The genetic landscape of histologically transformed marginal zone lymphomas.

BACKGROUND: Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma. METHODS: Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs. RESULTS: All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations. CONCLUSIONS: The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.

Exploring the low-carbon transition pathway of China's construction industry under carbon-neutral target: A socio-technical system transition theory perspective.

The carbon emissions growth in the construction industry hinders the achievement of global carbon-neutral target, especially in China. Studies suggest that developing low-carbon technologies is an effective means of achieving the low-carbon transition (LCT) in the construction industry. However, these studies ignore the fact that the LCT is a complex and systemic issue that needs to consider the interaction of technical and non-technical factors. Thus, based on the socio-technical system transition theory, this study identified the influencing factors and constructs a dynamics model to simulate the dynamic changes of the LCT in China's construction industry under different scenarios. The results showed that multi-level factors coordinated to drive the LCT of the construction industry. Environmental factors played a weak role and the effectiveness of government intervention decreased with the transition process. On the contrary, technological and market factors were indispensable drivers and especially played a dominant role during the later stages of the transition. Finally, the LCT pathway of China's construction industry was proposed based on the results. These findings expand the boundary of theoretical research on industrial transition and provide a decision-making reference for the advancement of international carbon-neutral work.

Impact of Sublingual Nitroglycerin on the Assessment of Computed Tomography-derived Fractional Flow Reserve: An Intraindividual Comparison Study.

OBJECTIVE: The aim of this study was to investigate the impact of nitroglycerin (NTG) on the assessment of computed tomography-derived fractional flow reserve (CT-FFR). MATERIALS AND METHODS: Seventy-seven patients with suspected coronary artery disease were recruited, and they underwent computed tomography angiography (CCTA) before and after NTG administration. The CT-FFRs were compared at 2 CCTAs. The difference was compared using the Wilcoxon signed rank test. Patients were divided into normal and stenosis groups according to CCTA results. Vessels in the stenosis group were further divided into different groups based on coronary artery calcium score (CACS) and stenosis degree. The poststenotic CT-FFR differences before and after NTG (DCT-FFR) were calculated to evaluate the impact of stenosis degree and CACS. Terminal CT-FFRs derived from CCTAs before and after NTG in total and vessel-specific levels were compared in the normal group. RESULTS: Of 47 patients in the stenosis group, poststenotic CT-FFR was significantly increased after NTG at per-vessel level. By taking CT-FFR of 0.75 or lower as the threshold, 5 and 4 patients showed abnormal CT-FFR before and after NTG, respectively. No significant differences were noted among the various stenosis degree and CACS groups regarding DCT-FFR. Of 30 patients in the normal group, terminal CT-FFR was significantly increased after NTG in total level and vessel-specific level of left anterior descending and right coronary artery, but not in the left circumflex. CONCLUSIONS: Both post lesion and distal vessel CT-FFR significantly improved after the administration of GTN with the degree of change not affected by stenosis severity or CACS.

Propagation dynamics and control policies of COVID-19 pandemic at early stages: Implications on future resurgence response.

The spreading of novel coronavirus (SARS-CoV-2) has gravely impacted the world in the last year and a half. Understanding the spatial and temporal patterns of how it spreads at the early stage and the effectiveness of a governments' immediate response helps our society prepare for future COVID-19 waves or the next pandemic and contain it before the spreading gets out of control. In this article, a susceptible-exposed-infectious-removed model is used to model the city-to-city spreading patterns of the disease at the early stage of its emergence in China (from December 2019 to February 2020). Publicly available reported case numbers in 312 Chinese cities and between-city mobility data are leveraged to estimate key epidemiological characteristics, such as the transmission rate and the number of infectious people for each city. It is discovered that during any given time period, there are always only a few cities that are responsible for spreading the disease to other cities. We term these few cities as transmission centers. The spatial and temporal changes in transmission centers demonstrate predictable patterns. Moreover, rigorously designed experiments show that in controlling the disease spread in a city, non-pharmaceutical interventions (NPIs) implemented at transmission centers are more effective than the NPI implemented in the city itself. These findings have implications on the control of an infectious disease at the early stage of its spreading: implementing NPIs at transmission centers at early stages is effective in controlling the spread of infectious diseases.

