Chronic spontaneous urticaria (CSU) greatly affects the quality of life of patients. Currently, no sensitive and convenient biomarkers are available to assess the severity of CSU and efficacy of drug therapies. It is particularly important to apply patient-reported outcome assessment tools with good reliability and validity in daily management of CSU, such as urticaria activity score, urticaria control test and chronic urticaria quality of life questionnaire. This review outlines the existing CSU assessment tools, analyzes their strengths, limitations and clinical application, aiming to establish a CSU clinical scoring system, and to facilitate personalized treatment and efficacy evaluation.

Objective:To retrospectively evaluate efficacy and safety of omalizumab in the treatment of chronic spontaneous urticaria (CSU) , as well as recurrence after its withdrawal.Methods:Clinical data on patients with CSU, who received omalizumab treatment in Peking University First Hospital from February 2018 to January 2021, were collected and analyzed retrospectively. Through outpatient follow-up, urticaria control test (UCT) and dermatology life quality index (DLQI) were recorded to assess disease severity, and adverse events and recurrence after omalizumab withdrawal were monitored. Comparisons of normally distributed measurement data between groups were carried out using t test or analysis of variance, comparisons of non-normally distributed measurement data between groups using Mann-Whitney U test, Wilcoxon signed-rank test or Kruskal-Wallis H test, and comparisons of enumeration data between groups using chi-square test or Fisher′s exact test. Results:A total of 59 patients with CSU were included and treated with omalizumab for at least 3 months, of whom, 45 were treated for more than 6 months, and 15 for more than 12 months. After the start of omalizumab treatment, UCT scores increased from 3.0 (1.0, 6.0) points at baseline to 11.0 (3.0, 14.0) points at 1 month and 15.0 (12.0, 16.0) points at 3 months (both P < 0.05) ; DLQI scores decreased from 16.0 (12.0, 20.0) points at baseline to 7.0 (1.0, 13.0) points at 1 month and 1.0 (0.0, 4.0) points at 3 months (both P < 0.05) . The proportion of patients achieving partial or complete disease control increased from 0 at baseline to 44.1% at 1 month, 78.0% at 3 months, and 88.9% at 6 months. The proportion of patients whose quality of life was severely or extremely severely affected by CSU decreased from 84.7% at baseline to 30.5% at 1 month, 15.3% at 3 months, and 4.4% at 6 months. The disease duration was significantly shorter in the complete response group and partial response group than in the non-response group ( t = -2.894, -2.511, P = 0.011, 0.036, respectively) ; the treatment duration was significantly longer in the complete response group than in the partial response group and non-response group ( t = 2.479, 2.677, P = 0.039, 0.022, respectively) . Compared with the rapid response group, the slow response group showed higher DLQI scores ( Z = -2.622, P = 0.009) and lower UCT scores ( Z = -2.746, P = 0.006) at baseline. Nineteen patients withdrew omalizumab after complete control of CSU, of whom 13 (68.4%) experienced relapse 7.0 (5.0, 8.0) weeks after the withdrawal, and showed significantly higher UCT scores at relapse than at baseline ( Z = 3.172, P = 0.001) . The disease duration was significantly longer in the recurrence group than in the non-recurrence group ( Z = -2.635, P = 0.007) . After recurrence, 5 patients restarted omalizumab treatment, and all of them regained partial or complete disease control. The adverse events reported during the treatment were all mild to moderate. Conclusions:Omalizumab can effectively and safely control symptoms of CSU and improve the quality of life of patients with CSU. However, recurrence frequently occurs after omalizumab withdrawal, and reinitiating omalizumab treatment after recurrence is still effective.

