[Advances in basic and clinical research of flumatinib].

Chronic myelogenous leukemia (CML) is a hematological malignancy originating from the pluripotent hematopoietic stem cells. Imatinib is the first generation of small molecule tyrosine kinase inhibitors (TKI) that revolutionized the treatment of CML. Flumatinib, as a novel oral TKI that independently developed in China, which can be used as a preferred treatment for CML. Basic researches suggested that the inhibitory effect of flumatinib on CML cell lines is stronger than imatinib. Flumatinib demonstrated that it has better efficacy than imatinib on CML in clinical trials and in real world studies. Flumatinib also showed a higher potency against CML with specific mutations, Ph(+) acute lymphoblastic leukemia and some solid tumors. The adverse events are manageable and tolerable.

[Clinical and genetic characteristics of patients with newly diagnosed acute promyelocytic leukemia: a single-center retrospective of 790 cases].

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.

Who are the real high-risk patients with pathological T2N0M0 non-small-cell lung cancer that can benefit from adjuvant chemotherapy?

BACKGROUND: The benefit of adjuvant chemotherapy (ACT) in pathological T2N0M0 non-small-cell lung cancer (NSCLC) patients is not clear. METHODS: One thousand and fifty pathological T2N0M0 NSCLC patients were included and divided into two groups: with and without ACT. A propensity score matching analysis was carried out to minimize selection bias. The significance of ACT in high-risk patients was further analyzed. The Kaplan-Meier method and Cox proportional hazards model were used to assess the impact of ACT on the overall survival (OS), disease-free survival (DFS), and cancer-specific survival. RESULTS: For the entire cohort, 31.9% (335/1050) of patients received ACT. After propensity score matching, 325 pairs of patients were matched. OS and DFS were comparable between groups in the original or matched cohort, which was confirmed by the multivariate analysis (all P > 0.05). In high-risk patients, the data suggest that ACT could improve OS and DFS only in patients with tumours >4 cm (OS: P = 0.003; DFS: P = 0.013). ACT could significantly improve the 5-year OS in patients with wild-type epidermal growth factor receptor (EGFR) (P = 0.022). ACT, however, could not improve cancer-specific survival in any subgroup, including patients with tumours >4 cm or wild-type EGFR (all P > 0.05). For patients with other high-risk factors, ACT failed to benefit patients in long-term outcomes. CONCLUSIONS: In resected pT2N0M0 NSCLC patients, those with tumours >4 cm and wild-type EGFR are real high-risk patients and could gain survival benefit from ACT. Further prospective study is needed to confirm the definition.

[Deep Learning-Based Cardiac Imaging Data Measurement and Its Application in Diagnosis of Sudden Cardiac Death].

ABSTRACT: In the field of forensic medicine, diagnosis of sudden cardiac death is limited by subjective factors and manual measurement methods, so some parameters may have estimation deviation or measurement deviation. As postmortem CT imaging plays a more and more important role in the appraisal of cause of death and cardiopathology research, the application of deep learning such as artificial intelligence technology to analyze vast amounts of cardiac imaging data has provided a possibility for forensic identification and scientific research workers to conduct precise diagnosis and quantitative analysis of cardiac diseases. This article summarizes the main researches on deep learning in the field of cardiac imaging in recent years, and proposes a feasible development direction for the application of deep learning in the virtual anatomy of sudden cardiac death at present.

Research Progress on Accumulated Degree Days for PMI Estimation.

ABSTRACT: Among many factors that affect postmortem interval （PMI）, temperature is undoubtedly the most important factor, but simply considering temperature in estimation of PMI has limitations. Accumulated degree days （ADD） is an important indicator related to biological growth and development, which considers two major variables, environmental temperature and elapsed time. Therefore, the establishment of mathematical model of ADD and some evaluation indicators to estimate PMI, is obviously better than single temperature variable. This article briefly describes the research history of ADD, its application in PMI estimation, and the problems it faces, to provide reference for the further development of ADD to improve the accuracy of PMI estimation.

