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*

We report a case of hemophagocytic syndrome (HPS) secondary to brucellosis, in which typhoidal cells were found in bone marrow, suggesting typhoidal cells present not only in Salmonella typhi infections but also in other bacterial infections. Typhoidal cells in bone marrow can be used to quickly identify the presence of bacterial infection pending the results of bone marrow and/or blood cultures.
Female ; Humans ; Typhoid Fever/microbiology* ; Lymphohistiocytosis, Hemophagocytic/etiology* ; Brucellosis/complications*

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

To comprehensively evaluate the quality of commercial Ginseng Radix et Rhizoma Rubra, 43 batches of commercial Ginseng Radix et Rhizoma Rubra were collected to determine the content of nine ginsenosides Rg_1, Re, Rb_1, Rk_3, Rh_4, 20(S)-Rg_3, 20(R)-Rg_3, Rk_1, and Rg_5 by high performance liquid chromatography(HPLC). The quality of the commercial Ginseng Radix et Rhizoma Rubra was evaluated by correlation analysis, principal component analysis, factor analysis, analysis of variance(ANOVA), and cluster heatmap analysis. The content determination indicated that the content of common ginsenosides in commercial Ginseng Radix et Rhizoma Rubra were higher while that of rare ginsenosides were lower. Multivariate statistical analysis revealed that ginsenosides Rg_1 and Rb_1 were significantly positively correlated with rare ginsenosides, and Rg_1, Rb_1 and rare ginsenosides played an important role in evaluating the quality of commercial Ginseng Radix et Rhizoma Rubra. In combination with the processing principle and current quality situation of Ginseng Radix et Rhizoma Rubra, it is recommended to improve the content limit of Rb_1 in the existing quality standards.
Panax ; Ginsenosides/analysis* ; Rhizome/chemistry* ; Plant Roots/chemistry* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal

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

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

Anomalous aortic origin of a coronary artery from the opposite sinus (AAOCA)is one of the con-genital coronary artery malformations that might cause syncope,myocardial ischemia and sudden cardiac death (SCD), particularly in adolescents and young people.The most important inducing factor of myocardial ischemia and syncope is strenuous exercise.In recent years,more and more young athletes SCD events have been reported,and SCD related to AAOCA is now becoming the hot issue of common concern. Now,the concept,classification,clinical manifestations, diagnosis,and treatment strategies of AAOCA were introduced.

BACKGROUNDTranscatheter closure of congenital coronary artery fistulas (CCAFs) is an alternative therapy to surgery; however, data regarding transcatheter closure for CCAF with a giant coronary artery aneurysm (CAA) in pediatric patients are still limited due to the rarity of the disease. We aimed to evaluate the efficacy and safety of transcatheter closure for CCAF with a giant CAA in a pediatric population at a single center.

METHODSMedical records of pediatric patients (<18 years old) who underwent transcatheter closure of CCAF with a giant CAA between April 2007 and September 2016 at Guangdong Cardiovascular Institute (Guangdong, China) were reviewed.

RESULTSTwelve patients (median age, 6.1 years; range, 1.9-11.0 years) underwent successful transcatheter closure procedures. One patient underwent closure at both the entry and exit points of the CAA, three patients underwent closure at the exit point of the CAA, and eight patients underwent closure at the entry point of the CAA. After a mean follow-up of 7.2 years (range, 0.5-9.8 years), one patient (with closure at the exit point of the CAA) underwent transcatheter re-intervention because of a significant residual shunt. She eventually underwent a surgical procedure due to aneurysm dilation after the second intervention. One patient experienced thrombus formation within the CAA after the procedure. Among those with closure at the entry point of the CAA, a mild-to-moderate residual shunt was detected in three patients.

CONCLUSIONSTranscatheter closure appears to be a safe and effective alternative therapy for CCAF with a giant CAA in the pediatric population. Closure at the entry point of the CAA, and closure at both the entry and exit points when feasible, may reduce the risk of postinterventional complications.