Objective:To evaluate clinical efficacy and safety of omalizumab in the treatment of symptomatic dermographism by analyzing real-world data.Methods:Clinical data were collected from patients with symptomatic dermographism who completed 16-week treatment with omalizumab in Department of Dermatology, Peking University First Hospital from February 2018 to May 2021, and retrospectively analyzed. The analysis was done by comparing data obtained before and after the treatment, including critical friction thresholds (CFTs) , pruritus scores in a provocation test, as well as urticaria control test (UCT) , dermatology life quality index (DLQI) and chronic urticaria quality of life questionnaire (CU-Q2oL) scores. Adverse events reported by patients during the treatment were recorded. Wilcoxon signed-rank test was applied for the analysis of clinical data before and after the treatment.Results:A total of 27 patients with symptomatic dermographism who completed 16 weeks of omalizumab treatment were included. At baseline, the CFTs of all the 27 patients were 4, and their UCT, DLQI and CU-Q2oL scores were 7.0 (5.0, 8.0) , 9.0 (6.0, 10.0) , 63.0 (50.0, 72.0) points respectively. At week 4, the CFTs decreased from 4 to 0 in 9 patients (33.3%) , the UCT scores increased to 14.0 (12.0, 16.0) points ( Z = 4.548, P<0.05) , and the DLQI and CU-Q2oL scores decreased to 2.0 (0.0, 2.0) and 32.0 (25.0, 41.0) points respectively in the 27 patients ( Z = 4.513, 4.433, respectively, both P<0.05) . At week 6, the UCT scores increased to 15.0 (14.0, 16.0) points, and the DLQI and CU-Q2oL scores decreased to 0.0 (0.0, 1.0) and 25.0 (23.0, 30.0) points respectively in the 27 patients. No drug-related serious adverse events were reported during the treatment. Conclusion:Omalizumab can effectively improve the symptoms of symptomatic dermographism and patients′ quality of life with a good safety profile.

Objective:To explore the value and threshold of steady-state trough plasma concentration (trough concentration) of imatinib mesylate (IM) and its active metabolite N-desmethyl imatinib (NDI) in predicting the risk of moderate to severe adverse reactions in patients with gastrointestinal stromal tumors (GIST).Methods:The subjects were selected from GIST outpatient who received IM treatment and re-visited doctor in the First Affiliated Hospital of Soochow University form July 2020 to March 2021. On the day of re-visiting, the relevant clinical information and occurrence of IM-related adverse reactions within 28 d prior to the trial of selected patients was asked and recorded and blood were collected (22 to 24 hours after the last medication) to determine IM and NDI trough concentration. Twenty-eight days after blood collection, telephone follow-up was conducted to record IM-related adverse reactions occurrence. Blood routine and blood biochemical examination results within 28 days before and after blood collection were collected through the hospital information system. After evaluating causality for adverse reactions and grading their severity, patients without or with grade I adverse reactions were regarded as the no/mild group and those with grade Ⅱ~Ⅴadverse reactions were regarded as the moderate-severe group. The risk factors of moderate-severe adverse reactions were analyzed by comparing the main clinical characteristics of patients in the 2 groups, and the value and threshold of IM and NDI trough concentrations in predicting the risk of moderate-severe adverse reactions were analyzed by receiver operating characteristic (ROC) curve.Results:A total of 119 patients were recruited in this study and 113 (95.0%) had adverse reactions. There were 65 patients in the no/mild group and 54 in the moderate-severe group. The differences in the gender and dose distribution of patients in the 2 groups were statistically significant ( χ2=19.772, P<0.001; χ2=9.817, P=0.020); proportions of females, patients at dose of 300 mg/d, and patients at dose of 600 mg/d in the moderate-severe group were greater than those in the no/mild group. The trough concentration of IM and NDI of patients in the moderate-severe group were significantly higher than those of patients in the no/mild group[1 695 (1 258, 2 261) μg/L vs. 1 360 (938, 1 643) μg/L, P<0.001; 324(223, 379) μg/L vs. 264(217, 338) μg/L, P=0.042]. ROC curve analysis results showed that the breakpoints of IM and NDI trough concentrations for moderate-severe adverse reactions in patients with GIST were 1 539 μg/L (sensitivity 62.3%, specificity 70.3%) and 303 μg/L (sensitivity 56.6%, specificity 68.7%) respectively. The 119 patients were grouped according to the breakpoint concentrations. The incidences of moderate-severe adverse reactions were 63.0% (34/54) and 30.8% (20/65) in patients with IM trough concentration >1 539 μg/L and ≤1 539 μg/L, respectively and 59.6% (31/52) and 34.3% (23/67) in patients with NDI trough concentration >303 μg/L and ≤303 μg/L, respectively. The differences were statistically significant ( P<0.001, P=0.006). Conclusions:The trough concentrations of IM and NDI are of some value in predicting the risk of moderate-severe adverse reactions in patients with GIST. Drug monitoring should be strengthened in patients with IM trough concentration >1 539 μg/L and NDI trough concentration >303 μg/L to ensure the safety of IM use.