CircEAF2 counteracts Epstein-Barr virus-positive diffuse large B-cell lymphoma progression via miR-BART19-3p/APC/ß-catenin axis.

BACKGROUND: Epstein-Barr virus (EBV) represents an important pathogenic factor of lymphoma and is significantly associated with poor clinical outcome of diffuse large B-cell lymphoma (DLBCL). Circular RNAs (circRNAs) play an essential role in lymphoma progression. However, the underlying mechanism of circRNA on DLBCL progression related to EBV remains largely unknown. METHODS: CircRNA was screened by high-throughput sequencing in tumor samples of 12 patients with DLBCL according to EBV infection status. Expression of circEAF2, as well as the relationship with clinical characteristics and prognosis, were further analyzed in tumor samples of 100 DLBCL patients using quantitative real-time PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of circEAF2 both in vitro and in vivo. The underlying mechanism of circRNA on DLBCL progression were further determined by RNA sequencing, RNA pull down assay, dual-luciferase reporter assay, rescue experiments and western blotting. RESULTS: We identified a novel circRNA circEAF2, which was downregulated in EBV + DLBCL and negatively correlated with EBV infection and DLBCL progression. In EBV-positive B lymphoma cells, circEAF2 overexpression induced lymphoma cell apoptosis and sensitized lymphoma cells to epirubicin. As mechanism of action, circEAF2 specifically targeted EBV-encoded miR-BART19-3p, upregulated APC, and suppressed downstream ß-catenin expression, resulting in inactivation of Wnt signaling pathway and inhibition of EBV + DLBCL cell proliferation. In EBV-positive B-lymphoma murine models, xenografted tumors with circEAF2 overexpression presented decreased Ki-67 positivity, increased cell apoptosis and retarded tumor growth. CONCLUSIONS: CircEAF2 counteracted EBV + DLBCL progression via miR-BART19-3p/APC/ß-catenin axis, referring circEAF2 as a potential prognostic biomarker. Therapeutic targeting EBV-encoded miRNA may be a promising strategy in treating EBV-associated lymphoid malignancies.

Weakly supervised deep learning for determining the prognostic value of 18F-FDG PET/CT in extranodal natural killer/T cell lymphoma, nasal type.

PURPOSE: To develop a weakly supervised deep learning (WSDL) method that could utilize incomplete/missing survival data to predict the prognosis of extranodal natural killer/T cell lymphoma, nasal type (ENKTL) based on pretreatment 18F-FDG PET/CT results. METHODS: One hundred and sixty-seven patients with ENKTL who underwent pretreatment 18F-FDG PET/CT were retrospectively collected. Eighty-four patients were followed up for at least 2 years (training set = 64, test set = 20). A WSDL method was developed to enable the integration of the remaining 83 patients with incomplete/missing follow-up information in the training set. To test generalization, these data were derived from three types of scanners. Prediction similarity index (PSI) was derived from deep learning features of images. Its discriminative ability was calculated and compared with that of a conventional deep learning (CDL) method. Univariate and multivariate analyses helped explore the significance of PSI and clinical features. RESULTS: PSI achieved area under the curve scores of 0.9858 and 0.9946 (training set) and 0.8750 and 0.7344 (test set) in the prediction of progression-free survival (PFS) with the WSDL and CDL methods, respectively. PSI threshold of 1.0 could significantly differentiate the prognosis. In the test set, WSDL and CDL achieved prediction sensitivity, specificity, and accuracy of 87.50% and 62.50%, 83.33% and 83.33%, and 85.00% and 75.00%, respectively. Multivariate analysis confirmed PSI to be an independent significant predictor of PFS in both the methods. CONCLUSION: The WSDL-based framework was more effective for extracting 18F-FDG PET/CT features and predicting the prognosis of ENKTL than the CDL method.

