[Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase].

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Alterations of regional homogeneity in perimenopause: a resting-state functional MRI study.

OBJECTIVE: Regional homogeneity (ReHo) was used to evaluate the changes of brain function and the relationship with cognitive function in perimenopausal women. METHODS：: The cross-sectional study recruited 25 perimenopausal women and 25 postmenopausal women who underwent sex hormone level measurements, clinical and neuropsychological assessments, and magnetic resonance imaging (MRI) scans. ReHo was measured based on the resting-state functional MRI (rs-fMRI) data and the differences in ReHo between the perimenopausal and postmenopausal groups were compared. Gray matter volume (GMV) values of brain regions with differences (region of interest [ROI]) in ReHo were extracted and the differences of GMV between the two groups were compared. We analyzed the correlations of the ReHo and GMV values of these ROIs with the results of sex hormone levels, clinical and neuropsychological assessments in the two groups. RESULTS: ReHo values in the left lingual gyrus and the right precentral gyrus increased in perimenopause, whereas ReHo values in the left inferior temporal gyrus and bilateral putamen decreased. Correlation analysis showed that the ReHo values of the left inferior temporal gyrus positively correlated with the reaction time of the Stroop color word test in perimenopausal women. CONCLUSIONS: Changes in abnormal patterns of the ReHo in perimenopausal women affect cognitive function. These changes in brain function may provide more insights and information on the neural mechanisms of cognitive dysfunction in perimenopausal women.

[Prognostic evaluation of nutritional indicators in patients with limited-stage small cell lung cancer].

Objective: To explore the effect of nutritional status pre-and during chemoradiotherapy on the prognosis of patients with limited- stage small cell lung cancer (LS-SCLC). Methods: We retrospectively collected medical records of 172 LS-SCLC patients undergoing concurrent chemoradiotherapy in our hospital from 2000 to 2014, with 126 males and 46 females. The data of complete blood count and hepatic and renal function were collected before initial treatment, before radiotherapy, 4 weeks during radiotherapy, and 1 month after complete of treatment. The prognostic nutritional index(PNI)was calculated. Kaplan-Meier method was used to calculate the survival rate. Log-rank test was performed used to compare the survival differences between groups. Multivariate prognostic analysis was performed using Cox regression model. Results: The median overall survival (OS) was 21 months, with median progression-free survival (PFS) of 11 months. At the beginning of treatment, patients with pre-treatment PNI ≥ 53 had significantly superior OS (median 37 vs 15 months, P=0.001) and PFS (median 16 vs 10 months, P=0.017). Patients with pre-treatment hemoglobin ≥140 g/L and <140 g/L had an median OS of 32 months and 17 months (P=0.019), and median PFS of 16 months and 9 months (P=0.040), respectively. During chemoradiation, patients with elevated hemoglobin had similar median OS compared with those had decreased hemoglobin (27 vs 18 months, P=0.063, but superior median PFS (15 vs 9 months, P=0.017). Multivariate analysis revealed that prophylactic cranial irradiation, pre-treatment hemoglobin ≥140 g/L, and pretreatment PNI ≥53 were independent predictors of OS and PFS in patients with LS-SCLC. Conclusion: Pre-treatment nutritional status and the changes of nutritional status during chemoradiotherapy is significantly associated with the prognosis of patients with limited-stage small cell lung cancer. The patients with better pre-treatment nutritional status have a better prognosis.

LncRNA TUG1 aggravates the progression of cervical cancer by binding PUM2.

OBJECTIVE: To illustrate the role of long non-coding RNA (lncRNA) TUG1 in the influence of the progression of cervical cancer (CC) and its underlying mechanism. PATIENTS AND METHODS: TUG1 level in CC tissues and adjacent normal ones was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Its level in CC patients with different tumor, node, and metastasis (TNM) staging and the tumor sizes were detected as well. The prognostic potential of TUG1 in CC was assessed by introducing the receiver operating characteristic (ROC) curves. The influences of TUG1 on proliferative and migratory abilities of HeLa and SiHa cells were evaluated. The subcellular distribution of TUG1 in CC cells was analyzed. Subsequently, the relative level of PUM2 (Pumilio2) in CC tissues and cell lines was examined. The prognostic potential of PUM2 in CC was assessed. RNA immunoprecipitation (RIP) and RNA pull-down were conducted to uncover the interaction between TUG1 and PUM2. Finally, the regulatory effect of TUG1/PUM2 axis on the viability of the CC cells was investigated. RESULTS: TUG1 was upregulated in CC, especially in those with worse TNM staging and larger tumor size. The overexpression of TUG1 enhanced proliferative and migratory abilities of Hela and SiHa cells. TUG1 was mainly distributed in the cytoplasm. PUM2 interacted with TUG1 and its level was positively regulated by TUG1. The silence of PUM2 reversed the promotive effect of TUG1 on the viability of the CC cells. CONCLUSIONS: TUG1 is upregulated in CC, which aggravates the progression of CC by interacting with PUM2.