Objective:To explore the value and threshold of steady-state trough plasma concentration (trough concentration) of imatinib mesylate (IM) and its active metabolite N-desmethyl imatinib (NDI) in predicting the risk of moderate to severe adverse reactions in patients with gastrointestinal stromal tumors (GIST).Methods:The subjects were selected from GIST outpatient who received IM treatment and re-visited doctor in the First Affiliated Hospital of Soochow University form July 2020 to March 2021. On the day of re-visiting, the relevant clinical information and occurrence of IM-related adverse reactions within 28 d prior to the trial of selected patients was asked and recorded and blood were collected (22 to 24 hours after the last medication) to determine IM and NDI trough concentration. Twenty-eight days after blood collection, telephone follow-up was conducted to record IM-related adverse reactions occurrence. Blood routine and blood biochemical examination results within 28 days before and after blood collection were collected through the hospital information system. After evaluating causality for adverse reactions and grading their severity, patients without or with grade I adverse reactions were regarded as the no/mild group and those with grade Ⅱ~Ⅴadverse reactions were regarded as the moderate-severe group. The risk factors of moderate-severe adverse reactions were analyzed by comparing the main clinical characteristics of patients in the 2 groups, and the value and threshold of IM and NDI trough concentrations in predicting the risk of moderate-severe adverse reactions were analyzed by receiver operating characteristic (ROC) curve.Results:A total of 119 patients were recruited in this study and 113 (95.0%) had adverse reactions. There were 65 patients in the no/mild group and 54 in the moderate-severe group. The differences in the gender and dose distribution of patients in the 2 groups were statistically significant ( χ2=19.772, P<0.001; χ2=9.817, P=0.020); proportions of females, patients at dose of 300 mg/d, and patients at dose of 600 mg/d in the moderate-severe group were greater than those in the no/mild group. The trough concentration of IM and NDI of patients in the moderate-severe group were significantly higher than those of patients in the no/mild group[1 695 (1 258, 2 261) μg/L vs. 1 360 (938, 1 643) μg/L, P<0.001; 324(223, 379) μg/L vs. 264(217, 338) μg/L, P=0.042]. ROC curve analysis results showed that the breakpoints of IM and NDI trough concentrations for moderate-severe adverse reactions in patients with GIST were 1 539 μg/L (sensitivity 62.3%, specificity 70.3%) and 303 μg/L (sensitivity 56.6%, specificity 68.7%) respectively. The 119 patients were grouped according to the breakpoint concentrations. The incidences of moderate-severe adverse reactions were 63.0% (34/54) and 30.8% (20/65) in patients with IM trough concentration >1 539 μg/L and ≤1 539 μg/L, respectively and 59.6% (31/52) and 34.3% (23/67) in patients with NDI trough concentration >303 μg/L and ≤303 μg/L, respectively. The differences were statistically significant ( P<0.001, P=0.006). Conclusions:The trough concentrations of IM and NDI are of some value in predicting the risk of moderate-severe adverse reactions in patients with GIST. Drug monitoring should be strengthened in patients with IM trough concentration >1 539 μg/L and NDI trough concentration >303 μg/L to ensure the safety of IM use.

