[Haploidentical donor peripheral blood stem cell transplantation using third-party cord blood compared with matched unrelated donor transplantation for patients with hematologic malignancies].

Objectives: To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases. Methods: A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021. Results: ①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9-22) days and 13 (10-24) days, respectively (P=0.834), whereas the median implantation time for platelets was 15 (7-103) days and 14 (8-38) days, respectively (P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% (P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% (P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% -38.1% ) and 28.8% (95% CI 17.2% -41.6% (P=0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% -14.0% ) and 9.6% (95% CI 3.5% -19.5% ) (P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% -44.1% ), respectively (P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively (P=0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% -20.5% ) and 10.0% (95% CI 3.6% -20.2% ), respectively (P=0.341), and the NRM were 14.7% (95% CI 8.4% -22.6% ) and 16.2% (95% CI 7.4% -28.0% ), respectively (P=0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% -90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively (P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% -79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively (P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% -79.3% ), respectively (P=0.284) . Conclusion: The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.

Risk factors analysis and establishment of predictive nomogram of extranodal B-cell lymphoma of mucosal-associated lymphoid tissue.

PURPOSE: The role of radiation therapy in mucosa-associated lymphoid tissue (MALT) lymphoma is poorly defined. The objective of this study was to explore the factors associated with the performance of radiotherapy and to assess its prognostic impact in patients with MALT lymphoma. PATIENTS AND METHODS: Patients with MALT lymphoma diagnosed between 1992 and 2017 were identified in the US Surveillance, Epidemiology, and End Results database (SEER). Factors associated with the delivery of radiotherapy were assessed by chi-square test. Overall survival (OS) and lymphoma-specific survival (LSS) were compared between patients with and without radiotherapy, using Cox proportional hazard regression models, in patients with early stage as well as those with advanced stage. RESULTS: Of the 10,344 patients identified with a diagnosis of MALT lymphoma, 33.6% had received radiotherapy; this rate was 38.9% for stage I/II patients and 12.0% for stage III/IV patients, respectively. Older patients and those who already received primary surgery or chemotherapy had a significantly lower rate of receiving radiotherapy, regardless of lymphoma stage. After univariate and multivariate analysis, radiotherapy was associated with improved OS and LSS in patients with stage I/II (HR=0.71 [0.65-0.78]) and (HR=0.66 [0.59-0.74]), respectively, but not in patients with stage III/IV (HR=1.01 [0.80-1.26]) and (HR=0.93 [0.67-1.29]). The nomogram built from the significant prognostic factors associated with overall survival of stage I/II patients had a good concordance (C-index=0.749±0.002). CONCLUSION: This cohort study shows that radiotherapy is significantly associated with a better prognosis in patients with early but not advanced MALT lymphoma. Prospective studies are needed to confirm the prognostic impact of radiotherapy in patients with MALT lymphoma.

[Study on binding kinetics profiles of tea polyphenols-α-glucosidase interaction].

The combination index(CI) method was used to evaluate the combination inhibition mechanism of epicatechin gallate(ECG) and other tea polyphenols [epigallocatechin gallate(EGCG) and gallocatechin gallate(GCG)] on α-glucosidase. Herein, using ECG as research object, the surface plasmon resonance(SPR) analysis were employed to study the binding affinities and kinetic parameters of three tea polyphenols components on α-glucosidase, respectively. The concentration-time curve mathematical model of the drug in the unstirred water layer(the adjacent region of α-glucosidase) established previously by our group was used to evaluate the concentration-time curves of the tea polyphenols in the α-glucosidase vicinity. The prediction model of drug-α-glucosidase binding kinetics established by our group was used to evaluate the dynamic process of drug-α-glucosidase binding kinetics of different oral administration processes of ECG. Using acarbose as a reference, the accuracy of the model prediction was judged based on the difference between the prediction results and the actual clinical performance. Using the mathematical model of drug-α-glucosidase interaction, the drug-α-glucosidase binding kinetic characteristic curves of ECG in different administration processes were obtained, which indirectly proved that the synergistic effect of multi-component combination of traditional Chinese medicine and the clinical characteristics of repeat administration were scientific and reasonable.

