Micro-morphological feature visualization, auto-classification, and evolution quantitative analysis of tumors by using SR-PCT.

Tissue micro-morphological abnormalities and interrelated quantitative data can provide immediate evidences for tumorigenesis and metastasis in microenvironment. However, the multiscale three-dimensional nondestructive pathological visualization, measurement, and quantitative analysis are still a challenging for the medical imaging and diagnosis. In this work, we employed the synchrotron-based X-ray phase-contrast tomography (SR-PCT) combined with phase-and-attenuation duality phase retrieval to reconstruct and extract the volumetric inner-structural characteristics of tumors in digesting system, helpful for tumor typing and statistic calculation of different tumor specimens. On the basis of the feature set including eight types of tumor micro-lesions presented by our SR-PCT reconstruction with high density resolution, the AlexNet-based deep convolutional neural network model was trained and obtained the 94.21% of average accuracy of auto-classification for the eight types of tumors in digesting system. The micro-pathomophological relationship of liver tumor angiogenesis and progression were revealed by quantitatively analyzing the microscopic changes of texture and grayscale features screened by a machine learning method of area under curve and principal component analysis. The results showed the specific path and clinical manifestations of tumor evolution and indicated that these progressions of tumor lesions rely on its inflammation microenvironment. Hence, this high phase-contrast 3D pathological characteristics and automatic analysis methods exhibited excellent recognizable and classifiable for micro tumor lesions.

High-resolution quantitative phase imaging based on a spatial light modulator and incremental binary random sampling.

We propose a single-beam high-resolution quantitative phase imaging method based on a spatial light modulator (SLM) and an incremental binary random sampling (IBRS) algorithm. In this method, the image of the test object presents on the image sensor through an optical microscopy system composed of an objective lens and a collimating lens. A transmittance SLM displaying a group of well-designed IBRS patterns is inserted in the optical microscopy system to modulate the object wavefront. The phase information of the object image can be quantitatively retrieved from the recorded intensities using the IBRS algorithm and the amplitude obtained directly from the diffraction intensity. The IBRS algorithm employed in our method has higher accuracy for phase retrieval compared with our previously proposed complementary random sampling algorithm, which is confirmed by simulations. Further, we demonstrate experimentally the feasibility of our method through several examples: phase imaging of immersion oil droplets with a diffraction-limited lateral resolution of 1.54 µm and a few microbiological specimens with 0.70 µm. Experimental results reveal that our proposed method provides a feasible single-beam technique for quantitative phase imaging with a high spatial resolution.

[Risk factors for minimally invasive surfactant administration failure in preterm infants with respiratory distress syndrome].

OBJECTIVE: To identify risk factors for minimally invasive surfactant administration (MISA) failure in the treatment of preterm infants with respiratory distress syndrome (RDS) and the influence of MISA failure on neonatal outcome. METHODS: A retrospective analysis was performed for the clinical data of 148 preterm infants with a gestational age of ≤32 weeks and a clinical diagnosis of RDS, who were admitted to the neonatal intensive care unit of eight tertiary hospitals in Beijing, Tianjin and Hebei Province from July 1, 2017 to December 31, 2018 and were treated with MISA (bovine pulmonary surfactant, PS). According to whether MISA failure (defined as the need for mechanical ventilation within 72 hours after MISA) was observed, the infants were divided into two groups: MISA failure group (n=16) and MISA success (n=132). A logistic regression analysis was used to investigate the risk factors for MISA failure and its influence on neonatal outcome. RESULTS: The MISA failure rate was 10.8% (16/148). The logistic regression analysis showed that a high incidence rate of grade >II RDS before PS administration, low mean arterial pressure and high pulse pressure before administration, a low dose of initial PS administration, and long injection time and operation time were the risk factors for MISA failure (OR=5.983, 1.210, 1.183, 1.055, 1.036, and 1.058 respectively, P<0.05). After the control for the above risk factors, the logistic regression analysis showed that the MISA failure group had a significantly higher incidence rate of bronchopulmonary dysplasia (BPD) (OR=8.537, P<0.05). CONCLUSIONS: A high grade of RDS, a low mean arterial pressure, and a high pulse pressure before administration are independent risk factors for MISA failure, and a low dose of initial PS administration, a long injection time, and a long operation time may increase the risk of MISA failure. MISA failure may increase the incidence rate of BPD in preterm infants.

