Objective To compare the differences of baseline characteristics of patients with myelodysplastic syndrome(MDS)who achieved platelet(PLT)response after arsenic-containing TCM compounds combined with Western medicine treatment.Methods Totally 72 MDS patients were selected from 12 outpatient departments and wards,such as Xiyuan Hospital,China Academy of Chinese Medical Sciences,Dongfang Hospital,Beijing University of Chinese Medicine from October 2021 to October 2024.Among them,45 patients received arsenic-containing TCM compounds combined with Western medicine treatment,27 patients received Western medicine treatment.The blood routine[white blood cell(WBC)count,hemoglobin,PLT,neutrophil count],TCM syndrome scores,safety indicators,and adverse events were observed before and after three courses of treatment.The efficacy of all patients was evaluated,and the baseline characteristics of patients who achieved PLT response in the arsenic-containing TCM compounds group and the Western medicine treatment group were compared.Results Comparing the differences of baseline characteristics of the two groups,it was found that the patients who achieved PLT response in the arsenic-containing TCM compounds group were compared with those in the Western medicine treatment group:Age<60 years old(P=0.038),longer disease duration(P=0.012),lower WBC(P=0.017),lower reticulocyte percentage(P=0.037),lower blood urea nitrogen(P=0.046),lower high-density lipoprotein cholesterol(P=0.014),and lower N-terminal pro-B-type natriuretic peptide(P=0.034),abnormal electrocardiogram(P=0.013),high blasts(P=0.009),grade 0 reticular fiber staining(P<0.01),normal chromosome karyotype(P<0.01),gene mutation(P<0.01)and high TCM syndrome scores(P=0.013)were found.Conclusion Arsenic-containing TCM compounds consisting of Qinghuang Powder and Bushen Jianpi Decoction combined with Western medicine is used to treat MDS.Patients with age<60 years old,long disease duration,low WBC count,low reticulocyte percentage,low blood urea nitrogen,low high-density lipoprotein cholesterol,low N-terminal pro-B-type natriuretic peptide,abnormal electrocardiogram,high blasts,grade 0 reticular fiber staining,normal chromosome karyotype,gene mutation and high TCM syndrome score are more likely to obtain PLT response.

Objective To investigate the characteristics of peripheral blood in the treatment of aplastic anemia(AA)with Bushen Shengxue Method and Yiqi Yangxue Method combined with Western medicine.Methods Totally 492 AA patients who were treated in 19 centers including Xiyuan Hospital China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected,and were randomized into three groups:161 cases in the Bushen Shengxue group,164 cases in the Yiqi Yangxue group,and 167 cases in the control group.All three groups were orally administered cyclosporine and androgens.Bushen Shengxue group was given Bushen Shengxue Granules,Yiqi Yangxue group was given Yiqi Yangxue Granules,and the control group was given placebo(half dosage of Bushen Shengxue granules).The general data,overall efficacy,and peripheral blood at the 1st month,the 4th month,and 6th month after treatment were analyzed.Results The total effective rate of Bushen Shengxue group was 98.8％(159/161),which was significantly higher than that of Yiqi Yangxue group(79.9％)and the control group(61.7％),with statistical significance(P＜0.001);The total effective rate of Yiqi Yangxue group was significantly higher than that of the control group(P＜0.001).Compared with before treatment,the hemoglobin(HGB)levels of all three groups of patients significantly increased after treatment(P＜0.001,P＜0.01),and the platelet levels of Bushen Shengxue group and the control group significantly increased after treatment(P＜0.001);after treatment,the HGB levels in the three groups were ranked from high to low as the Bushen Shengxue group,Yiqi Yangxue group and the control group(P＜0.01).25％of patients had HGB levels exceeding 20％of baseline values,Bushen Shengxue group took 1 month,while Yiqi Yangxue group and control group took 4 months;25％of patients had an increase in HGB levels exceeding 50％of the baseline value,Bushen Shengxue group took 6 months,while Yiqi Yangxue group and control group took more than 6 months.At 6 months,the number of patients with HGB elevation exceeding 20％and 50％of baseline values in Bushen Shengxue group was higher than that in Yiqi Yangxue group