[Susceptibility vessel sign in subacute stroke patients with large vessel occlusion].

OBJECTIVE: To investigate the presentation of susceptibility vessel sign (SVS) in subacute stroke patients with large vessel occlusion. METHODS: We collected consecutive stroke patients who were admitted to Peking University First Hospital from December 2017 to August 2019 retrospectively. Those who had intracranial large vessel occlusion and received sensitivity weighted imaging (SWI) within 3 to 14 days after stroke onset were included in our analysis. The diagnosis of large vessel occlusion was based on magnetic resonance angiography (MRA), CT angiography (CTA) or digital subtraction angiography (DSA). The demographic information, clinical characteristics and imaging results were obtained from medical record. The occurrence rates of SVS sign were compared between stroke patients with cardioembolism (CE) and large artery atherosclerosis (LAA). In the sensitivity analysis, we performed a subgroup analysis in those patients who received SWI within 7 to 14 days after stroke onset. We also compared the occurrence rate of SVS sign between the patients with and without atrial fibrillation. RESULTS: A total of 51 patients, 19 females and 32 males, with an average age of (63.04±11.23) years were analyzed in this study. Compared with LAA group, the patients in CE group were older and more likely to have an atrial fibrillation (P < 0.05). There were no significant differences between the CE group and LAA group in gender, hypertension, diabetes, coronary heart disease, hyperlipidemia, smoking, or National Institute of Health stroke scale(NIHSS) score at admission. SVS sign was found in 30 patients. Of whom, 3 were in CE group and 27 in LAA group. The occurrence rate of SVS sign was higher in the LAA group than in the CE group significantly (65.9% vs. 30.0%, P=0.039). The subgroup analysis showed that, in the patients who received SWI examination within 7 to 14 days after stroke onset, the differences between the two groups were still statistically significant (0 vs. 72.7%, P=0.006). Another sensitivity analysis showed that, the rate of SVS in the patients with atrial fibrillation was significantly lower than those patients without atrial fibrillation (25% vs. 65.1%, P=0.043). CONCLUSION: In subacute stroke patients, the occurrence rate of SVS sign in CE group was lower than that of LAA group. The significance of SVS sign in the differentiation of stroke subtype needs further validation.

A case of GNE myopathy mimicking hereditary motor neuropathy.

A 36-year-old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.

[Correlation between DCE-MRI quantitative perfusion histogram parameters, apparent diffusion coefficient and Ki-67 in different pathological types of lung cancer].

Objective: To explore the efficacy of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) histogram molecular imaging index, apparent diffusion coefficient (ADC) in different types of lung cancer and explore their correlation with Ki-67. Methods: A total of 33 cases of lung cancer patients confirmed by pathology in Shaoxing People's Hospital from March 2017 to March 2018 were collected, 28 males and 5 females aged 50-85 years old, including 15 cases of squamous cell carcinoma, 12 cases of adenocarcinoma, and 6 cases of small cell carcinoma. All patients performed DCE-MRI and DWI imaging within one week before surgery or puncture. ADC values, DCE-MRI quantitative perfusion parameters by histogram metrics analysis (mean value, skewness, kurtosis, uniformity, entropy, energy, quantile) of K(trans), K(ep), V(e), and V(p) were then collected. Ki-67 expression in lung cancer tissue was detected by immunohistochemical method. One-way analysis of variance and least significant difference were used to compare the differences among the parameters of the three groups which were normal distribution and equal variances, while Kruskal-Walls test and Mann-Whitney U test were used to compare the parameters that did not conform to normal distribution or variance. Pearson correlation analysis was used to compare the correlations between quantitative perfusion histogram parameters, ADC values and immunohistochemical scores of Ki-67. Results: The Ki-67 count in small cell lung cancer(458±82, P=0.011) and squamous cell carcinoma(355±277, P=0.034)were significantly higher than that in adenocarcinoma (168±164). The correlation analysis showed that there was a significant negative correlation between ADC values and Ki-67 (P=0.018, r=-0.416). And V(e) (Q5, Q10) was negatively related to Ki-67 (P=0.017, r=-0.420; P=0.040, r=-0.366). In squamous cell carcinoma patients, V(e) (homogeneity) was significantly negatively correlated with the expression of Ki-67 (P=0.033, r=-0.570). K(trans)(homogeneity) and V(e) (homogeneity, Q5, Q10, Q25) were significantly positively correlated with ADC values (P value from 0.001 to 0.035, r value from 0.545 to 0.765). Conclusion: DCE-MRI quantitative perfusion histogram parameters, ADC value can evaluate the lung cancer cell proliferation activity in different pathological types.