Study on the structure and behaviour of cavitation bubbles generated in a high-intensity focused ultrasound (HIFU) field.

In this study, structures and behaviours of acoustic cavitation bubbles induced by a high-intensity focused ultrasound (HIFU) transducer, operating at its resonance frequency of 250kHz, are experimentally explored with corresponding observations captured by a high-speed video camera system. The experiments were conducted in an open-top Perspex water tank with deionized water, and illumination was provided by a LED spotlight which is placed beside the water tank throughout the whole experiment. Experimental results show that the structure of ultrasonically generated bubbles forms in a conical shape with several concentric bubble rings above the transducer. The distance between the adjacent rings with equal spacing as determined by the driving frequency of the HIFU transducer is experimentally measured and compared with the theoretical value. Then, the distribution of acoustic pressure in the acoustically driven liquid is further studied to investigate the behaviours of cavitation bubbles generated in a HIFU field. Additionally, the analysis of Bjerknes forces on the bubble surface which are induced by the gradient of acoustic pressure and the adjacent oscillating bubbles is quantitatively carried out, and the radius and velocity of a typical larger bubble are measured to characterize the behaviours of ultrasonically induced bubbles. Particularly, the physical phenomena of large bubbles including the coalescence, attraction or repulsion between adjacent bubbles, as well as the jumping of an acoustic bubble from the lower concentric ring level to the higher level, are analysed. The moving trajectory of the bubble is next obtained, and some conclusions are summarized to provide a greater understanding of the complex behaviours of the ultrasonically generated bubbles.

Evaluation on the impact of spontaneous reperfusion on cardiac muscle of acute myocardial infarction by three-dimensional speckle tracking imaging.

OBJECTIVE: To explore the effect of spontaneous reperfusion (SR) on three-dimensional myocardial strain in patients with acute anterior myocardial infarction by three-dimensional speckle tracking imaging (3D-STI) technology. PATIENTS AND METHODS: Patients diagnosed with acute anterior myocardial infarction during 2013 to 2016 were consecutively selected and divided into SR group and non-spontaneous reperfusion (Non-SR) group based on whether there was SR. Patients in both groups received direct percutaneous coronary intervention (PCI) in time window. Baseline information, patency rates of culprit vessel, durations of operation, intraoperative non-reflow phenomenon ratios, and thrombolysis in myocardial infarction (TIMI) blood flows after reperfusion of patients in each group were recorded. Hospital stays of patients were compared between the two groups. Before discharge, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) were measured. Global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of left ventricular (LV) were also detected by 3D-STI, so as to assess movement situations of ventricular wall and cardiac muscle in occlusive blood vessel distribution area. LVEF, LVEDd and various 3D-STI parameters were reexamined and compared one year after discharge. RESULTS: There were no significant differences between the Non-SR group and the SR group regarding the patency rate of culprit vessel, duration of operation, intraoperative non-reflow phenomenon ratio, TIMI blood flow after reperfusion, and LVEDd (p>0.05). Both LVEF before discharge and LV three-dimensional strain indexes of the SR group, were clearly higher than those of the Non-SR group (p<0.05). After one-year follow-up, the SR group had a remarkably lower LVEDd than the Non-SR group (p<0.05). LVEF of the SR group was overtly higher than that of the Non-SR group (p<0.05). LV three-dimensional strain indexes were also distinctly higher in the SR group than in the Non-SR group (p<0.05). There were good correlations between GLS, GRS, GCS and LVEF (r values were -0.620, -0.674 and 0.723, respectively). CONCLUSIONS: SR can improve nosocomial and long-term LV remodeling in patients with acute anterior myocardial infarction, and 3D-STI is able to assess ventricular remodeling after myocardial infarction.

[Reoperation for residual aneurysm of coronary anastomosis after Bentall procedure].

Objective: To introduce a new operative method for residual aneurysm of coronary anastomosis after Bentall procedure. Methods: Between March 2011 and December 2012, six patients in Beijing Anzhen Hospital with residual aneurysm of coronary anastomosis (CT showed goldfish eye sign at the openings of coronary) after Bentall procedure underwent the operation of concentric circular patch procedure under cardiopulmonary bypass. Femoral artery, right atrium and upper right pulmonary artery cannulation were used for cardiopulmonary bypass, and the artificial vessel was transected after cardiac arrest. A concentric circular patch was pruned, whose outside diameter was slightly larger than the aneurysm and the inside diameter was equal to the openings of coronary. The outer edge of the patch was anastomosed to the outer edge of the aneurysm (opening of artificial vessel in primary surgery) with 4-0 prolene. The inner edge of the patch was anastomosed to the openings of coronary with 5-0 prolene. Results: All patients had clinical recovery. Postoperative CT demonstrated the disappearance of residual aneurysm during follow-up (the goldfish eye sign disappeared). Conclusion: The concentric circular patch procedure is a feasible treatment for residual aneurysm of coronary anastomosis.

