MRI-based bone marrow radiomics for predicting cytogenetic abnormalities in multiple myeloma.

AIM: To develop a radiomics signature applied to magnetic resonance imaging (MRI)-images to predict cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: Patients with newly diagnosed MM were enrolled retrospectively from March 2019 to September 2022. They were categorised into the high-risk cytogenetics (HRC) group and standard-risk cytogenetics (SRC) group. The patients were allocated randomly at a ratio of 7:3 into training and validation cohorts. Volumes of interest (VOI) was drawn manually on fat suppression T2-weighted imaging (FS-T2WI) and copied to the same location of the T1-weighted imaging (T1WI) sequence. Radiomics features were extracted from two sequences and selected by reproducibility and redundant analysis. The least absolute shrinkage selection operation (LASSO) algorithm was applied to build the radiomics signatures. The performance of the radiomics signatures to distinguish HRC with SRC was evaluated by ROC curves. The area under the curve (AUC), specificity, and sensitivity were also calculated. RESULTS: A total of 105 MM patients were enrolled in this study. The four and 11 most significant and relevant features were selected separately from T1WI and FS-T2WI sequences to build the radiomics signatures based on the training cohort. Compared to the T1WI sequence, the radiomics signature based on the FS-T2WI sequence achieved better performance with AUCs of 0.896 and 0.729 in the training and validation cohorts respectively. A sensitivity of 0.833, specificity of 0.667, and Youden index of 0.500 were achieved for the FS-T2WI radiomics signature in the validation cohort. CONCLUSIONS: The radiomics signature based on MRI provides a non-invasive and convenient tool to predict cytogenetic abnormalities in MM patients.

[Clinicopathological features and prognosis of sporadic mismatch repair deficient colorectal cancer].

Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side (P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial.

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented. PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population. RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage). CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

Experimental Validation of a Kinetic Ballooning Mode in High-Performance High-Bootstrap Current Fraction Fusion Plasmas.

We report the observation of a set of coherent high frequency electromagnetic fluctuations that leads to a turbulence induced self-regulating phenomenon in the DIII-D high bootstrap current fraction plasma. The fluctuations have frequency of 130-220 kHz, the poloidal wavelength and phase velocity are 16-30 m^{-1} and ∼30 km/s, respectively, in the outboard midplane with the estimated toroidal mode number n∼5-9. The fluctuations are located in the internal transport barrier (ITB) region at large radius and are experimentally validated to be kinetic ballooning modes (KBM). Quasilinear estimation predicts the KBM to be able to drive experimental particle flux and non-negligible thermal flux, suggesting its significant role in regulating the ITB saturation.

Discriminating minimal residual disease status in multiple myeloma based on MRI: utility of radiomics and comparison of machine-learning methods.

AIM: To explore the possibility of discriminating minimal residual disease (MRD) status in multiple myeloma (MM) based on magnetic resonance imaging (MRI) and identify optimal machine-learning methods to optimise the clinical treatment regimen. MATERIALS AND METHODS: A total of 83 patients were analysed retrospectively. They were divided randomly into training and validation cohorts. The regions of interest were segmented and radiomics features were extracted and analysed on two sequences, including T1-weighted imaging (WI) and fat saturated (FS)-T2WI, and then radiomics models were built in the training cohort and evaluated in the validation cohort. Clinical characteristics were calculated to build a traditional model. A combined model was also built using the clinical characteristics and radiomics features. Classification accuracy was assessed using area under the curve (AUC) and F1 score. RESULTS: In the training cohort, only the bone marrow (BM) infiltrate ratio (p=0.005) was retained after univariate and multivariable logistic regression analysis. In T1WI, the linear support vector machine (SVM) achieved the best performance compared to other classifiers, with AUCs of 0.811 and 0.708 and F1 scores of 0.792 and 0.696 in the training and validation cohorts, respectively. Similarly, in FS-T2WI sequence, linear SVM achieved the best performance with AUCs of 0.833 and 0.800 and F1 score of 0.833 and 0.800. The combined model constructed by the FS-T2WI-linear SVM and BM infiltrate ratio outperformed the traditional model (p=0.050 and 0.012, Delong test), but showed no significant difference compared with the radiomics model (p=0.798 and 0.855). CONCLUSION: The linear SVM-based machine-learning method can offer a non-invasive tool for discriminating MRD status in MM.

