[Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion-derived mesenchymal stem cells].

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

[VIPR1 promoter methylation promotes transcription factor AP-2α binding to inhibit VIPR1 expression and promote hepatocellular carcinoma cell growth in vitro].

OBJECTIVE: To explore the transcriptional regulation mechanism and biological function of low expression of vasoactive intestinal peptide receptor 1 (VIPR1) in hepatocellular carcinoma (HCC). METHODS: We constructed plasmids carrying wild-type VIPR1 promoter or two mutant VIPR1 promoter sequences for transfection of the HCC cell lines Hep3B and Huh7, and examined the effect of AP-2α expression on VIPR1 promoter activity using dual-luciferase reporter assay. Pyrosequencing was performed to detect the changes in VIPR1 promoter methylation level in HCC cells treated with a DNA methyltransferase inhibitor (DAC). Chromatin immunoprecipitation was used to evaluate the binding ability of AP-2α to VIPR1 promoter. Western blotting was used to assess the effect of AP-2α knockdown on VIPR1 expression and examine the differential expression of VIPR1 in the two cell lines. The effects of VIPR1 overexpression and knockdown on the proliferation, cell cycle and apoptosis of HCC cells were analyzed using CCK8 assay and flow cytometry. We also observed the growth of HCC xenograft with lentivirus-mediated over-expression of VIPR1 in nude mice. RESULTS: Compared with the wild-type VIPR1 promoter group, co-transfection with the vector carrying two promoter mutations and the AP-2α-over-expressing plasmid obviously restored the luciferase activity in HCC cells (P < 0.05). DAC treatment of the cells significantly decreased the methylation level of VIPR1 promoter and inhibited the binding of AP-2α to VIPR1 promoter (P < 0.01). The HCC cells with AP-2α knockdown showed increased VIPR1 expression, which was lower in Huh7 cells than in Hep3B cells. VIPR1 overexpression in HCC cells caused significant cell cycle arrest in G2/M phase (P < 0.01), promoted cell apoptosis (P < 0.001), and inhibited cell proliferation (P < 0.001), while VIPR1 knockdown produced the opposite effects. In the tumor-bearing nude mice, VIPR1 overexpression in the HCC cells significantly suppressed the increase of tumor volume (P < 0.001) and weight (P < 0.05). CONCLUSION: VIPR1 promoter methylation in HCC promotes the binding of AP-2α and inhibits VIPR1 expression, while VIPR1 overexpression causes cell cycle arrest, promotes cell apoptosis, and inhibits cell proliferation and tumor growth.

Therapeutic effect of Qinghuayin against chronic atrophic gastritis through the inhibition of toll or interleukin-1 receptor domain-containing adaptor inducing interferon-ß signaling pathway.

OBJECTIVE: To examine the efficacy of Qinghuayin (, QHY) in rat chronic atrophic gastritis (CAG) models and explored the molecular mechanism of QHY in treating CAG. METHODS: In total, 65 Wistar rats were randomly divided into the control (= 10) and CAG groups ( = 55). CAG model rats were further divided into five groups: model ( = 10), vitacoenzyme ( = 10), low-dose QHY ( = 10), medium-dose QHY ( = 10), and high-dose QHY groups ( = 10). We analyzed histopathological changes using hematoxylin and eosin staining and measured interleukin (IL)-6 and IL-8 levels in serum using enzyme-linked immunosorbent assay (ELISA) (Boster Bio, Pleasanton, USA). In addition, gastrin (GAS), pepsinogen I (PGI), and PGII expressions were evaluated using ELISA. The protein and mRNA expression of toll-like receptor 4 (TLR4) and toll or interleukin-1 receptor domain-containing adaptor inducing interferon-ß (TRIF) was detected by Western blotting and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: Our results revealed that histopathological changes in CAG model rates could be restored by low-, medium-, and high-dose QHY. The changes in GAS and PGI/II expression demonstrated that QHY improved CAG. Serum IL-6 and IL-levels were decreased by QHY administration. TLR4 and TRIF were upregulated at the mRNA and protein levels in the model group but downregulated by QHY administration. CONCLUSION: We concluded that QHY could effectively improve the histopathological changes of the gastric mucosa induced by CAG in rats. The therapeutic mechanism of QHY may be related to inhibition of the inflammatory factors IL-6 and IL-8 and suppression of TLR4/TRIF mRNA and protein expression.

