[Clinical features and prognosis of core binding factor acute myeloid leukemia children in South China: a multicenter study].

Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFß-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×109/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFß-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFß-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×109/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFß-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.

[Association of small dense low-density lipoprotein cholesterol with H-type hypertension and MTHFR gene polymorphism].

To investigate the expression of small dense low-density lipoprotein cholesterol (sdLDL-C) in patients with H-type hypertension and its association with H-type hypertension and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. The retrospective study method was used,and a total of 207 hospitalized hypertensive patients (76 males and 131 females, aged 40-82 years, median age 66 years) admitted to the Zibo First Hospital from March 2021 to March 2022 were enrolled in this study. The levels of homocysteine (Hcy), sdLDL-C, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein (a) [Lp(a)] were measured. The patients were divided into H-type hypertensive group (n=105, 40 males and 65 females) and non-H-type hypertensive group (n=102, 36 males and 66 females) according to Hcy levels. The C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene was detected in each group. Logistic regression analysis was performed for the related factors of H-type hypertension. The serum sdLDL-C levels were (0.92±0.31) and (0.65±0.28) mmol/L in H-type hypertension group and non-H-type hypertension group, respectively. The sdLDL-C levels in H-type hypertension group were significantly higher than those in non-H-type hypertension group (t=6.500, P<0.01). There was no significant difference in the serum sdLDL-C levels between males and females in H-type hypertension group (t=-1.543, P=0.129). The CC, CT, TT genotypes and C and T allele frequencies of MTHFR C677T in H-type hypertension group were significantly different from those in non-H-type hypertension group (P<0.05). The Hcy and sdLDL-C levels in different genotypes of MTHFR in H-type hypertension group were significantly different (H=12.742, P=0.002; F=3.345, P=0.042). Among them, Hcy levels were higher in TT genotype than in CT and CC genotypes, respectively (Z=-28.099, P=0.003; Z=-16.112, P=0.040), and sdLDL-C levels were higher in TT genotype than in CC genotype (t=-2.587, P=0.012). Logistic regression analysis showed that age, sdLDL-C, and MTHFRC677T TT genotypes were associated with the development for H-type hypertension. In conclusion, the level of sdLDL-C is associated with MTHFR gene polymorphisms and may be associated with the development of H-type hypertension.

[Application effects of feedforward control theory in the rollover bed treatment of mass patients with burn-explosion combined injury].

Objective: To explore the application effects of feedforward control theory in the rollover bed treatment of mass patients with burn-explosion combined injury. Methods: A retrospective observational research was conducted. From June 13 to 14, 2020, 15 patients with severe burn-explosion combined injury caused by liquefied natural gas tank car explosion and conforming to the inclusion criteria were admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine. There were 13 males and 2 females, aged 33-92 (66±17) years. All the patients were treated with rollover bed from 48 h post admission, and the feedforward control theory was introduced, including establishing a special feedforward control management team for rollover bed, clarifying the duties of the medical staff in the rollover bed treatment of patients, implementing the cooperation strategy of multidisciplinary physician, training and examining for 80 nurses in the temporarily organized nurse team in the form of "rollover bed workshop", and formulating the checklist and valuation list of rollover bed treatment for continuous quality control. The frequency and the total number of turning over, and successful rate of one-time posture change with the rollover bed of patients within 30 days of admission were recorded, the occurrences of adverse events caused by improper operation for the rollover bed during the treatment were observed, including respiratory and cardiac arrests, treatment interruption, unplanned extubation, bed falling, and skin graft displacement. The lowest levels of arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), the number of patients with oxygenation index>300 mmHg (1 mmHg=0.133 kPa), and the occurrence of acute respiratory distress syndrome (ARDS) of patients within 2 days of admission and on the 30th day of admission were recorded. Results: Within 30 days of admission, the patients were turned over with the rollover bed for 2 to 6 times each day, with a total of 1 320 turning over operations, the successful rate of one-time posture change reached 99.9% (1 319/1 320), and no adverse event occurred. Within 2 days of admission, the lowest levels of PaO2 and PaCO2 of the patients were (100±19) and (42±4) mmHg, respectively, and the number of patients with mild, moderate, and severe ARDS were 10, 2, and 3, respectively, and none of the patients had oxygenation index>300 mmHg. On the 30th day of admission, the lowest levels of PaO2 and PaCO2 of the patients were (135±28) and (37±8) mmHg, respectively, 3 patients developed moderate ARDS, 1 patient developed severe ARDS, and 11 patients had oxygenation index>300 mmHg. Conclusions: The introduction of feedforward control theory in the treatment of rollover bed of mass patients with burn-explosion combined injury can ensure safe and successful completion of turning over with the rollover bed, promote the repair of burn wound, and improve respiratory function, and therefore improve the treatment quality of patients.

[Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development].

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Circular RNA circHIPK3 serves as a prognostic marker to promote chronic myeloid leukemia progression.

Increasing evidence demonstrate that circular RNAs (circRNAs) play critical role in regulation of gene expression, which participate in the pathogenesis of cancer, including chronic myeloid leukemia (CML). In this study, we aimed to investigate the expression profiling of circHIPK3 in CML. We found that circHIPK3 was significantly upregulated in peripheral blood mononuclear cells (PBMC) and serum samples from CML compared with healthy controls. High circHIPK3 expression predicted a poor outcome of CML patients. Further loss-function experiments suggested the oncogenic role of circHIPK3 in CML. Our findings provide insights on the role of circHIPK3 in the development and treatment of CML.

Parametric investigations on the saturation intensity of Coumarin 102 for stimulated emission depletion application.

Stimulated emission depletion (STED) microscopy performed using continuous-wave (CW) lasers has been investigated and developed by Willig et al. (Nature Methods, 2007, 4(11):915) for nearly a decade. Kuang et al. (Review of Scientific Instruments, 2010, 81:053709) developed the CW STED microscopy technique with 405 nm excitation and 532 nm depletion beams. In their research, Coumarin 102 dye was adopted and was found to be depletable. In this study, a parametric investigation of the depletion of Coumarin 102 dye is carried out experimentally. The influence of the excitation and depletion beam intensities and dye concentrations on the depletion efficiency are studied in detail. The results indicate the following: (1) The highest depletion occurs for the 100 µM Coumarin 102 solution, with a 1.4 µW excitation beam and a 115.3 mW depletion beam. (2) The minimum saturation intensity (Is) of STED, that is 13 MW cm-2 , is observed when the Coumarin 102 solution concentration is 10 µM. (3) Is values calculated directly from the depletion power derived with the cross-sectional area due to the full-width-at-half-maximum (FWHM) of the depletion beam show poor accuracy, where Is may be overestimated. Thus, a correction factor for the cross-sectional area is proposed. We also find that Is is not exactly constant for a fixed excitation beam power and dye concentration. This trend indicates that the conventional suppression function η(x)=e- ln (2)ISTED(x)/Is derived from picosecond STED may cause errors in evaluating the depletion process in CW STED microscopy.

Describing the quality of life of boys with haemophilia in China: Results of a multicentre study using the CHO-KLAT.

INTRODUCTION: The treatment of haemophilia varies across countries and across regions within some countries. Similar variation has been observed in health-related quality of life (HR-QoL). Relatively little is known about the HR-QoL of boys with haemophilia in China. AIM: The aim of this study was to describe the HR-QoL of boys with haemophilia in China using the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT). METHODS: Boys (4-18 years of age) with haemophilia and their parents were enroled in a cross-sectional study. All parents/guardians of study subjects were requested to complete a CHO-KLAT questionnaire during a clinic visit, and report on several other clinical and socioeconomic factors in the past year. Boys who were > 7 years also completed the CHO-KLAT. RESULTS: A total of 269 parents of boys with haemophilia, from 13 hospitals in 12 provinces, were enroled during 2014. The boys ranged from 4.0 to 17.9 years of age; 91% had haemophilia A, most had moderate (52%) or severe (36%) disease, and most were receiving sub-optimal on-demand therapy or low-dose prophylactic therapy. Child self-report CHO-KLAT scores were available for 171 boys ≥7 years of age and ranged from 24.2 to 85.3 with a mean of 57.6 (n = 171). Parent proxy-reported CHO-KLAT scores ranged from 25.0 to 88.7 with a mean of 55.1 (n = 269). CONCLUSION: HR-QoL scores in boys with haemophilia in China were substantially lower than reported from Canadian and European boys with haemophilia. Longer term prospective studies are required to examine the factors impacting the HR-QoL for boys with haemophilia in China.