Improved Particle Confinement with Resonant Magnetic Perturbations in DIII-D Tokamak H-Mode Plasmas.

Experiments on the DIII-D tokamak have identified a novel regime in which applied resonant magnetic perturbations (RMPs) increase the particle confinement and overall performance. This Letter details a robust range of counter-current rotation over which RMPs cause this density pump-in effect for high confinement (H mode) plasmas. The pump in is shown to be caused by a reduction of the turbulent transport and to be correlated with a change in the sign of the induced neoclassical transport. This novel reversal of the RMP induced transport has the potential to significantly improve reactor relevant, three-dimensional magnetic confinement scenarios.

ß-Nuclear-Recoil Correlation from

We report the first precise measurement of a ß-recoil correlation from a radioactive noble gas (^{6}He) confined via a magneto-optical trap. The measurement is motivated by the search for exotic tensor-type contributions to the charged weak current. Interpreted as tensor currents with right-handed neutrinos, the measurements yield |C_{T}/C_{A}|^{2}≤0.022 (90% confidence limit, C.L.). On the other hand, for left-handed neutrinos the limits are 0.007

Multiscale Chirping Modes Driven by Thermal Ions in a Plasma with Reactor-Relevant Ion Temperature.

A thermal ion driven bursting instability with rapid frequency chirping, considered as an Alfvénic ion temperature gradient mode, has been observed in plasmas having reactor-relevant temperature in the DIII-D tokamak. The modes are excited over a wide spatial range from macroscopic device size to microturbulence size and the perturbation energy propagates across multiple spatial scales. The radial mode structure is able to expand from local to global in ∼0.1 ms and it causes magnetic topology changes in the plasma edge, which can lead to a minor disruption event. Since the mode is typically observed in the high ion temperature ≳10 keV and high-ß plasma regime, the manifestation of the mode in future reactors should be studied with development of mitigation strategies, if needed. This is the first observation of destabilization of the Alfvén continuum caused by the compressibility of ions with reactor-relevant ion temperature.

Dual-energy CT for differentiating early glottic squamous cell carcinoma from chronic inflammation and leucoplakia of vocal cord: comparison with simulated conventional 120 kVp CT.

AIM: To evaluate the value of dual-energy (DE) computed tomography (CT) in discriminating early glottic squamous cell carcinoma (eGSCC) from chronic inflammation and leucoplakia of the vocal cord, and to compare the diagnostic efficiency of DECT with that of simulated conventional 120 kVp CT. MATERIALS AND METHODS: Seventy patients with glottic lesions confirmed by histopathology (38 cases with eGSCC, 11 cases with chronic inflammation, 21 cases with leucoplakia) were enrolled in this prospective study. The DECT-derived parameters were measured and compared using independent sample t-test. Receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance, and comparison of the area under the ROC curve (AUC) was made using the Z test to further select the best diagnostic parameters. RESULTS: Significantly higher iodine concentration (IC), normalised IC (NIC), effective atomic number (Zeff), 40-100 keV (20 keV-interval), slope(k), and Mix-0.3 values were found in eGSCC than those in chronic inflammation, leucoplakia, and inflammation + leucoplakia (all p<0.05). Compared with attenuation measurement of simulated conventional 120 kVp CT, the NIC, 60 keV values derived from DECT showed significantly higher AUC in discriminating these glottic lesions (p<0.05). CONCLUSIONS: DECT is more accurate for differentiating eGSCC from chronic inflammation and leucoplakia when compared with simulated conventional 120 kVp CT.

Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies.