[Analysis of bacterial pathogens and clinical characteristics of children with respiratory tract infections in Tianjin].

Objective: To analyze the pathogenic bacteria and epidemiological characteristics in children with respiratory tract infection in Tianjin area. Methods: Retrospective case analysis was performed on 2 392 hospitalized children in the wards of respiratory diseases, intensive care unit and special care ward of Tianjin Children's Hospital from June 2018 to May 2019. Thirteen pathogenic bacteria in deep sputum and bronchoalveolar lavage fluid samples were detected by loop-mediated isothermal amplification. The laboratory data and clinical characteristics of the infected children were analyzed, and the comparison between groups was performed by t test or χ2 test. Results: Among 2 392 cases, 1 407 were males and 985 females. There was no significant difference in the detection rate between males and females (72.5% (1 020/1 407) vs.74.2% (731/985), χ2=0.87, P=0.35). A total of 1 751 strains and 12 kinds of positive respiratory pathogens were detected, with a detection rate of 73.2%. Among them, 913 (38.2%) strains were Mycoplasma pneumoniae (MP), 514 (21.5%) were Streptococcus pneumoniae (Sp), 381 (15.9%) were Methicillin-resistant Staphylococcus aureus (MRSA) and 279 (11.7%) were Hemophilus influenzae (Hi). There was significant difference in the detection rate of pathogens among different age groups (χ²=83.67, P<0.01). The positive rate of alveolar lavage fluid group was higher than that of deep sputum fluid group [81.6% (614/752) vs. 69.3% (1 137/1 640), χ2=39.89, P<0.01]. The length of hospital stay of children infected with different pathogens was significantly different (all P<0.01). There was significant difference in duration of fever among children infected with different pathogens (χ²=228.69,103.56, 3.96, 27.38,24.50,41.66, all P<0.05). There were 63 (7.7%) cases of atelectasis, 260 (31.9%) cases of pleurisy and 120 (14.7%) cases of pleural effusion in MP children. Children with Sma were most likely to involve the heart system (2/9), and children with Eco infection had a higher incidence of complications such as those of blood (3/19), urinary (2/19), digestive systems(4/19), systemic inflammatory response syndrome and sepsis (1/19). Conclusions: The main bacterial pathogens of respiratory tract infection in children in Tianjin were MP, Sp, MRSA and Hi. It is suggested that clinicians should not only pay attention to the respiratory symptoms of children, but also pay attention to the complications caused by bacterial pathogen infection, so as to prevent the deterioration of the disease and improve the prognosis.

[Typical case analysis of COVID-19 cluster epidemic in Shaanxi, 2020].

Objective: By analyzed the transmission patterns of 4 out of the 51 COVID-19 cluster cases in Shaanxi province to provide evidences for the COVID-19 control and prevention. Methods: The epidemiological data of RT-PCR test-confirmed COVID-19 cases were collected. Transmission chain was drawn and the transmission process was analyzed. Results: Cluster case 1 contained 13 cases and was caused by a family of 5 who traveled by car to Wuhan and returned to Shaanxi. Cluster case 2 had 5cases and caused by initial patient who participated family get-together right after back from Wuhan while under incubation period. Cluster case 3 contained 10 cases and could be defined as nosocomial infection. Cluster case 4 contained 4 cases and occurred in work place. Conclusion: Higher contact frequency and smaller places were more likely to cause a small-scale COVID-19 cluster outbreak, with potential longer incubation period. COVID-19 control strategies should turn the attention to infection prevention and control in crowded places, management of enterprise resumption and prevention of nosocomial infection.

[Analysis of transmission characteristics of COVID-19 in Shaanxi Province].