[Surgical treatment of aortic dissection with lower extremity ischemia].

Objective: To explore the clinical outcome of the surgical treatment for aortic dissection with lower extremity ischemia. Methods: Between March 2009 and April 2013, 14 patients with type A aortic dissection and lower extremity ischemia underwent Sun's procedure in Beijing Anzhen Hospital. Ascending aorta-iliac artery bypass, ascending aorta-femoral artery bypass, femoral-femoral artery bypass and axillary -femoral artery bypass were performed on some severe patients at the same time. Results: Two death occurred, and the others were improved or recovered from symptoms. Follow-up was complete with an average time of 24 months and no aortic relevant complications occurred. Conclusion: As for patients with type A aortic dissection and lower extremity ischemia, simultaneous radical femoral artery bypass procedure is effective in improving their survival rate and quality of life.

[Progress of problems related to the reconstruction of aortic arch in acute type A aortic dissection].

Aortic arch reconstruction is one of the most challenging operations in aortic surgery. Anatomical abnormalities of the aortic arch, including bovine aortic arch, aberrant right subclavian artery, and single vertebral artery have direct impact on the choice of surgical procedures and methods of brain protection.The risk of aortic arch reconstruction and the difficulty of operation, it is possible to avoid the injury of patients by strictly grasping the indication of operation. Intraoperative arterial cannulation and brain protection strategies are directly related to the success of the operation. This article makes a brief review of the above problems in the reconstruction of the aortic arch, hoping to be helpful to the cardiovascular surgeon.

[The application of laser in endodontics].

Since laser was introduced in the field of medicine in 1970's, its application range has continuously expanded. The application of laser in endodontics also increased due to its safety and effectiveness in dental treatments. The majority of the laser application researches in dentistry focused on dentin hypersensitivity, removal of carious tissues, tooth preparations, pulp capping or pulpotomy, and root canal treatment. In this article, we reviewed literature on the effects of laser in the treatments of dental and pulp diseases.

Regulation of pancreatic exocrine secretion in goats: differential effects of short- and long-term duodenal phenylalanine treatment.

Four yearling goats (31.2 ± 2.5 kg), surgically fitted with common bile duct reentrant and duodenal catheter, were used in two 4 × 4 Latin square design experiments to investigate the effects of duodenal infusion of phenylalanine for different times on pancreatic exocrine secretion (PES). In experiment 1 (the long-term experiment), goats were duodenally infused with 0, 2, 4 or 8 g/day phenylalanine for 14 day. Pancreatic juice and jugular blood samples were collected over 1-h intervals for 6 h daily from day 11 to day 14 to encompass a 24-h day. In experiment 2 (the short-term experiment), goats were infused with phenylalanine for 10 h continuously at the same infusion rate as experiment 1 after feed deprivation for 24 h repeated every 10 day. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The volume and pH of pancreatic juice were measured, and a 5% subsample was composited and frozen until analysis of enzyme activities. Plasma was frozen until analysis of insulin and cholecystokinin (CCK). In experiment 1, pancreatic juice, α-amylase secretion and plasma CCK concentration responded quadratically (p < 0.05), with the top value observed at the 2 g/day phenylalanine. Trypsin secretion had a quadratic response (p < 0.05), with secretion increasing up to 4 g/day phenylalanine and decreasing thereafter. Phenylalanine linearly decreased pancreatic protein and lipase secretion (p < 0.05). The results of correlation analysis showed significant correlations (p < 0.05) between plasma CCK concentration and secretion of α-amylase and trypsin. However, the short-term phenylalanine infusion did not influence (p > 0.05) pancreatic juice, protein, α-amylase, lipase, trypsin secretion and plasma CCK concentration. These results indicate PES of ruminants is stimulated by phenylalanine and is potentially mediated by CCK in the long-term duodenal infusion treatment, but is not influenced by phenylalanine in the short-term duodenal infusion treatment.

Neuroprotective effect of deep hypothermic circulatory arrest with low priming volume: study in a rabbit model.