Objective:To translate the Urticaria Control Test (UCT) into Chinese, and to assess reliability, validity, sensitivity and screening accuracy of the new-version scale.Methods:After forward-backward translation and cultural adaption, items of the Chinese version of UCT were determined. The scale was used in 51 patients with chronic spontaneous urticaria (CSU) , 41 with chronic inducible urticaria (CIndU) , and 11 with CSU complicated by CIndU. Within 8 weeks after enrollment, 81 patients were treated with antihistamines, 8 with omalizumab, and 14 with antihistamines combined with omalizumab. At the time of enrollment and 4 and 8 weeks after enrollment, dermatology life quality index (DLQI) and urticaria activity score (UAS) were used to assess the quality of life impairment and disease activity. The internal consistency reliability of the questionnaire was estimated using Cronbach′s α coefficient. By comparing with DLQI and UAS28 scores, the Chinese version of UCT was tested for convergent validity, known-group validity, sensitivity and screening accuracy.Results:The Chinese version of UCT contained 4 items, and could be used to retrospectively evaluate clinical symptoms and signs of the disease, impact on quality of life, treatment effects and overall disease control in the past 4 weeks. The Cronbach′s α coefficient of each item in the UCT scale was 0.886 - 0.945 in the CSU group, and 0.834 - 0.958 in the CIndU group. At the time of enrollment, the UCT score was significantly negatively correlated with the DLQI score in both the CSU group and CIndU group ( rs = -0.672, -0.578, respectively, both P < 0.01) . At 4 and 8 weeks, the UCT score was significantly negatively correlated with UAS28 and DLQI scores in the CSU group (4 weeks: rs = -0.654, -0.829, respectively, both P < 0.01; 8 weeks: rs = -0.717, -0.765, respectively,both P < 0.01) , and it was also significantly negatively correlated with the DLQI score in the CIndU group ( rs = -0.834, -0.778, respectively, both P < 0.01) . In the CSU group, the change in the UCT score between weeks 4 and 8 was significantly negatively correlated with the change in UAS score ( rs = -0.569, P < 0.01) ; compared with the baseline, the change in the UCT scores was also significantly negatively correlated with the change in the DLQI scores at weeks 4 and 8 ( rs = -0.693, -0.447, respectively, both P < 0.01) . In the CIndU group, compared with the baseline, the change in the UCT scores at weeks 4 and 8 also showed a significant correlation with the change in DLQI scores ( rs = -0.615, -0.408, respectively, both P < 0.01) . The UCT score significantly differed among different UAS and DLQI score groups (all P < 0.05) . Conclusions:The Chinese version of the UCT is a valid and reliable tool for the clinical management of patients with CSU/CIndU. It can be used to evaluate disease control, and reflect disease activity and disease-related quality of life to a certain extent.

Objective:To evaluate the reliability, validity and sensitivity of the Chinese version of pruritus-specific quality of life instrument (ItchyQoL) .Methods:Based on the English version of ItchyQoL, items of the Chinese version of ItchyQoL were determined after forward-backward translation and cultural adaption. Totally, 218 patients with pruritus caused by skin diseases were enrolled from Department of Dermatology, Peking University First Hospital from January to December 2019, and a questionnaire survey was conducted. At the time of enrollment and 2 weeks after enrollment, the Chinese version of ItchyQoL, dermatology life quality index (DLQI) and numerical rating scale (NRS) were used to evaluate the effect of pruritus on the quality of life of patients. Confirmatory factor was used to assess the structural validity of the Chinese version of ItchyQoL, and Cronbach′s α coefficient was used to estimate its internal consistency reliability. Spearman correlation coefficient was used to analyze correlations (convergent validity) of the Chinese version of ItchyQoL score with DLQI and NRS scores, and correlations (sensitivity) of changes in the Chinese version of ItchyQoL score with changes in DLQI and NRS scores.Results:The Chinese version of ItchyQoL contained a total of 22 items, including 3 dimensions, i.e., "symptoms", "functions" and "emotions", with the Cronbach′s α coefficients being 0.946, 0.883 and 0.953 respectively, suggesting excellent internal consistency. At 2 weeks after enrollment, the NRS score was strongly correlated with the total ItchyQoL score ( rs = 0.700, P < 0.01) , and moderately correlated with the subscores of "emotions", "functions" and "symptoms" ( rs = 0.452, 0.673, 0.692 respectively, all P < 0.01) ; the DLQI score was also strongly correlated with the total ItchyQoL score ( rs = 0.887, P < 0.01) and the subscores of "functions" and "symptoms" ( rs = 0.886, 0.750 respectively, both P < 0.01) , and moderately correlated with the "emotions" subscore ( rs = 0.674, P < 0.01) . Compared with the scores at the time of enrollment, the change in the total ItchyQoL score after 2 weeks was moderately correlated with the change in the NRS score ( rs = 0.642, P < 0.01) , and strongly correlated with the change in the DLQI score ( rs = 0.757, P < 0.01) ; the changes in "symptoms" and "functions" subscores were moderately correlated with the change in the NRS score ( rs = 0.648, 0.549 respectively, both P < 0.01) , while there was a weak correlation between the changes in "emotions" subscore and NRS score ( rs = 0.225, P < 0.01) ; the changes in "symptoms" and "functions" subscores were strongly correlated with the change in the DLQI score ( rs = 0.755, 0.703 respectively, both P < 0.01) , while the change in "emotions" subscore was moderately correlated with the change in the DLQI score ( rs = 0.401, P < 0.01) . Moreover, the total score of the Chinese version of ItchyQoL and subscores of "symptoms", "functions" and "emotions" all significantly differed among different NRS and DLQI score groups at 2 weeks after enrollment (all P < 0.05) . Conclusion:The Chinese version of ItchyQoL has good reliability and validity, and can be used to evaluate the quality of life of patients with pruritus caused by skin diseases in China.

