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.

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.

Objective To investigate the clinical characteristics of survival in patients with high-risk myelodysplastic syndromes(HR-MDS)and provide a reference for the clinical prognosis of patients with HR-MDS.Methods General data,blood routine test,bone marrow smear with histopathology,cytogenetics,and other clinical data of 200 patients diagnosed with HR-MDS at Xiyuan Hospital of China Academy of Chinese Medical Sciences,during the period of January 2016-September 2022,were retrospectively analyzed.The included patients were categorized into the arsenic-containing herbal combination combined with demethylating agents(HMAs)treatment group and the arsenic-containing Chinese medicine compound combined with androgen treatment group.The influence of clinical indices on the survival characteristics of each group was analyzed.Results Comparison of the impact of clinical indicators on survival in 200 patients with HR-MDS who were treated with arsenic-containing herbal compounds in combination with HMAs or androgens showed that high-risk vs.very high-risk(P=0.018),hemoglobin(Hb)<80 g/L vs.Hb≥80 g/L(P=0.035),platelet(PLT)counts<50×109 L-1 vs.PLT counts≥50×109 L-1(P<0.001),and the difference in median progression-free survival(PFS)time between myelodysplastic syndromes converted to leukemia(MDS-AML)and non-MDS-AML(P=0.003)were statistically significant.Comparison of survival effects of clinical indicators in 68 patients with HR-MDS who were treated with arsenic-containing Chinese medicine compound combined with HMAs showed that the difference in median PFS between PLT count<50×109 L-1 and PLT count≥50×109 L-1(P<0.001)and the difference in median PFS between<5 and≥5 courses of chemotherapy(P=0.018)were statistically significant.Comparison of survival effects of clinical indicators in 132 patients with HR-MDS who were treated with arsenic-containing Chinese medicine compound combined with androgens showed that Hb<80 g/L and Hg≥80 g/L(P=0.028),PLT count<50×109 L-1 and PLT count≥50×109 L-1(P=0.002),and the mean differences in PFS between MDS-AML and non-MDS-AML(P=0.024)were statistically significant.Conclusion The clinical characteristics of long-surviving patients treated with arsenic-containing herbal combination in combination with HMAs included PLT counts≥50×109 L-1 and≥5 courses of chemotherapy.The clinical characteristics of long-surviving patients treated with arsenic-containing herbal combination in combination with androgens included Hg≥80 g/L,PLT count≥50×109 L-1,and non-MDS-AML.

Objective:To analyze the etiology of chronic pancreatitis(CP) and evaluate the impact of different intervention methods on the prognosis.Methods:This is a retrospective analysis conducted on clinical data of pediatric patients with CP admitted to Beijing Children's Hospital between January 2010 and December 2023,including etiology,clinical manifestations,imaging data and treatments.Follow-up assessments included height,weight,complications occurrence,and long-term nutritional status evaluated by using Z scores.Results:A total of 98 patients with CP were included in the study,containing 51 males and 47 females,with an age range of 1.95 to 15.96 years (median 8.49 years).The etiological contained the gene mutation (39.8%,39/98) (involving PRSS1, SPINK1, CFTR),the anatomical abnormality (26/98,26.5%),idiopathic pancreatitis (33.7%,33/98).Predominant clinical manifestations included abdominal pain (79/98,79.6%),nausea/vomit(48/98,49.0%),chest tightness/chest pain (10/98,10.2%),with malnutrition (44/98,44.9%) and the serum amylase increased in some patients.Imaging findings revealed heterogeneous pancreatic echoes,dilated pancreatic ducts and pancreatic stones via abdominal ultrasound,and a full or atrophic pancreas with irregular margins,tortuous or dilated pancreatic ducts through abdominal magnetic resonance imaging.Compared with CP caused by other reasons,hereditdry CP had a higher rate of pancreatic morphological changes(100.0% vs.88.1%, P<0.05).By March 2024,follow-up showed all 98 patients underwent initial medical treatment,followed by surgical intervention in 13 cases,endoscopic retrograde cholangiopancreatography intervention in 51 cases,and no surgical or endoscopic intervention in 34 cases.Six children developed diabetes,six had reduced fecal pancreatic elastase-1 but without fat diarrhea.Long-term follow-up indicated improved nutritional status among children who underwent endoscopic retrograde cholangiopancreatography intervention(Z score,-1.22 vs.0.74, P<0.001). Conclusion:Gene mutations and anatomical abnormalities is the main etiological factors in pediatric patients with CP.Early endoscopic intervention can significantly improve the long-term prognosis of the children.