and the control group(P＜0.05,P＜0.001).25％of patients had white blood cell elevation exceeding 50％of the baseline value,Bushen Shengxue group took 4 months,Yiqi Yangxue group took 6 months,and the control group took more than 6 months.25％of patients showed an increase in platelet levels exceeding 100％of the baseline value,Bushen Shengxue group took 4 months,while Yiqi Yangxue group and control group took 6 months;at 6 months,the number of patients in Bushen Shengxue group and Yiqi Yangxue group with platelet elevation exceeding 20％of the baseline value was significantly higher than that in the control group(P＜0.01,P＜0.05).Conclusion Bushen Shengxue method combined with Western medicine intreating AA is better than the method of Yiqi Yangxue method combined with Western medicine.In terms of improving HGB,it is reflected in shortening the recovery time and increasing the number of beneficiaries,and the dosage can affect the recovery time and the number of beneficiaries at the same time;in terms of improving white blood cell and platelet,it is reflected in shortening the recovery time,and the dosage can affect the recovery time.

Objective To investigate the characteristics of peripheral blood in the treatment of aplastic anemia(AA)with Bushen Shengxue Method and Yiqi Yangxue Method combined with Western medicine.Methods Totally 492 AA patients who were treated in 19 centers including Xiyuan Hospital China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected,and were randomized into three groups:161 cases in the Bushen Shengxue group,164 cases in the Yiqi Yangxue group,and 167 cases in the control group.All three groups were orally administered cyclosporine and androgens.Bushen Shengxue group was given Bushen Shengxue Granules,Yiqi Yangxue group was given Yiqi Yangxue Granules,and the control group was given placebo(half dosage of Bushen Shengxue granules).The general data,overall efficacy,and peripheral blood at the 1st month,the 4th month,and 6th month after treatment were analyzed.Results The total effective rate of Bushen Shengxue group was 98.8％(159/161),which was significantly higher than that of Yiqi Yangxue group(79.9％)and the control group(61.7％),with statistical significance(P＜0.001);The total effective rate of Yiqi Yangxue group was significantly higher than that of the control group(P＜0.001).Compared with before treatment,the hemoglobin(HGB)levels of all three groups of patients significantly increased after treatment(P＜0.001,P＜0.01),and the platelet levels of Bushen Shengxue group and the control group significantly increased after treatment(P＜0.001);after treatment,the HGB levels in the three groups were ranked from high to low as the Bushen Shengxue group,Yiqi Yangxue group and the control group(P＜0.01).25％of patients had HGB levels exceeding 20％of baseline values,Bushen Shengxue group took 1 month,while Yiqi Yangxue group and control group took 4 months;25％of patients had an increase in HGB levels exceeding 50％of the baseline value,Bushen Shengxue group took 6 months,while Yiqi Yangxue group and control group took more than 6 months.At 6 months,the number of patients with HGB elevation exceeding 20％and 50％of baseline values in Bushen Shengxue group was higher than that in Yiqi Yangxue group and the control group(P＜0.05,P＜0.001).25％of patients had white blood cell elevation exceeding 50％of the baseline value,Bushen Shengxue group took 4 months,Yiqi Yangxue group took 6 months,and the control group took more than 6 months.25％of patients showed an increase in platelet levels exceeding 100％of the baseline value,Bushen Shengxue group took 4 months,while Yiqi Yangxue group and control group took 6 months;at 6 months,the number of patients in Bushen Shengxue group and Yiqi Yangxue group with platelet elevation exceeding 20％of the baseline value was significantly higher than that in the control group(P＜0.01,P＜0.05).Conclusion Bushen Shengxue method combined with Western medicine intreating AA is better than the method of Yiqi Yangxue method combined with Western medicine.In terms of improving HGB,it is reflected in shortening the recovery time and increasing the number of beneficiaries,and the dosage can affect the recovery time and the number of beneficiaries at the same time;in terms of improving white blood cell and platelet,it is reflected in shortening the recovery time,and the dosage can affect the recovery time.