[Prediction of syncope with nonlinear dynamic analysis during head-up tilt in vasovagal syncope patients].

OBJECTIVE: To quantify the relationship between cerebral blood flow velocity and peripheral blood pressure during hypotension period, aiming to predict the brain hypotension before symptomatic occurrence. METHODS: Twenty vasovagal syncope (VVS) patients who had a previous clinical history were selected in groups and 20 pair-matched control subjects underwent 70° tilt-up test. The subjects remained supine for 30 minutes before recordings when Doppler probes, electrodes and Finapres device were prepared. After continuous baseline recordings for 10 min, the subjects underwent head up tilt (HUT) test (70°), and were standing upright for 30 minutes or until syncope was imminent. For ethical reasons, the subjects were turned back to supine position immediately after SBP dropped to ≥20 mmHg, when their consciousness persisted. The point of syncope was synchronized for all the subjects by the point SBP reached the minima. Their beat-to-beat blood pressures (BP) were recorded continuously and bilateral middle cerebral artery (MCA) flow velocities were obtained with two 2 MHz Doppler probes from a transcranial Doppler ultrasonography (TCD) system. A nonlinear dynamic method--multimodal pressure flow (MMPF) analysis was introduced to access cerebral autoregulation during different time intervals. We introduced a new indicator--syncope index (SI), which was extracted from blood flow velocity (BFV) signal to evaluate the variation of cerebral vascular tension, and could reflect the deepness of dicrotic notch in BFV signal. RESULTS: Compared with the syncope index of the baseline value at the beginning of the tilt test, SI in VVS group showed significantly lower when the VVS occurred (0.16±0.10 vs.0.27±0.10,P<0.01),while there was no significant difference in syncope index between the control group at the end of the tilt test and the baseline value at the beginning of the tilt test. For those VVS patients, pulse index and resistance index had no significant change. Syncope index decreased significantly 3 minutes before the point of syncope (0.23±0.07 vs.0.29±0.07,P<0.01). CONCLUSION: Dynamic regulation is exhausted when vasovagal syncope occurred. Tension decrease of small vessels could have some relationship with loss of the cerebral autoregulation capability. The proposed syncope index could be a useful parameter in predicting syncope of VVS patients since it decreased significantly up to 3 minutes earlier from the point of syncope.

[The correlation between the cell density of local advanced lung cancer tumor and the ADC value of 3.0 T MRI diffusion weighted imaging].

Objective: To investigate the correlation between tumorous cellular density (TCD) and apparent diffusion coefficient (ADC) of 3.0 T magnetic resonance diffusion weighted imaging (DWI) in local advanced lung cancer. Methods: From January 2015 to December 2017, a total of 59 patients with locally advanced lung cancer confirmed by pathology in Shaoxing People's Hospital who underwent DWI by 3.0 T magnetic resonance imaging were included.The ADC and TCD values of tumor were measured. The difference and correlation between ADC value and TCD in lung cancer were analyzed. Results: Among 59 lung cancer cases who were examined with DWI, 45 cases of TCD were obtained. Statistical analysis showed that the ADC value of small cell lung cancer (SCLC) was significantly higher than that of squamous cell carcinoma (P=0.011)and adenocarcinoma (P=0.004). TCD of small cell carcinoma was significantly higher than that of squamous cell carcinoma (P=0.007) and adenocarcinoma (P<0.01). There was no statistical difference in ADC value and TCD between squamous cell carcinoma and adenocarcinoma (all P>0.05). There was negative correlation between the ADC value and TCD in lung cancer (P=0.001, r=-0.534). Conclusions: DWI is not only beneficial to distinguish SCLC from squamous cell carcinoma and adenocarcinoma, but also can indirectly reflect the tumorous cellular density.It can provide a basis for monitoring the therapeutic effect of clinical lung cancer.

Analysis of specific serum markers of colon carcinoma using a Bhattacharyya-based support vector machine.

