Objective To search for application ways for the safe and effective clinical methods of arsenic-containing Compound Qinghuang Powder (Compound QHP) for the treatment of myelodysplastic syndrome (MDS). Methods Totally 200 patients with MDS were included in the study and treated with Compound QHP. After one-month treatment, the 60 patients with the blood arsenic concentrations <20 μg/L were randomly divided into control group and treatment group, with 30 cases in each group. Control group was given stable treatment, while the treatment group was given increased dose of realgar; blood arsenic concentration was detected monthly; realgar 0.1 g was increased each time until blood arsenic concentrations ≥20 μg/L and realgar ≤0.3 g/d. The blood arsenic concentration, clinical efficacy and safety in the two groups were observed. Results Totally 24 cases in each group were included for evaluation finally. The average blood arsenic concentration of treatment group was significantly higher than those of control group (P<0.05). The rate of hematologic improvement was significantly higher in treatment group (54.2％, 13/24) than that in control group (29.2％, 7/24) , with significant difference (P<0.05). The Hb, ANC, and PLT significantly increased in treatment group after treatment (P<0.05). There was no significant difference of incidence rate of adverse reaction observed between treatment group and control group (P>0.05). Conclusion In application of Compound QHP, the blood arsenic concentration can be monitored to adjust the daily dose of realgar, thus to increase the effective blood arsenic concentration, and then improving efficacy without increasing the clinical toxicity.

The treatment of patients with myelodysplastic syndromes (MDS) has included primarily supportive care (blood transfusions, colony stimulating agents, iron chelation, etc.) and new drugs, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For those who are no longer benefiting from these agents, there is nearly nothing to do with effective therapies. When those drugs are ineffective, what the doctors could do is optimizing the delivery of hypomethylating agents (HMT) by dosing appropriately, sequencing appropriately, and using thoughtful combinations; as well as improving drug formulations (oral formulations and/or novel formulations) and working toward better selection of patients for best upfront mutation-directed therapy. Hopefully, the drug targeting and patient selection for optimal HMT treatment of MDS will be improved. Furthermore, ongoing research is focused on identifying unique agents to rescue MDS patients who have progressed despite HMT. Agents such as rigosertib are now focused on its application in specific MDS populations who might most likely benefit from this therapeutic approach [primary refractory and high-risk international prognostic scoring system (IPSS) patients]. Doctors eagerly await results of single-agent programmed death 1 (PD-1) and its inhibitors, or combination with HMT to the upfront and relapsed MDS setting. For the minority of patients who have specific targetable mutations, the selective agents (IDH1/2) are highly promising. Bone marrow transplantation remains the only offer for cure, but is depressingly unrealistic given the majority of the elderly and frail patients at the time of MDS progression.