A series of imidazothiazole derivatives possessing potential activity against melanoma cells were investigated for molecular mechanism of action. The target compounds were tested against V600E-B-RAF and RAF1 kinases. Compound 1zb is the most potent against both kinases with IC50 values 0.978 and 8.2 nM, respectively. It showed relative selectivity against V600E mutant B-RAF kinase. Compound 1zb was also tested against four melanoma cell lines and exerted superior potency (IC50 0.18-0.59 µM) compared to the reference standard drug, sorafenib (IC50 1.95-5.45 µM). Compound 1zb demonstrated also prominent selectivity towards melanoma cells than normal skin cells. It was further tested in whole-cell kinase assay and showed in-cell V600E-B-RAF kinase inhibition with IC50 of 0.19 µM. Compound 1zb induces apoptosis not necrosis in the most sensitive melanoma cell line, UACC-62. Furthermore, molecular dynamic and 3D-QSAR studies were done to investigate the binding mode and understand the pharmacophoric features of this series of compounds.

[Cost-effectiveness of primary prophylaxis with PEG-rhG-CSF in early-stage breast cancer patients receiving chemotherapy in China].

Objective: To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China. Methods: Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio (HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results: Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion: Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

[Treatment of postprandial discomfort syndrome in the elderly: a multi-centered prospective randomized controlled clinical study].

Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym(®)) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym(®) group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym(®) group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym(®) group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym(®) group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym(®) group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym(®) group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions: The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.

Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study.

Background: Concurrent chemoradiotherapy (CCRT) is superior to radiotherapy alone for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Whether adding induction chemotherapy (IC) further improves the outcome warrants investigation. Patients and methods: This open-label multicenter phase III trial was conducted at 11 institutions in Taiwan. Patients with stage IVA or IVB NPC were randomized to receive IC followed by CCRT (I-CCRT) or CCRT alone. Patients in the I-CCRT arm received three cycles of mitomycin C, epirubicin, cisplatin, and 5-fluorouracil/leucovorin (MEPFL). All patients received 30 mg/m2 cisplatin weekly during radiotherapy, which was delivered as 1.8-2.2 Gy per fraction with five daily fractions per week, to a total dose of 70 Gy or greater to the primary tumor and 66-70 Gy to the involved neck. The primary end point was disease-free survival (DFS). Results: In this study, 240 and 239 patients were randomized to CCRT and I-CCRT arm, respectively. The most prominent toxicities of induction were leukopenia (grade 3 and 4: 47% and 12%) and thrombocytopenia (grade 3 and 4: 24% and 3%). During radiotherapy, severe mucositis was the major side-effect in both arms; an increased number of patients in the I-CCRT arm had myelosuppression; hence, discontinuation of weekly cisplatin was more common. After a median follow-up of 72.0 months, the I-CCRT arm had significantly higher DFS than that of the CCRT arm [5-year rate 61% versus 50%; hazard ratio=0.739, 95% confidence interval (CI)=0.565-0.965; P = 0.0264], after stratified for N3b and LDH, and adjusted for T stage. Conclusion: Induction with MEPFL before CCRT was tolerable and significantly improved the DFS of patients with stage IVA and IVB NPC though overall survival not improved. Clinical trial information: NCT00201396.

Tracing the Pathway from Drift-Wave Turbulence with Broken Symmetry to the Production of Sheared Axial Mean Flow.

This study traces the emergence of sheared axial flow from collisional drift-wave turbulence with broken symmetry in a linear plasma device-the controlled shear decorrelation experiment. As the density profile steepens, the axial Reynolds stress develops and drives a radially sheared axial flow that is parallel to the magnetic field. Results show that the nondiffusive piece of the Reynolds stress is driven by the density gradient, results from spectral asymmetry of the turbulence, and, thus, is dynamical in origin. Taken together, these findings constitute the first simultaneous demonstration of the causal link between the density gradient, turbulence, and stress with broken spectral symmetry and the mean axial flow.