Sequential Changes of Total Adenine Nucleotide and Adenylic-Acid Energy Charge in Muscles of Rats after Death.

ABSTRACT: Objective To determine the purine adenylate [adenosine triphosphate （ATP）, adenosine diphosphate （ADP）, adenosine monophosphate （AMP）] content in the muscles of both hind limbs of rats at different postmortem interval （PMI）, calculate the changes in the total adenine nucleotide （TAN） content and the adenylic-acid energy charge （AEC）, and explore their relationship with PMI. Methods Healthy rats were sacrificed by cervical dislocation and kept at 20 ℃. The muscles of their hind limbs were extracted at 0, 24, 48, 72, 96, 120, 144, and 168 h after death. Reversed-phase high performance liquid chromatography was used to determine the content of purine adenylates, the TAN and AEC of the muscles of the both hind limbs were calculated, and the related regression equations of their relationship with PMI were established. Results Within 168 h of death of rats, the trend of ATP change was different from ADP, and the content of AMP continuously increased. The TAN value gradually increased with the extension of PMI, and the AEC showed a downward trend within 168 h after death. Among them, the patterns of AEC changes with PMI were obvious, the correlation coefficient was high （ R2=0.903）, and the curve fitting relationship was good; the fitting relationship between ATP, ADP, AMP, TAN and PMI was poor （ R2=0.198-0.754）. Conclusion The postmortem change patterns of AEC provide new research ideas for PMI estimation in the forensic field.

Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137, by J.-G. Liu, H.-B. Wang, G. Wan, M.-Z. Yang, X.-J. Jiang, J.-Y. Yang, published in Eur Rev Med Pharmacol Sci 2019; 23 (13): 5675-5681-DOI: 10.26355/eurrev_201907_18304-PMID: 31298319" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18304.

[Autologous hematopoietic stem cell transplantation treatment for T cell lymphoblastic lymphoma].

Objective: To investigate the efficacy and predictors of autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of T lymphoblastic lymphoma (T-LBL) . Methods: 41 patients with T-LBL who underwent auto-HSCT from April 2006 to July 2017 in the Department of Hematology, the First Affiliated Hospital of Soochow University and the Department of Lymphoma, Peking University Cancer Hospital were analyzed retrospectively. Results: ①Among 41 patients, there were 30 males and 11 females with median age of 24 (11-53) years old. According to the Ann Arbor staging, 33 (80.5%) patients were in stage Ⅲ/Ⅳ. 12 (29.3%) patients have mediastinal involvement, and 20 (48.8%) patients have bone marrow (BM) involvement. Before transplantation, there were 26 (63.4%) patients who achieved first complete remission (CR(1)) , the other 15 (36.6%) patients were in the non-CR(1) group, and there were 29 (70.7%) patients in the low-intermediate risk group (IPI<3 scores) , the other 12 (34.1%) patients were in the middle-high risk group (IPI≥3 scores) . ②The median follow-up was 29 (3-98) months. The 3-year overall survival (OS) and progression-free survival (PFS) for 41 patients were (64.3±8.2) % and (66.0±7.8) %, respectively. 3-year cumulative recurrence rate (CIR) was (30.7±7.4) %, and 3-year non-recurring mortality (NRM) was (4.8±4.6) %. ③The 3-year OS of the CR(1) group and the non-CR(1) group were (83.4±7.6) % and (38.9±12.9) % (P=0.010) , and the 3-year PFS of two groups were (83.8±7.4) % and (40.0±12.6) % (P=0.006) , respectively. The 3-year CIR of these two groups were (16.2±7.4) % and (53.3±12.9) % (P=0.015) , and the 3-year NRM were 0 and (14.3±13.2) % (P=0.157) , respectively. ④The 3-year OS of the IPI low-intermediate risk group and the high-intermediate risk group were (76.9±8.4) % and (35.7±15.2) % (P=0.014) and the 3-year PFS were (77.4±8.2) % and (40.0±14.6) (P=0.011) , respectively. The 3-year CIR of these two groups were (18.1±7.3) % and (60.0±14.6) % (P=0.006) , and the 3-year NRM were (5.6±5.4) % and 0 (P=0.683) , respectively. The OS and PFS of patients with low-intermediate risk group were significantly higher than the other group. Conclusion: Auto-HSCT could improve the survival of T-LBL. Pre-transplant status and IPI score are important predictors for survival T-LBL patients with auto-HSCT.

Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137.

OBJECTIVE: Recently, long noncoding RNAs (lncRNAs) have attracted more attention for their roles in tumor progression. The aim of this study was to investigate the role of lncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) in the progression of renal cell cancer (RCC), and to explore the possible underlying mechanism. PATIENTS AND METHODS: Expression levels of ZFPM2-AS1 in both RCC cells and 50 paired tissue samples were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the relationship between lncRNA ZFPM2-AS1 expression level and clinic-pathological characteristics as well as patients' disease-free survival rate was explored, respectively. Furthermore, cell proliferation assay, wound healing assay and transwell assay were performed to investigate the role of lncRNA ZFPM2-AS1 in vitro. In addition, Western blot assay, Luciferase reporter gene assay and RNA immunoprecipitation assay were used to explore the possible underlying mechanism. RESULTS: The expression level of ZFPM2-AS1 in tumor tissues was significantly higher than that of corresponding normal tissues. ZFPM2-AS1 expression was associated with lymph node metastasis, tumor stage and survival time of RCC patients. Moreover, the overexpression of ZFPM2-AS1 significantly promoted the growth, invasion and migration of tumor cells, whereas remarkably inhibited cell apoptosis in vitro. Further experiments revealed that miR-137 was a direct target of ZFPM2-AS1. In addition, miR-137 expression in tumor tissues was negatively correlated with ZFPM2-AS1 expression. CONCLUSIONS: Our findings indicated that ZFPM2-AS1 could promote metastasis and proliferation, whereas inhibiting the apoptosis of RCC via targeting miR-137. This study might provide a new vision for interpreting the mechanism of RCC development.

[Research Progress on Postmortem Interval Estimation by Vitreous Humor].

Postmortem interval （PMI） estimation is one of the most challenging problems in the field of forensic science. Vitreous humor is a hotspot which has been used for PMI estimation and postmortem chemical analysis in forensic pathology. In order to provide novel perspectives for the future research of PMI estimation using vitreous humor, the comparison between vitreous humor with other common body fluids, the effect of temperature on vitreous humor, vitreous humor detection method and data fitting method have been reviewed in this paper.

[Application of Mixed-effect Model in PMI Estimation by Vitreous Humor].

OBJECTIVES: To test the changes of the potassium （K⁺） and magnesium （Mg²âºï¼‰ concentrations in vitreous humor of rabbits along with postmortem interval （PMI） under different temperatures, and explore the feasibility of PMI estimation using mixed-effect model. METHODS: After sacrifice, rabbit carcasses were preserved at 5 ℃, 15 ℃, 25 ℃ and 35 ℃, and 80-100 µL of vitreous humor was collected by the double-eye alternating micro-sampling method at every 12 h. The concentrations of K⁺ and Mg²âº in vitreous humor were measured by a biochemical-immune analyser. The mixed-effect model was used to perform analysis and fitting, and established the equations for PMI estimation. The data detected from the samples that were stoned at 10 ℃, 20 ℃ and 30 ℃ with 20, 40 and 65 h were used to validate the equations of PMI estimation. RESULTS: The concentrations of K⁺ and Mg²âº [f（x,y）] in vitreous humor of rabbits under different temperature increased along with PMI （x）. The relative equations of K⁺ and Mg²âº concentration with PMI and temperature under 5 ℃~35 ℃ were fK⁺（x,y）=3.413 0+0.309 2 x+0.337 6 y+0.010 83 xy-0.002 47 x² （P<0.000 1）, and fMg²âºï¼ˆx,y）=0.745 6+0.006 432 x+0.033 8 y （P<0.000 1）, respectively. It was proved that the time of deviation for PMI estimation by K⁺ and Mg²âº was in 10 h when PMI was between 0 to 40 h, and the time of deviation was in 21 h when PMI was between 40 to 65 h. CONCLUSIONS: the ambient temperature range of 5 ℃-35 ℃, the mixed-effect model based on temperature and vitreous humor substance concentrations can provide a new method for the practical application of vitreous humor chemicals for PMI estimation.