Objective To explore the performance of routine blood test parameters,bone marrow parameters and the risk factors of leukemia conversion in higher-risk patients with myelodysplastic syndrome(MDS)treated with Bushen Jiedu Huayu Method in the real world.Methods The clinical data of 162 patients with higher-risk MDS who were admitted to the Department of Hematology,Xiyuan Hospital,China Academy of Chinese Medical Sciences from September 2017 to September 2022 were collected,and their clinical data,blood routine parameters,and bone marrow parameters were analyzed.Results A total of 162 higher-risk MDS patients were included,and the overall effective rate of the combination of traditional Chinese and Western medicine treatment,mainly using Bushen Jiedu Huayu Method being 48.8%.Patients with higher-risk MDS who were younger than 70 years old were more likely to obtain curative effect when treated with Bushen Jiedu Huayu Method combined with chemotherapy(P<0.05).After treatment with Bushen Jiedu Huayu Method,PLT levels in higher-risk MDS patients were significantly higher than those before treatment(P<0.05),and PLT levels in the ineffective group increased more significantly(P<0.05).After treatment,the HGB level in the effective group significantly increased(P<0.05).After treatment,the proportion of bone marrow granulocytes,megakaryocytes and lymphocytes in higher-risk MDS patients were significantly higher than those before treatment(P<0.05).Conclusion Bushen Jiedu Huayu Method,mainly using arsenic containing TCM compound,can treat higher-risk MDS.It can increase the HGB content and PLT level of patients,increase the proportion of bone marrow granulocytes,megakaryocytes and lymphocytes,and also play a certain role in reducing the proportion of bone marrow primitive cells,namely demethylation.

Objective:To investigate the correlation between adverse events and antiplatelet drug resistance after neurovascular intervention for cerebrovascular stenosis.Methods:A total of 148 patients with cerebrovascular stenosis who underwent neurovascular intervention at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2020 to December 2020 were included in this study. The platelet function of patients before and 24 hours after antiplatelet drug treatment was recorded. Platelet drug resistance was analyzed. At 3, 6 months, and 1 year after neurovascular intervention, adverse events were recorded through follow-up. The patients were divided into the occurrence group and the non-occurrence group according to whether adverse events occurred or not using the case-control study method. The Spearman correlation coefficient was used to analyze the correlation between adverse events and antiplatelet drug resistance after neurovascular intervention for cerebrovascular stenosis.Results:After 1 year of follow-up, among the 148 patients, 29 patients lost their follow-up, and 119 were included in the final analysis. Of the 119 patients, 41 patients had adverse events and 78 patients had no adverse events. In the occurrence group, the expression levels of platelet membrane glycoprotein P-selectin and platelet activating complex were (20.22 ± 6.33)% and (68.80 ± 11.52)%, respectively, before drug treatment, and they were (15.77 ± 4.12)% and (43.19 ± 5.90%)%, respectively, after drug treatment, all of which were significantly higher than those in the non-occurrence group [before drug treatment: (16.85 ± 3.24)%, (62.34 ± 10.77)%, after drug treatment: (8.31 ± 2.97)%, (35.85 ± 5.14)%] (before drug treatment: t = 3.20, 2.97, both P < 0.05; after drug treatment: t = 10.28, 6.74, both P < 0.05). The incidences of aspirin resistance and clopidogrel resistance in the occurrence group were 51.2% (21/41) and 43.9% (20/41), respectively, which were significantly higher than 26.9% (8/78) and 19.2% (9/78) in the non-occurrence group ( χ2 = 24.47, 20.23, both P < 0.001). Spearman correlation analysis showed that both aspirin resistance and clopidogrel resistance were moderately positively correlated with adverse events after neurovascular intervention ( r = 0.45, 0.41, both P < 0.05). Conclusion:Adverse events after neurovascular intervention are moderately positively correlated with resistance to the antiplatelet drugs aspirin and clopidogrel.