Objective To analyze the clinical efficacy and safety of compound Qinghuang powder (compound QHP) for treatment of myelodysplastic syndromes (MDS) and its association with blood arsenic concentration (BAC). Methods 40 patients with MDS were treated with compound QHP, and the clinical efficacy, safety, and its association with BAC were evaluated after treatment for 6, 9 months, respectively. Results After treatment for 6 months, the rate of hematology improvement was 32.5 % (13/40), and the effective rate was 87.5%(35/40). 21 cases depended on the blood transfusion before treatment, after treatment 6 cases completely got rid of blood transfusion and the blood transfusion of another 6 cases was decreased by more than 50 %. The absolute neutrophil count was increased from (0.50±0.13)×109/L to (0.93±0.33)×109/L (t= 4.130, P= 0.0008). The hemoglobin content was increased from (71.06±14.82) g/L to (80.41±27.35) g/L (t= 2.233, P= 0.0321). After treatment for 9 months, 76.2 % (16/40) of the patients got rid of blood transfusion or blood transfusion reduction was more than 50%. The platelet count was increased from (45.04 ± 24.38)×109/L to (60.65±29.46)×109/L (t= 2.241, P= 0.0335). The incidence of abdominal pain and diarrhea after treatment for 1, 3 and 6 months were 12.5 % (5/40), 10.0 % (4/40) and 5.0 % (2/40), respectively, all belonging to mild level . Before treatment , there were 12 patients with abnormal liver function , including 6 cases back to normal after treatment, and 6 cases of significantly relieved, without new case with abnormal liver function. Before treatment, there were 10 cases with abnormal myocardial enzymes, including 1 cases back to normal after treatment and 9 cases significantly relieved, without new case with abnormal myocardial enzymes. No patient with abnormal renal function was observed before and after treatment. The BAC was (7.71±5.65) μg/L before treatment, which was significantly lower than that of 1, 3 and 6 months [(29.27±9.07)μg/L, (27.79 ±10.18) μg/L and (31.98 ±12.55) μg/L respectively, all P< 0.0001]. There was no significant change of BAC among the patients after treatment for 1, 3 and 6 months (P> 0.05). The BAC in efficacy group [(33.48 ±12.56) μg/L] was significantly higher than that in non-efficacy group [(21.46 ±6.00) μg/L] (t=2.089, P=0.035). 12.5% (5/40) of the patients had mild gastrointestinal side effects after treatment for 1 month, while the BAC of them [(16.93 ±1.80) μg/L] was significantly lower than that in patients without gastrointestinal side effects [(31.78±1.39 ) μg/L, P<0.0001]. The occurrence rate of abdominal pain and diarrhea was decreased after treatment for 3 and 6 months, while the BAC was increased gradually. Conclusions Compound QHP is effective in the treatment of MDS with mild adverse reactions. There is no damage to the heart, liver, and renal function. Besides, it shows that reducing the gastrointestinal adverse reactions and maintaining the effective concentration of BAC play a significant role in the effect of compound QHP in the treatment of MDS.

Myelodysplastic syndromes (MDS) is a clinical heterogeneous disease characterized by impaired hematopoietic function and morphologic abnormalities of the bone marrow. Genomic studies show that MDS is usually driven by a series of multistep somatic cell genetic processes that affect the core genome. By definition, reproducible MDS drives mutations leading to cloning advantage. In addition, exposure factors, such as cytotoxic chemotherapy or genetic propensity of the reproductive system, could affect the pathogenesis and clinical outcomes of the disease. Combined with the reports in the 59th American Society of Hematology (ASH) Annual Meeting, the article introduces the genetic characteristics of MDS, in order to improve the diagnosis of MDS and the understanding of the pathogenesis of treatment-related MDS as well as the genetic tendency of MDS in the reproductive system.

The support treatment of low-risk myelodysplastic syndromes (MDS) patients whose revised international prognostic score system (IPSS-R) is defined as 3.5 points remains the main treatment. The erythropoiesis stimulating agent (ESA) is the best choice for patients with del (5q) MDS as long as the endogenous erythropoietin (EPO) level is less than 500 U/L (preferably<200 U/L). The application of EPO for patients with treatment failure or relapsed after transfusion, chooses are immunosuppressant, transforming growth factor beta inhibitors and lenalidomide. Del (5q) syndrome could benefit from lenalidomide, and some patients after discontinuation of treatment still have been stable in peripheral blood. Thrombocytopenia caused serious hemorrhage rarely; thrombopoietin receptor analogs could reduce bleeding and improve the platelet count. These drugs can be used in patients with bone marrow blast counts of < 0.05. If treatment failed or advanced to high-risk MDS or transformed to acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation might be required. Combined with reports in the 59th American Society of Hematology (ASH) Annual Meeting, this article describes the treatment strategies for low-risk MDS.