OBJECTIVE: The aim of the study was to investigate the possible neuroprotective effects of a low priming volume following deep hypothermic circulatory arrest (DHCA) in a rabbit model. METHODS: Rabbits were randomized into three groups: DHCA with low priming volume (Group L), DHCA with high priming volume (Group H), and sham-operated group (Group S). The priming volume of Groups L and H were 75 ml and 210 ml, respectively. The rabbits were simultaneously placed on CPB and brain microdialysis, cooled to 16 to 18 degrees C with DHCA for 60 minutes. Physiological parameters were regularly recorded. The extracellular levels of glutamate, glucose, lactate, and pyruvate in the hippocampus were collected by microdialysis and measured by HPLC and a microdialysis analyzer. Brain damage was evaluated with light microscopy and electron microscopy and TUNEL staining. RESULTS: In order to keep the mean arterial pressure and acid-base balance within defined physiological ranges, more doses of dopamine and sodium bicarbonate were administered in Group H than in Group L (P < 0.05). The ratios of lactate/glucose and lactate/pyruvate in Group H increased significantly compared with those in Group L from the beginning of weaning from CPB (P < 0.05). The levels of extracellular glutamate in the two DHCA groups increased significantly (P < 0.05). After weaning from CPB, the glutamate values in Group H remained at higher levels compared with those in Group L (P < 0.05). The percentage of injured neurons, TUNEL positive staining, and the mitochondria score of the hippocampus CA1 in Group H were significantly higher than in Group L (P < 0.05). CONCLUSIONS: A low priming volume during DHCA could have a neuroprotective effect compared with a high priming volume.

A mouse model of a human multiple GIST family with KIT-Asp820Tyr mutation generated by a knock-in strategy.

Several families exhibiting multiple gastrointestinal stromal tumours (GISTs) and germline c-kit gene mutations at exons 8, 11, 13, or 17 have been reported. These patients also exhibit diffuse hyperplasia of the interstitial cells of Cajal (ICCs) as a pre-existing lesion of multiple GISTs. We generated a mouse model of a family with germline c-kit gene mutation at exon 17, and compared the phenotypes between the mice and humans. The mouse counterpart (KIT-Asp818Tyr) of the human KIT-Asp820Tyr mutation was transmitted into germline by a knock-in strategy. Mating of male and female heterozygotes (KIT-Asp818Tyr/+) resulted in the generation of homozygotes (KIT-Asp818Tyr/KIT-Asp818Tyr). Histological examination revealed that all heterozygotes had both a small KIT-positive mesenchymal tumour at the caecum, consistent with GIST, and KIT-positive diffuse spindle-shaped cell proliferation in the distal oesophagus, stomach, proximal duodenum, and colon consistent with ICC hyperplasia. All homozygotes exhibited a larger caecal tumour and more prominent spindle-shaped cell proliferation compared with the heterozygous mice, and they usually died within 10 weeks after birth, likely due to ileus. The small intestine of both genotypes showed no apparent morphological abnormality, and autonomous contraction of the ileal segments appeared normal. Western blotting demonstrated that the caecal tumours expressed phosphorylated KIT, MAPK, Stat1, and Stat5. These mutant mice are considered to be useful for further investigation of the mechanism of GIST development as a result of ICC hyperplasia and for assessment of the in vivo effects of drugs against molecular targets.

Brillouin study of the quantization of acoustic modes in nanospheres.

The vibrational modes in three-dimensional ordered arrays of unembedded SiO2 nanospheres have been studied by Brillouin light scattering. Multiple distinct Brillouin peaks are observed whose frequencies are found to be inversely proportional to the diameter (approximately 200-340 nm) of the nanospheres, in agreement with Lamb's theory. This is the first Brillouin observation of acoustic mode quantization in a nanoparticle arising from spatial confinement. The distinct spectral peaks measured afford an unambiguous assignment of seven surface and inner acoustic modes. Interestingly, the relative intensities and polarization dependence of the Brillouin spectrum do not agree with the predictions made for Raman scattering.

Comparative toxicity of seven insecticides to immature stages of Musca domestica (Diptera: Muscidae) and two of its important biological control agents, Muscidifurax raptor and Spalangia cameroni (Hymenoptera: Pteromalidae).

The toxicity of seven insecticides was evaluated against unparasitized Musca domestica L. pupae and pupae parasitized by Muscidifurax raptor Girault & Sanders or Spalangia cameroni Perkins, two important biological control agents. Only pyrethrins + piperonyl butoxide (Pyrenone) was less toxic to M. raptor compared with house flies. Conversely, all of the insecticides except crotoxyphos were less toxic to S. cameroni compared with house flies. A plateau in the tetrachlorvinphos bioassay line for S. cameroni suggested that this colony had approximately 45% resistant individuals. The selectivity observed between immature stages of house flies and M. raptor or S. cameroni is different from that reported against adult stages of these same species, suggesting that selectivity of an insecticide varies considerably between different life stages.