Desmoid-type fibromatosis of the mesentery: a clinicopatho-logical and genetic analysis of 9 cases. / è‚ ç³»è†œéŸ§å¸¦æ ·çº¤ç»´ç˜¤ç— æ‚£è€ ä¸´åºŠç— ç†å­¦åˆ†æž.

Nine cases of mesenteric desmoid-type fibromatosis were diagnosed and treated in Taizhou Hospital, Wenzhou Medical University between January 2010 and May 2022, including 2 females and 7 males, aged 16 to 59 years. The lesions were in the mesentery of small intestine with 7 cases, ileocecal junction with 1 cases and transverse colon with 1 case. The tumors had an unclear boundary and no envelope, the section was solid, gray and tough. The mean maximum diameter was (10.7±8.5) cm (range 3.5-33.0 cm). Microscopically, fusiform fibroblasts and myofibroblasts were parallel, bunched or staggered, buried in a large amount of extracellular collagen. The cell morphology was relatively consistent, without obvious atypia, and mitosis was rare. Immunohistochemistry showed that the tumor cells were positive for vimentin (9/9), ß-catenin (9/9), while smooth muscle actin (5/9) stains were focally positive. Ki-67 proliferation index was 1%-10%. Cytokeratin Pan, S-100, STAT6, CD117, DOG1, CD34, desmin and anaplastic lymphoma kinase stains were negative. Genetic analysis showed that there were 7 cases of c.121G>A(p.Thr41Ala) mutation of CTNNB1 gene, 1 case of c.121G>A(p.Thr41Ala) and 1 case of c.134C>T(p.Ser45Phe) double mutation, and 1 case of wild type. Tumors were surgically resected in all 9 cases. Eight cases had no recurrence or metastasis, 1 case had recurrence 6 months later, and no recurrence or metastasis after additional surgical resection.

Design Method for a Higher Order Extended Kalman Filter Based on Maximum Correlation Entropy and a Taylor Network System.

This paper proposes one new design method for a higher order extended Kalman filter based on combining maximum correlation entropy with a Taylor network system to create a nonlinear random dynamic system with modeling errors and unknown statistical properties. Firstly, the transfer function and measurement function are transformed into a nonlinear random dynamic model with a polynomial form via system identification through the multidimensional Taylor network. Secondly, the higher order polynomials in the transformed state model and measurement model are defined as implicit variables of the system. At the same time, the state model and the measurement model are equivalent to the pseudolinear model based on the combination of the original variable and the hidden variable. Thirdly, higher order hidden variables are treated as additive parameters of the system; then, we establish an extended dimensional linear state model and a measurement model combining state and parameters via the previously used random dynamic model. Finally, as we only know the results of the limited sampling of the random modeling error, we use the combination of the maximum correlation estimator and the Kalman filter to establish a new higher order extended Kalman filter. The effectiveness of the new filter is verified by digital simulation.

[Expression of IgG4 in Rosai-Dorfman disease and its significance].

OBJECTIVE: To study the prevalence of IgG4-positive plasma cells in Rosai-Dorfman disease and to assess the association between Rosai-Dorfman disease and IgG4-related sclerosing disease (IgG4-SD). METHODS: The clinicopathologic features of 12 tissue samples of Rosai-Dorfman disease (11 extranodal and one nodal) from nine patients were reviewed. The degree of fibrosis and occlusive phlebitis was studied by HE staining. The expression of IgG4 and IgG in plasma cells were studied by immunohistochemistry (EnVision) and quantitatively analyzed by medical image analysis system. RESULTS: Nine tissue samples showed different degree of fibrosis (four tissue samples were mild, one tissue sample was moderate and four tissue samples were severe) and two tissue samples showed occlusive phlebitis in the lesional tissue. Immunohistochemical study showed marked infiltration by IgG4-positive plasma cells (> 50 per high-power field) in four tissue samples, moderate infiltration (30 to 50 per high-power field) in two tissue samples, mild (10 to 29 per high-power field) in three cases and negative infiltration (< 10 per high-power field) in three tissue samples (P < 0.01). Three tissue samples fulfilled the diagnostic criteria of IgG4-SD (> 50 IgG4-positive plasma cells per high-power field and IgG4-to-IgG ratio > 40%), including one tissue sample each of Rosai-Dorfman disease in the left facial skin, above the left eye socket, and in the right parotid. CONCLUSIONS: Some cases of Rosai-Dorfman disease fulfill the diagnostic criteria and show the histologic features of IgG4-SD. They may represent members of the IgG4-SD spectrum. The detection of IgG4-positive plasma cells in the lesional tissues of Rosai-Dorfman disease may have clinical pathological significance.