[A clinical analysis of late-onset sepsis in very low birth weight and extremely low birth weight infants].

OBJECTIVE: To study the clinical features and pathogenic bacteria of late-onset sepsis (LOS) in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. METHODS: Among the VLBW/ELBW infants with a gestational age of <32 weeks who were admitted to the hospital between January 2012 and December 2016, those with LOS were enrolled as the LOS group, and those without sepsis were matched for the infant with LOS in gestational age were enrolled as the control group. According to the presence or absence of in-hospital death, the LOS group was further divided into a death subgroup and a survival subgroup. Risk factors for LOS, clinical features, distribution of pathogenic bacteria, drug resistance, and high-risk factors for LOS-related death were analyzed. RESULTS: A total of 513 VLBW/ELBW infants were enrolled, and there were 65 infants in the LOS group and 130 in the control group. The incidence rate of LOS was 12.7%. In the LOS group, 6 infants died and 59 survived. Compared with the control group, the LOS group had a significantly lower birth weight (P<0.05) and significantly longer indwelling time of peripherally inserted central catheter (PICC), duration of mechanical ventilation, and length of hospital stay (P<0.05). Compared with the control group, the LOS group had a significantly higher proportion of small-for-gestational-age infants, infants undergoing mechanical ventilation, infants with neonatal necrotizing enterocolitis, or infants who died (P<0.05). Low birth weight, small-for-gestational-age infant, and long indwelling time of PICC were independent risk factors for LOS in VLBW/ELBW infants (OR=1.396, 2.550, and 1.068 respectively, P<0.05). Purulent meningitis was an independent risk factor for LOS-related death in VLBW/ELBWIs infants (OR=13.443, P<0.05). A total of 65 strains of pathogenic bacteria were cultured in the LOS group, among which there were 39 strains (60%) of Gram-negative bacteria, including 15 strains producing extended spectrum beta-lactamases (ESBLs), and antibiotics were applied for 67% (10/15) of the ESBL strains within 2 weeks before the onset of LOS. The rate of antibiotic use for ESBL strains was significantly higher than that for non-resistant strains [67% (10/15) vs 29% (7/24); P<0.05]. CONCLUSIONS: Low birth weight, SGA infant, and long indwelling time of PICC are independent risk factors for LOS in VLBW/ELBW infants, and death tends to occur in LOS infants with purulent meningitis. Most pathogenic bacteria of LOS are Gram-negative bacteria, and use of antibiotics within 2 weeks before disease onset may increase the risk of ESBL strain infection.

Synthesis and evaluation of pyrimidoindole analogs in umbilical cord blood ex vivo expansion.

The scarcity of hematopoietic stem cells (HSCs) significantly hindered their clinical potentials. Umbilical cord blood (UCB) has become the leading source of HSCs for both research and clinical applications. But the low content of HSCs in a single UCB unit limited its use only to pediatric patients. Various cytokines and small molecules have demonstrated strong abilities in promoting HSC ex vivo expansion, of which UM171 is the newest and by far the most potent HSC ex vivo expansion agent. In this study, we synthesized 37 pyrimidoindole analogs and identified 6 compounds to be potent in promoting HSC ex vivo expansion. In particular, analog 11 was found to be the most effective in stimulating ex vivo expansion of UCB CD34+ cells and CD34+CD38- cells. Initial data indicated that compound 11 promoted the absolute number of long term HSCs and inhibited their differentiation. UCB HSCs expanded with 11 retained adequate multi-lineage differentiation capacity. In addition, compound 11 is not cytotoxic at its test concentrations, suggesting that it merits further investigation for potential clinical applications.

Predictive Value of Free ß-hCG Multiple of the Median for Women with Preeclampsia.