Objective:To assess the reliability and validity of the Chinese version of chronic urticaria quality of life questionnaire (CU-Q2oL) .Methods:The original English version of CU-Q2oL was translated into Chinese after forward-backward translation and cultural adaption, and items of the Chinese version of CU-Q2oL were determined. From January to December 2019, 195 chronic spontaneous urticaria patients with or without chronic inducible urticaria were enrolled from Department of Dermatology and Venereology, Peking University First Hospital, and followed up every 2 weeks. A total of 2 follow-ups were carried out, and a questionnaire survey was conducted by using the Chinese version of CU-Q2oL, dermatology life quality index (DLQI) and urticaria activity score over 7 days (UAS7) during each follow-up. After each follow-up, the treatment protocol for each patient was adjusted by clinicians based on the patient′s condition. The number of questionnaire factors was extracted by exploratory factor analysis, convergent validity was estimated by analyzing correlations of CU-Q2oL with DLQI and UAS, and the internal consistency reliability of CU-Q2oL was evaluated by calculating Cronbach′s α coefficient; the sensitivity of CU-Q2oL was assessed by analyzing correlations of changes in UAS7 scores with changes in CU-Q2oL scores.Results:Four factors were extracted from the Chinese version of CU-Q2oL, namely "symptoms", "daily functional activities", "sleep problems" and "restrictions" factors. There were 23 items in total, and the cumulative variance contribution rate was 74.011%. The Cronbach′s α coefficient of all items in CU-Q2oL was 0.961, and the Cronbach′s α coefficient of the 4 factors ranged from 0.804 to 0.933, suggesting excellent internal consistency. The total score of CU-Q2oL was moderately correlated with DLQI and UAS7 scores, with correlation coefficients of 0.437 and 0.560, respectively (both P < 0.01) . A total of 71 patients completed the second follow-up. The change in the total score of CU-Q2oL was moderately correlated with that in the UAS7 score, with a correlation coefficient of 0.392 ( P < 0.01) . Conclusion:The Chinese version of CU-Q2oL has excellent internal consistency, good reliability and validity, and can be used to evaluate the quality of life of patients with chronic spontaneous urticaria in China.

