Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

This study aims to reveal the effects of different growth patterns and years on the quality of Saposhnikoviae Radix samples. The apparent colors of the powder samples were quantified by a colorimeter, and the total color values(E~*ab) were calculated. The content of prim-O-glucosylcimifugin, cimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and 3'-O-angeloylhamaudol in the samples was simultaneously determined by high performance liquid chromatography(HPLC). Cluster analysis, principal component analysis, partial least squares discriminant analysis, and Pearson correlation analysis were performed to analyze the powder chromatic values and the content of 5 components. The results showed that the E~*ab values of the samples were in the order of wild group Powders ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/analysis* ; Apiaceae ; Plant Roots/chemistry*

Based on the systematic retrieval and the reported components of Sojae Semen Nigrum and Sojae Semen Praeparatum, this study conducted in-depth analysis of conversion of components in the fermentation process, and discussed types and possible mec-hanisms of conversion of chemical components, so as to provide the basis for studying technology, medicinal ingredients and quality standards. According to the analysis, there is a certain degree of conversion of nutrients(like protein, sugar, lipid), bioactive substances(like isoflavones, saponins, γ-aminobutyric acid) and other substances(like nucleosides, melanoids, biamines, etc) in the process of fermentation.
Chromatography, High Pressure Liquid ; Fermentation ; Isoflavones/analysis* ; Semen/chemistry* ; Soybeans

The historical evolution， fermentation technology and key links of Sojae Semen Praeparatum （SSP） were sorted out by consulting ancient books and modern literature， and the influencing factors and control methods of quality were analyzed and summarized in order to provide reference for the quality control of SSP. After analysis， it was found that in the fermentation process of SSP， fermentation strains， miscellaneous bacteria， temperature and humidity were all important factors affecting the quality of SSP. The condition control of "post fermentation" process has been paid more attention to in the past dynasties. In addition， the delicious SSP recognized in ancient times should be made from mold fermentation， and the breeding and application of fermented mold may be the key point to solve the quality problem of SSP. Therefore， based on the evaluation indexes of SSP in the past dynasties， it is of great significance to study and optimize the technological conditions such as strain， temperature and humidity in depth to improve the quality of SSP.

Objective: To assess the efficacy and long-term outcome of percutaneous balloon aortic valvuloplasty (PBAV) for children with congenital aortic stenosis (CAS) and to explore risk factors for significant aortic regurgitation (AR) and reintervention after PBAV during follow up. Methods: This was a retrospective study. Children (≤18 years old) with CAS, who underwent PBAV in Guangdong Provincial Hospital from January 2004 to December 2018, were included in this study. Demographic, preoperative transthoracic echocardiography (TTE) and surgical data were collected. Postoperative complications were closely observed, and the patients were followed up at 1, 6, 12 months after the operation, and then at one year interval thereafter. Endpoint events included significant AR and reintervention. Reintervention was defined as any intervention that needed to be performed on the valve for various reasons, including re-PBAV, surgical valvuloplasty and valve replacement. Significant AR was defined as AR grade≥3 by TTE criteria. The results of the last TTE examination before the end of the study were collected. The Kaplan-Meier curve for long-term AR-free and intervention-free survival was plotted. Cox regression model was used to further analyze the risk factors for significant AR and reintervention after PBAV in CAS patients. Results: A total of 55 patients were enrolled in this study, and the age was 4.6(1.6, 6.5) years, with 37(67.3%) males. The peak systolic valve gradient fell from (80.3±30.6)mmHg to (38.5±18.5)mmHg(P<0.001, 1 mmHg=0.133 kPa). Surgical success rate was 89% (49/55). Acute post-PBAV AR occurred in 18 patients, including 3 patients with RA≥3 grade. In-hospital complications occurred in 6 patients (2 deaths, 2 cases of transient arrhythmia, and 2 cases of femoral artery embolization). Fifty patients accomplished the follow-up and the follow-up time was 6.2(3.4, 8.5) years. Significant AR was found in 20 patients. Significant AR-free survival rate was 53% at 5 years and 19% at 10 years. Reintervention was performed in 11 patients (4 with valvuloplasty and 7 with valve replacement), and the 5-year and 10-year intervention-free survival rates were 87% and 62%, respectively. Multivariate Cox regression analysis showed that acute post-PBAV AR was a risk factor for long-term significant AR (HR=2.398, 95%CI 1.007-5.712, P=0.048). Post-PBAV residual pressure gradient ≥ 35 mmHg (HR=4.747, 95%CI 1.116-19.329, P=0.030)and acute post-PBAV AR (HR=5.104, 95%CI 1.083-24.065, P=0.039)were risk factors for re-intervention. Conclusions: PBAV is safe and effective in the treatment of CAS in children, but attention should be paid on significant AR post procedure. Acute post-PBAV AR is a risk factor for re-intervention and significant AR post PBAV, and high post-PBAV residual pressure gradient is a risk factor for re-intervention.
Aorta ; Aortic Valve Insufficiency ; Aortic Valve Stenosis/surgery* ; Cardiac Surgical Procedures ; Child ; Humans ; Male ; Retrospective Studies