Discrimination between Glioblastoma and Solitary Brain Metastasis: Comparison of Inflow-Based Vascular-Space-Occupancy and Dynamic Susceptibility Contrast MR Imaging.

BACKGROUND AND PURPOSE: Accurate differentiation between glioblastoma and solitary brain metastasis is of vital importance clinically. This study aimed to investigate the potential value of the inflow-based vascular-space-occupancy MR imaging technique, which has no need for an exogenous contrast agent, in differentiating glioblastoma and solitary brain metastasis and to compare it with DSC MR imaging. MATERIALS AND METHODS: Twenty patients with glioblastoma and 22 patients with solitary brain metastasis underwent inflow-based vascular-space-occupancy and DSC MR imaging with a 3T clinical scanner. Two neuroradiologists independently measured the maximum inflow-based vascular-space-occupancy-derived arteriolar CBV and DSC-derived CBV values in intratumoral regions and peritumoral T2-hyperintense regions, which were normalized to the contralateral white matter (relative arteriolar CBV and relative CBV, inflow-based vascular-space-occupancy relative arteriolar CBV, and DSC-relative CBV). The intraclass correlation coefficient, Student t test, or Mann-Whitney U test and receiver operating characteristic analysis were performed. RESULTS: All parameters of both regions had good or excellent interobserver reliability (0.74∼0.89). In peritumoral T2-hyperintese regions, DSC-relative CBV (P < .001), inflow-based vascular-space-occupancy arteriolar CBV (P = .001), and relative arteriolar CBV (P = .005) were significantly higher in glioblastoma than in solitary brain metastasis, with areas under the curve of 0.94, 0.83, and 0.72 for discrimination, respectively. In the intratumoral region, both inflow-based vascular-space-occupancy arteriolar CBV and relative arteriolar CBV were significantly higher in glioblastoma than in solitary brain metastasis (both P < .001), with areas under the curve of 0.91 and 0.90, respectively. Intratumoral DSC-relative CBV showed no significant difference (P = .616) between the 2 groups. CONCLUSIONS: Inflow-based vascular-space-occupancy has the potential to discriminate glioblastoma from solitary brain metastasis, especially in the intratumoral region.

[Application experience of integrated nursing mode for extremely severe burn patients in August 2nd Kunshan factory aluminum dust explosion accident].

Objective: To explore the application experience of integrated nursing mode in the treatment of extremely severe burn patients in August 2nd Kunshan factory aluminum dust explosion accident. Methods: On August 2nd, 2014, 35 extremely severe burn patients involved in the August 2nd Kunshan factory aluminum dust explosion accident were admitted to Wuxi Third People's Hospital, including 18 males and 17 females, aged 21-50 years. According to the characteristics of the wounded, the situation of the nursing staff, and the characteristics of the nursing work, the integrated nursing mode was constructed and implemented to improve overall nursing quality. The standardized management measures such as cluster management of facilities and equipments in wards, improving and unifying nursing system, standardized training, drawing up " Nurses Compulsory Reading" , optimizing nursing shift handover and so on were taken. Professional quality control groups such as continuous renal replacement therapy (CRRT) group, static therapy group, airway group, and burn group were established, and standardized writing nursing group, wound nursing group, psychological nursing group, and enteral nutrition nursing group were set up under burn group. The treatment outcomes of patients and effects of nursing management, nursing methods, and specialty nursing were recorded. Results: Twenty-seven patients survived the shock period, infection period, and recovery period smoothly. The success rate of rescue was 77.14%. During the treatment, the ward was in good order. The implementation rate of disinfection and isolation system, the completion rate of shift handover, the standard rate of intravenous therapy, the implementation rate of bed head elevation, the correct rate of posture placement, and the success rate of CRRT were all 100%. Successful turn over of rotating bed without interruption of CRRT for 24 hours was implemented in two patients. In many cases, the single filter for hemodialysis continuously run for more than 72 hours. The airway mucosa of patients healed around 20 days after injury. No adverse nursing events such as tracheal cannula detachment/blockage, respiratory distress, atelectasis, lung consolidation, aspiration by mistake, rotating bed rollover, ear chondritis, nasal septal pressure ulcer, vacuum sealing drainage (VSD) catheter blockage, VSD dressing leakage, severe abdominal distension/diarrhea, non-planned extubation/blockage of various intravenous treatment catheters implanted into deep veins and arteries were observed. Conclusions: The integrated nursing mode significantly optimizes the nursing work process in the treatment of extremely severe mass burns, clarifies the duties of nursing staff, and improves the quality of nursing. This mode is worthy of taking reference by other burn treatment units.