Intratumorally Establishing Type 2 Innate Lymphoid Cells Blocks Tumor Growth.

A long-standing question in the field of tumor immunotherapy is how Th2 cytokines block tumor growth. Their antitumor effects are particularly prominent when they are secreted continuously in tumors, suggesting that Th2 cytokines may create a tumor microenvironment unfavorable for tumor growth independently of adaptive immunity. In this study, we show that local production of IL-33 establishes a high number of type 2 innate lymphoid cells (ILC2s) with potent antitumor activity. IL-33 promotes secretion of a massive amount of CXCR2 ligands from ILC2s but creates a tumor microenvironment where tumor cells express CXCR2 through a dysfunctional angiogenesis/hypoxia/reactive oxygen species axis. These two signaling events converge to reinforce tumor cell-specific apoptosis through CXCR2. Our results identify a previously unrecognized antitumor therapeutic pathway wherein ILC2s play a central role.

Ste20-like kinase is upregulated in glioma and induces glioma invasion.

The malignant development and poor prognosis of gliomas are associated with a high degree of invasion and a high recurrence rate. However, the molecular mechanism underlying the invasiveness of glioma remains to be elucidated. Ste20- like kinase (SLK) is one of the members of the Ste20 family, which has been implicated in cellular migration and invasion. In this study, we intended to explore the expression of SLK significantly related to clinicopathologic stages of gliomas. Immunohistochemical staining and western blot analysis demonstrated that SLK was highly expressed in human glioma tissues and cell lines. Kaplan-Meier analysis revealed that poor survival was associated with high SLK expression. The inhibition of SLK by RNA interference significantly suppressed the invasion ability of glioma, and on protein level, knock- down of SLK leaded to an up-regulation of E-cadherin and a down-regulation of Vimentin in glioma cells. Collectively, this research shed light on mechanisms of invasion and progression of malignant gliomas and suggested that SLK may be a potential therapeutic strategy for glioma.

IL-33 Enhances Host Tolerance to Candida albicans Kidney Infections through Induction of IL-13 Production by CD4+ T Cells.

Susceptibility to systemic Candida albicans infection is determined by immune resistance, as well as by the ability to control Candida-induced immunopathologies. We showed previously that exogenous IL-33 can increase resistance to peritoneal C. albicans infection by regulating multiple steps of the neutrophil anti-Candida response. In this study, using a mouse model of systemic candidiasis, we observed that IL-33 administration limited fungal burden and inflammation and increased survival. In kidneys, IL-33 seemed to directly act on neutrophils and CD4(+) T cells: IL-33 administration enhanced fungal clearance by increasing neutrophil phagocytic activity without which Candida proliferation was uncontrollable. In contrast, IL-33 stimulated CD4(+) T cells to produce IL-13, which, in turn, drove the polarization of macrophages toward the M2 type. Furthermore, the absence of IL-13 abolished IL-33-mediated polarization of M2 macrophages and renal functional recovery. In addition, IL-33 and IL-13 acted synergistically to increase M2 macrophage polarization and its phagocytic activity. Overall, this study identifies IL-33 as a cytokine that is able to induce resistance and tolerance and suggests that targeting resistance and tolerance simultaneously with therapeutic IL-33 may benefit patients with systemic candidiasis.

IL-33-induced hematopoietic stem and progenitor cell mobilization depends upon CCR2.