We aimed to evaluate the specificity of 12 tumor markers related to colon carcinoma and identify the most sensitive index. Bhattacharyya distance was used to evaluate the index. Then, different index combinations were used to establish a support vector machine (SVM) diagnosis model of malignant colon carcinoma. The accuracy of the model was checked. High accuracy was assumed to indicate the high specificity of the index. The Bhattacharyya distances of carcinoembryonic antigen, neuron-specific enolase, alpha-feto protein, and CA724 were the largest, and those of CYFRA21-І, CA125, and UGT1A83 were the second largest. The specificity of the combination of the above seven indexes was higher than that of other combinations, and the accuracy of the established SVM identification model was high. Using Bhattacharyya distance detection and establishing an SVM model based on different serum marker combinations can increase diagnostic accuracy, providing a theoretical basis for application of mathematical models in cancer diagnosis.

Sensitive measurement of quantity dynamics of FLT3 internal tandem duplication at early time points provides prognostic information.

BACKGROUND: The level of minimal residual disease (MRD) in acute myeloid leukemia (AML) at early time points (TPs) may be an important prognostic factor. Although internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been questioned for its instability based on semi-quantitative methods, we hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time PCR at early TPs before appearance of instability may provide prognostic information. PATIENTS AND METHODS: We measured mutant quantity in 493 serial samples from 55 patients with a median follow-up time of 64.8 months. The FLT3-ITD quantities after induction (TP1) and after the first post-induction chemotherapy (TP2) were analyzed. RESULTS: We found that lower FLT3-ITD levels at TP2 predicted longer overall survival (OS) and disease-free survival (DFS) regardless of cytogenetic risk. Multivariate analysis showed that ≥3 log reduction of FLT3-ITD at TP2 independently predicted better DFS and a trend toward better OS. FLT3-ITD disappeared at relapse in 16.7% of patients and none in those harboring mutant NPM1 compared with 29.4% in those with wild-type NPM1 (P = 0.032). CONCLUSIONS: Though the mutation may disappear at relapse in a few patients, FLT3-ITD levels at early TPs after chemotherapy provide prognostic information. FLT3-ITD is significantly more stable in those with mutant NPM1.

Acute myeloid leukemia bearing t(7;11)(p15;p15) is a distinct cytogenetic entity with poor outcome and a distinct mutation profile: comparative analysis of 493 adult patients.

Acute myeloid leukemia (AML) with t(7;11)(p15;p15), which results in a NUP98-HOXA9 fusion, is a distinct entity, but this subtype has not been characterized in detail. In a comprehensive study comparing 11 such patients with another 482 adult patients, we found that those with t(7;11) were younger (P=0.0076) and female (P=0.0111), with almost all having the M2-subtype of AML (P<0.0001). Even when those with low-risk karyotypes were excluded, patients with t(7;11) had poorer overall survival than the other AML group (median 13.5 and 20 months, respectively, P=0.045) and poorer relapse-free survival (median 6 and 12 months, respectively, P=0.003). The NUP98-HOXA9 fusion was strongly associated with KRAS and WT1 mutations (P=0.015 and P=0.0018, respectively). We characterized four varieties of this fusion, among which NUP98 exon 12/HOXA9 exon 1b was present in all 11 patients. We developed a highly sensitive and specific assay to quantify the abundance of leukemic cells, and found that the fusion remained detectable in morphological complete remission, even after allogeneic stem cell transplantation, suggesting that this disease was highly refractory to very intensive treatment. AML with NUP98-HOXA9 fusion therefore appears to have a distinct clinical and biological profile, and should be regarded as a poor prognostic group.

A door-to-door survey of intracranial atherosclerosis in Liangbei County, China.

We studied 590 asymptomatic villagers aged > or =40 years in Liangbei County in central rural China and found 41 subjects (prevalence 6.9%) with intracranial atherosclerosis. In a multivariate analysis, the significant risk factors for intracranial stenosis were hypertension (OR 2.53; 95% CI 1.12 to 5.72), glycosuria (OR 3; 1.19 to 7.97), heart disease (OR 4; 1.39 to 11.6), and family history of stroke (OR 5.2; 1.38 to 20). Intracranial atherosclerosis is not uncommon among asymptomatic Chinese subjects.

Indiscernible benefit of high-resolution HLA typing in improving long-term clinical outcome of unrelated umbilical cord blood transplant.