Objective To analyze the blood arsenic concentration and the safety of compound Qinghuang powder(compound QHP)in patients with myelodysplastic syndrome(MDS).Methods A total of 45 MDS patients received treatment with compound QHP (the treatment group, n=45). The concentration of blood arsenic in different time was determined by atomic fluorescence spectrometry. The clinical safety of compound QHP was evaluated by analyzing the symptoms of adverse reaction and organ function. The comparison were MDS patients with Qinghuang powder (QHP group, n=47) and healthy people. Results There was no significant difference of the blood arsenic concentration between the treatment group and the healthy control group (P=0.450),while after the treatment for 1 month those concentrations significantly increased (P=0.000). There were no significant difference between the blood arsenic concentration after treatment for 1, 3, and 6 months (P=0.240). The incidence of adverse reaction in the treatment group was significantly lower than that in QHP group(χ2=4.720, P=0.030). The incidence of adverse reactions in the digestive tract was significantly lower in the treatment group than that in QHP group (χ2=4.650, P=0.034). The blood arsenic concentration of patients with abdominal pain diarrhea was significantly lower than those without abdominal pain diarrhea (P=0.020). Before treatment in the compound QHP group, there were 21 cases with increased myocardial enzymes, 10 cases with abnormal liver function and 4 cases with renal dysfunction, respectively. After treatment at 6th month, these indicators returned to normal with 7 cases of myocardial enzymes, 6 cases of liver function and 1 case of renal function, respectively. There was no new case with abnormal myocardial enzymes, liver function and renal dysfunction, respectively. Conclusions Arsenic could be absorbed in the digestive tract into blood in MDS patients after treatment with arsenic-containing compound QHP, and the blood arsenic concentration remained stable during the course of treatment. The adverse reactions were mainly mild gastrointestinal symptoms, but no heart, liver or renal function damage was observed. The incidence of abdominal pain diarrhea in patients treated with compound QHP was significantly lower than that with QHP.

Objective:To investigate the feasibility, safety and reasonable operation of nasointestinal canal indwelling guided by miniature system in severe neurosurgery patients, and compare its advantages and disadvantages with traditional blind insertion.Methods:A prospective randomized controlled trial design was used to select 128 critically ill patients in need of enteral nutrition support at the Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University from March 2022 to October 2023 by convenient sampling method. They were divided into blind insertion group and visualization group by random number table method, with 64 cases in each group. Nasointestinal canal indwelling was performed in the blind insertion group by traditional blind insertion method, and in the visualization group, nasointestinal canal indwelling was performed by indentations guided by the miniature visualization system. The success rate of initial catheterization, the time of catheterization, complications, changes of vital signs during catheterization and changes of nutritional indexes after catheterization were evaluated in 2 groups.Results:In the blind insertion group, there were 35 males and 29 females, aged (59.44 ± 13.84) years old. In the visualization group, there were 41 males and 23 females, aged (58.28 ± 12.08) years old. The success rate of the first catheter placement in the visual group was 96.8% (62/64), higher than that in the blind group 82.8% (53/64), and the difference was statistically significant ( χ2=6.94, P<0.05). The catheter placement time of the visualization group was (20.08 ± 2.69) min, which was shorter than that of the blind insertion group (38.19 ± 3.79) min, and the difference between the two groups was statistically significant ( t=29.99, P<0.05). There was no significant difference in the incidence of complications, changes of vital signs during catheterization and the changes of nutritional indexes after catheterization between two groups (all P>0.05). Conclusions:Compared with traditional blind nasointestinal canal indwelling, nasointestinal canal indwelling guided by the miniature visualization system can improve the success rate of the first catheterization and shorten the catheterization time. Although there is no difference in the complication rate, changes in vital signs during catheterization and changes in nutritional indexes after catheterization, it is believed that with the continuous development and upgrading of this technology, it will further reflect the advantages of this technology, which is worthy of further clinical trials and application.