Implication of immune cell signature of tumor microenvironment in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with complex tumor microenvironment (TME) alterations. However, immune cell signatures of TME and their prognostic value remain unclear in DLBCL. We aimed to identify high-risk DLBCL with specific immune cell signatures in TME. Clinical and gene expression data of DLBCL patients were obtained from previously reported retrospective datasets in Gene Expression Omnibus (GSE108466 and GSE5378616 ) and a multi-center prospective clinical trial NHL001 (NCT01852435). Patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (n = 159) from GSE10846 were referred as training cohort for CHOP regimen, while patients treated with rituximab-CHOP (R-CHOP) regimen (n = 192) from GSE10846 as training cohort for R-CHOP regimen. Patients from NHL001 (n = 68) and GSE53786 (n = 57) were referred as validation cohorts for R-CHOP regimen. CIBERSORT was applied to estimate the relative proportions of 22 subtype of immune cells. We established a prognostic model for model for R-CHOP regimen included Age, performance status, lactate dehydrogenase, T cells follicular helper and macrophages M0, defining a low-risk group with 2-years OS of 92.9% and a high-risk group with 2-years OS of 52.5% (HR 6.57 [3.27-13.18], p < 0.0001). Immune cell signatures could be used as prognostic markers and provided further insights for individualized immunotherapeutic strategies in DLBCL.

Dynamic evaluation of the prognostic value of 18F-FDG PET/CT in extranodal NK/T-cell lymphoma, nasal type.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a type of rare and distinct entity of non-Hodgkin lymphoma with poor prognosis. It is important to evaluate the early treatment response accurately to decide further treatment strategy. 18F-FDG PET/CT plays an important role in response evaluation and prognostic prediction in some kinds of lymphomas. However, data available regarding patients with ENKTL are limited. Thus, in this prospective study, we analyzed the prognostic value of 18F-FDG PET/CT in ENKTL. Thirty-four patients with newly diagnosed ENKTL were enrolled in this phase 2 study (NCT02825147, July 7, 2016). The patients received pre-, mid-, and end-treatment 18F-FDG PET/CT scans. Deauville score (DS), maximal standardized uptake values (SUVmax), and the change in SUVmax (ΔSUVmax) were recorded for response assessment. The median follow-up period was 42.2 months. The 2-year overall survival (OS) and progression-free survival (PFS) were 82.4% and 73.5%, respectively. Univariate analysis revealed that Ann Arbor stage (P < 0.002), mid-treatment DS (P = 0.005), mid-SUVmax (P = 0.001), mid-∆SUVmax (P = 0.004), end-treatment DS (P < 0.001), and end-SUVmax (P = 0.014) were prognostic factors for OS. Ann Arbor stage (P = 0.001), mid-treatment DS (P = 0.008), mid-SUVmax (P = 0.029), mid-∆SUVmax (P < 0.001), and end-treatment DS (P =0.021) were of prognostic significance for PFS. Multivariate analysis showed that mid-SUVmax (P = 0.042) and DS at the middle (P = 0.050) and end (P = 0.044) of treatment were significant independent predictors of PFS. 18F-FDG PET/CT is useful for predicting the prognosis of ENKTL.

PDK1 promotes metastasis by inducing epithelial-mesenchymal transition in hypopharyngeal carcinoma via the Notch1 signaling pathway.

Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare malignancy and has the worst prognosis among head and neck cancer. Metastasis is the major cause of poor prognosis in HSCC patients. In this study, we found that 3-phosphoinositide-dependent protein kinase 1 (PDK1 or PDPK1) was overexpressed in HSCC. The overexpression was positively correlated lymph node metastasis, clinical stage, and distant metastasis and indicated poor outcome. Loss and gain-of-function revealed that PDK1 increased cell proliferation, migration and invasion in vitro as well as tumor growth and metastasis in vivo. Mechanically, PDK1 induced epithelial-mesenchymal transition and promoted metastasis by activating the Notch1 signaling pathway. We further illustrated that PDK1 bound with the Notch1 intracellular domain, thereby inhibiting its ubiquitin-mediated degradation in a protein kinase B (Akt-) independent manner. In summary, PDK1/Notch1 axis played an important role in HSCC metastasis, and this investigation provided a new perspective on potential therapeutic targets for HSCC.

Prognostic impact of B-vitamins involved in one-carbon metabolism in patients with diffuse large B-cell lymphoma.

One-carbon metabolism (OCM) plays a pivotal role in both the stability and integrity of DNA and is mainly regulated by B-vitamins. This study aims to investigate the clinical relevance of B-vitamins and single nucleotide polymorphisms (SNPs) on OCM-related genes in diffuse large B-cell lymphoma (DLBCL). A total of 322 newly diagnosed DLBCL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone-based immunochemotherapy were recruited into this study. The serum levels of B-vitamins (folate, vitamin B2 [riboflavin], vitamin B6 [pyridoxal 5'-phosphate], and vitamin B12 [cobalamin]), as well as SNPs on methylenetetrahydrofolate reductase, methionine synthase (MTR), MTR reductase (MTRR) and cystathionine gamma-lyase (CTH) genes, were assessed at diagnosis. The prognostic values were estimated using the Kaplan-Meier method and Cox proportional hazards regression methods. Overall, the low serum concentration of folate and vitamin B2, as well as the presence of CTH1364 TT genotype, were significantly associated with poor treatment response in DLBCL. Multivariate analysis indicated that compared with patients in the medium and high serum folate tertiles, low serum folate tertile patients had both significantly inferior progression-free survival (P = .033, Tertile 2 vs Tertile 1, and P = .031, Tertile 3 vs Tertile 1) and overall survival time (P < .001, Tertile 2 vs Tertile 1, and P = .001, Tertile 3 vs Tertile 1). Compared with patients in the medium and high serum vitamin B2 tertiles, low serum vitamin B2 tertile patients had both significantly inferior progression-free survival (P = .006, Tertile 2 vs Tertile 1, and P = .001, Tertile 3 vs Tertile 1) and overall survival time (P = .030, Tertile 2 vs Tertile 1, and P = .255, Tertile 3 vs Tertile 1). In conclusion, alterations in B-vitamin metabolism significantly affected disease progression and had a prognostic impact on DLBCL.

The descriptive epidemiology of coronavirus disease 2019 during the epidemic period in Lu'an, China: achieving limited community transmission using proactive response strategies.

Hubei province in China has had the most confirmed coronavirus disease 2019 (COVID-19) cases and has reported sustained transmission of the disease. Although Lu'an city is adjacent to Hubei province, its community transmission was blocked at the early stage, and the impact of the epidemic was limited. Therefore, we summarised the overall characteristics of the entire epidemic course in Lu'an to help cities with a few imported cases better contain the epidemic. A total of 69 confirmed COVID-19 cases and 11 asymptomatic carriers were identified in Lu'an during the epidemic from 12 January to 21 February 2020. Fifty-two (65.0%) cases were male, and the median age was 40 years. On admission, 56.5% of cases had a fever as the initial symptom, and pneumonia was present in 89.9% of cases. The mean serial interval and the mean duration of hospitalisation were 6.5 days (95% CI: 4.8-8.2) and 18.2 days (95% CI: 16.8-19.5), respectively. A total of 16 clusters involving 60 cases (17 first-generation cases and 43 secondary cases) were reported during the epidemic. We observed that only 18.9% (7/37) index cases resulted in community transmission during the epidemic in Lu'an, indicating that the scale of the epidemic was limited to a low level in Lu'an city. An asymptomatic carrier caused the largest cluster, involving 13 cases. Spread of COVID-19 by asymptomatic carriers represents an enormous challenge for countries responding to the pandemic.