The success of allogeneic hematopoietic stem cell transplantation depends in part on the accuracy of human leukocyte antigen (HLA) matching between the donor-recipient pair. The higher the number of matching HLA alleles, the smaller the chance that the transplant recipient will develop complications. Umbilical cord blood (UCB) transplantation was noted to result in a remarkably low frequency and severity of graft-versus-host disease (GvHD) and graft rejection compared to that in unrelated bone marrow transplant recipients. At present most banks match UCB donors for respective recipients by HLA-A, -B low-resolution typing and -DRB1 high-resolution typing. We retrospectively conducted high-resolution sequence-based HLA typing on DNA samples available from 65 Chinese UCB-recipient pairs typed previously by using low-resolution sequence-specific oligonucleotide probes and sequence-specific primers, and evaluated the clinical outcome. High-resolution typing revealed imperceptible HLA alleles that were hardly identified in low-resolution typing. Univariate analyses demonstrated no significant correlation between the extents of high-resolution HLA disparity with engraftment, graft failure, acute GvHD, transplant-related mortality and long-term 6-year overall survival. Data from the study suggest that high-resolution typing for HLA-A, -B and -DRB1 contributed no substantial improvement to UCB transplant outcome. Low-resolution typing appears to be amenable to matching UCB-recipient pairs without compromising the quality of transplant.

Visualization of Rab3A dissociation during exocytosis: a study by total internal reflection microscopy.

Rab3A is a small G protein in the Rab3 subfamily, and is thought to act at late stage of exocytosis. However, the detailed mechanism of its action is not completely understood. To study the role of Rab3A in exocytosis, we used a total internal reflection fluorescence microscope to examine the fluorescence changes of EGFP-Rab3A-labeled and NPY-EGFP-labeled vesicles in PC12 cells upon stimulation. The fluorescence of EGFP-Rab3A-labeled and NPY-EGFP-labeled vesicles decreased while showing different patterns. The NPY-EGFP-labeled vesicles that exocytosed showed a transient fluorescence increase before NPY-EGFP fluorescence disappearance, which represents fusion and NPY release. This transient increase was diminished in cells that co-expressed the GDP-bound Rab3A mutant. The fluorescence of EGFP-Rab3A-labeled vesicles dispersed before disappearance, which represents the dissociation of Rab3A from the vesicles. The dispersion was not found in GTP-bound Rab3A mutant-labeled vesicles. Interestingly, EGFP-Rab3A F59S, a mutant unable to bind rabphilin, dissociates slower from the vesicles than wild type Rab3A and caused a slower release of NPY-EGFP. The results provide direct evidence to support the hypothesis that GTP hydrolysis and rabphilin are involved in Rab3A dissociation from the vesicles and the occurrence of exocytosis.

Banking and transplantation of umbilical cord blood in Guangzhou, China.

BACKGROUND: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells (HSC) for transplantation of patients with hematologic malignancies or hereditary diseases. METHODS: We developed a provincial UCB bank in Guangzhou, China, using good manufacturing practices and standard operating procedures to address donor eligibility, collection, characterization, processing, storage and release from quarantine. The banking activities were analyzed. RESULTS: From June 1998 to May 2005, 8623 UCB units of Han ethnic origin were collected; 4147 (48.1%) were stored, while 4476 (51.9%) were discarded as a result of pre-determined exclusion criteria. A median volume of 95.5 mL (range 60-227.7) and 1.2 x 10(9) (0.8-9.3) nucleated cells were collected. The cell viability was 97.8% (90-100%). The CD34+ cell count of 3691 (89.0%) UCB units was 5.2 x 10(6) (0.3-131.6) and clonogenic assays of 4036 (97.3%) UCB units demonstrated 9.8 x 10(5) (0.04-135.8) CFU-GM, 0.3 x 10(5) (0.0-18.6) CFU-GEMM and 8.8 x 10(5) (0.0-74.2) BFU-E. A total of 0.4% (15/3863) UCB derived from babies known to have health problems at age 6 months was discarded. Up to May 2005, 151 units were issued for transplantation to 127 patients [90 (70.9%) children and 37 (29.1%) adults]. The infused nucleated cells in unrelated single-unit recipients were 3.4 x 10(7)/kg (1.7-14.9) for adults (n=19) and 5.7 x 10(7)/kg (2.0-20.5) for children (n=71), respectively. The numbers of days for the engraftment of neutrophils among 65 children and 22 adults were 17 (7-41) and 20 (10-42), respectively. DISCUSSION: Data of this study show that stringent procedures and comprehensive policies are requisite for pursuing the banking and release of quality UCB for successful transplantation.