[Efficacy and safety of a novel ultrafiltration device for treating patients with refractory heart failure].

OBJECTIVE: To evaluate the efficacy and safety of a new ultrafiltration device for treating refractory heart failure patients. METHODS: A total of 52 patients (37 male, age 29-85(33±44)years) with refractory heart failure were treated using a new ultrafiltration device (FQ-16). Body weight, dyspnea score, oxygen saturation (SatO2), left ventricular ejection fraction(LVEF), BUN, creatinine, electrolytes and blood gas analysis were assessed before and after the treatment. Hypotension event and other main adverse events were recorded. RESULTS: Ultrafiltration duration ranged between 8-22 hours. Total ultrafiltration volume was (4 489±1 548) ml. Compared with baseline, patients' body weight decreased from (75.3±8.74) kg to (69.8±8.39) kg (P<0.01), dyspnea score improved from 2.47±1.55 to 12.87±3.61 (P<0.01) and SatO2 increased from 91.0±6.01 to 96.4±2.52 (P<0.01) and LVEF increased from (30.0±4.1)% to (36.0±4.3)% (P<0.01) after ultrafiltration. Blood creatinine, BUN, electrolytes and blood gas analysis values were similar at baseline and post ultrafiltration. No hypotension event and other main adverse events occurred during the ultrafiltration treatment. CONCLUSIONS: The novel ultrafiltration device adequately relieved hypervolemia and dyspnea in patients with refractory heart failure and the treatment process is safe in this patient cohort.

[Analysis on the nuclear division index of peripheral blood lymphocytes in the 281 general population of Anhui, China].

OBJECTIVE: To investigate the reference range and influeing factors of the nuclear division index (NDI) of peripheral blood lymphocyte in Chinese general population in Anhui province. METHODS: We selected 281 subjects from the general poulation in Anhui province, without occupational exposure to genetic toxicants and no chronic disease history. We used questionnaires to collect occupational history, age, gender, region, body mass index, smoking, and alcohol drinking status etc. NDI was measured by cytokinesis block micronucleus assay in peripheral blood lymphocytes, and the related factors were also analyzed. And NDI was used as the dependent variable, age, gender and other factors as independent variables to conduct stepwise multiple linear regression. RESULTS: We found the data of NDI according with normal distribution, and the nuclear division index was 1.71±0.22, the minimum value was 1.10 while the maximum was 2.36. The results showed that NDI value of the males (1.67±0.20) were lower than that of the females (1.76±0.24), the difference was statistically significant (t=-3.65, P<0.001); current smokers NDI (1.66±0.18) lower than non-smokers (1.73±0.24) differences were statistically significant (t=3.06, P=0.002); the NDI of drinking groups (1.66±0.20) was lower than that of non-drinking population (1.74±0.23), the differences was statistically significant (t=3.15, P=0.002); Using multiple stepwise linear regression calibration factors and found that gender was an independent factor of NDI (ß=0.098, Sx=0.027, t=3.66, P< 0.001). CONCLUSION: We set the reference value on the nuclear division index among general population of survey areas in this study, it could provide a reference for similar studies and will provide reference for better evaluation of the effects of hazards on the body.

Establishing a conceptual model for photochemical ozone pollution in subtropical Hong Kong.