[Nursing human resource management in the early phase of treatment of severe mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion accident].

In August 2nd Kunshan factory aluminum dust explosion accident 2014, 35 severe mass burn patients were admitted to our hospital, including 18 men and 17 women, aged 21 to 50 (38±9) years. Their severe injuries caused much difficulty to the treatment. In the early period of treatment, a series of measures of nursing human resource management were implemented, such as carrying out training program for non-burn speciality nurses of different levels and origin, grouping and task-dividing, organizing work schedule and assigning in a unified way, and establishing monitoring team of speciality quality. Except for 2 cases of deaths in the early period, the other 33 patients were treated and nursed timely and effectively in the early period. The rescue rate arrived at 94.3% (33/35) on the 17th day post burn. In this period, no such nursing adverse event and complication occurred as bed-dropping, unplanned extubation, coagulation in veins of lower limb, catheter-related infection, or cross infection.

Apparent diffusion coefficient measurement in luminal breast cancer: will tumour shrinkage patterns affect its efficacy of evaluating the pathological response?

AIM: To determine which region of interest (ROI) placement method of apparent diffusion coefficient (ADC) measurement has the best performance for predicting pathological complete response (PCR) at two cycles of neoadjuvant chemotherapy (NAC) according to different tumour shrinkage patterns of luminal breast cancer and to assess the evaluative accuracy of ADC value combined with other clinicopathological indicators. MATERIALS AND METHODS: Sixty-one patients who underwent NAC for histopathologically confirmed breast cancer were enrolled in this retrospective study. The ADC values of different shrinkage patterns (concentric shrinkage, nest or dendritic shrinkage, and mixed shrinkage) for tumours shown by diffusion-weighted imaging (DWI) were measured independently using three ROI placement methods (single-round, three-round, and freehand). Intraclass correlation coefficients (ICCs) were used to assess the interobserver variability in the ADC values. Multivariate logistic regression analysis was performed to identify the independent predictors of PCR. RESULTS: The best placement method found was single-round ROI in all the patients (AUC=0.863). When analysed separately, the effectiveness results differed: the single-round method was optimal for concentrically shrinking tumours (AUC=0.970); the freehand method was optimal for nest or dendritically shrinking tumours (AUC=0.714); and the three-round method was optimal for mixed shrinking tumours (AUC=0.975). Multivariate logistic analysis showed that oestrogen receptor (ER), ΔADC% and tumour diameter reduction (ΔD%) were independent factors in evaluating the PCR. CONCLUSION: The methods for measuring ADC values vary across different shrinkage patterns of luminal tumours. ΔADC%, ER and ΔD% were independent factors for evaluating the PCR.

[Effect of lipid-induced macrophage M1/M2 polarization on lipid metabolism in hepatocytes].