High expression of circulating exosomal PD-L1 contributes to immune escape of hepatocellular carcinoma and immune clearance of chronic hepatitis B.

OBJECTIVE: To investigate the expression of programmed death ligand-1 (PD-L1) in circulating exosomes, and to define the role of exosomal PD-L1 in promoting immune escape mechanism during chronic hepatitis B infection (CHB) and related liver diseases. METHODS: The levels of PD-L1 expressed in exosomes were detected by ELISA. CD8+T cells were sorted and cytotoxicity test was assessed by flow cytometry. PD-L1 protein expression in hepatocellular carcinoma (HCC) and normal adjacent tissues were detected by immunohistochemistry. RESULTS: Circulating exosomal PD-L1 levels were significantly higher in patients with CHB and HCC than in healthy controls (F =7.46, P=0.001). Levels of CD107a on CD8+T cells in patients with CHB receiving PD-L1 blocking antibody were significantly lower than in patients receiving isotype blocking antibody (t = 4.96, P < 0.01). Levels of TNF-α in cell culture supernatants of the PD-L1 blocking antibody group were significantly higher than in the isotype blocking antibody group (t =5.92, P < 0.01). Compared with patients receiving isotype blocking antibody, levels of CD107a on CD8+T cells significantly increased in patients with HCC receiving anti-PD-L1 antibody (t = 3.51, P<0.05). Compared with adjacent tissues, the levels of PD-L1 protein expression in HCC tissues were slightly higher; however, no significant difference between the two groups was observed. CONCLUSIONS: PD-L1 blockade in exosomes might promote the cytotoxic function of CD8+T cells and inhibit immune evasion during progression of HCC. Blocking PD-L1 in exosomes reduced the cytotoxic function of CD8+T cells in patients with CHB while enhancing the production of proinflammatory cytokines.

Corrigendum: High expression of nectin-1 indicates a poor prognosis and promotes metastasis in hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.953529.].

High expression of nectin-1 indicates a poor prognosis and promotes metastasis in hepatocellular carcinoma.

Objectives: Nectins are a new class of cell-adhesion molecules that play an important role in tumorigenesis and disease progression. The aim of this study was to investigate the prognostic and pathogenetic roles of nectins in hepatocellular carcinoma (HCC). Methods: The expression levels of the nectin family in HCC and their role in prognosis were analyzed by bioinformatics analysis based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma database. The correlations between nectins and immune cells were analyzed using TIMER. The functional enrichment of the nectin-1 coexpression network was evaluated in TCGA cohort, and the expression levels of nectin-1 were detected by immunohistochemistry and Western blot analysis. A Transwell kit was used for cell migration experiments. Cell proliferation was analyzed using Cell Counting Kit-8. Results: The expression levels of nectin-1 protein in the cancer tissues of 28 patients with HCC were higher than those in paracancerous tissues. The Kaplan-Meier plotter analysis showed that the high expression of all nectin family numbers was related to the poor prognosis of HCC patients. The abnormal expression of nectin-1 effectively distinguished the prognosis at different stages and grades of HCC. The high expression of 17 methylation sites of the nectin-1 gene was related to the high overall survival of HCC patients. Kyoto Encyclopedia of Genes and Genomes analysis of genes negatively correlated with nectin-1, revealing their close relation to the regulation of the immune-effector process. Pearson's correlation analysis showed that nectin-1 was significantly positively correlated with multiple immune genes and B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cell infiltration. Cell proliferation of the knockdown (KD) group decreased significantly compared to the NC-KD group. The number of metastatic cells in the KD group decreased significantly compared to that in the NC-KD group. Conclusions: Abnormal expression of nectins and multiple methylation sites closely correlates with poor prognosis in HCC patients. Nectins are related to immune cell infiltration and immune-related genes. In particular, nectin-1 can promote the proliferation and migration of liver cancer cells and distinguish the prognosis at different stages and grades of HCC. Nectin-1 might be a new potential molecular marker for prognostic evaluation and also a therapeutic target for HCC.

The transmission dynamics of Middle East Respiratory Syndrome coronavirus.