A total of 245 cases of COVID-19 in Shaanxi Province reported in the China information system for disease control and prevention as of February 24, 2020 were selected as the research objects, the cases are divided into imported cases (116 cases, 47.3%) and local cases (129 cases, 52.7%), their basic characteristics, time distribution, transmission mode, intergenerational interval and latent period transmission are analyzed. The age of local cases [(51.74±15.67) years old], female patients (69 cases, 53.5%), housework and retired staff (40 cases, 31.0%), and patients isolated at the time of onset (50 cases, 38.8%) were higher than imported cases, respectively[(40.66±15.41) years old, (45 cases, 38.8%), (21 cases, 18.1%), (17 cases, 14.6%)] (P values were < 0.05); The infection rate was 0.8% (31/3 666) in close contacts with local cases, which was lower than imported cases 2.0% (69/3 435) (P<0.001); The main source of infection in local cases was relatives (70 cases, 54.3%), and the main way of infection was living together and party (90 cases, 69.8%); the proportion of latent period transmission in our province was 15.5% (20 cases), and the interval between the second-generation case and the source of infection was about 4 days, and the interval between generations was about 6 days. In summary, the main way of infection of local cases in Shaanxi Province was living together and party, there were a certain proportion of latent period transmission cases at present, it's suggested that the investigation of close contacts should be started 4 days or earlier before the onset of the case.

[Epidemiological characteristics of COVID-19 in Shaanxi province].

Objective: To understand the incidence trend and epidemiological characteristics of COVID-19 in Shaanxi province. Methods: The incidence data of COVID-19 reported in Shaanxi as of 22 February, 2020 were collected for an epidemiological descriptive analysis. Results: A total of 245 confirmed cases of COVID-19 were reported in Shaanxi. Most cases were mild (87.76%). As time passed, the areas where confirmed cases were reported continued to increase. The case number in Xi'an was highest, accounting for nearly half of the total reported cases in the province. The epidemic pattern in Shaanxi had gradually shifted from imported case pattern to local case pattern, and the transmission of local cases was mainly based on family cluster transmission. The confirmed cases from different sources had caused the secondary transmission in Shaanxi. After February 7, the number of reported cases began to fluctuate and decrease stably, indicating a decrease-to-zero period. Conclusions: At present, the overall epidemic of COVID-19 in Shaanxi has gradually been mitigated. However, considering the approaching of return to work and study and the increasing of imported cases from other countries, the prevention and control of COVIS-19 in Shaanxi will face new challenges.

[Dynamics and epidemiological characteristics of hand, foot and mouth disease in Shaanxi province, 2009-2018].

Objective: To understand the dynamics and epidemiological characteristics of hand, foot and mouth disease (HFMD) in Shaanxi province during 2009-2018 and provide evidence for prevention and control of HFMD. Methods: Information on HFMD was collected from the Chinese Disease Prevention and Control Information System in Shaanxi Province during 2009-2018 and was analyzed by descriptive, dynamic geometric series averaging and circular distribution methods. Results: The annual average incidence rate of HFMD was 140.04/100 000 in Shaanxi province during 2009-2018. The highest incidence rates were seen in age groups as 1-year olds (3 494.24/100 000), 2-year olds (2 734.79/100 000) and 3-year olds (2 608.58/100 000). The highest reported mortality rates appeared in: 1-year olds as 1.42/100 000, 2-year olds as 0.77/100 000) and 0-year olds (0.53/100 000). The incidence rate increased most rapidly in the 1-year olds and the 0-year olds groups. The top three incidence rates were reported in Xi'an (251.34/100 000), Weinan (161.21/100 000) and Xianyang (123.73/100 000) cities in Guanzhong area of Shaanxi province. In the whole province, incidence rate was on the rise, and the average increases of incidence rates were all greater than zero in these cities. The proportion of severe cases in most cities somehow declined. Results from the circular distribution method estimated that the peak incidence would appear in April 10-11 each year, and the high incidence season was from April to July. In 2018, the composition of enterviruses (EV) 71 was 26.47% (1 303/4 922). In 2014 to 2018, the proportion of Coxsackie virus A16 (Cox A16) was between 20.06%(753/3 753) and 23.08% (855/3 705). The proportions of other EVs increased from 6.09% (14/230) to 51.91% (2 555/4 922) during 2009-2018. Conclusions: The overall incidence rate of HFMD was increasing, with high risk population appeared in children under 3 year olds, in Shaanxi province during 2009-2018. However, both mortality and fatality rates were declining, with severe cases also showing a downward trend in most of the areas. Composition of pathogens was changing over time.

Effects of lncRNA ANRIL on proliferation and apoptosis of oral squamous cell carcinoma cells by regulating TGF-ß/Smad pathway.