ObjectiveTo explore the effects of Bushen Jianpi prescription on the autophagy and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the patients with aplastic anemia （AA）. MethodA total of 30 AA patients admitted to Xiyuan Hospital and 6 healthy donors who were prepared to undergo peripheral blood hematopoietic stem cell transplantation in 304 Hospital from September 2020 to August 2021 were enrolled and assigned into an AA group and a control group. The AA group was treated with Bushen Jianpi prescription combined with cyclosporin A （CsA） and androgen for 3 months. The mononuclear cells from bone marrow in the AA group before and after treatment and the peripheral blood of the control group were collected. Transmission electron microscopy was then employed to detect autophagosomes. Western blotting was employed to determine the protein levels of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， mTOR， phosphorylated （p）-mTOR， Akt， p-Akt， PI3K， and p-PI3K， and real-time polymerase chain reaction （PCR） to determine the mRNA levels of LC3， mTOR， Akt， and PI3K. ResultIn the AA group， the treatment was completed in 29 patients， and the total response rate was 51.72% （15/29）. ① The AA group showed lower levels of white blood cell （WBC）， hemoglobin （HGB）， platelet （PLT）， and absolute neutrophil count （ANC） in the peripheral blood （P<0.01） and lower number of intracellular autophagosomes than the control group before treatment. Moreover， the AA group showed lower mRNA level of LC3 （P<0.01） and protein levels of LC3Ⅰ and LC3Ⅱ （P<0.01） and higher mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and protein levels of Akt， p-Akt， PI3K， p-PI3K， mTOR， and p-mTOR （P<0.01） than the control group. ② In AA group， the levels of HGB and PLT elevated （P<0.05） and the number of intracellular autophagosomes increased after treatment compared with those before treatment. Moreover， the mRNA level of LC3 and the protein levels of LC3Ⅰ and LC3Ⅱ were up-regulated （P<0.01）， the mRNA levels of mTOR， Akt， and PI3Kα （P<0.01） and the protein levels of Akt， p-PI3K （P<0.01）， p-Akt， PI3K， mTOR， p-mTOR （P<0.05） were down-regulated after treatment. ConclusionAA patients show lower autophagy levels， while Bushen Jianpi prescription can effectively improve the autophagy level and down-regulated the expression of PI3K/Akt/mTOR signaling pathway in AA patients.

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.

ObjectiveTo explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia （AA） in non-elderly adults， so as to provide a reference for predicting the prognosis of this therapy. MethodA retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine. According to the efficacy evaluation results at the 6^th month of treatment， the patients were assigned into effective and ineffective groups. The two groups were compared in terms of the gender， age， disease classification ［non-severe aplastic anemia （NSAA）/severe aplastic anemia （SAA）］， course of disease， family history， complications， history of drug allergy， baseline blood routine examination ［hemoglobin （HGB）， white blood cell （WBC）， neutrophil （ANC）， platelet （PLT）， and reticulocyte （Ret）］， T lymphocyte subsets， degree of proliferation of nucleated cells in bone marrow， and expression of T-bet and GATA-3. ResultA total of 101 non-elderly adult AA patients were enrolled in this study， including 81 in the effective group and 20 in the ineffective group. The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group （P<0.05）. The body height， body weight， gender， age， disease classification， course of disease， family history， and complications showed no significant differences between two groups. The effective group had higher levels of ANC and PLT before treatment （P<0.05） and higher proportion of patients with ANC≥1.6×10⁹/L and PLT≥25×10⁹/L （P<0.05， P<0.01） than the ineffective group. The baseline levels of WBC， HGB， and Ret showed no significant statistical differences between two groups. The levels of CD3⁺HLA-DR⁺T cells in the effective group before treatment was higher than that in the ineffective group （P<0.05）. The levels of CD3⁺CD19^-T cells， CD4⁺T cells， CD8⁺T cells， Th1 cells， Th2 cells， and CD3⁺CD25⁺T cells showed no significant statistical differences between two groups before treatment. The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group, while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group （P<0.05）. The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy （P<0.05， P<0.01）， while other indicators were not influencing factors for efficacy. The receiver operating characteristic （ROC） curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 （P<0.05）， with the critical value of 1.595×10⁹/L， the sensitivity of 0.42， and the specificity of 0.95. ConclusionThe history of drug allergy， pre-treatment ANC， PLT， CD3⁺HLA-DR⁺ T cell levels， and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy， higher ANC and PLT levels before treatment， especially those with ANC≥1.6×10⁹/L， PLT≥25×10⁹/L， and higher CD3⁺ HLA-DR⁺T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.