Photochemical ozone (O3) formation is related to its precursors and meteorological conditions. A conceptual model of O3 air pollution is developed based on the analysis of data obtained at Tung Chung (TC) in Hong Kong. By comparing meteorological parameters between O3 and non-O3 episode days, it was found that high temperatures, strong solar radiation, low wind speeds and relative humidity, northeasterly and/or northwesterly prevailing winds were favorable for the O3 formation, while tropical cyclones were most conducive to the occurrence of O3 episodes. Backward trajectories simulation and graphical illustration of O3 pollution suggested that super-regional (i.e. central and eastern China) and regional (i.e. Pearl River Delta, southern China) transport was another factor that contributed to high O3 levels in Hong Kong. The photochemical O3 formation, generally VOC-limited in Hong Kong, was controlled by a small number of volatile organic compounds (VOCs). Furthermore, the positive matrix factorization (PMF) simulation suggested that solvent usage and vehicular emissions are the major contributors to ambient VOCs in Hong Kong. Finally, this paper presents recommendations for further O3 research and implementation of O3 control strategies.

The relationship between management safety commitment and patient safety culture.

AIM: The study aims to explore the relationship between management safety commitment and patient safety culture using data from a Chinese hospital. BACKGROUND: Developing a positive patient safety culture has been suggested as an important strategy to improve the quality of health services and patient safety. Management safety commitment has been identified as key to establishing a culture of safety. However, little empirical evidence could be found in the literature to substantiate the relationship between management safety commitment and patient safety culture. Even less is known about the relationship in a Chinese hospital setting. METHODS: The study used a correlational research methodology with a cross-sectional survey design. A total of 248 registered nurses, including 20 nurse managers and 228 staff nurses, were surveyed using self-administered questionnaires. Both descriptive and inferential statistics were used to explore the relationship between management safety commitment and patient safety culture. FINDINGS: The mean score of safety commitment was 8.38 on a 0-10 visual analogue scale. The mean score of patient safety culture was 148.66. Staff nurses scored patient safety culture significantly lower than those of nurse managers (F = 18.88, P < 0.01). In addition, management safety commitment was significantly related to patient safety culture (r = 0.46, P < 0.01) and was an important predictor of patient safety culture (F = 65.29, P < 0.01). CONCLUSIONS: The findings provide significant empirical evidence that management safety commitment is associated with the culture of patient safety. Thus, to build a positive safety culture, managers need to visibly commit to patient safety and be a role model to ensure patient safety.

Experimental study on the mechanical properties of the horn sheaths from cattle.

Bovine horn is composed of a sheath of keratin overlying a bony core. Previous studies of the bovine horn sheath have focused mainly on its morphology and compositions. In the present paper, we performed a series of uniaxial tension, three-point bending, and fracture tests to investigate the structural and mechanical properties of the horn sheaths from subadult cattle, Bos taurus. The effects of hydration on the mechanical properties were examined and their variations along the longitudinal direction of the horn sheath were addressed. Scanning electron microscopy of the fracture surfaces showed that the horn sheath has a layered structure and, more interestingly, the laminae have a rippled appearance. The Young's modulus and tensile strength increase from 850 MPa and 40 MPa at 19% water content to 2.3 GPa and 154 MPa at 0% water content, respectively. The Poisson's ratio of the horn sheath was about 0.38. The critical stress intensity factor was about 4.76 MPa m1/2 at an intermediate hydration (8% water content), greater than that at 0% water content (3.86 MPa m1/2) and 19% water content (2.56 MPa m1/2). The bending properties of the samples varied along the length of the horn. The mean flexural moduli of the specimens in the distal, middle and proximal parts were about 6.26 GPa, 5.93 GPa and 4.98 GPa, respectively; whereas the mean yield strength in the distal segment was about 152.4 MPa, distinctly higher than that in the middle (135.7 MPa) and proximal parts (116.4 MPa). This study deepens our understanding of the relationships among optimal structure, property and function of cattle horn sheaths.

Effect of interfacial slippage in peel test: theoretical model.