OBJECTIVE: To investigate the role of the long non-coding ribonucleic acid (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) in the proliferation and apoptosis of the oral squamous cell carcinoma (OSCC) cells by regulating the transforming growth factor-beta (TGF-ß)/Smad pathway. PATIENTS AND METHODS: Human OSCC cells were cultured, and then transfected with small interfering (si)-ANRIL to inhibit the lncRNA ANRIL and ANRIL-OE to overexpress the lncRNA ANRIL. Next, the flow cytometry was carried out to detect the apoptosis rate, the proliferation was determined via methyl thiazolyl tetrazolium (MTT) assay, and the changes in the protein level were detected through Western blotting (WB). RESULTS: The lncRNA ANRIL was highly expressed in the tissues and serum of patients. The proliferation ability of the cells transfected with si-ANRIL was significantly reduced, while that of the cells transfected with ANRIL-OE was overtly increased. The apoptosis rate was (9.21±5.22)%, (22.3±1.34)%, and (13.21±6.22)% in lncRNA ANRIL-OE group, si-ANRIL group and control group, respectively. The protein expression level of the apoptotic protein active caspase-3 was lowered after the treatment with ANRIL-OE, and the key molecules of the TGF-ß/Smad pathway were notably down-regulated after inhibiting ANRIL with si-ANRIL. CONCLUSIONS: The lncRNA ANRIL regulates the TGF-ß/Smad signaling pathway to promote the proliferation and suppress the apoptosis of OSCC cells.

[The prognosis value of comprehensive geriatric assessment in elder patients with acute myeloid leukemia in a single center].

Objective: To evaluate the prognostic significance of comprehensive geriatric assessment (CGA) in Chinese elderly acute myeloid leukemia (AML) patients. Methods: 73 AML patients over the age of 60 were enrolled. CGA stratification included the following 3 instrument assessment: activity of daily living (ADL) ; instrumental activity of daily living (IADL) ; comorbidity score according to the Modified cumulative illness rating score for geriatrics (MCIRS-G) . According to CGA and age, the enrolled patients were grouped into 'fit', 'unfit' and 'frail' categories. Results: The median age of 73 elderly AML patients were 75 years old. According to CGA, 37 (50.1%) patients were classified as 'fit', 14 (19.2%) as 'unfit', and 22 (30.7%) as 'frail'. 33 (89.2%) patients in fit group received induction chemotherapy, or demethylation treatment, as 8 (57.9%) in unfit, 10 (45.5%) in frail. The overall response rate was 68.7%、62.5%, 75.0% in fit, unfit, and frail group, respectively (χ(2)=0.615, P=0.769) .The early mortality (8 weeks) in three groups were different: 5.4%, 7.1%, 27.3%, respectively (P<0.05) . The 1-year overall survival in the 'fit', 'unfit' and 'frail' groups was 64.9%, 28.6% and 22.7%, respectively (P<0.05) . The CGA score, age, ECOG score, WHO classification (2016) were the prognostic factors of AML patients. Conclusion: CGA can be used to determine the prognosis of elderly AML patients.

MiR-21 inhibitor improves locomotor function recovery by inhibiting IL-6R/JAK-STAT pathway-mediated inflammation after spinal cord injury in model of rat.

OBJECTIVE: To investigate the function of miRNA-21 and interleukin-6 receptor/Janus Kinase-Signal transducer and activator of transcription (IL-6R/JAK-STAT) pathway in microglia on inflammatory responses after spinal cord injury (SCI). MATERIALS AND METHODS: This study first detected respectively the protein level of inflammatory factor inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) by Western blotting after transfection of miR-21 or administration of miR-21 inhibitor in activated microglia cells of rat in vitro. The quantitative Real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of IL-6R under two different interventions. Next, we established a model of spinal cord injury in rat and inspected miR-21 and IL-6R in SCI rat by qRT-PCR. In addition, the protein levels of iNOS and TNF-α in SCI rat were detected by Western blotting. MiR-21 inhibitor was injected into the injured area of SCI rat to delve into the function of miR-21 down-expression on iNOS and TNF-α expression by Western blot as well as the RNA levels of IL-6R, JAK and STAT3 by qRT-PCR. Furthermore, the SCI rat with movement and coordination of hindlimbs was observed by Basso-Beattie-Bresnahan locomotor rating scale (BBB scale) after miR-21 down-expression. RESULTS: Compared with the microglia transfected with miR-21, the execution of inhibitor in microglia effectively relieved the expression of IL-6R and the breakout of iNOS and TNF-α. Meanwhile, the increase of miR-21 was significantly observed in SCI rat along with significant improvement of inflammatory response-related factors including iNOS and TNF-α. After that, we injected SCI rat with miR-21 inhibitor into the spinal cord injury area and found the inhibition of miR-21 decreased the protein levels of iNOS and TNF-α. Simultaneously, down-expression of miR-21 evidently declined the RNA levels of IL-6R, JAK, and STAT3 in SCI rat. Compared with the sham-operated rat, the movement and coordination of hindlimbs of the SCI group displayed dramatic dysfunction. However, miR-21 down-expression elevated the movement and coordination of hindlimbs of the SCI rat than those of the only injury group. CONCLUSIONS: Inhibition of miR-21 can promote the recovery of spinal cord injury by down-regulating IL-6R/JAK-STAT signaling pathway and inhibiting inflammation.

Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis.

BACKGROUND: The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift nature of indel mutations, which create novel open reading frames and a large quantity of mutagenic peptides highly distinct from self, might contribute to the immunogenic phenotype. METHODS: We analysed whole-exome sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer Genome Atlas. We compared the proportion and number of indels across the cohort, with a subset of results replicated in two independent datasets. We assessed in-silico tumour-specific neoantigen predictions by mutation type with pan-cancer analysis, together with RNAseq profiling in renal clear cell carcinoma cases (n=392), to compare immune gene expression across patient subgroups. Associations between indel burden and treatment response were assessed across four checkpoint inhibitor datasets. FINDINGS: We observed renal cell carcinomas to have the highest proportion (0·12) and number of indel mutations across the pan-cancer cohort (p<2·2 × 10-16), more than double the median proportion of indel mutations in all other cancer types examined. Analysis of tumour-specific neoantigens showed that enrichment of indel mutations for high-affinity binders was three times that of non-synonymous SNV mutations. Furthermore, neoantigens derived from indel mutations were nine times enriched for mutant specific binding, as compared with non-synonymous SNV derived neoantigens. Immune gene expression analysis in the renal clear cell carcinoma cohort showed that the presence of mutant-specific neoantigens was associated with upregulation of antigen presentation genes, which correlated (r=0·78) with T-cell activation as measured by CD8-positive expression. Finally, analysis of checkpoint inhibitor response data revealed frameshift indel count to be significantly associated with checkpoint inhibitor response across three separate melanoma cohorts (p=4·7 × 10-4). INTERPRETATION: Renal cell carcinomas have the highest pan-cancer proportion and number of indel mutations. Evidence suggests indels are a highly immunogenic mutational class, which can trigger an increased abundance of neoantigens and greater mutant-binding specificity. FUNDING: Cancer Research UK, UK National Institute for Health Research (NIHR) at the Royal Marsden Hospital National Health Service Foundation Trust, Institute of Cancer Research and University College London Hospitals Biomedical Research Centres, the UK Medical Research Council, the Rosetrees Trust, Novo Nordisk Foundation, the Prostate Cancer Foundation, the Breast Cancer Research Foundation, the European Research Council.

Clinical significance and expression of PUMA, MCL-1, and p53 in human renal cell carcinoma and para-carcinoma tissues.

We investigated the expression level of p53 upregulated modulator of apoptosis (PUMA), myeloid cell leukemia-I (MCL-1), and p53 in renal cell carcinoma (RCC) and para-carcinoma tissues, as well as their clinical significance. The expression levels of PUMA, MCL-1, and p53 in RCC and para-carcinoma tissues were measured using immunohistochemical and quantitative real-time PCR methods. Correlations between protein expression and pathological characteristics were analyzed. Renal clear cell carcinoma showed elevated MCL-1 and p53 protein expression (P > 0.05) and reduced PUMA expression as compared to that in para-carcinoma tissues. Spearman ranking correlation analysis showed that expression of PUMA, MCL-1, and p53 in was negatively correlated with RCC (r = -0.504, P = 0.001; r = -0.413, P = 0.008). We also observed significant correlation between MCL-1 expression and tumor differentiation (P < 0.05), where MCL-1 expression was significantly higher in well-differentiated adenocarcinoma as compared to that in medium or lowly differentiated adenocarcinoma. In addition, p53 expression was highly correlated with TNM staging (P < 0.05). Single factor analysis on COX's proportional hazard model indicated that postoperative survival rate and prognosis of renal clear cell carcinoma was highly correlated with TNM staging (P < 0.05). Quantitative real-time PCR analysis indicated higher expression of PUMA, MCL-1, and p53 in cancer tissues as compared to that in para-carcinoma tissues (P < 0.05).The expression of PUMA, MCL-1, and p53 can reflect the biological behavior of renal cell carcinoma, and can be used to indicate tumor invasion, progression, and prognosis.

