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Objective: To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia (AML)., Methods: High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center, the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML. The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML. The expression of IGF2BP3 in two anthracycline-resistant cell lines (HL60/ADR, K562/ADR) was detected by RT-qPCR and Western blot, and the expression difference of IGF2BP3 was compared with that in sensitive cells (HL60, K562). The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML, and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis., Results: In the bone marrow primary leukemia cells of 27 AML patients in our center, the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients ( P =0.0343). The expression of IGF2BP3 in leukemia patients with extramedullary infiltration (EMI) was significantly higher than that in AML patients without extramedullary infiltration ( P =0.0049). Compared with healthy subjects ( n =20), IGF2BP3 expression in AML patients ( n =26) was higher ( P =0.0009). The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines (HL60/ADR, K562/ADR) was significantly higher than that in the sensitive cell lines (K562/ADR vs K562, P =0.0430; HL60/ADR vs HL60, P =0.7369). Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells ( P < 0.001). qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive ( P =0.002). High expression of IGF2BP3 was associated with poor prognosis in AML ( P < 0.05) in 3 large sample cohorts of AML patients. Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival (EFS, HR =1.887, P =0.024) and overall survival (OS, HR =1.619, P =0.016)., Conclusion: The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML, suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.

Objective: To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML)., Methods: The study was a singlecenter prospective clinical trial. The enrolled patients met the criteria for R/R AML. Treatment included Azacidine(75 mg/m 2 ，d 1-7), Ara-C (75-100 mg/m 2 , q12h, d 1-5), Aclacinomycin(20 mg d1,d3,d5), Chidamide(30 mg d1,d4), Venetoclax(100 mg d1, 200 mg d2, 400 mg d3-d14, in combination with Triazole Drug, reduced to 100 mg/d), and granulocyte colony-stimulating factor (300 μg /d until neutrophil recovery). The primary endpoint of observation was overall response rate after 1 course of treatment., Results: A total of 19 patients were enrolled from January 2022 to April 2023. After 1 course of treatmen, the overall response rate was 81.3%(13/16), the CR rate was 68.8%(11/16), and the PR was 12.5%(2/16). Among the 11 patients who got CR/CRi, 8 cases achieved CRm (minimal residual disease negative CR) and 3 cases did not. As of March 27, 2023, the median follow-up time was 111(19-406) days. The six-month overall survival and progression-free survival rates were both 55.7%, the 1-year overall survival and progression-free survival rates were 46.4% and 47.7%, respectively. In addition, compared with the non-CRm group, CRm patients had a better PFS (377 days vs 111 days, P =0.046). Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression, complicated by various degrees of infection( n =12), hypokalemia( n =12) and hypocalcemia ( n =10) and elevated liver enzymes ( n =8), of which 3/4 degrees accounted for 47.4%(9/19)., Conclusion: The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML, with high remission rate and safety profile.

Objectives: To investigate the clinical manifestations and laboratory examination results of children with Kawasaki disease complicated by macrophage activation syndrome (KD-MAS), and to provide a basis for identifying early warning indicators for the early diagnosis and treatment of KD-MAS., Methods: A retrospective study was performed on 27 children with KD-MAS (KD-MAS group) and 110 children with KD (KD group) who were admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2014 to January 2022. Clinical and laboratory data were compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the value of laboratory markers with statistical significance in the diagnosis of KD-MAS., Results: Compared with the KD group, the KD-MAS group had significantly higher incidence rates of hepatomegaly, splenomegaly, incomplete KD, no response to intravenous immunoglobulin, coronary artery damage, multiple organ damage, and KD recurrence, as well as a significantly longer length of hospital stay ( P <0.05). Compared with the KD group, the KD-MAS group had significantly lower levels of white blood cell count, absolute neutrophil count, hemoglobin, platelet count (PLT), erythrocyte sedimentation rate, serum albumin, serum sodium, prealbumin, and fibrinogen (FIB), a significantly lower incidence rate of non-exudative conjunctiva, and significantly higher levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and serum ferritin (SF) ( P <0.05). The ROC curve analysis showed that SF, PLT, FIB, and LDH had high value in the diagnosis of KD-MAS, with areas under the curve (AUC) of 0.989, 0.966, 0.932, and 0.897, respectively ( P <0.001), and optimal cut-off values of 349.95 μg/L, 159×10 9 /L, 3.85 g/L, and 403.50 U/L, respectively. The combination of SF, PLT, FIB, and LDH had a larger AUC than PLT, FIB, and LDH alone in the diagnosis of KD-MAS ( P <0.05), but there was no significant difference in the AUC between the combination of SF, PLT, FIB, and LDH and SF alone ( P >0.05)., Conclusions: KD-MAS should be considered when children with KD have hepatosplenomegaly, no response to intravenous immunoglobulin, coronary artery damage, and KD recurrence during treatment. SF, PLT, FIB, and LDH are of high value in the diagnosis of KD-MAS, especially SF is of great significance in the diagnosis of KD-MAS.