Objective: This study aims to explore the effect of lipid-induced macrophage M1/M2 polarization on lipid metabolism in hepatocytes. Methods: RAW264.7 macrophages were incubated with different kinds of fatty acids including saturated fatty acids-palmitic acid (PA), monounsaturated fatty acids-oleic acid (OA) and polyunsaturated fatty acids-docosahexaenoic acid (DHA), and cell culture supernatants were collected to prepare conditioned medium (CM). Hepatocytes were isolated by in situ perfusion of the liver with collagenase in mice, and a macrophage-hepatocyte CM co-culture system was established. Macrophage M1/M2 phenotype markers were detected by Real-time PCR. Lipid synthesis and decomposition related mRNA and protein expressions in hepatocytes were detected by Real-time PCR and Western Blot. Lipid depositions in hepatocytes were detected by oil red O staining. An analysis of variance was used for comparison of means between multiple groups. Results: Compared with control groups, PA polarized macrophages to a M1 phenotype (expression of TNF-α and IL-6 significantly increased, F≥22.68, P < 0.01), OA polarized macrophages to a M1/M2 mixed phenotype (expression of IL-6, Mrc2 and IL-10 increased F≥4.94, P < 0.05) and DHA polarized macrophages to a M2 phenotype (expression of Mrc2 and IL-10 significantly increased, F≥4.94, P < 0.01). CM-PA significantly increased lipid synthesis related genes, including SREBP1C, ACC1 mRNA expression (F≥5.66, P < 0.01) and FASN, ACC1 protein expression (F≥38.34, P < 0.05) in hepatocytes, and decreased lipid decomposition gene ACOX1 protein expression (F=154.48, P < 0.01). CM-OA affected several lipid metabolism genes expression. CM-DHA significantly increased CPT1A mRNA expression (F = 10.30, P < 0.01) and ACOX1, CPT1A protein expression (F≥47.06, P < 0.05), and decreased SREBP1C, ACC1 protein expression (F≥65.84, P < 0.05) in hepatocytes. Massive lipid droplets were deposited in hepatocytes in CM-PA treated hepatocytes, and a few amount of lipid droplets were deposited in CM-DHA treated hepatocytes. Conclusion: Different fatty acids affect the balance of lipid metabolism in hepatocytes and liver by inducing macrophage M1 / M2 polarization, thus promoting or delaying the progression of non-alcoholic fatty liver disease.

Utility of apparent diffusion coefficient as an imaging biomarker for assessing the proliferative potential of invasive ductal breast cancer.

AIM: To determine the clinical utility of apparent diffusion coefficient (ADC) metrics for the non-invasive assessment of tumour proliferation indicated by Ki-67 labelling index (LI) in invasive ductal breast cancer. MATERIALS AND METHODS: Eighty patients with 80 histopathologically proven invasive ductal breast cancers underwent diffusion-weighted imaging with b-values of 0 and 800 s/mm2 at a 3-T system. ADC metrics including ADCmean, ADCmedian, ADCmin, ADCmax, and ΔADC (ADCmax-ADCmin) were recorded from the entire tumour volume on ADC maps, and correlated with the Ki-67 LI. Ki-67 staining of ≥14% was considered to indicate high proliferation and <14% was considered to indicate low proliferation. RESULTS: ADCmin, ADCmax, and ΔADC showed significant correlations with the Ki-67 LI (for all tumours, r=-0.311, 0.436, and 0.551, respectively; for luminal/human epidermal growth factor receptor 2 (HER2)-negative group, r=-0.437, 0.512, and 0.639, respectively; all p<0.01), whereas ADCmean and ADCmedian showed no significant correlation (both p>0.05). Receiver operating characteristic (ROC) curve analysis for the differentiation of high- from low-proliferation groups showed that ΔADC yielded the highest area under the ROC curve for the whole tumour population (0.825; 95% confidence interval [CI]: 0.724, 0.901), as well as for the luminal/HER2-negative group (0.844; 95% CI: 0.692, 0.940). CONCLUSION: ΔADC may serve as a promising imaging biomarker for the prediction of Ki-67 proliferation status in invasive ductal breast cancer.

Physical Mechanism of the Transverse Instability in Radiation Pressure Ion Acceleration.

The transverse stability of the target is crucial for obtaining high quality ion beams using the laser radiation pressure acceleration (RPA) mechanism. In this Letter, a theoretical model and supporting two-dimensional (2D) particle-in-cell (PIC) simulations are presented to clarify the physical mechanism of the transverse instability observed in the RPA process. It is shown that the density ripples of the target foil are mainly induced by the coupling between the transverse oscillating electrons and the quasistatic ions, a mechanism similar to the oscillating two stream instability in the inertial confinement fusion research. The predictions of the mode structure and the growth rates from the theory agree well with the results obtained from the PIC simulations in various regimes, indicating the model contains the essence of the underlying physics of the transverse breakup of the target.