Sensitive immunoassay of cardiac troponin I using an optimized microelectrode array in a novel integrated microfluidic electrochemical device.

A sensitive and portable microfluidic electrochemical array device (µFED) was developed for the immunoassay of trace amounts of human cardiac troponin I (cTnI), which is an attractive biomarker for acute myocardial infarction (AMI). The classical "sandwich" method was adopted for the immunoassay. The capture antibody was immobilized using a self-assembled monolayer (SAM) technique, and the process was reorganized to be compatible with the bonding process. The detection antibody was labeled with alkaline phosphatase (AP) for signal amplification. The performance of the µFED was improved by eliminating the shielding effect of the microelectrode array (MEA) integrated in the µFED. The effects of the interstice and the width of the MEA on the response peak current were analyzed and simulated. The concentration gradient, about 3% of the gradient at the surface, was considered as the criterion for estimation of the optimal interstice between electrodes, and its effectiveness was proved. A stable and miniaturized reference electrode was integrated in the µFED, and its potential deviation was less than 5 mV in 15 min. These efforts resulted in the enhanced immunoassay performance of the µFED. A low limit of detection of about 5 pg/mL was obtained in serum samples, and the response current was proportional to the logarithm of concentration from 50 pg/mL to 1 µg/mL. The immunoassay process was accomplished in 15 min. The µFED was thus qualified and is a promising candidate for point-of-care immunoassay of cTnI. Graphical abstract.

Therapeutic Erythrocytapheresis Is Effective in Treating High Altitude Polycythemia on the Qinghai-Tibet Plateau.

INTRODUCTION: High altitude polycythemia (HAPC) is a common chronic disease at high altitudes. It is characterized by excessive erythrocytosis (≥190 g·L-1 in females or ≥210 g·L-1 in males). HAPC severely jeopardizes the health status of plateau dwellers. The Qinghai-Tibet plateau, with an elevation above 4000 m, is the highest plateau in the world. Both Han and Tibetan populations residing there face the threat of HAPC. Therapeutic erythrocytapheresis (TE) was introduced to Tibet as an alternative to phlebotomy in 2015. METHODS: In this study, we retrospectively analyzed 155 patients with HAPC treated with TE in Tibet. Routine blood testing values before and after TE were compared to evaluate treatment efficacy. The efficiency rate, defined as the rate of increase in red blood cell depletion attained by TE compared with 450 mL whole blood phlebotomy, was calculated using whole blood volume and hematocrit before and after treatment and used to identify patients who maintained a normal hemoglobin level in the year after the TE procedure. RESULTS: On average, TE reduced red blood cell levels by 1.5×1012·L-1, hemoglobin concentration by 52 g·L-1, and hematocrit by 14% (P<0.001 for each). Patients who underwent TE with an efficiency rate ≥1.9 were more likely to maintain a normal hemoglobin level in the following year than those who underwent TE with an efficiency rate <1.9 (90 vs 28%, P<0.01). CONCLUSIONS: TE is a feasible therapeutic method to treat HAPC on the Qinghai-Tibet plateau. The efficiency rate is a useful tool to predict the expected interval between TE procedures.

Lessons from an active surveillance pilot to assess the pneumonia of unknown etiology surveillance system in China, 2016: the need to increase clinician participation in the detection and reporting of emerging respiratory infectious diseases.

BACKGROUND: We sought to assess reporting in China's Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system's detection of respiratory infections of public health significance. METHODS: From February 29-May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. RESULTS: Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive. < 10% PUE case medical records documented whether or not there were exposures to animals or others with respiratory illness. Most commonly cited reasons for not reporting cases were no awareness of the PUE system (76%) and not understanding the case definition (53%). CONCLUSIONS: Most clinicians have limited awareness of and are not reporting to the PUE system. Exposures related to respiratory infections are rarely documented in medical records. Increasing clinicians' awareness of the PUE system and including relevant exposure items in standard medical records may increase reporting.