Autologous hematopoietic stem cell transplantation in patients with end-stage liver disease: a 5-year follow-up study of 48 patients.

OBJECTIVE: To investigate the long-term therapeutic effect of autologous hematopoietic stem cell transplantation in patients with End-stage Liver Disease (ESLD). PATIENTS AND METHODS: Forty-eight ESLD patients underwent autologous CD34+ stem cell transplantation were retrospectively reviewed. Changes in clinical and biochemical data, complications, and quality of life were monitored at 3, 6, 12, 36, and 60 months following the stem cell transplantation. Liver biopsies were obtained for histopathological analysis using Ishak system. RESULTS: Marked improvement in clinical and biochemical data was observed during the long-term follow-up. Serum albumin was significantly increased (p<0.001), while total serum bilirubin, prothrombin time (PT), and international normalized ratio (INR) were all significantly decreased (p<0.001). Ishak inflammation and fibrosis scores were significantly decreased with the increased time (p<0.001). The number of patients with ascites, model of end-stage liver disease (MELD) score, Child-Pugh class, and indocyanine green (ICG) score were all markedly reduced with increased time. Meanwhile, the quality of life score of the patients was significantly increased (p<0.001). Six patients died during the 5-years follow-up, and complications occurred in 17 patients. The incidence of complications was significantly associated with mortality of the patients (p<0.05). CONCLUSIONS: The study provided the evidence that autologous CD34+ stem cell transplantation could offer a long-term therapeutic benefit to patients with ESLD. The complications occurred during the process was significantly associated with survival of the patients. Future studies on a large cohort of patients are needed to confirm the long-term effect of stem cell therapy on ESLD.

In situ study of mass transfer in aqueous solutions under high pressures via Raman spectroscopy: a new method for the determination of diffusion coefficients of methane in water near hydrate formation conditions.

A new method was developed for in situ study of the diffusive transfer of methane in aqueous solution under high pressures near hydrate formation conditions within an optical capillary cell. Time-dependent Raman spectra of the solution at several different spots along the one-dimensional diffusion path were collected and thus the varying composition profile of the solution was monitored. Diffusion coefficients were estimated by the least squares method based on the variations in methane concentration data in space and time in the cell. The measured diffusion coefficients of methane in water at the liquid (L)-vapor (V) stable region and L-V metastable region are close to previously reported values determined at lower pressure and similar temperature. This in situ monitoring method was demonstrated to be suitable for the study of mass transfer in aqueous solution under high pressure and at various temperature conditions and will be applied to the study of nucleation and dissolution kinetics of methane hydrate in a hydrate-water system where the interaction of methane and water would be more complicated than that presented here for the L-V metastable condition.

[Studies on sultamicillin hydrolysis].

Sultamicillin is an oral mutual pro-drug composed of double esters of formaldehyde hydrate in which one of the hydroxyl groups is esterified with ampicillin and the other with sulbactam. It is hydrolyzed fast in neutral or weakly alkaline condition. When hydrolyzed, it forms ampicillin and hydroxylmethyl sulbactam or sulbactam and hydroxylmethyl ampicillin by different routes. Usually, the former has priority as the two ester bonds have different activities. The ratio of ampicillin to sulbactam in the products is about 3:1. Both the hydroxylmethyl sulbactam and the hydroxylmethyl ampicillin can be further catalyzed by esterase to produce formaldehyde.