Colocalization of cerebral iron with Amyloid beta in Mild Cognitive Impairment.

Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aß) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aß-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aß-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aß-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aß-plaques.

Quantitative Susceptibility Mapping Suggests Altered Brain Iron in Premanifest Huntington Disease.

BACKGROUND AND PURPOSE: In patients with premanifest (nonsymptomatic) and advanced Huntington disease, changes in brain iron levels in the basal ganglia have been previously reported, especially in the striatum. Quantitative susceptibility mapping by using MR phase imaging allows in vivo measurements of tissue magnetic susceptibility, which has been shown to correlate well with iron levels in brain gray matter and is believed to be more specific than other imaging-based iron measures. The purpose of this study was to investigate the use of magnetic susceptibility as a biomarker of disease progression. MATERIALS AND METHODS: Fifteen subjects with premanifest Huntington disease and 16 age-matched healthy controls were scanned at 7T. Magnetic susceptibility, effective relaxation, and tissue volume in deep gray matter structures were quantified and compared with genetic and clinical measures. RESULTS: Subjects with premanifest Huntington disease showed significantly higher susceptibility values in the caudate nucleus, putamen, and globus pallidus, indicating increased iron levels in these structures. Significant decreases in magnetic susceptibility were found in the substantia nigra and hippocampus. In addition, significant volume loss (atrophy) and an increase effective relaxation were observed in the caudate nucleus and putamen. Susceptibility values in the caudate nucleus and putamen were found to be inversely correlated with structure volumes and directly correlated with the genetic burdens, represented by cytosine-adenine-guanine repeat age-product-scaled scores. CONCLUSIONS: The significant magnetic susceptibility differences between subjects with premanifest Huntington disease and controls and their correlation with genetic burden scores indicate the potential use of magnetic susceptibility as a biomarker of disease progression in premanifest Huntington disease.

Intracranial EEG analysis in tumor-related epilepsy: Evidence of distant epileptic abnormalities.

OBJECTIVE: In patients with tumor-related epilepsy (TRE), surgery traditionally focuses on tumor resection; but identification and removal of associated epileptogenic zone may improve seizure outcome. Here, we study spatial relationship of tumor and seizure onset and early spread zone (SOSz). We also perform quantitative analysis of interictal epileptiform activities in patients with both TRE and non-lesional epilepsy in order to better understand the electrophysiological basis of epileptogenesis. METHODS: Twenty-five patients (11 with TRE and 14 with non-lesional epilepsy) underwent staged surgery using intracranial electrodes. Tumors were outlined on MRI and images were coregistered with post-implantation CT images. For each electrode, distance to the nearest tumor margin was measured. Electrodes were categorized based on distance from tumor and involvement in seizure. Quantitative EEG analysis studying frequency, amplitude, power, duration and slope of interictal spikes was performed. RESULTS: At least part of the SOSz was located beyond 1.5 cm from the tumor margin in 10/11 patients. Interictally, spike frequency and power were higher in the SOSz and spikes near tumor were smaller and less sharp. Interestingly, peritumoral electrodes had the highest spike frequencies and sharpest spikes, indicating greatest degree of epileptic synchrony. A complete resection of the SOSz resulted in excellent seizure outcome. CONCLUSIONS: Seizure onset and early spread often involves brain areas distant from the tumor. SIGNIFICANCE: Utilization of epilepsy surgery approach for TRE may provide better seizure outcome and study of the intracranial EEG may provide insight into pathophysiology of TRE.

PRMT5 enhances generation of induced pluripotent stem cells from dairy goat embryonic fibroblasts via down-regulation of p53.

