Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months， which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset，and rapid changes，which coincides with the characteristics of refractory angina which is complex and changeable，prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation， with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine （TCM） employs a holistic approach known as "activating blood circulation and removing toxins"， which is supplemented by various methods to tonify Qi and warm Yang， nourish the kidneys and invigorate the spleen， clear heat and transform phlegm. This approach applies anti-inflammatory measures， regulates lipid metabolism， inhibits oxidative stress and thrombus formation， protects endothelial function in blood vessels， as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore，based on the theory of "stasis and toxin"，combined with TCM theory and modern medical research，this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM，and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris，coronary microvascular dysfunction，coronary artery spasm and obstructive coronary artery disease，hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.

Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease that affects the intestines.Drug therapy includes 5-aminosalicylic acid (5-ASA) drugs, glucocorticoids, immunomodulators, and biological agents, which can effectively induce and maintain remission and prevent complications.5-ASA is the first-line drug for inducing and maintaining remission in children with mild to moderate UC.Glucocorticoids are the first-line therapy for moderate to severe UC and the second-line remission inducing therapy for patients with mild to moderate UC who do not respond to 5-ASA.Immunomodulators(purine preparations)are suitable for maintenance remission therapy after steroid dependence, 5-ASA intolerance, frequent recurrence, and acute severe UC response to hormone-induced therapy.Calcineurin inhibitors and the biological agent infliximab can be used as second-line treatment for patients with acute severe UC who do not respond to glucocorticoids therapy.Vedolizumab and ustekinumab can be used as second-line biotherapy after failure of anti-tumor necrosis factor-α, but data are lacking in studies of pediatric UC.The purpose of this article is to review the progress of drug therapy for children with UC, and provide reference for clinical practice.

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 Adalimumab(ADA) in the treatment of pediatric Crohn′s disease (CD).Methods:The clinical data of 20 CD patients treated with ADA at Beijing Children′s Hospital, Capital Medical University from September 2016 to September 2021 were retrospectively analyzed.The disease activity status and mucosal inflammation in CD patients were evaluated using the Pediatric Crohn′s Disease Activity Index (PCDAI) and Crohn′s Disease Endoscopic Severity Index(CDEIS). Data were compared between groups using the rank sum test or Fisher′ s exact test. Results:A total of 20 CD patients were recruited, including 12 males and 8 females.The mean age at diagnosis of CD was (9.5 ± 4.9) years old, ranging from 0.9-15.1 years old.The mean age of the first use of ADA was (10.4 ± 4.8) years old, ranging from 1.2-16.7 years old.The median duration of CD symptoms before ADA treatment was 0.9 (0.4, 1.7) years.The mean PCDAI score of 20 CD patients before ADA treatment was (28.5±19.8) points (range: 0-65.0 points). Of the 20 cases, 8 cases (40.0%) had severe disease activity, and 4 cases (20.0%) were in remission.A total of 15 CD patients underwent CDEIS assessment.The results showed that 9 patients had moderate to severe disease activity, and the symptoms were improved in 1 case under endoscopy.Ten patients (10/20 cases, 50.0%) received Infliximab (IFX) treatment preceding ADA treatment.IFX discontinuation was due to the loss of response(8/10 cases, 80.0%) and allergic reactions (2/10 patients, 20.0%). After 6 weeks of ADA treatment, the median PCDAI score of the 20 CD patients was 5.0 (0, 10.0) points, which was significantly lower than that before ADA treatment ( P<0.001). The clinical remission rate and clinical response rate of 16 patients with active CD treated with ADA for 6 weeks were 62.5% (10/16 cases) and 87.5% (14/16 cases), respectively.There were no significant differences in the clinical remission rate and clinical response rate between the patients who did not receive IFX and those who had previously received IFX(all P> 0.05). The median ADA treatment period was 5.5 (2.6, 17.8) months.During the follow-up period, 6 patients (6/20 cases, 30.0%) suffered from clinical recurrence of CD.At the end of the follow-up visit, seventeen patients(17/20 cases, 85.0%) maintained clinical remission, one had primary non-response and two experienced secondary non-response.Adverse events were reported in 7 patients, mainly including pneumonia (4 cases) or upper respiratory tract infection (2 cases). No tumor or other serious adverse events were recorded. Conclusions:ADA has good efficacy in inducing and maintaining clinical remission in pediatric CD patients, and does not cause serious adverse events.

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.