Objective:To investigate the effects of perioperative intracranial pressure monitoring-guided treatment on cerebrospinal fluid brain-derived neurotrophic factor (BDNF) and S100B protein levels, and prognosis in patients with severe traumatic brain injury.Methods:A total of 84 patients with severe traumatic brain injury who received treatment at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from March 2015 to August 2020 were included in this case-control study. These patients were divided into a study group ( n = 48) and a control group ( n = 36) based on different treatment methods. The control group was treated with routine treatment, while the study group underwent perioperative intracranial pressure monitoring-guided treatment. Clinical efficacy, BDNF, S100B protein, and prognosis were compared between the two groups. Results:The total effective rate in the study group was 87.5% (42/48), which was significantly higher than 69.4% (25/36) in the control group ( χ2 = 4.15, P = 0.042). After treatment, the BDNF level [(0.181 ± 0.021) μg/L] in the study group was significantly higher, and S100B [(4.3 ± 1.8) μg/L] level in the study group was significantly lower, compared with the control group ( t = 3.09, -4.86, both P < 0.001). The poor prognosis rate in the study group was 47.9% (23/48), which was significantly lower than 69.4% (25/36) in the control group ( χ2 = 3.89, P = 0.048). According to patient prognosis, these patients were divided into a good prognosis group and a poor prognosis group. The intracranial pressure level of patients in the poor prognosis group was significantly higher than that in the good prognosis group ( t = 4.12, P < 0.001). The area under the curve of intracranial pressure level for evaluating prognosis in patients with severe traumatic brain injury was 0.880 (95% CI: 0.809-0.950, P < 0.001). Conclusion:Perioperative intracranial pressure monitoring-guided treatment can greatly improve the levels of cerebrospinal fluid BDNF and S100B in patients with severe traumatic brain injury and improve the prognosis.

Objective:To investigate the clinical features and risk factors of the extraintestinal manifestations(EIM)in children with ulcerative colitis(UC).Methods:A retrospective case-control study was conducted.The clinical data of 99 children with UC diagnosed in Department of Gastroenterology, Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2021 were analyzed.According to whether the patients had EIM or not, they were divided into EIM-positive group and EIM-negative group.Rank sum test, χ2test 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 EIM in children with UC. Results:A total of 99 children with UC were enrolled, including 57 males and 42 females; the age of onset was 10.3(6.4, 12.6)years, and the course of disease was 4.2(1.6, 10.1)months.The patients were mainly characterized by extensive disease(E3)and pancolitis(E4)(69/99, 69.7%), moderate to severe activity(63/99, 63.6%)and moderate to severe inflammation of colonic mucosa(89/99, 89.9%). There were 77 patients(77.8%)in the EIM-negative group and 22 patients(22.2%)in the EIM-positive group, of which 5 patients had two types of EIMs; the most common EIMs were oral ulcers(9 cases), joint lesions(7 cases), and skin lesions(6 cases). Compared with the EIM-negative group, those in the EIM-positive group, such as the E4 type(77.3% vs 44.2%, χ2=7.513, P=0.006), moderate to severe activity(81.8% vs 58.4%, χ2=4.041, P=0.044), pediatric ulcerative colitis activity index score[47.5(35.0, 57.5)score vs 35.0(25.0, 50.0)score, Z=-2.260, P=0.024], the proportion of C-reactive protein≥8mg/L at diagnosis(54.5% vs 19.5%, χ2=10.607, P=0.001), erythrocyte sedimentation rate[30.0(13.8, 47.8)mm/h vs 10.0(4.0, 19.5)mm/h, Z=-3.918, P<0.001], the proportion of glucocorticoid treatment within one year after diagnosis(77.3% vs 49.4%, χ2=5.403, P=0.020)and the proportion of biological agents treatment(45.5% vs 23.4%, χ2=4.112, P=0.043)were significantly higher; the E3 type were significantly lower than those in the EIM-negative group(0 vs 23.4%, χ2=4.813, P=0.028), and the differences were statistically significant.Multivariate Logistic regression analysis showed that erythrocyte sedimentation rate at diagnosis was an independent risk factor of EIM in children with UC( OR=1.063, 95% CI: 1.025~1.103, P=0.001). Conclusion:The UC patients with EIM had more extensive lesions, more severe disease activity, significantly increased inflammatory indicators, and more commom glucocorticoid and biologic therapy.Increased erythrocyte sedimentation rate was an high risk factor of EIM in children with UC.

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 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.