OBJECTIVES: Protein arginine methyltransferase 5 (PRMT5), is thought to play a role in epigenetic reprogramming of mouse germ cells. However, up to now there has been little information concerning its expression profile and effects on generation of induced pluripotent stem cells (iPSCs) from somatic cells, in livestock. Here, we have explored PRMT5 expression profiles in dairy goats and its consequences to derivation of iPSCs from dairy goat embryonic fibroblasts (GEFs). MATERIALS AND METHODS: We investigated effects of PRMT5 on iPS-like cells production in vitro. alkaline phosphatase (AP) staining, QRT-PCR and western blotting analysis of expression of related markers were used to evaluate efficiency of generation of iPSCs derived from GEFs. RESULTS: These showed PRMT5 to be a conservative gene widely expressed in various tissues and different-aged testes. PRMT5 overexpression in combination with OCT3/4, SOX2, KLF4 and C-MYC (POSKM) significantly increased number of AP positive iPS-like colony-derived GEFs compared to OSKM alone, in our dairy goats. Moreover, our results demonstrated that PRMT5 overexpression stimulated GEF proliferation and down-regulated p53, p21 (a target gene of p53) and the apoptotic marker caspase 3, to enhance somatic cell reprogramming. CONCLUSION: This study provides an efficient model for future studies on mechanisms underlying goat somatic cell reprogramming and differentiation.

Smoking topography in Korean American and white men: preliminary findings.

UNLABELLED: This is the first study of Korean Americans' smoking behavior using a topography device. Korean American men smoke at higher rates than the general U.S. POPULATION: Korean American and White men were compared based on standard tobacco assessment and smoking topography measures. They smoked their preferred brand of cigarettes ad libitum with a portable smoking topography device for 24 h. Compared to White men (N = 26), Korean American men (N = 27) were more likely to smoke low nicotine-yield cigarettes (p < 0.001) and have lower Fagerstrom nicotine dependence scores (p = 0.04). Koreans smoked fewer cigarettes with the device (p = 0.01) than Whites. Controlling for the number of cigarettes smoked, Koreans smoked with higher average puff flows (p = 0.05), greater peak puff flows (p = 0.02), and shorter interpuff intervals (p < 0.001) than Whites. Puff counts, puff volumes, and puff durations did not differ between the two groups. This study offers preliminary insight into unique smoking patterns among Korean American men who are likely to smoke low nicotine-yield cigarettes. We found that Korean American men compensated their lower number and low nicotine-yield cigarettes by smoking with greater puff flows and shorter interpuff intervals than White men, which may suggest exposures to similar amounts of nicotine and harmful tobacco toxins by both groups. Clinicians will need to consider in identifying and treating smokers in a mutually aggressive manner, irrespective of cigarette type and number of cigarette smoked per day.

Regulation of alternative VEGF-A mRNA splicing is a therapeutic target for analgesia.

Vascular endothelial growth factor-A (VEGF-A) is best known as a key regulator of the formation of new blood vessels. Neutralization of VEGF-A with anti-VEGF therapy e.g. bevacizumab, can be painful, and this is hypothesized to result from a loss of VEGF-A-mediated neuroprotection. The multiple vegf-a gene products consist of two alternatively spliced families, typified by VEGF-A165a and VEGF-A165b (both contain 165 amino acids), both of which are neuroprotective. Under pathological conditions, such as in inflammation and cancer, the pro-angiogenic VEGF-A165a is upregulated and predominates over the VEGF-A165b isoform. We show here that in rats and mice VEGF-A165a and VEGF-A165b have opposing effects on pain, and that blocking the proximal splicing event - leading to the preferential expression of VEGF-A165b over VEGF165a - prevents pain in vivo. VEGF-A165a sensitizes peripheral nociceptive neurons through actions on VEGFR2 and a TRPV1-dependent mechanism, thus enhancing nociceptive signaling. VEGF-A165b blocks the effect of VEGF-A165a. After nerve injury, the endogenous balance of VEGF-A isoforms switches to greater expression of VEGF-Axxxa compared to VEGF-Axxxb, through an SRPK1-dependent pre-mRNA splicing mechanism. Pharmacological inhibition of SRPK1 after traumatic nerve injury selectively reduced VEGF-Axxxa expression and reversed associated neuropathic pain. Exogenous VEGF-A165b also ameliorated neuropathic pain. We conclude that the relative levels of alternatively spliced VEGF-A isoforms are critical for pain modulation under both normal conditions and in sensory neuropathy. Altering VEGF-Axxxa/VEGF-Axxxb balance by targeting alternative RNA splicing may be a new analgesic strategy.