Peel test is an efficient method to assess the performance and characteristics of materials such as adhesives and adhesive tapes. Recent experiments evidenced that the measured adhesive strength is closely related to the shear-induced interfacial slippage near the delamination front due to the concomitant Poisson contraction effect of the adhesive. Based on the experimental observations, a theoretical model is presented in this paper to examine the effect of the shear-induced interfacial slippage in the peel test. The influence of the interfacial slippage, represented by the shear displacement in the cohesive zone, on the fracture energy of decohesive zone is analyzed. An implicit expansion method with a Gauss-Chebyshev quadrature scheme is used to derive the solution. It is found that the length of the slippage zone and the receding contact angle of adhesives are the two most significant contributors to the total fracture energy of the decohesive zone. These results demonstrate that the mechanism of interfacial slippage plays a significant role in the adhesion and peeling behaviors of adhesives.

Activation of presynaptic D1 dopamine receptors by dopamine increases the frequency of spontaneous excitatory postsynaptic currents through protein kinase A and protein kinase C in pyramidal cells of rat prelimbic cortex.

To determine the effect of dopamine on the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in pyramidal cells of layers V-VI of the prelimbic cortex, whole-cell patch-clamp recordings were made from 92 pyramidal cells of layers V-VI of the rat prelimbic cortex. In normal buffer, dopamine 100 microM apparently increased the frequency of spontaneous EPSCs. Decreasing the concentration of dopamine from 100 to 50 microM was accompanied by a decreased effect of dopamine. Further decreasing the dopamine concentration to 10 and 1 microM had no effects on the frequency of spontaneous EPSCs. In the presence of tetrodotoxin or cadmium, the increasing effect of dopamine was eliminated. The increasing effect of dopamine was blocked by the dopamine D1 receptor antagonist SCH23390, but not by the dopamine D2 receptor antagonist sulpiride. The D1 receptor agonist SKF38393 partially mimicked the increasing effect, but the D2 receptor agonist quinpirole did not. The alpha(1)-adrenoceptor antagonist prazosin could not block the increasing effect of dopamine on the frequency of spontaneous EPSCs in most cells tested. The protein kinase A inhibitor H-89 and the protein kinase C inhibitor chelerythrine could antagonize the effect of dopamine. The protein kinase A activator forskolin and the protein kinase C activator phorbol 12,13-dibutyrate could mimic the effect of dopamine. These results indicate that dopamine, presynaptically acting on dopamine D1 receptors, increases the frequency of spontaneous EPSCs via intracellular protein kinase A and protein kinase C signaling pathways in pyramidal cells of layers V-VI of the prelimbic cortex.

Antihyperlipidemic capsules in the treatment of hyperlipidemia and its clinical effect on hemorheology and aggregation of thrombocytes.

The authors treated 54 cases of hyperlipidemia with the antihyperlipidemic capsules and the total short-term effective rate was 77.8%. The capsules also showed obvious effects in improving hemorheology, reducing aggregation of thrombocytes, and lowering the blood pressure. The authors believe they would be useful in the prevention and treatment of ischemic apoplexy and coronary disease.

[Clinical application of carcinoembryonic antigen (CEA) monoclonal antibodies (McAbs)].

CEA McAbs, recognizing three different epitopes on CEA molecules, were used to measure serum CEA level in cancer patients by enzyme-immunoassay (EIA). The results, as compared with those using polyclonal antibodies, indicated that the positive rate was higher while the false positivity was lower. Immunohistochemistry of tumour sections showed that the CEA McAbs are bonded to 80-90% of gastrointestinal cancers. Although the normal colon epithelium occasionally reacted with CEA McAbs, other normal tissues did not. After in vivo administration of radio-labeled CEA McAbs to nude mice xenograft with human colon cancer, the radio-isotope was found to be concentrated preferentially in the tumour. The ratio of tumour and normal tissue was 3.6-11.8 after 48 hours following administration. Thus, the CEA McAbs can be used clinically not only for serum CEA determination but also for diagnostic imaging.