OBJECTIVE To discuss the impact of Wenyang lishui formula on ventricular remodeling in rats with pulmonary hypertension-induced right heart failure （RHF） based on the Hippo/Yes-associated protein （YAP） signaling pathway. METHODS Ten rats were randomly selected as the control group. The remaining 63 rats were given a single intraperitoneal injection of monocrotaline to establish the pulmonary hypertension-induced RHF model. The 50 rats that successfully underwent the model establishment were randomly divided into the RHF group， low-dose group of Wenyang lishui formula （4.25 g/kg）， high-dose group of the Wenyang lishui formula （17.00 g/kg）， furosemide group （20 mg/kg）， and high-dose group of Wenyang lishui formula+ Hippo/YAP signaling pathway activator group （17.00 g/kg of Δ Wenyang lishui formula+16 mg/kg of PY-60）， with 10 rats in each group. The rats in each group were given the corresponding drug solution or normal saline by gavage or/andtail vein injection， once a day， for 4 consecutive weeks. During the experiment， the general conditions of the rats in each group were observed； after the last administration， the right ventricular diameter， right atrial diameter， end-diastolic volume， pulmonary artery blood flow acceleration time （PAAT） and its ratio to ejection time （ET） （PAAT/ET）， pulmonary artery pressure and its ratio to pulmonary arterial flow velocity （pulmonary artery pressure/velocity） were measured. The plasma levels of brain natriuretic peptide and angiotensin Ⅱ （Ang Ⅱ） were detected. The pathological changes of the right ventricular tissue were observed， and the collagen volume fraction， the phosphorylation levels of the large tumor suppressor 1/2 （LATS1/2） and YAP， and the protein expression of the transcriptional coactivator of PDZ-binding motif （TAZ） were also detected. RESULTS Compared with the RHF group， the rats in Wenyang lishui formula low-dose and high-dose groups showed improved hair color， movement， diet， and mental state. The atrophy of right ventricular myocardial cells， the increase of inflammatory cells， collagen deposition， and hypertrophy of myocardial fibers were significantly alleviated. The right ventricular internal diameter， right atrial internal diameter， end-diastolic volume， pulmonary artery pressure， pulmonary artery pressure/velocity， the plasma levels of brain natriuretic peptide and AngⅡ ， collagen volume fraction， the phosphorylation level of YAP and protein expression of TAZ were significantly decreased， while the PAAT， PAAT/ET and the phosphorylation level of LATS1/2 were significantly increased （P＜0.05）. PY-60 could significantly reverse the improvement effects of high-dose Wenyang lishui formula on the above quantitative indicators （P＜ 0.05）. CONCLUSIONS Wenyang lishui formula can restore the right heart function of pulmonary hypertension-induced RHF rats， reduce their pulmonary artery pressure， alleviate the pathological changes in their cardiac tissues， and the above effects may be related to the activation of Hippo expression and the inhibition of YAP phosphorylation.

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVE: To summarize and analyze the characteristics of delayed hemolytic transfusion reaction in children, in order to provide a scientific basis for clinical prevention, and ensure the safety of children's blood transfusion. METHODS: The basic situation, clinical symptoms and signs, diagnosis time and disappearance time of alloantibody of delayed hemolytic transfusion reaction in children were retrospectively analyzed. The serological test, routine blood test, biochemical detection and urine analysis results were compared pre- and post-transfusion. RESULTS: Among 15 164 children with repeated blood transfusion, 23 cases occurred delayed hemolytic transfusion reactions, with an incidence rate of 0.15%, and mainly children with thalassemia and acute leukemia. 39.13% of delayed hemolytic reactions occurred in children with more than 20 times of blood transfusions. Anemia was the main clinical symptom in 86.96% of children. 4.35% of children had hypotension and dyspnea. Serological test results showed that the positive rate of direct antiglobulin test was 91.30%, and that of erythrocyte homologous antibody test was 100%. Erythrocyte alloantibodies were common in Rh and Kidd blood group systems, accounting for 73.91% and 13.04%, respectively. Laboratory test results showed that hemoglobin, reticulocyte, spherocyte, total bilirubin, indirect bilirubin, lactate dehydrogenase, serum ferritin and urine color were significantly different after transfusion compared with those before transfusion (all P <0.05). The average diagnosis time of delayed hemolytic transfusion reactions was 18.56 days, and the average disappearance time of erythrocyte alloantibodies was 118.43 days. CONCLUSION The incidence of delayed hemolytic transfusion reaction is high in children with repeated blood transfusion, and the disappearance time of erythrocyte homologous antibody is long. Blood matched ABO, Rh and Kidd blood group antigens should be transfused prophylactically. Once diagnosed, erythrocyte alloantibody corresponding to antigen-negative blood should be used throughout the whole process.
Humans ; Child ; Retrospective Studies ; Child, Preschool ; Transfusion Reaction ; Male ; Female ; Infant ; Adolescent ; Isoantibodies/blood* ; Blood Transfusion