Background: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy. Patient prognosis cannot be accurately assessed in National Comprehensive Cancer Network (NCCN) risk stratification subgroups based on the current criteria. This study aimed to develop a novel prognostic score model for the quantitative prediction of prognosis in AML., Results: We developed a prognostic risk scoring model of AML using differentially expressed genes to predict prognosis in patients with AML. Furthermore, we evaluated the effectiveness and clinical significance of this prognostic model in 4 AML cohorts and 905 patients with AML. A prognostic risk scoring model of AML containing eight prognosis-related genes was constructed using a multivariate Cox regression model. The model had a higher predictive value for the prognosis of AML in the training and validation sets. In addition, patients with lower scores had significantly better overall survival (OS) and even-free survival (EFS) than those with higher scores among patients with intermediate-risk AML according to the NCCN guidelines, indicating that the model could be used to further predict the prognosis of the intermediate-risk AML populations. Similarly, patients with high scores had remarkably poor OS and EFS in the normal-karyotype populations, indicating that the scoring model had an excellent predictive performance for patients with AML having normal karyotype., Conclusions: Our study provided an individualized prognostic risk score model that could predict the prognosis of patients with AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Wang, Yang, Fang, Wen, Jiao, Qian, Le, Shan, Gao, Hua and Li.)

Background: Accumulating studies have suggested the airway microbiota in lung cancer patients is significantly different from that of healthy controls. However, little is known about the relationship between airway microbiota and important clinical parameters of lung cancer. In this study, we aimed to explore the association between sputum microbiota and lung cancer stage, lymph node metastasis, intrathoracic metastasis, and epidermal growth factor receptor (EGFR) gene mutation., Methods: The microbiota of sputum samples from 85 newly-diagnosed NSCLC patients were sequenced via 16S rRNA sequencing of the V3-V4 region. Sequencing reads were filtered using QIIME2 and clustered against UPARSE., Results: Alpha- and β-diversity was significantly different between patients in stages I to II (early stage, ES) and patients in stages III to IV (advanced stage, AS). Linear discriminant analysis Effect Size (LEfSe) identified that genera Granulicatella and Actinobacillus were significantly enriched in ES, and the genus Actinomyces was significantly enriched in AS. PICRUSt2 identified that the NAD salvage pathway was significantly enriched in AS, which was positively associated with Granulicatella. Patients with intrathoracic metastasis were associated with increased genus Peptostreptococcus and incomplete reductive TCA cycle, which was associated with increased Peptostreptococcus. Genera Parvimonas, Pseudomona and L-valine biosynthesis were positively associated with lymph node metastasis. L-valine biosynthesis was related with increased Pseudomona. Finally, the genus Parvimonas was significantly enriched in adenocarcinoma patients with EGFR mutation., Conclusion: The taxonomy structure differed between different lung cancer stages. The tumor stage, intrathoracic metastasis, lymph node metastasis, and EGFR mutation were associated with alteration of specific airway genera and metabolic function of sputum microbiota., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objective: To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876)., Methods: We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23)., Results: Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4 + CD29 + T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4 + CD29 + T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8 + CD28 - T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8 + CD28 - T / CD8 + CD28 + T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P 3 =0.01, P 7 =0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P 3 =0.0351; P 7 =0.0142; P 14 =0.0369)., Conclusion: We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.

Background: Clinical drugs for herpesvirus exhibit high toxicity and suffer from significant drug resistance. The development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action is greatly required., Objective: Novel inhibitors against herpesvirus with different mechanisms of action from that of clinical drugs., Methods: A series of novel 5-(benzylamino)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against Human Cytomegalovirus (HCMV), Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) were evaluated in vitro., Results: Some compounds present antiviral activity. Compounds 5s and 5t are potent against both HCMV and VZV. Compounds 5m, 5n, 5s, and 5t show similar EC50 values against both TK+ and TK- VZV strains., Conclusion: 5-(Benzylamino)-1H-1, 2,3-triazole-4-carboxamides are active against herpesviruses and their activity is remarkably affected by the nature and the position of substituents in the benzene ring. The results indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. Their mechanisms of action may differ from those of the clinic anti-herpesvirus drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: All of the clinical drugs for herpesvirus infections exhibit high toxicity and suffer from significant drug-resistantance. There is a great need for the development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action., Methods: A series of novel 5-(benzylthio)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against human cytomegalovirus (HCMV), varicella-zoster virus (VZV) and herpes simplex virus (HSV) were evaluated in vitro., Results: Some compounds possess antiviral activity. Compound 7f exhibits promising inhibitory activity against both HCMV and VZV. Our results also indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs., Conclusion: 4,5-Bissubstiuted triazoles are active against herpesviruses and the nature and the position of substituents in the benzene ring remarkably affect their activity, such as bromo, cyano and cyanovynil substituents. Future studies should be undertaken to investigate the mechanism of action of these compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