BACKGROUND: In this study, we aimed to quantify the contribution of different transmission routes of the Middle East respiratory syndrome (MERS) and determine its transmissibility. METHODS: Based on the natural history and transmission features of MERS in different countries, a susceptible-exposed-symptomatic-asymptomatic-recovered/death (SEIARD) model and a multi-route dynamic model (MMDM). The SEIARD model and MMDM were adopted to simulate MERS in South Korea and Saudi Arabia, respectively. Data on reported MERS cases in the two countries were obtained from the World Health Organization. Thereafter, the next generation matrix method was employed to derive the equation for the basic reproduction number (R0), and the model fitting procedure was adopted to calculate the R0 values corresponding to these different countries. RESULTS: In South Korea, 'Person-to-Person' transmission was identified as the main mode of MERS transmission in healthcare settings, while in Saudi Arabia, in addition to 'Person-to-Person' transmission, 'Host-to-Host' and 'Host-to-Person' transmission also occurred under certain scenarios, with camels being the main host. Further, the fitting results showed that the SEIARD model and MMDM fitted the data well. The mean R0 value was 8.59 (95% confidence interval [CI]: 0-28.02) for MERS in South Korea, and for MERS in Saudi Arabia, it was 1.15 and 1.02 (95% CI: 0.86-1.44) for the 'Person-to-Person' and 'Camel-to-Camel' transmission routes, respectively. CONCLUSIONS: The SEIARD and MMDM model can be used to simulate the transmission of MERS in different countries. Additionally, in Saudi Arabia, the transmissibility of MERS was almost the same among hosts (camels) and humans.

HSF1 regulates expression of G-CSF through the binding element for NF-IL6/CCAAT enhancer binding protein beta.

Heat shock factor 1 (HSF1) is the major heat shock transcription factor and plays an essential role in mediating the cellular response to physiological and environmental stress. We found that LPS-induced expression of the granulocyte-colony stimulating factor (G-CSF) gene was upregulated in HSF1 knock-out (HSF1(-/-)) mice using a gene array. In order to determine whether and how HSF1 regulates the induced expression of G-CSF, mRNA, and protein levels of G-CSF were detected by Northern blotting and ELISA, the promoter of G-CSF was analyzed with an online transcription element search system and the transcriptional activity of the G-CSF promoter was analyzed by EMSA and a reporter gene assay. The results showed that transcription and protein secretion of G-CSF induced by LPS are both inhibited by HSF1. Three high affinity binding sites for NF-IL6/CCAAT enhancer binding protein beta, but no heat shock element, were identified in the core promoter of G-CSF. The DNA-binding capability of NF-IL6 to the G-CSF promoter was reinforced by LPS but not influenced by heat shock or HSF1. However, HSF1 was observed to bind to the binding sites of NF-IL6 in the G-CSF promoter. The transcriptional activity of the G-CSF promoter was enhanced by LPS or NF-IL6 and inhibited by HSF1 in a dose dependent manner. We conclude that HSF1 regulates expression of G-CSF through binding to the NF-IL6-binding element.

Differences in Immune Responses between Children and Adults with COVID-19.

Over 85 590 000 individuals have been infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although there have been an increasing number of reports on coronavirus disease 2019 (COVID-19), it is unclear why infected children show milder symptoms than adults. A retrospective case study was performed at two designated hospitals for COVID-19. Patients (56 children and 63 adults) with confirmed SARS-CoV-2 infection and mild pneumonia were randomly enrolled in this study. The median age of the children was 7.0 years, and 51.79% of them were boys. The median age of the adults was 57 years, and 47.62% were men. The most common symptoms were fever, cough, sputum and diarrhoea. There were no significant differences in symptoms between children and adult patients. In terms of immunological indices on admission, adult patients displayed typical leukopenia and markedly higher levels of IL-2, IL-4, and IL-6 than child patients. The elevation of IL-2, IL-4 and IL-6 in adults induced more extensive lung injury. The effective and non-aggressive immune response successfully resisted SARS-CoV-2 invasion and maintained mild symptoms in child patients. The correlation of higher IL-2, IL-4, and IL-6 with the lung injury might be evidence that preventing excessive cytokine production can avoid further lung damage in these patients.

Containing the Transmission of COVID-19: A Modeling Study in 160 Countries.

Background: It is much valuable to evaluate the comparative effectiveness of the coronavirus disease 2019 (COVID-19) prevention and control in the non-pharmacological intervention phase of the pandemic across countries and identify useful experiences that could be generalized worldwide. Methods: In this study, we developed a susceptible-exposure-infectious-asymptomatic-removed (SEIAR) model to fit the daily reported COVID-19 cases in 160 countries. The time-varying reproduction number (R t ) that was estimated through fitting the mathematical model was adopted to quantify the transmissibility. We defined a synthetic index (I AC ) based on the value of R t to reflect the national capability to control COVID-19. Results: The goodness-of-fit tests showed that the SEIAR model fitted the data of the 160 countries well. At the beginning of the epidemic, the values of R t of countries in the European region were generally higher than those in other regions. Among the 160 countries included in the study, all European countries had the ability to control the COVID-19 epidemic. The Western Pacific Region did best in continuous control of the epidemic, with a total of 73.76% of countries that can continuously control the COVID-19 epidemic, while only 43.63% of the countries in the European Region continuously controlled the epidemic, followed by the Region of Americas with 52.53% of countries, the Southeast Asian Region with 48% of countries, the African Region with 46.81% of countries, and the Eastern Mediterranean Region with 40.48% of countries. Conclusion: Large variations in controlling the COVID-19 epidemic existed across countries. The world could benefit from the experience of some countries that demonstrated the highest containment capabilities.