Rethinking safety in numbers: are intersections with more crossing pedestrians really safer?

OBJECTIVE: To advance the interpretation of the 'safety in numbers' effect by addressing the following three questions. How should the safety of pedestrians be measured, as the safety of individual pedestrians or as the overall safety of road facilities for pedestrians? Would intersections with large numbers of pedestrians exhibit a favourable safety performance? Would encouraging people to walk be a sound safety countermeasure? METHODS: We selected 288 signalised intersections with 1003 pedestrian crashes in Hong Kong from 2010 to 2012. We developed a Bayesian Poisson-lognormal model to calculate two common indicators related to pedestrian safety: the expected crash rate per million crossing pedestrians and the expected excess crash frequency. The ranking results of these two indicators for the selected intersections were compared. RESULTS: We confirmed a significant positive association between pedestrian volumes and pedestrian crashes, with an estimated coefficient of 0.21. Although people who crossed at intersections with higher pedestrian volumes experienced a relatively lower crash risk, these intersections may still have substantial potential for crash reduction. CONCLUSIONS: Conclusions on the safety in numbers effect based on a cross-sectional analysis should be reached with great caution. The safety of individual pedestrians can be measured based on the crash risk, whereas the safety of road facilities for pedestrians should be determined by the environmental hazards of walking. Intersections prevalent of pedestrians do not always exhibit favourable safety performance. Relative to increasing the number of pedestrians, safety strategies should focus on reducing environmental hazards and removing barriers to walking.

Estimation of the incidence of severe fever with thrombocytopenia syndrome in high endemic areas in China: an inpatient-based retrospective study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a severe viral disease caused by SFTSV. It is important to estimate the rate of missed SFTS diagnosis and to further understand the actual incidence in high endemic areas in China. METHODS: This study was conducted in two high SFTS endemic provinces in 2015. Patients hospitalized in 2014 or within 1 year before investigation were selected after considering their clinical manifestations, specifically, fever, platelet, and white blood cell. During retrospective investigation, sera were collected to detect SFTSV antibodies to assess SFTSV infection. To further understand SFTSV infection, acute phase sera were detected; SFTSV infection rate among a healthy population was also investigated to determine the basic infection level. RESULTS: In total, 246 hospitalized cases were included, including 83 cases (33.7%) with fever, thrombocytopenia and leukopenia, 38 cases (15.4%) with fever and thrombocytopenia but without leukopenia, and 125 cases (50.8%) without fever but with thrombocytopenia and leukopenia. In total, 13 patients (5.3%) were SFTSV IgM antibody-positive, 48 (19.5%) were IgG-positive. Of the 13 IgM-positive cases, 11 (84.6%) were IgG-positive (9 with titres ≥1:400). Seropositive rates of antibodies were high (8.4% for IgM and 30.1% for IgG) in patients with fever, thrombocytopenia and leukopenia. Furthermore, among IgG-positive cases in this group, 76% (19/25) of patients' IgG antibody titres were ≥1:400. Additionally, 28 of 246 cases were initially diagnosed with suspected SFTS and were then excluded, and 218 patients were never diagnosed with SFTS; the seropositive rates of IgM and IgG in these two groups were 25% and 67.9% and 2.8% and 13.3%, respectively. These rates were 64.3% and 21.4% in 14 sera collected during acute phase of the 28 cases mentioned above. Seropositive rate of SFTSV IgG was only 1.3% in the patient-matched healthy group, and no IgM antibody was detected. A preliminary estimate of 8.3% of SFTS cases were missed in SFTS high endemic provinces. CONCLUSIONS: The actual SFTS incidence was underestimated. Effective measures such as adding a new SFTS case category - "SFTS clinical diagnosis cases" or using serological detection methods during acute phase should be considered to avoid missed diagnoses.

