Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ²=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ²=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ²=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Male ; Female ; Child ; Humans ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Retrospective Studies ; Survival Analysis ; Mutation ; Hematopoietic Stem Cell Transplantation

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.

China ; Humans ; Otolaryngology

OBJECTIVE: To investigate the overview of thrombosis in myeloproliferative neoplasms(MPN) patients, and to explore the risk factors of thrombosis at diagnosis and during follow-up. METHODS: The clinical data of 388 MPN patients treated in our hospital were collected. The patients were followed up by outpatient and phone. The risk factors of thrombosis were analyzed by statistical methods. RESULTS: Among 388 MPN patients, 161 patients (41.49%) showed thromboses at diagnosis or during follow-up. Among them, 92.55% were arterial thromboses, 146 cases (96.27%) were complicated with thromboses at diagnosis, and 36 cases (11.46%) showed newly thromboses or progression of previous thromboses among the 314 received full follow-up patients. Age (P＜0.001, HR:1.033, 95%CI:1.016-1.051), JAK2V617F mutation (P=0.037, HR:1.72, 95%CI: 1.033-2.862), hypertension (P＜0.001, HR:2.639, 95%CI:1.659-4.197) and hyperlipidemia (P＜0.001, HR:2.659, 95%CI:1.626-4.347) were the independent risk factors affecting thrombosis at diagnosis of the patients. During the follow-up, age (P=0.016, HR:1.032, 95%CI: 1.006-1.059) and previous thrombosis history (P=0.019, HR:2.194, 95%CI: 1.135-4.242) were the independent risk factors affecting the progression of thrombosis at different sites or on the basis of the previous thrombosis in the patients. CONCLUSION Patients with advanced age, JAK2V617F mutation or complicated with hypertension and hyperlipidemia shows a higher risk of thrombosis at diagnosis, while the patients with advanced age or previous thrombosis history shows a higher risk of progression of thrombosis during the follow-up.
Humans ; Myeloproliferative Disorders/genetics* ; Neoplasms ; Philadelphia Chromosome ; Risk Factors ; Thrombosis

Shugoshin-1 (SGOLl) is one of the human homologues of yeast Shugoshin that locates in the centromeric region. It prevents premature division of the eentromerie cohesin complex and maintaining chromosome stability. Very recently, the role of SGOLl in tumors has emerged, but its role in lung cancer is unclear. In this study, we identify that SGOLl was upregulated in lung cancer samples from the TCGA database (n=529, P< 0.00001), which was correlated to the overall survival time of lung cancer patients (P = 0.0049). Detected by qRT-PCR and Western blotting, we demonstrate that SGOLl was consistently upregulated in lung cancer cell lines than normal epithelial cell line. Regulatory effects of SGOLl on cell viability, clonality, migration and invasion of lung cancer cells A549 and NCI-H2405 were examined by Cell Counting Kit-8 (CCK8), Colony formation, Scratch and Transwell assays, respectively. Compared with the control group, knockdown of SGOLl significantly inhibited proliferation, migration and invasion in A549 and NCI-H2405 cells (P<0. 05). A positive correlation was identified between expression levels of pyruvate kinase muscle isoenzyme 2 (PKM2) and SGOLl in the TCGA data-base (r=0. 38, P = 0). Western blotting results showed that knockdown of SGOLl in A549 and NCI-H2405 cells down-regulated PKM2 as well. In addition, co-interventions of SGOLl and PKM2 were performed in A549 and NCI-H2405 cells to clarify the interaction mechanism between them. The results showed that overexpression of PKM2 in lung cancer cells could partially reverse the regulatory effects of SGOLl knockdown on proliferation, migration and invasion (P<0. 05). Therefore, our study showed that SGOLl promoted the proliferation, migration and invasion of lung cancer cells by regulating PKM2. This study provided a theoretical basis for the mechanism of SGOLl in lung cancer.

【Objective】Platelet hyper- reactivity plays an important role in thrombosis and cardiovascular diseases. As a dietary supplement，Fruitflow，a water-soluble tomato concentrate，plays an important role in preventing cardiovascular diseases，but the mechanisms have been poorly understood，and there is no direct evidence about the effect of Fruitflow on thrombosis. This study intends to explore the effects of Fruitflow on platelet aggregation，activation and thrombosis in healthy people，and explore its possible mechanism.【Methods】Platelets from healthy men and women were incubated with different concentrations（0，20，40，80 mg/L）of Fruitflow，and the platelet aggregation was measured by platelet aggregometer. Platelet αIIbβ3 activation and fibrinogen binding to the activated platelets was measured by flow cytometry. The thrombosis in FeCl3- induced mesenteric artery thrombosis model in mice was observed by stereoscopic fluorescence microscope. The bleeding time was measured by tail clipping in mice. The total and phosphorylation levels of platelet Akt， Erk1/2 and JNK were determined by Western blotting.【Results】After the stimulation of ADP，Fruitflow could significantly attenuate platelet aggregation in the dose of 20，40，80 mg/L. Compared with that in the control group（43.75±5.91）%， platelet aggregation in the 80 mg/L group decreased to（8.25 ± 4.57）%（P < 0.000 1）. Fruitflow also inhibited the activation of platelet αIIbβ3. Compared with that in the control group（79.36±6.26），the platelet αIIbβ3 in the 80 mg/L group decreased to（65.79±5.73，P < 0.01）. Fruitflow reduced the platelet fibrinogen binding to the activated platelets. Compared with that in the control group（69.34 ± 6.63），platelet fibrinogen binding to the activated platelets in the 80 mg/L group decreased to（56.70±8.86，P < 0.05）. Fruitflow attenuated the thrombosis in FeCl3-induced mesenteric artery thrombosis model. Compared with that in the control group（22.50±4.86），the vessel occlusion in the 80 mg/L group was extended to（39.20 ± 4.61，P < 0.01）. There was no statistical difference between the control group （5.95 ± 0.69） and the 80 mg/L group（5.74 ± 0.76）in bleeding time（P > 0.05）. Fruitflow down- regulated the phosphorylation levels of platelet Akt， Erk1/2 and JNK proteins. Compared with the control group，P- Akt/Akt decreased from 0.97 ± 0.07 to 0.33 ± 0.13（P <0.001），P-Erk1/2/Erk1/2 decreased from 0.89±0.09 to 0.24±0.02（P < 0.01），and P-JNK/JNK decreased from 0.97±0.12 to 0.45±0.04（P < 0.01）in the 80 mg/L group.【Conclusion】Inhibition of platelet PI3K/Akt and MAPKs signaling pathway may be one of the mechanisms that Fruitflow inhibits platelet aggregation ，activation and thrombosis.