MRI-Based Texture Analysis to Differentiate Sinonasal Squamous Cell Carcinoma from Inverted Papilloma.

BACKGROUND AND PURPOSE: Because sinonasal inverted papilloma can harbor squamous cell carcinoma, differentiating these tumors is relevant. The objectives of this study were to determine whether MR imaging-based texture analysis can accurately classify cases of noncoexistent squamous cell carcinoma and inverted papilloma and to compare this classification performance with neuroradiologists' review. MATERIALS AND METHODS: Adult patients who had inverted papilloma or squamous cell carcinoma resected were eligible (coexistent inverted papilloma and squamous cell carcinoma were excluded). Inclusion required tumor size of >1.5 cm and preoperative MR imaging with axial T1, axial T2, and axial T1 postcontrast sequences. Five well-established texture analysis algorithms were applied to an ROI from the largest tumor cross-section. For a training dataset, machine-learning algorithms were used to identify the most accurate model, and performance was also evaluated in a validation dataset. On the basis of 3 separate blinded reviews of the ROI, isolated tumor, and entire images, 2 neuroradiologists predicted tumor type in consensus. RESULTS: The inverted papilloma (n = 24) and squamous cell carcinoma (n = 22) cohorts were matched for age and sex, while squamous cell carcinoma tumor volume was larger (P = .001). The best classification model achieved similar accuracies for training (17 squamous cell carcinomas, 16 inverted papillomas) and validation (7 squamous cell carcinomas, 6 inverted papillomas) datasets of 90.9% and 84.6%, respectively (P = .537). For the combined training and validation cohorts, the machine-learning accuracy (89.1%) was better than that of the neuroradiologists' ROI review (56.5%, P = .0004) but not significantly different from the neuroradiologists' review of the tumors (73.9%, P = .060) or entire images (87.0%, P = .748). CONCLUSIONS: MR imaging-based texture analysis has the potential to differentiate squamous cell carcinoma from inverted papilloma and may, in the future, provide incremental information to the neuroradiologist.

A novel method to detect circulating antigens of Schistosoma japonicum using a gold nanorod optical sensor.

Diagnostic method of Schistosoma japonicum (S.japonicum) is the key of schistosomiasis prevention and control. In China, schistosomiasis reached the stage of transmission control, and almost of the epidemic areas tend to have low infection rate and intensity, but it is difficult for the existing detection methods to achieve accurate monitoring. In this study, a novel method to detect the circulating antigens of S.japonicum using gold nanorods optical sensor was developed. Gold nanorods were prepared by seed-mediated growth followed by deposition onto Indium-Tin-Oxide (ITO) glass to fabricate a solid phase biosensor. In order to assembly between the ITO glass and gold nanorod, hydroxylation and sulfhydrylation were carried out to modify the ITO glass. Surface of gold nanorods was conjugated with an SIEA26-28kDaSjscFv antibody against S.japonicum circulating antigens, and the sensor optical changed upon antigen-antibody recognition. The sensor was used to detect S.japonicum infection in rabbits by testing the serum once a week for 8 weeks. Results revealed different displacement of localized surface plasmon resonance (LSPR) of the gold nanorod optical sensor each week while the control group showed no such change in LSPR. Simultaneously, Indirect Hemagglutination Assay(IHA) and Fast Enzyme-Linked Immuno Sorbent Assay (F-ELISA) method were used to test these samples. Ten human serum samples from S.japonicum infected patients were analyzed using the gold nanorods optical sensor, which revealed that health human serum did not show any spectrum displacement. We developed a specificity gold nanorod optical sensor by combining the SIEA26-28kDaSjscFv, which was used to detect circulating antigens of S.japonicum. This method is expected to overcome the issues pertaining to the testing of circulating antigens of S.japonicum.

