapy which keeps the previous medicine dose when the pollen count decreased. Method:This was a randomized, open-labelled, parallel control study. During the period after the pollen peak when the cypress pollen count decreased and stayed at a low level, allergic rhinitis patients were randomly divided into two groups. In the step-down group（n=67） medicine dose was reduced, while the maintaining group（n=68） kept taking the same dose as in the peak season. The rhinitis symptom score and medicine score of these two groups were recorded and compared. Result:The daily rhinitis symptom score of the step-down group showed no significant difference with the symptom score of the maintaining group, 2.45±0.32 vs 2.43±0.41, P=0.788. But the medicine score of step-down group（3.67±0.98） was significantly lower than that of maintaining group（4.78±0.70）, P<0.001. The compliance of step-down group（80.6%） was also better than maintaining group（60.3%）, P=0.014. However, in the subgroup of patients with severe rhinitis symptoms, the symptoms of patients taking step-down therapy tended to be more severe than those maintaining the same dose. Conclusion:During the later period of the pollen season when the pollen count was relatively low, the step-down pharmacotherapy guided by pollen count could reduce the medication use, increase the compliance of patients while controlling their rhinitis symptoms effectively. But this strategy might be more suitable for patients with milder symptoms, the severe rhinitis sufferers should be cautious before reducing their medicine dose.

Agonist of farnesoid X receptor protects against bile acid induced damage and oxidative stress in mouse placenta--a study on maternal cholestasis model.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder, which is characterized by raised serum bile acid level and potential adverse fetal outcome. Farnesoid X receptor (FXR), also known as a bile acid receptor, was found to be expressed in placenta with low level. Whether activation of FXR by specific agonists could regulate the pathogenesis of ICP is still unclear. METHODS: A model of maternal cholestasis was induced by administration of 17α-ethynylestradiol (E2) in pregnant mice for 6 days. We explored the regulatory effect of WAY-362450 (W450), a highly selective and potent FXR agonist on placenta. RESULTS: In this study, we demonstrated that administration of E2 increased bile acid levels in mouse serum, liver and amniotic fluid. Bile acid levels were significantly decreased after W450 treatment. W450 protected against the impairment of placentas induced by E2, including severe intracellular edema and apoptosis of trophoblasts. Moreover, W450 significantly induced the expressions of FXR target bile acid transport gene ATP-binding cassette, sub-family B (MDR/TAP), member 11 (Abcb11;Bsep) in placenta. W450 could also attenuate placental oxidative stress and increase the expressions of antioxidant enzymes Prdx1 and Prdx3. DISCUSSION AND CONCLUSION: In conclusion, our data demonstrated that FXR agonist W450 modulated bile acid balance and protected against placental oxidative stress. Thus, our results support that potent FXR agonists might represent promising drugs for the treatment of ICP.

[The effects of Salvia miltiorrhizae Bge and Ligustrazine on thromboxane A2 and prostacyclin in pregnancy induced hypertension].

The clinical efficiency and mechanism of traditional Chinese medicinal herb Salvia Miltiorrhizae Bge (SMB) and Ligustrazine (L) on pregnancy induced hypertension (PIH) were studied in 30 patients. Before and after the administration of SMB and L, the following parameters: mean arterial pressure (MAP), proteinuria, levels of Thromboxane A2 (TXA2) and Prostacyclin (PGI2) were observed. TXA2 and PGI2 were measured by their stable hydration products Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by an established radioimmunoassay. The results of treatment were compared with the base line values and showed as follows: MAP and proteinuria decreased significantly (P < 0.05); no marked difference existed in TXB2; the level of 6-keto-PGF1 alpha increased significantly (P < 0.05); the rate of TXB2/6-keto-PGF1 alpha decreased significantly (P < 0.05). The results suggested that SMB and L can invigorate blood circulation by decreasing vasoconstriction.