OBJECTIVE: To explore the value of water swallow test(WST)and simple two-step swallowing provocation test(SSPT)in the diagnosis of aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease. METHODS:87 hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease were recruited from the First Affiliated Hospital of Guangzhou Medical University during the period between December 2014 to December 2015. RESULTS: The number of patients of grade1,2,3,4 and 5 of water swallow test successively were 44,39,4,0 and 0. Patients with positive aspiration by the first-step(water injection of 0.4 mL)and the second-step(water injection of 2.0 m L)were 16 and 0. Patients with positive aspiration by radionuclide imaging was 35. Comparison of radionuclide imaging, the rate of missed diagnosis applying water swallow test was high 37.3%(31/83). Both the water swallow test and simple two-step swallowing provocation test have poor consistency with radionuclide imaging in the diagnosis of aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(McNemar consistency test P=0.00).CONCLUSION: There is a high rate of missed diagnosis applying water swallow test and simple two-step swallowing provocation test to diagnosis aspiration in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and combined use of multiple assessment methods can reduce the missed diagnosis rate of aspiration.

Objective:To observe the clinical efficacy of fire-needle therapy in treating deglutition disorders due to pseudobulbar palsy in the remission stage of stroke.Methods:Sixty-two eligible subjects were divided into a fire-needle group and a rehabilitation group by a simple randomization method at a ratio of 1:1.The two groups received same basic intervention;in addition,the fire-needle group received fire-needle treatment,while the rehabilitation group received rehabilitation training.The two groups of subjects all received a 3-week treatment and were evaluated by the dysphagia severity rating scale (DSRS),modified Mann assessment of swallow ability (MMASA) and Kubota Toshio swallow test (KTST) before and after the intervention.The complications and adverse events occurred during the trial were recorded.The data were statistically analyzed.Results:At the third week,the DSRS,MMASA and KTST scores changed significantly compared with the baseline in both groups (P＜0.05),and the changes in the fire-needle group were more significant than those in the rehabilitation group (P＜0.05).The between-group comparison at the third week showed that the therapeutic efficacy in the fire-needle group was superior to that in the rehabilitation group (P＜0.05).Conclusion:Fire-needle therapy can obviously change the DSRS,MMASA and KTST scores in pseudobulbar palsy in the remission stage of stroke,and significantly enhance the therapeutic efficacy of the treatment of deglutition disorders in this stage.

Through the traditional Chinese medicine inheritance platform system, with the help of medical records, Ye Tianshi and Wu Jutong's medication characteristics for summer heat sickness were analyzed, the laws of the two people's medication were summarized, and the similarities and differences between the two were explored to explore the relationship. As a result, it was found that both of them recognized the relationship between summer heat and wetness, and Wu Jutong believed that "wind" was also an important pathogenic factor. Both of the patients were treated with cold medicine and warm medicine. They used mostly bitter, sweet, pungent taste and lungs, spleen, stomach, and heart meridian are the main components; two are commonly used Armeniacae Semen Amarum, Talcum, Rehmanniae Radix, Ophiopogonis Radix, Pinelliae Rhizoma and other drugs, Ye Tianshi use Scrophulariae Radix, Tetrapanacis Medulla, Coicis Semen and other drugs more, Wu Jutong use Gypsum Fibrosum, Sojae Semen Praeparatum, Menthae Haplocalycis Herba and other drugs more; at the same time, a combination of two high-frequency medicines used by two people has been excavated, and a new prescription has been deduced to provide a reference for further understanding and treatment of summer diseases.

Objective To investigate the effect of different calcification patterns on the outcome of transcatheter aortic valve implantation (TAVI) by the finite element method. Methods Three calcified human aortic root models (coaptation line calcification model, attachment line calcification model and circular calcification model) were developed according to the location of calcified plaques on the aortic valve leaflets. The processes of self-expanding transcatheter aortic valve implanted into the 3 calcified models were simulated by ABAQUS software. The effects of different calcification patterns on the aortic root stresses, valve frame distortions and paravalvular gaps were analyzed. Results Circular calcification model had the largest maximum principal stress on calcified plaques (18.42 MPa), which might result in a higher risk of stroke after implantation; the circular calcification model also had the greatest distortion of the valve frame, which might lead to worse prosthetic durability; the paravalvular gaps area of the attachment line calcification model was 37.2 mm2, which was more than twice that of the other 2 models, causing more serious paravalvular regurgitation. Conclusions Different aortic valve calcification patterns are related to aortic root stresses, valve frame distortions and paravalvular gaps after TAVI, which will have an impact on postoperative complications and prothesis durability. The research findings provide references for the prediction of clinical outcome after TAVI.