Objective To compare the differences of baseline characteristics of patients with myelodysplastic syndrome(MDS)who achieved platelet(PLT)response after arsenic-containing TCM compounds combined with Western medicine treatment.Methods Totally 72 MDS patients were selected from 12 outpatient departments and wards,such as Xiyuan Hospital,China Academy of Chinese Medical Sciences,Dongfang Hospital,Beijing University of Chinese Medicine from October 2021 to October 2024.Among them,45 patients received arsenic-containing TCM compounds combined with Western medicine treatment,27 patients received Western medicine treatment.The blood routine[white blood cell(WBC)count,hemoglobin,PLT,neutrophil count],TCM syndrome scores,safety indicators,and adverse events were observed before and after three courses of treatment.The efficacy of all patients was evaluated,and the baseline characteristics of patients who achieved PLT response in the arsenic-containing TCM compounds group and the Western medicine treatment group were compared.Results Comparing the differences of baseline characteristics of the two groups,it was found that the patients who achieved PLT response in the arsenic-containing TCM compounds group were compared with those in the Western medicine treatment group:Age<60 years old(P=0.038),longer disease duration(P=0.012),lower WBC(P=0.017),lower reticulocyte percentage(P=0.037),lower blood urea nitrogen(P=0.046),lower high-density lipoprotein cholesterol(P=0.014),and lower N-terminal pro-B-type natriuretic peptide(P=0.034),abnormal electrocardiogram(P=0.013),high blasts(P=0.009),grade 0 reticular fiber staining(P<0.01),normal chromosome karyotype(P<0.01),gene mutation(P<0.01)and high TCM syndrome scores(P=0.013)were found.Conclusion Arsenic-containing TCM compounds consisting of Qinghuang Powder and Bushen Jianpi Decoction combined with Western medicine is used to treat MDS.Patients with age<60 years old,long disease duration,low WBC count,low reticulocyte percentage,low blood urea nitrogen,low high-density lipoprotein cholesterol,low N-terminal pro-B-type natriuretic peptide,abnormal electrocardiogram,high blasts,grade 0 reticular fiber staining,normal chromosome karyotype,gene mutation and high TCM syndrome score are more likely to obtain PLT response.

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 investigate the immunological characteristics of the patients with aplastic anemia （AA） and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters， thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted， involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital， China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters ［including hemoglobin （HGB）， white blood cell count （WBC）， platelet （PLT）， and absolute neutrophil count （ANC）］ after 6 months of treatment. One group had the elevation <50%， and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%， the group with HGB elevation≥50% showed elevated level of CD3⁺ human leukocyte antigen-DR （HLA-DR）⁺ and increased proportion of patients with T-helper cell type 2 （Th2）<5%， CD8⁺≥50%， and CD3⁺HLA-DR⁺≥9% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD8⁺≥50% before treatment was the independent influencing factor for HGB elevation ≥50% ［odds ratio （OR）=12.000， 95% confidence interval （CI） 2.218， 64.928， P<0.01］. ② Compared with the group with WBC elevation<50%， the group with WBC elevation≥50% showed increased proportion of patients with CD3⁺HLA-DR⁺<6% and T-box transcription factor （T-bet）≥200% before treatment （P<0.05）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<6% （OR=2.998， 95%CI 1.036， 8.680， P<0.05） and T-bet≥200% （OR=3.634， 95%CI 1.076， 12.273， P<0.05） before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%， the group with PLT elevation≥50% presented lowered Th1 and CD3⁺HLA-DR⁺ levels and increased proportion of patients with Th1<12%， CD4⁺≥6%， and CD3⁺HLA-DR⁺<5% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<5% before treatment was the independent influencing factor for PLT elevation≥50% （OR=16.190， 95%CI of 3.430 to 76.434， P<0.01）. ④ Compared with the group with ANC elevation<50%， the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB， Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3⁺HLA-DR⁺≥9%， especially those with CD8⁺≥50%. As for the AA patients with rapid elevation in WBC， the therapy was particularly effective in the patients with CD3⁺HLA-DR⁺<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT， the therapy was particularly effective in the patients with Th1<12% and CD4⁺≥6%， especially those with CD3⁺HLA-DR⁺<5%.