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Objective:To compare the prognostic value of two predictive models based on C-reactive protein(CRP)and albumin(ALB),namely the CRP to ALB ratio(CAR)and the Glasgow prognostic score(GPS),in newly diagnosed patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed.A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical,laboratory data and follow-up information were included.The receiver operating characteristic(ROC)curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival.Furthermore,the association between CAR and baseline clinical,laboratory characteristics of patients was evaluated,and progression-free survival(PFS)and overall survival(OS)were compared between different CAR and GPS subgroups.Finally,the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes.Results:ROC curve showed that the area under the curve(AUC)of CAR predicting PFS and OS in DLBCL patients was 0.687(P=0.002)and 0.695(P=0.005),respectively,with the optimal cut-off value of 0.11 for both predicting PFS and OS.Compared with the lower CAR(＜0.11)group,the higher CAR(≥0.11)group had more clinical risk factors,including age＞60 years(P=0.025),ECOG score ≥2(P=0.004),Lugano stage Ⅲ-Ⅳ(P＜0.001),non-germinal center B-cell-like(non-GCB)subtype(P=0.035),elevated lactate dehydrogenase(LDH)(P＜0.001),extranodal involved site＞1(P=0.004)and IPI score＞2(P＜0.001).The interim response evaluation of patients showed that the overall response rate(ORR)and complete response rate(CRR)in the lower CAR group were both significantly better than those in the higher CAR group(ORR:96.9％vs 80.0％,P=0.035;CRR:63.6％vs 32.5％,P=0.008).With a median follow-up of 24 months,patients with lower CAR had significantly longer median PFS and OS than those with higher CAR(median PFS:not reached vs 67 months,P=0.0026;median OS:not reached vs 67 months,P=0.002),while there was no statistical difference in PFS(P=0.11)and OS(P=0.11)in patients with GPS of 0,1,and 2.Multivariate Cox regression analysis indicated that only sex(male)and IPI score＞2 were independent risk factors for both PFS and OS.Conclusion:CAR is significantly correlated with disease progression and survival in DLBCL patients;And compared with GPS,CAR has more advantages in predicting disease outcomes in DLBCL patients.

Objective:To compare the efficacy and safety of flumatinib (FM)and imatinib (IM)as first-line treatment in newly-diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP ) in real world. Methods:A total of 84 newly-diagnosed CP-CML patients in our center from December 2019 to December 2022 were retrospectively analyzed.Among them,32 cases received FM as first-line treatment,and 52 cases received IM. Molecular response (MR),disease progression,survival and incidence of adverse events (AEs)were compared between the two groups.Results:At 3 months of treatment,the incidences of early molecular response (EMR ),MR2.0 and MR3.0 were 96.7％,70.0％ and 20.0％ in FM group,respectively,which were significantly higher than 77.1％,29. 2％ and 0 in IM group (all P<0.05 ).At 6,9 and 12 months of treatment,the incidences of major molecular response (MMR)in FM group were 68.2％,85.7％ and 90.0％,respectively,which were significantly higher than 22.9％,34.0％ and 51.1％ in IM group (all P<0.01).The median time to achieve MMR in FM group was 6(6-9)months,which was significantly shorter than 18(12-22)months in IM group (P<0.001 ).The 3-year progression-free survival rate and 3-year event-free survival rate in FM group were 100％ and 68.8％,respectively,while in IM group were 98.1％ and 55.8％.There were no significant differences between the two groups (P>0.05). The incidence of grade 3-4 hematologic AEs in FM group was 21 .9％,which was slightly lower than 25.0％ in IM group,but the difference was not significant (P>0.05 ).Conclusion:In real clinical practice,FM as first-line treatment achieves MMR earlier than IM,and exhibits good safety profile in newly-diagnosed CML-CP patients,which potentially leads to improved long-term survival and treatment-free remission.

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P＜0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P＜0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P＞0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.