Adolescent ; Adult ; Child ; Decision Trees ; Female ; HIV Infections ; economics ; transmission ; Humans ; Infectious Disease Transmission, Vertical ; economics ; prevention & control ; Kenya ; Middle Aged ; Mothers ; South Africa ; Vietnam ; Young Adult

BACKGROUND: Pulmonary artery hypertension associated with congenital heart disease (PAH-CHD) occurs predominantly among patients with uncorrected CHD. Treatment of severe pediatric PAH-CHD remains a major intractability. This study evaluated the predictors and prognoses of children with PAH-CHD who underwent surgical correction. METHODS: The data for 59 children with severe PAH-CHD who underwent surgical correction, with or without postoperative medication, between May 2011 and June 2015 at the Guangdong Provincial People's Hospital were analyzed retrospectively. A regression analysis, receiver-operating characteristic (ROC) curves, and Kaplan-Meier curves were used for survival analysis. RESULTS: Fifty-nine children with severe PAH-CHD underwent heart catheterization and correction, with or without specific anti-PAH drugs postoperatively, were included in this study. The pulmonary pressure, heart function, and ending events were observed and median observation period was 49 ± 20 months. Twenty-eight patients (50%) received at least one additional anti-PAH drug after correction. The survival rate after 2 years was 91.5% (54/59); two patients were in a critical condition, and three were lost to follow-up. Twelve patients (29%) still received over one additional PAH-specific therapy at follow-up, whereas 42 (75%) had successfully stopped drug treatment. Two patients (3.5%) died and one underwent a second thoracotomy to remove the ventricular septal defect patch. Acute vasoreactivity test (AVT) criteria had limited efficacy in predicting pediatric PAH-CHD, whereas pulmonary vascular resistance (PVR) ≤ 6.65 Wood units (WU)/m or PVR/systemic vascular resistance (SVR) ≤ 0.39 during AVT indicated a good prognosis after surgical correction with an AUC of 98.3% (95% confidence interval [CI]: 96.0-100%), 98.4% (95% CI: 96.0-100%) sensitivity of 100%, 100% and specificity of 82.1%, 92.9%, respectively. CONCLUSIONS Although the criteria for positive AVT currently used are unsuitable for pediatric patients with PAH-CHD, PVR and PVR/SVR during AVT are excellent predictors of outcome in pediatric PAH-CHD. Surgery aided by anti-PAH drugs is an effective strategy and should be recommended for severe pediatric PAH-CHD with PVR ≤ 6.65 WU/m and PVR/SVR ≤ 0.39 after iloprost aerosol inhalation.
Adolescent ; Child ; Child, Preschool ; Echocardiography ; Female ; Heart Defects, Congenital ; pathology ; surgery ; Humans ; Hypertension, Pulmonary ; pathology ; surgery ; Kaplan-Meier Estimate ; Male ; Prognosis ; ROC Curve ; Retrospective Studies ; Risk Factors

