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 analyze the efficacy of arsenic-containing TCM compounds in treating high-risk myelodysplastic syndromes(HR-MDS)with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome;To provide references for the clinical treatment of HR-MDS.Methods The medical records of HR-MDS with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome treated with arsenic-containing TCM compounds in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to September 2022 were retrospectively analyzed.The patients were divided into arsenic-containing TCM compounds combined with demethylation drugs(HMAs)treatment group and arsenic-containing TCM compounds combined with androgen treatment group.The clinical efficacy of both groups were evaluated,including overall response rate(ORR),median overall survival(OS),1-,2-and 3-year survial rates,median progression free survival(PFS),and 1-,2-and 3-year PFS rates.Results Among 200 cases of HR-MDS,68 cases were treated with arsenic-containing TCM compounds combined with HMAs,and 132 cases were treated with arsenic-containing TCM compounds combined with androgen.The ORR was 30%,and the OS of HR-MDS after treatment was 42 months.The 1-,2-and 3-year survival rates were 78.6%,60.4%and 50.2%respectively.The median PFS was 15 months,and the 1-year,2-year and 3-year PFS rates were 57.8%,28.8%and 18.2%respectively.The ORR of 68 cases HR-MDS treated with arsenic-containing TCM compounds combined with HMAs was 44.1%.After treatment,the median OS of HR-MDS was 42 months,and the survival rates of 1-,2-and 3-years were 84%,75.6%and 61.9%respectively,and the median PFS was 24 months,and the PFS rates of 1-,2-and 3-years were 74.3%,48.5%and 35.2%,respectively.The ORR of 132 cases of HR-MDS treatmented with arsenic-containing TCM compounds combined with androgen was 26.5%,including 33.3%in the high-risk group of HR-MDS and 13.3%in the extremely high-risk group of HR-MDS.There was statistical significance between the two groups(P=0.014).After treatment,the median OS of HR-MDS was 29 months,and the survival rates of 1-,2-and 3 years were 78.6%,54.1%and 45.1%respectively.The median PFS was 13 months,and the PFS rates of 1-,2-and 3 years were 54.1%,28.2%and 12.9%respectively.Conclusion The arsenic-containing TCM compounds combined with HMAs can significantly prolong survival and delay disease progression in HR-MDS.Although the arsenic-based TCM compounds combined with androgen therapy demonstrate inferior efficacy compared to HMAs-based regimens,it has achieved significantly higher OS and PFS than historical controls,serving as an effective alternative for patients intolerant to HMAs.

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.

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.

Objective To analyze the efficacy of arsenic-containing TCM compounds in treating high-risk myelodysplastic syndromes(HR-MDS)with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome;To provide references for the clinical treatment of HR-MDS.Methods The medical records of HR-MDS with spleen-kidney deficiency and toxic stagnation and blood stasis syndrome treated with arsenic-containing TCM compounds in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to September 2022 were retrospectively analyzed.The patients were divided into arsenic-containing TCM compounds combined with demethylation drugs(HMAs)treatment group and arsenic-containing TCM compounds combined with androgen treatment group.The clinical efficacy of both groups were evaluated,including overall response rate(ORR),median overall survival(OS),1-,2-and 3-year survial rates,median progression free survival(PFS),and 1-,2-and 3-year PFS rates.Results Among 200 cases of HR-MDS,68 cases were treated with arsenic-containing TCM compounds combined with HMAs,and 132 cases were treated with arsenic-containing TCM compounds combined with androgen.The ORR was 30%,and the OS of HR-MDS after treatment was 42 months.The 1-,2-and 3-year survival rates were 78.6%,60.4%and 50.2%respectively.The median PFS was 15 months,and the 1-year,2-year and 3-year PFS rates were 57.8%,28.8%and 18.2%respectively.The ORR of 68 cases HR-MDS treated with arsenic-containing TCM compounds combined with HMAs was 44.1%.After treatment,the median OS of HR-MDS was 42 months,and the survival rates of 1-,2-and 3-years were 84%,75.6%and 61.9%respectively,and the median PFS was 24 months,and the PFS rates of 1-,2-and 3-years were 74.3%,48.5%and 35.2%,respectively.The ORR of 132 cases of HR-MDS treatmented with arsenic-containing TCM compounds combined with androgen was 26.5%,including 33.3%in the high-risk group of HR-MDS and 13.3%in the extremely high-risk group of HR-MDS.There was statistical significance between the two groups(P=0.014).After treatment,the median OS of HR-MDS was 29 months,and the survival rates of 1-,2-and 3 years were 78.6%,54.1%and 45.1%respectively.The median PFS was 13 months,and the PFS rates of 1-,2-and 3 years were 54.1%,28.2%and 12.9%respectively.Conclusion The arsenic-containing TCM compounds combined with HMAs can significantly prolong survival and delay disease progression in HR-MDS.Although the arsenic-based TCM compounds combined with androgen therapy demonstrate inferior efficacy compared to HMAs-based regimens,it has achieved significantly higher OS and PFS than historical controls,serving as an effective alternative for patients intolerant to HMAs.

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.

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 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 analyze the cases referred to a higher-level hospital from the Department of Neonatology in a primary hospital, and evaluate the efficiency of clinical works related to the referrals.Methods:Data of neonates admitted to the Department of Neonatology at Maternal and Child Health Hospital of Dabu County from January 2018 to December 2020 and referred to the superior hospital were retrospectively analyzed.Results:A total of 1 670 neonates were included and 128 neonates were referred.The median age of the neonates referred was 0.5 hours(0 hours, 25 days), the median gestational age was 38 + 3(29 + 1, 42 + 4) weeks, the median weight was 3 000(1 250, 4 800) g, and the transport distance was 78 km.Twenty-four cases were assessed as critical cases before the referral, 125 cases were improved and discharged after treatment in the superior hospital, and three cases died.The referral rate in 2018, 2019 and 2020 showed a downward trend year by year (10.3%, 7.6% and 4.0%, respectively), and the difference was statistically significant( χ2=14.362, P=0.001). The proportion of critical cases in referral cases increased year by year (9.4%, 23.9% and 38.9%, respectively), and the difference was statistically significant( χ2=9.289, P=0.010). The incidence of critical case was higher in those whose mothers didn′t have regular prenatal examination during pregnancy( χ2=5.129, P=0.032). Conclusion:The ability of neonatal treatment in primary hospitals has been improved.The neonates need to be referred and critical cases are not rare in primary hospitals.More attention should be paid to the safety and effectiveness of the regional transport network.Also, enhancing the health awareness of residents and improving the primary medical technics are important to maximize the life safety and optimal transition of newborns.