The correlation between platelet activation and liver injury by conditioning and bone marrow transplantation.

Hepatic veno-occlusive disease (HVOD) is a common severe complication after transplantation which is closely related to liver sinusoidal endothelial cell (LSEC) injury. Although platelet activation might play a key role in the progress of HVOD, the relationship between the P-selectin and HVOD is still unclear. In this study, the P-selectin, liver functions, and observed damage of LSEC after transplantation were detected. The P-selectin, alanine aminotransferase (ALT) and bilirubin were first detected in the patients. The ALT of patients reached the first peak of 144 ± 45.04 U/L, on day 7 after busulfan + cyclophosphamide (BU/CY) pretreatment, and reached the second peak of 220.5 ± 40.58 U/L on day 7 after transplantation. Similarly, the concentration of bilirubin increased BU/CY pretreatment and reached peak on day 15 after transplantation at 38.8 ± 5.99 µmol/L. However, the level of P-selectin was significantly higher than normal levels for a long time and peaked on day 3 after BU/CY pretreatment and on day 12 after transplantation (P < .05). Then the P-selectin, liver function, liver index, hepatocytes, and LSEC were observed using a transplantation model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient. The P-selectin, liver index, and liver function of total body irradiation (TBI) mice and bone marrow transplantation (BMT) mice were significantly increased, but the increase of TBI mice were more significant. On day 5, the ratio of TBI mice peripheral blood platelets which expressed P-selectin was higher and reached an earlier peak at 15.6 ± 2.63%, whereas that of BMT mice was 6.59 ± 1.17%, and peaked on day 15 at 8.36 ± 1.55% (P < .05). Moreover, the ALT and bilirubin levels of TBI mice were higher and reached earlier peaks on day 5 at 58.65 ± 1.43 U/L and 27.14 ± 1.32 µmol/L, respectively, whereas those of BMT mice peaked on day 5 at 50.22 ± 2.02 U/L and day 30 at 39.57 ± 1.55 µmol/L, respectively (P < .05). The LSEC damage and hepatocyte edema in BMT mice were most serious at day 15, and at day 30 injuries did not allow recovery. The liver score of TBI mice peaked on day 5, whereas that of BMT mice peaked on day 15. Moreover, the degree of damage and platelet activation positively correlated. This study implied that P-selectin could be used as a predictor of HVOD.

BMP4 promotes SSEA-1(+) hUC-MSC differentiation into male germ-like cells in vitro.

OBJECTIVES: Recent studies have demonstrated that primordial germ cells (PGC) can be differentiated from human umbilical cord mesenchymal stem cells (hUC-MSCs), and embryonic stem cells (ESCs) in vitro. Nevertheless, efficiencies were low and unstable. Here, whether hUC-MSCs can be induced to differentiate into germ-like cells with the aid of bone morphogenetic protein (BMP4) was investigated. MATERIALS AND METHODS: Human umbilical cord mesenchymal stem cells were freshly isolated and cultured with BMP4. SSEA-1(+/-) cells were purified using magnetic-activated cell sorting (MACS) from the hUC-MSCs, and further induced with BMP4. Quantitative real-time PCR (qRT-PCR) and immunofluorescence analysis were used to determine PGC and germ-like cell-specific markers. RESULTS: Human umbilical cord mesenchymal stem cells differentiated into SSEA-1(+) spherical PGC-like cells efficiently with 12.5 ng/ml BMP4. qRT-PCR and immunofluorescence analysis demonstrated that SSEA-1(+) cells expressed higher levels of PGC-specific markers than SSEA-1(-) cells. Furthermore, SSEA-1(+) cells were induced with BMP4 to differentiate into STRA8, SCP3, DMRT1 and PLZF-positive male germ-like cells, and some sperm-like cells were obtained by 7-14 days after induction. CONCLUSION: These results suggest that SSEA-1(+) hUC-MSCs can differentiate into male germ-like cells in the presence of BMP4. This study provides an efficient protocol to study germ-cell development using hUC-MSCs.