Survey of public awareness, understanding, and attitudes toward epilepsy in Henan province, China.

The awareness, understanding, and attitudes toward epilepsy in 1,278 men and women were surveyed in Henan, China in 1988. Results showed that 93% had read or heard about epilepsy; 77% knew someone who had epilepsy; 72% had seen someone who was having a seizure; 57% would object to having their children associate with persons with epilepsy in school or at play; 87% would object to having their children marry a person with epilepsy; 53% believed that epileptic persons should not be employed in jobs as other persons are; 16% believed that epilepsy was a form of insanity; 40% did not know the cause of epilepsy; 10% did not know what an epileptic attack was like; and 17% did not know what to recommend if their friends or relatives had epilepsy. The relationship between the responses and the respondents' age, sex, marital status, number of offspring, level of education, occupation, and residence was analyzed. Education reduced the respondent's prejudice against play and employment, but did not change their objection to marriage and appeared to have reinforced their linking epilepsy with insanity. As compared with the surveys conducted in Western countries, our survey showed that awareness of epilepsy in China was greater, if not the same, but the attitudes toward epilepsy were much more negative.

Reaction of Se with SH groups in spectrin is involved in the stabilization of erythrocyte membrane skeleton.

Na2SeO3 supplementation in the dialysis medium could obviously prevent the dissociation of spectrin from the erythrocyte membranes. Such Se effect could be eliminated by pretreatment of erythrocyte membranes with a SH-blocking reagent, iodoacetamide(IAA) or addition of a SH-compound, dithio-threitol. The fluorescence intensity of erythrocyte membranes labelled with the fluorescent probe N-(3-pyrenyl)-maleimide decreased with increasing Na2SeO3 concentration used for pretreatment of ghosts. 31P-NMR spectra of erythrocyte membrane dialyzed in the presence or absence of Na2SeO3 concentration showed a difference in chemical shift anisotropy (delta sigma) between these two samples. These data suggest that the stabilization effect is based on changes in lipid-protein interaction and conformation of membrane skeletal components induced by reaction of their SH groups with Na2SeO3.

[Retention index of essential oil in temperature-programmed capillary column gas chromatography].

Kovats retention indexes of more than 200 kinds of natural and synthetic compounds of alcohol, aldehyde, acetal, ketone, ether, alkene, nitrile, carboxylic acid, ester, etc. were determined on polar liquid phase (DB-WAX) and nonpolar liquid phase (DB-1) by linear temperature-program capillary column gas chromatography. Some rules of part of the homologous series of compounds were summed up from the retention indexes: the rules of RI vs carbon, RI vs boiling point and RI on two columns. In order to keep the retention indexes practical, effects of initial temperature (T0), program rate (r) and average linear carrier gas velocity (u), etc. on the retention indexes were investigated. The conclusion is that the retention indexes are highly reproducible so long as the program parameters change in a certain range. Two kinds of essences, Meigui and Linglan, were identified successfully on IBM-PC/XT microcomputer by the Data Base Management System of essential oil and essence by capillary column gas chromatography and the results are satisfactory.

Effects of gossypol on Na+, K+ transmembrane fluxes in human red cells.

The effects of gossypol-acetic acid (a male contraceptive) on transmembrane fluxes of sodium and potassium in human red cells were studied, in comparison with the effects of ouabain (an inhibitor of Na+-K+-ATPase) and furosemide (an inhibitor of Na+, K+ cotransport). It was found that gossypol may be an inhibitor of outward (Na+, K+) cotransport in human red cells but has no significant effect on (Na+, K+)-ATPase. The results provide new evidence for elucidating the mechanism of hypokalemia caused by gossypol.