Objective To observe on the clinical effect and the influence of the level of plasma vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) and basic fibroblast growth factor (bFGF) in acute leukemia before and after treatment by thalidomide combined with chemotherapy. Methods Thirty-six cases of acute leukemia patients were randomly divided into experimental group and control group by 18 cases each. Each group was treated with conventional chemotherapy in the standard-dose, meanwhile in the experimental group additional thalidomide 100 mg/day were taken orally. Before treatment and 8 weeks after treatment, plasma were collected for the detection of VEGF, VEGFR and bFGF content by double antibody sandwich enzyme-linked immunosorbent assay (ELISA).Results The ratio of experimental group and control group, were 88.9 % (16/18), 77.8 % (14/18)respectively and the difference was statistically significant (x2 =4.103, P ＜0.05). The level of plasma VEGF (389.78+249.94 pg/ml, 318.54±125.78 pg/ml) of experimental group and control group before treatment was statistically significant (t = 3.141, t =3.024, P ＜0.01) compared with healthy group [(132.91±26.66) pg/ml] respectively. The level of plasma VEGF of those groups after treatment [(211.74+36.72) pg/ml, (288.02±31.77) pg/ml] was statistically significant (t =2.413, t =2.324, P ＜0.05) compared with healthy group respectively. The difference of the level of plasma VEGF of experimental group and control group before treatment was not statistically significant (t =1.384, P ＞0.05). The difference of the level of plasma VEGF of experimental group and control group after treatment was statistically significant(t =2.793,P ＜0.05). The level of plasma VEGFR [(2490.75+1695.9) pg/ml, (2322.78+1105.87) pg/ml] of experimental group and control group before treatment was statistically significant (t =2.914, t =2.783, P ＜0.01) compared with healthy group [(1134.98+378.45) pg/ml] respectively. The level of plasma VEGFR of those groups after treatment [(1359.71± 390.24) pg/ml, (1753.89±337.04) pg/ml] was statistically significant(t =2.572, t =2.447, P ＜0.05) compared with healthy group respectively. The difference of the level of plasma VEGFR of experimental group and control group before treatment was not statistically significant (t =1.276, P ＞0.05). The difference of the level of plasma VEGFR of experimental group and control group after treatment was statistically significant (t = 2.486, P ＜0.05). The level of plasma bFGF [(2.43±0.27) ng/ml, (2.41±0.33) ng/ml] of experimental group and control group before treatment was statistically significant(t =4.982, t =4.171, P ＜0.05) compared with healthy group (1.83±0.44) ng/ml respectively; the level of plasma bFGF of those groups after treatment [(2.09±0.17) ng/ml,(2.11±0.31) ng/ml] was statistically significant (t =3.011, t =2.773, P ＜0.05) compared with healthy group respectively. The difference of the level of plasma bFGF of experimental group and control group before treatment was not statistically significant (t =0.953, P ＞0.05). The difference of the level of plasma bFGF of experimental group and control group after treatment was not statistically significant (t =1.282, P ＞0.05).Conclusion The remission rate could be improved by thalidomide combined with chemotherapy in acute leukemia, which could be an effective treatment by anti-angiogenesis and inhibiting the growth and infiltration of acute leukemia cells.

Objective To evaluate the effect of hydrogen sulfide combined with mild hypothermia on cerebral ischemia-reperfusion (I/R) injury in rats. Methods Eighty male SD rats, aged 3 months, weighing 250-300 g, were randomly divided into 5 groups ( n = 16 each): sham operation group (group S), cerebral I/R group,mild hypothermia group (group M), sodium hydrosulfide group (group NaHS) and NaHS + mild hypothermia group (group NM). In group I/R, M, NaHS and NM, cerebral I/R was induced by occlusion of 4 vessels (cauterization of bilateral vertebral arteries and 15 min occlusion of bilateral common carotid arteries) followed by reperfusion. In group NaHS and NM, intraperitoneal NaHS 14 μmol/kg was injected immediately after reperfusion, while the equal volume of normal saline was injected in the other three groups. At the same time, the rectal temperature was reduced to 32-33 ℃ within 15 min, lasting for 6 h, in group M and NM, while it was maintained at 36-37 ℃by physical method in other groups. Twelve rats of each group were sacrificed after 6 h of reperfusion, and then the hippocampus was removed for determination of the content of H2 S by using spectrophotometer and the expression of p-CREB and BDNF mRNA by using Western blot and RT-PCR respectively. Four rats in each group were sacririced after 72 h of reperfusion and then the hippocampus was removed for microscopic examination. Results The cerebral I/R injury was attenuated in group M, NaHS and NM compared with group I/R, with the slightest injury in group NM. The H2S content was significantly higher in group I/R, M, NaHS and NM than in group S, and in group NaHS and NM than in group I/R and M. The expression of p-CREB and BNDF mRNA was significantly higher in group I/R, M, NaHS and NM than in group S, and in group M, NaHS and NM than in group I/R. The BDNF mRNA expression was significantly higher in group NM than in group M and NaHS. There was no significant difference in the H2S content and the expression of p-CREB and BNDF mRNA between group NaHS and M.Conclusion Hydrogen sulfide combined with mild hypothermia can attenuate cerebral I/R injury by up-regulating the expression of p-CREB and BDNF mRNA in hippocampus in rats.