Objective To study on the role of histone methylation enzyme enhancer of zeste homolog 2 (EHZ2) and vascular endothelial growth factor 165 (VEGF165) in momymoya disease. Methods The animal model of moyamoya disease was established by ear vein injection of horse serum in New Zealand rabbits. VEGF165 was over-expressed in situ by packaging lentivirus. Real-time quantitative PCR and Western Blot were used to detect the expression of VEGF165, EZH2 and H3K27me3 in the brain tissues of the animal models. Results Compared with the normal control group, the expression levels of mRNA and protein of EZH2 in the moyamoya disease model group were increased (EZH2 mRNA:P<0.01), and the level of histone H3K27me3 was increased. After overexpression of VEGF165 in the moyamoya disease model group, the expression levels of mRNA and protein of EZH2 was further increased (EZH2 mRNA: P<0.01), and the level of histone H3K27me3 was also increased. Conclusions EZH2 plays a certain role in the pathogenesis of moyamoya disease, and the expression of EZH2 is regulated by VEGF 165, which provides a theoretical basis for the study of the pathogenesis of moyamoya disease.

Objective: To examine the association of abnormal metabolic indexes and its clustering with carotid intima-media thickness (cIMT) in childhood. Methods: A convenient sampling method was used to conduct a cross-sectional survey from November 2017 to January 2018 in a primary school in Huantai County, Zibo City, Shandong Province. A total of 1 240 children who had complete data of questionnaires, physical examinations, and blood biochemical tests were included for analysis. Covariance analysis was used to analyze the association of the single abnormal metabolic indices and its clustering with cIMT. The multivariable linear regression model was used to quantify the relationship between the number of abnormal metabolic indices and cIMT. Results: The age of 1 240 children was (8.9±1.5) years, and 657 boys accounted for 53.0%. The highest detection rate of abnormal metabolic indicators was found in abdominal obesity, accounting for 30.9% (203/657) of boys and 29.7% (173/583) girls respectively.The cIMT of boys and girls were (0.49±0.08) and (0.45±0.07) mm, respectively. After adjusting for sex, age, consumption of fruits, vegetables and carbonated drinks, sleep duration, screen time and physical activity, abdominal obesity, elevated blood pressure, total triglyceride and fasting glucose were associated with cIMT (all P values <0.001). Children with 0, 1, 2 and ≥3 abnormal metabolic indicators had cIMT values of (0.45±0.07), (0.48±0.08), (0.50±0.09) and (0.53±0.08) mm, respectively. That was, cIMT values increased with the number of abnormal metabolic indexes (P_trend<0.001). Conclusion Abdominal obesity, elevated blood pressure, total triglyceride, fasting glucose and clustering of the above factors are associated with cIMT.

Objective To construct a human renal epithelial cell line HEK293T by CRISPR-Cas9-based site-directed knock-in of vascular endothelial growth factor 165 (VEGF165) gene, and avoid the off-target effect caused by lentivirus infection. Methods The VEGF165 expression vector with homologous arm (pUCm-T-VEGF165 plasmid) and the sgRNA expression vector [pSpCas9(BB)-2A-Puro-sgRNA plasmid] were designed and constructed based on the DNA sequence of the EZH2 gene, and then co-transfected into HEK293T cells. The expression of VEGF165 mRNA was detected by qPCR and the expressions of VEGF165 proteins were detected by Western Blot. Results The qPCR and Western Blot results showed that, comparing with the control, the pUCm-T-VEGF165 plasmid and pSpCas9(BB)-2A-Puro-sgRNA plasmid, the expression of the co-transfection plasmid were significantly increased, i.e. 3.42±0.30 vs. 1.02±0.21, 1.13±0.16 and 0.98±0.18 for the VEGF165 mRNA level (all P<0.01), and 1.13±0.16 vs. 1.02±0.06, 0.88±0.03 and 0.80±0.05 for the VEGF165 protein level (all P<0.01), respectively. Besides, the expression of EZH2 was significantly down-regulated, i.e. 0.14±0.06 vs. 1.08±0.11, 1.02±0.12 and 1.13±0.16 for the EZH2 mRNA level (all P<0.01), and 0.23±0.03 vs. 1.05±0.13, 0.91±0.04 and 0.81±0.06 for the EZH2 protein level (all P<0.01), respectively. This result showed that the VEGF165 was successfully inserted into the EZH2 genome, interfering the EZH2 expression. Conclusions VEGF165 gene can be successfully knocked into HEK293T cells by CRISPR/Cas9 system.