ObjectiveTo investigate the predictive indicators of early efficacy of Bushen Shengxue prescription combined with western medicine in the treatment of aplastic anemia， and provide prognosis indicators for the treatment of aplastic anemia （AA） with kidney-tonifying therapy in traditional Chinese medicine （TCM） combined with western medicine. MethodA total of 126 patients treated by Bushen Shengxue prescription combined with western medicine in 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 were selected for a retrospective study. The therapy was proven to be effective after six months of treatment. According to the efficacy after 4 months of treatment， the patients were assigned into a 4-month effective group and a 4-month ineffective group. The age， sex， disease severity （including severe aplastic anemia and non-severe aplastic anemia）， course of disease， degree of bone marrow nucleated cell proliferation， baseline hemogram levels ［including white blood cell count （WBC）， absolute neutrophil count （ANC）， hemoglobin （HGB）， platelets （PLT）， and reticulocytes （RET）］， T lymphocytes subsets， and the expression levels of T-box transcription factor （T-bet） and GATA-binding protein-3 （GATA-3） were compared between the two groups before treatment. ResultThe proportions of patients within the age ranges of ［20， 40） and ［60， 80） were higher in the 4-month effective group （P<0.05）. The sex， disease severity， course of disease， and comorbidities had no significant differences between the two groups. The 4-month effective group had higher baseline levels of HGB， WBC， ANC， and PLT than the 4-month ineffective group （P<0.05）， and there was no significant difference in the RET level between the two groups before treatment. Binary Logistic regression analysis showed that the PLT level before treatment was an independent factor affecting the onset time， while other indicators did not affect the onset time. The receiver operating characteristic （ROC） curve was established to analyze the value of PLT level before treatment for predicting the onset time， and the area under the curve was 0.691. With the critical value of 40.5×10⁹/L， the sensitivity and specificity of the prediction that the therapy will take effect within 4 months were 0.569 and 0.893， respectively. The two groups of patients were graded according to age ｛（14， 20）， ［20， 40）， ［40， 60）， and ［60， 80）｝ and PLT level before treatment （PLT<40×10⁹/L， PLT≥40×10⁹/L）. The proportion of the patients with PLT≥40×10⁹/L before treatment in the 4-month effective group was significantly higher than that in the 4-month ineffective group （P<0.05）. The degree of bone marrow nucleated cell proliferation before treatment had no significant difference between the two groups. The level of total T lymphocytes in the 4-month effective patients was lower than that in the 4-month ineffective patients before treatment （P<0.05）. The levels of Th1 cells， Th2 cells， CD4⁺ T cells， and CD8⁺ T cells showed no significant differences between the two groups before treatment. The T-bet expression level in the 4-month effective group was higher than that in the 4-month ineffective group before treatment （P<0.05）， while the expression level of GATA-3 showed no significant difference between the two groups before treatment. ConclusionBushen Shengxue prescription combined with western medicine will achieve faster effect for the patients within the age ranges of ［20， 40） or ［40， 60）， with higher levels of HGB， WBC， ANC， and PLT （especially those with PLT≥40×10⁹/L）， lower level of total T lymphocytes， or higher T-bet expression level before treatment.

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.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.