IL-33 has been implicated in the pathogenesis of asthma, atopic allergy, anaphylaxis, and other inflammatory diseases by promoting the production of proinflammatory cytokines and chemokines or Th2 immune responses. In this study, we analyzed the in vivo effect of IL-33 administration. IL-33 markedly promoted myelopoiesis in the bone marrow and myeloid cell emigration. Concomitantly, IL-33 induced hematopoietic stem and progenitor cell (HSPC) mobilization and extramedullary hematopoiesis. HSPC mobilization was mediated mainly through increased levels of CCL7 produced by vascular endothelial cells in response to IL-33. In vivo treatment of IL-33 rapidly induced phosphorylation of ERK, JNK, and p38, and inhibition of these signaling molecules completely blocked the production of CCL7 induced by IL-33. Consistently, inhibitor of CCR2 markedly reduced IL-33-mediated HSPC mobilization in vivo and migration of HSPCs in response to CCL7 in vitro. IL-33-mobilized HSPCs were capable of homing to, and of long-term reconstitution in, the bone marrow of irradiated recipients. Immune cells derived from these recipients had normal antifungal activity. The ability of IL-33 to promote migration of HSPCs and myeloid cells into the periphery and to regulate their antifungal activity represents a previously unrecognized role of IL-33 in innate immunity. These properties of IL-33 have clinical implications in hematopoietic stem cell transplantation.

[Establishment and evaluation of a prognostic model for acute pulmonary embolism].

OBJECTIVE: To identify the factors influencing the prognosis of patients with acute pulmonary embolism(PE) and to establish a prognostic model. METHODS: The clinical data of 331 patients (141 males and 190 females, aged 9 to 87 years ) with acute PE in Fujian Hospital from January 2007 to September 2013 were analyzed. Univariate analysis and logistic regression analysis were used for selecting the independent prognostic factors for acute PE. Based on logistic regression analysis, a prognostic model for PE was established. RESULTS: Univariate analysis showed that statistically significant (all P<0.05) factors influencing the prognosis of PE were diabetes, tricuspid systolic murmur, body temperature, respiratory rate, heart rate, aspartate aminotransferase, triglycerides, abnormal ECG, mechanical ventilation, circulatory failure during hospitalization, risk stratification of PE, types of treatment, and use of low-molecular-weight heparin and Warfarin. Logistic regression analysis showed that recent (<1 month) operation or fracture, tricuspid systolic murmur, high triglyceride level, circulatory failure during hospitalization and mechanical ventilation were independent factors for poor prognosis of PE, while combined use of low-molecular-weight heparin and Warfarin was a protective factor for the prognosis of PE. The Fisher prognostic model equation was y=0.144+ 1.266x1+ 0.869x2+ 1.794x3-0.517x4+ 3.555x5+ 0.661x6. The accuracy of the Fisher discriminant function was 93.0%. CONCLUSION: Recent (<1 month) operation or fracture, tricuspid systolic murmur, high triglyceride level, shock during hospitalization and mechanical ventilation were signs of poor prognosis for PE, while combined use of low-molecular-weight heparin and Warfarin were beneficial for the prognosis. The discriminant function based on these data can be helpful for predicting the prognosis of patients with PE.

TLR2 signaling in tubular epithelial cells regulates NK cell recruitment in kidney ischemia-reperfusion injury.

Damage-associated molecular patterns released from damaged kidney cells initiate postischemic inflammation, an essential step in the progression of kidney ischemia-reperfusion injury (IRI). However, the mechanism that coordinates this highly specific process in ischemic kidneys remains to be clarified. Previously, we demonstrated that CD137 from NK cells specifically stimulates CD137 ligand (CD137L) on tubular epithelial cells (TECs) such that TECs produced the high CXCR2 chemokine levels required for neutrophil chemotaxis. We report in the present study that endogenous TLR2 ligands released from ischemic TECs induce CCR5 chemokine expression, which is critical to promoting NK cell recruitment. By implanting CD137L(-/-) TECs into the kidney capsule of TLR2(-/-) mice, we further showed that TLR2-mediated NK cell recruitment is an uncoupled event that can occur independently of CD137L signaling in TECs, which is responsible for recruiting neutrophils. Therefore, our findings identify TECs as both a target for kidney damage and also as a master regulator that actively modulates stepwise signaling, leading to the initiation and amplification of acute sterile inflammation that inflicts kidney IRI. Being clinically important, the signaling pathway of innate receptors in epithelial cells may therefore be a good target to block acute sterile inflammation resulting from tissue damage, including kidney IRI.