LMP1 signaling pathway activates IRF4 in latent EBV infection and a positive circuit between PI3K and Src is required.

Interferon (IFN) regulatory factors (IRFs) have crucial roles in immune regulation and oncogenesis. We have recently shown that IRF4 is activated through c-Src-mediated tyrosine phosphorylation in virus-transformed cells. However, the intracellular signaling pathway triggering Src activation of IRF4 remains unknown. In this study, we provide evidence that Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) promotes IRF4 phosphorylation and markedly stimulates IRF4 transcriptional activity, and that Src mediates LMP1 activation of IRF4. As to more precise mechanism, we show that LMP1 physically interacts with c-Src, and the phosphatidylinositol 3 kinase (PI3K) subunit P85 mediates their interaction. Depletion of P85 by P85-specific short hairpin RNAs disrupts their interaction and diminishes IRF4 phosphorylation in EBV-transformed cells. Furthermore, we show that Src is upstream of PI3K for activation of both IRF4 and Akt. In turn, inhibition of PI3K kinase activity by the PI3K-speicfic inhibitor LY294002 impairs Src activity. Our results show that LMP1 signaling is responsible for IRF4 activation, and further characterize the IRF4 regulatory network that is a promising therapeutic target for specific hematological malignancies.

[The prevalence and etiology of anemia in urban community dwelling elderly population in Beijing].

OBJECTIVE: To estimate the prevalence of anemia in urban community dwelling elderly population. METHODS: This study was a cross-sectional survey of prevalence of anemia in randomly selected community dwelling residents aged over 65 years in Beijing. Anemia was defined as hemoglobin concentration less than 130 g/L in men and 120 g/L in women. RESULTS: The hemoglobin concentration was (135.65±14.48) g/L in total of 1 947 eligible participants and was much higher in men than in women [(142.56±15.56) g/L vs (130.95±11.53) g/L, P<0.001]. There were 288 (14.8%) patients with anemia, including 16.3%(129/789) in men and 13.7%(159/1 158) in women. The prevalence of anemia increased significantly with age, which was 7.6% in 65-69 years, 10.8% in 70-74 years, 18.8% in 75-79 years and 24.1% over 80 years (P<0.001). Two hundred and seventy-nine (96.9%) subjects were mild anemia, 8 (2.8%) moderate, only 1 subject (0.3%) severe. Unexplained anemia was predominant, which accounted for 63.2%. Only 16.7% people were diagnosed as nutritional anemia, renal anemia 5.2%, anemia of chronic disease (ACD) 12.2%. There were 2.4% people with overlapped renal anemia and ACD. Compared with non-anemic subjects, more subjects with unexplained anemia represented macrocytosis (7.1% vs 3.2%, P=0.007). CONCLUSIONS: Anemia is a common health problem in urban community dwelling elderly population. Most subjects have anemia with unknown origin. Further investigation is needed to explore the mechanism and related factors of elderly anemia.

HCV-induced miR146a controls SOCS1/STAT3 and cytokine expression in monocytes to promote regulatory T-cell development.

Host innate and adaptive immune responses must be tightly regulated by an intricate balance between positive and negative signals to ensure their appropriate onset and termination while fighting pathogens and avoiding autoimmunity; persistent pathogens may usurp these regulatory machineries to dampen host immune responses for their persistence in vivo. Here, we demonstrate that miR146a is up-regulated in monocytes from hepatitis C virus (HCV)-infected individuals compared to control subjects. Interestingly, miR146a expression in monocytes without HCV infection increased, whereas its level in monocytes with HCV infection decreased, following Toll-like receptor (TLR) stimulation. This miR146a induction by HCV infection and differential response to TLR stimulation were recapitulated in vitro in monocytes co-cultured with hepatocytes with or without HCV infection. Importantly, inhibition of miR146a in monocytes from HCV-infected patients led to a decrease in IL-23, IL-10 and TGF-ß expressions through the induction of suppressor of cytokine signalling 1 (SOCS1) and the inhibition of signal transducer and activator transcription 3 (STAT3), and this subsequently resulted in a decrease in regulatory T cells (Tregs) accumulated during HCV infection. These results suggest that miR146a may regulate SOCS1/STAT3 and cytokine signalling in monocytes, directing T-cell differentiation and balancing immune clearance and immune injury during chronic viral infection.