BACKGROUNDPercutaneous balloon pulmonary valvuloplasty (PBPV) is the preferred therapy for pulmonary valve stenosis (PVS). This study retrospectively reviewed recent PBPV outcomes in infants with PVS. The aim of this study was to evaluate factors associated with immediate therapeutic outcomes and restenosis during medium-term follow-up.

METHODSThe study included 158 infants with PVS who underwent PBPV from January 2009 to July 2015. Demographic characteristics and patient records were reviewed, including detailed hospitalization parameters, hemodynamic data before and immediately after balloon dilation, cineangiograms, and echocardiograms before PBPV and at each follow-up. All procedures were performed by more than two experienced operators.

RESULTSImmediately after balloon dilation, the pressure gradient across the pulmonary valve decreased from 73.09 ± 21.89 mmHg (range: 43-151 mmHg) to 24.49 ± 17.00 mmHg (range: 3-92 mmHg; P < 0.001) and the right ventricular systolic pressure decreased from 95.34 ± 23.44 mmHg (range: 60-174 mmHg) to 52.07 ± 18.89 mmHg (range: 22-134 mmHg; P < 0.001). Residual transvalvular pressure gradients of 67.31 ± 15.19 mmHg (range: 50-92 mmHg) were found in 8.2% of patients, indicating poor therapeutic effects; 6.4% of patients had variable-staged restenosis at follow-up and 3.8% underwent reintervention by balloon dilation or surgical repairs. Further analysis demonstrated that the balloon/annulus ratio showed statistically significant differences (P < 0.05) among groups with different therapeutic effects and between the restenosis and no-stenosis groups. Binary logistic regression analysis further revealed that higher balloon/annulus ratio (odds ratio: 0.005, 95% confidence interval: 0-0.39) was an independent protective factor for restenosis. The rate of severe complications was 1.9%.

CONCLUSIONSPBPV is a definitive therapy for infants with PVS based on its effectiveness, feasibility, and safety. Restenosis upon medium-term follow-up is relatively rare.

OBJECTIVETo investigate microwave-induced morphological and functional injury of natural killer (NK) cells and uncover their mechanisms.

METHODSNK-92 cells were exposed to 10, 30, and 50 mW/cm2 microwaves for 5 min. Ultrastructural changes, cellular apoptosis and cell cycle regulation were detected at 1 h and 24 h after exposure. Cytotoxic activity was assayed at 1 h after exposure, while perforin and NKG2D expression were detected at 1 h, 6 h, and 12 h after exposure. To clarify the mechanisms, phosphorylated ERK (p-ERK) was detected at 1 h after exposure. Moreover, microwave-induced cellular apoptosis and cell cycle regulation were analyzed after blockade of ERK signaling by using U0126.

RESULTSMicrowave-induced morphological and ultrastructural injury, dose-dependent apoptosis (P < 0.001) and cell cycle arrest (P < 0.001) were detected at 1 h after microwave exposure. Moreover, significant apoptosis was still detected at 24 h after 50 mW/cm2 microwave exposure (P < 0.01). In the 30 mW/cm2 microwave exposure model, microwaves impaired the cytotoxic activity of NK-92 cells at 1 h and down regulated perforin protein both at 1 h and 6 h after exposure (P < 0.05). Furthermore, p-ERK was down regulated at 1 h after exposure (P < 0.05), while ERK blockade significantly promoted microwave-induced apoptosis (P < 0.05) and downregulation of perforin (P < 0.01).

CONCLUSIONMicrowave dose-dependently induced morphological and functional injury in NK-92 cells, possibly through ERK-mediated regulation of apoptosis and perforin expression.

Apoptosis ; radiation effects ; Cell Cycle ; radiation effects ; Cell Line ; Dose-Response Relationship, Radiation ; Down-Regulation ; Humans ; Killer Cells, Natural ; radiation effects ; MAP Kinase Signaling System ; Microwaves ; adverse effects ; NK Cell Lectin-Like Receptor Subfamily K ; genetics ; metabolism ; Signal Transduction