A series of novel trisubstituted 1,2,3-triazole purine nucleosides were efficiently synthesized via Huisgen 1,3-dipolar cycloaddition in good yields. Bioactivity against cytomegalovirus (CMV) and varicella-zoster virus (VZV) in human embryonic lung cell cultures was evaluated and all compounds show low antiviral activity.

Background: Resistant hypertension is associated with adverse clinical outcome in hypertensive patients. However, the prognostic significance of resistant hypertension in patients with heart failure remains uncertain., Methods and Results: The 1 year survival and heart failure re-hospitalization rate of 1288 consecutive patients admitted to a university hospital for either newly diagnosed heart failure or an exacerbation of prior chronic heart failure was analyzed. Resistant hypertension was defined as uncontrolled blood pressure (> 140/90 mmHg) despite being compliant with an antihypertensive regimen that includes 3 or more drugs (including a diuretic). A total of 176 (13.7%) heart failure patients had resistant hypertension. There was no difference in all cause mortality, cardiovascular mortality, and heart failure related re-hospitalization between patients with versus without resistant hypertension. Diabetes [hazard ratio = 1.62, 95% confidence interval = 1.13-2.34; P = 0.010] and serum sodium > 139 mmol/L (hazard ratio = 1.54, 95% confidence interval = 1.06-2.23; P = 0.024) were independently associated with resistant hypertension. Patients with resistant hypertension had a relatively higher survival rate (86.9% vs. 83.8%), although the difference was not significant (log-rank x2 = 1.00, P = 0.317). In patients with reduced ejection fraction, heart failure related re-hospitalization was significantly lower in patients with resistant hypertension (45.8% vs. 59.1%, P = 0.050)., Conclusions: Resistant hypertension appears to be not associated with adverse clinical outcome in patients with heart failure, in fact may be a protective factor for reduced heart failure related re-hospitalization in patients with reduced ejection fraction.

Cardiac auscultation by stethoscope is widely used but limited by low sensitivity and accuracy. Phonocardiogram was developed in an attempt to provide quantitative and qualitative information of heart sounds and murmurs by transforming acoustic signal into visual wavelet. Although phonocardiogram provides objective heart sound information and holds diagnostic potentials of different heart problems, its examination procedure is time-consuming and it requires specially trained technicians to operate the device. Acoustic cardiography (AUDICOR, Inovise Medical, Inc., Portland, OR, USA) is a major recent advance in the evolution of cardiac auscultation technology. The technique is more efficient and less operator-dependent. It synchronizes cardiac auscultation with ECG recording and provides a comprehensive assessment of both mechanical and electronic function of the heart. The application of acoustic cardiography is far beyond auscultation only. It generates various parameters which have been proven to correlate with gold standards in heart failure diagnosis and ischemic heart disease detection. Its application can be extended to other diseases, including LV hypertrophy, constrictive pericarditis, sleep apnea and ventricular fibrillation. The newly developed ambulatory acoustic cardiography is potentially used in heart failure follow-up in both home and hospital setting. This review comprehensively summarizes acoustic cardiographic research, including the most recent development., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

As the leading global risk for mortality, hypertension (HT) is a common healthcare problem in the world. The total number of patients with HT is likely to grow in the next few decades as the population age and the prevalence of obesity and diabetes increase. HT, as a major modifiable risk factor for cardiovascular disease, results in more deaths than any other risk factors, including diabetes and cigarette smoking. High prevalence, inadequate awareness, suboptimal treatment and low rate of achieving guideline-recommended target blood pressure control are key factors leading to severe cardiovascular complications that impose a heavy socioeconomic burden, especially in developing countries. Asia is the world's largest and most populous continent with approximately 4.3 billion people, hosting 60% of the world's current human population, and has a high growth rate. Asia differs very widely from the West with regard to ethnic groups, cultures, environments, economics, historical ties and government systems. Therefore, the purpose of this review is to comprehensively summarise the epidemiology, treatment practice and the status of control of HT in different Asian countries in order to guide the future prevention and management in this part of the world.