Nuclear import of Nkx2-2 is mediated by multiple pathways.

Nkx2-2 homeoprotein is essential for the development of the central nervous system and pancreas. Although the nuclear localization signals of Nkx2-2 have been identified, the responsible transport receptor is still unknown. Here, we demonstrate that imp α1 not only interacts with Nkx2-2 but also transports it into the nucleus in vitro by acting together with imp ß1. However, the nuclear import of Nkx2-2 in cells was not inhibited in response to knockdown expression of endogenous imp ß1 or over-expression of Bimax2. Furthermore, imp ß1 and imp 13, but not imp 4, directly interact with Nkx2-2 and are capable of transporting Nkx2-2 in an in vitro import assay. By GST pull-down assay, we demonstrate that mutation of NLS1 or NLS2 has no effect on interaction with imp α1 or imp 13, but significantly reduced binding to imp ß1. Thus, the nuclear import of Nkx2-2 is mediated not only by the classical import pathway but also directly by imp ß1 or imp 13.

Analysis of prognostic factors and comparison of prognostic scores in peripheral T cell lymphoma, not otherwise specified: a single-institution study of 105 Chinese patients.

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous subtype of non-Hodgkin's lymphoma. This study aims to better define the prognostic factors and compare the predictive value of the prognostic scores in Chinese patients with PTCL-NOS. One hundred and five patients diagnosed as PTCL-NOS from our institution were retrospectively studied and grouped according to four previously described prognostic scores [International Prognostic Index (IPI), Prognostic Index for PTCL-NOS (PIT), modified PIT (m-PIT), and International PTCL Project (IPTCLP)]. In addition to clinical parameters, peripheral lymphopenia and thrombocytopenia, serum Epstein-Barr virus positivity, and tumor Ki-67 were significantly associated with poor disease outcome. Multivariate analysis revealed that age >60 years, poor performance status, elevated lactic dehydrogenase, and bone marrow involvement were independent adverse variables for survival. All prognostic scores were successful for survival estimation. Risk subgroups in IPI and PIT could be further discriminated by platelet count (IPTCLP factor) and Ki-67 (m-PIT factor), respectively. Together, patient- and tumor-specific characteristics may be incorporated in risk stratification of PTCL-NOS patients. The prognostic scores could be mutually active to improve their predictive value of disease outcome.

Constraints of Sedimentary Environment on Shale Organic Matter Enrichment: Insights from Elemental Geochemistry and Multiple Factor Analysis.

The organic-rich shale of the Wufeng-Longmaxi formation is an important section for shale gas exploration. The traditional univariate or bivariate analysis causes researchers to have great controversy about its enrichment mechanism. This study explores the combination of multiple factor analysis (MFA) and element geochemistry to calculate the contribution rate of a paleoenvironment to organic matter enrichment and clarify the main controlling factors of organic matter enrichment. Research has shown that there is generally high productivity from the Wufeng (O3w)-Longmaxi formation (S1l) deposition. The degree of terrigenous clastic input and weathering during the period of the O3w is relatively low, and sedimentary water restriction is strong, mainly developing an anoxic-dysoxic sedimentary environment. During the deposition of S1l1, the input intensity and weathering of terrigenous debris were slightly enhanced, and the increase of the water column led to the development of an anoxic environment at the bottom of the water layer. During the S1l2+3 period, the degree of terrigenous debris and weathering is the largest, and the high oxygen content of the water column is mainly a normal oxic environment. An MFA calculation shows that the paleoproductivity and paleoredox environment of the organic-rich shale section have the highest contribution rate of about 59.57% to the enrichment of organic matter, which is higher than that of paleoclimate conditions and terrigenous clastic input, indicating that the enrichment of organic matter is mainly controlled by paleoproductivity and the preservation environment. This study provides a basis for the application of MFA in element geochemistry and can serve as a model for other studies.