BACKGROUND: Preeclampsia (PE) is relatively common and is unpredictable in its onset and progression. AIMS: We investigated the clinical value of using the multiple of the median (MoM) of free ß-human chorionic gonadotropin (ß-hCG) concentrations in women with normal pregnancy and PE. METHODS: This study was based on a dataset available from published studies, and the relevant studies were retrieved from multiple electronic databases. Data were extracted from case-control studies; a random-effects model was employed, and standardized mean difference and 95% confidence intervals were calculated. Twelve case-control studies (eleven English-based articles and one Chinese-based article) were analyzed in the current meta-analysis and included 702 patients with PE and 8,233 women with normal pregnancies. RESULTS: Statistical analysis revealed a higher MoM of ß-hCG serum levels in patients with PE. Ethnicity subgroup analysis showed that the MoM of serum ß-hCG levels was significantly higher in women with PE in both Asian and Caucasian populations. CONCLUSION: The MoM of ß-hCG serum levels was significantly increased in women with PE compared to women with normal pregnancies. Screening for serum ß-hCG MoM levels will be helpful in the early identification of pregnancies at risk of developing PE. © 2015 S. Karger AG, Basel.

P16INK4A and survivin: Diagnostic and prognostic markers in cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

OBJECTIVE: To explore the the correlations of p16INK4A (p16) and survivin expressions with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma. METHODS: The p16 and survivin expressions were detected in 50 cervical squamous cell carcinoma tissues, 150 various grades of CIN tissues and 30 normal cervical tissues using immunohistochemistry. All data were analyzed applying SPSS 17.0 software. RESULTS: The p16 and survivin expressions showed the presence of statistical significance in cervical cancer, CINI, CINII, CINIII and normal cervical tissues (P<0.05), and the comparison also revealed statistical significance among groups (all P<0.05); the p16 and survivin expressions were positively correlated with the grade of cervical diseases (both P<0.05). Moreover, p16 protein was associated with CIN grade and lymph node metastases in cervical cancer (all P<0.05); survivin protein was also related with clinical stages, CIN grade and lymph node metastases (all P<0.05); the p16 and survivin expressions were positively correlated with cervical cancer (r=0.854, P<0.001), and associated with poor prognosis of cervical cancer. CONCLUSION: Briefly, p16 and survivin expression may be correlated with the clinico-pathological and prognosis of cervical cancer.

Anti-VEGFR2-conjugated PLGA microspheres as an x-ray phase contrast agent for assessing the VEGFR2 expression.

The primary goal of this study was to evaluate the feasibility of using anti-vascular endothelial growth factor receptor 2 (VEGFR2)-conjugated poly(lactic-co-glycolic acid) (PLGA) microspheres as an x-ray phase contrast agent to assess the VEGFR2 expression in cell cultures. The cell lines, mouse LLC (Lewis lung carcinoma) and HUVEC (human umbilical vein endothelial cell), were selected for cell adhesion studies. The bound PLGA microspheres were found to better adhere to LLC cells or HUVECs than unbound ones. Absorption and phase contrast images of PLGA microspheres were acquired and compared in vitro. Phase contrast imaging (PCI) greatly improves the detection of the microspheres as compared to absorption contrast imaging. The cells incubated with PLGA microspheres were imaged by PCI, which provided clear 3D visualization of the beads, indicating the feasibility of using PLGA microspheres as a contrast agent for phase contrast CT. In addition, the microspheres could be clearly distinguished from the wall of the vessel on phase contrast CT images. Therefore, the approach holds promise for assessing the VEGFR2 expression on endothelial cells of tumor-associated vessels. We conclude that PLGA microsphere-based PCI of the VEGFR2 expression might be a novel, promising biomarker for future studies of tumor angiogenesis.

Visualization of microvasculature by x-ray in-line phase contrast imaging in rat spinal cord.

Computed tomography combined with angiography has recently been developed to visualize three-dimensional (3D) vascular structure in experimental and clinical studies. However, there remain difficulties in using conventional x-ray angiography to detect small vessels with a diameter less than 200 µm. This study attempted to develop a novel method for visualizing the micro-angioarchitecture of rat spinal cord. Herein, synchrotron radiation-based x-ray in-line phase contrast computed tomography (IL-XPCT) was used to obtain 3D micro-vessel structure without angiography. The digital phase contrast images were compared with conventional histological sections. Our results clearly demonstrated that the resolution limit of the spatial blood supply network in the normal rat thoracic cord appeared to be as small as ~10 µm. The rendered images were consistent with that obtained from histomorphology sections. In summary, IL-XPCT is a potential tool to investigate the 3D neurovascular morphology of the rat spinal cord without the use of contrast agents, and it could help to evaluate the validity of the pro- or anti-angiogenesis therapeutic strategies on microvasculature repair or regeneration.