A mathematical model for simulating the phase-based transmissibility of a novel coronavirus.

BACKGROUND: As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. METHODS: In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R0) from the RP model to assess the transmissibility of the SARS-CoV-2. RESULTS: The value of R0 was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. CONCLUSIONS: Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.

Low-Grade Adenosquamous Carcinoma of the Axilla of Breast Origin in a Male: A Case Report and Literature Review.

Low-grade adenosquamous carcinoma (LGASC) is a rare invasive tumor that occurs in breast parenchyma. It has previously only been reported in females. Herein, we describe the case of a 52-year-old male who presented with a palpable mass in his right axilla that he reported had been present for 20-years. This is the first report of a male patient with LGASC. Core needle biopsy pathology revealed a benign mass of mammary origin, but its type was initially misdiagnosed. It was only correctly identified via postoperative pathology after local excision, which indicated that the mass exhibited the typical pathological characteristics of LGASC. Immunohistochemical analysis revealed positive expression of estrogen receptor, which was inconsistent with the typical "triple-negative" immunophenotype of LGASC. After resection of the mass the patient was advised to participate in regular outpatient follow-up. In conclusion, LGASC should be considered in male patients with a mass lesion in their breast or axilla, even when core needle biopsy indicates a benign mass of breast origin. One-stage local resection is recommended for the treatment of male patients with LGASC, but it is crucial to ensure that the margins are negative and postoperative adjuvant radiotherapy is not recommended.

[HSF1 inhibits heat stress-induced apoptosis in Raw264.7 macrophages].

OBJECTIVE: To observe the effect of heat shock factor 1 (HSF1) on heat stress-induced apoptosis in Raw264.7 macrophages. METHODS: Raw264.7 cells transfected with pcDNA3.1 and pcDNA3.1-HSF1 were exposed to heat stress (42.5 degrees C +/- 0.5 degrees C) for 1 h and recovered at 37 degrees C for 6, 9, 12, and 24 h respectively. Flow cytometry (FCM), Hoechst 33258 staining and DNA ladder assays were performed to assess the apoptosis. RESULTS: After heat stress, FCM showed that apoptotic cells were increased significantly and reached the peak at 9 h in Raw 264.7 cells transfected with pcDNA3.1, and were characterized with classical morphologic changes including apoptotic body and nuclear condensation. Agarose gel electrophoresis showed that "DNA ladder" could be observed clearly at 6, 9, and 12 h after the heat stress. But the overexpression of HSF1 could reduce the number of apoptotic cells and inhibit DNA fragmentation. CONCLUSION: HSF1 can inhibit heat stress-induced apoptosis in Raw264.7 macrophages.

[Screen of inflammatory genes regulated by heat shock factor 1 and corroboration with SOCS3 gene].

OBJECTIVE: To screen the inflammatory mediators genes regulated by HSF1, and explore the mechanism of downstream genes regulated by HSF1. METHODS: HSF-/- and HSF1+/+ mice were injected with 15 mg/kg LPS intraperitoneally (ip), respectively, and were treated as previous after HSR. The total RNA of lung tissues were extracted and filtrated by SuperArray gene Microarry. The promoter of candidate genes were analyzed by transcription element search software to search for heat shock element (HSE). Select the suppressor of cytokine signaling 3 (SOCS3) with HSE. Macrophage cells were stimulated with 400 ng/mL LPS, and were treated as previous after HSR, then the total RNA was extracted respectively. RT-PCR and northern blot assay were performed to detect the expression levels of SOCS3 mRNA. RESULTS: Fifteen genes were repressed by HSF1, including 9 genes with complete HSE. Eleven genes were accelerated by HSF1 possibly, including 8 genes with complete HSE. The promoter of SOCS3 gene contained one complete HSE. LPS stimulation obviously increased the levels of SOCS3 mRNA in macrophages of RAW264.7 mice, which was inhibited by HSR and over-expression of HSF1. CONCLUSION: HSR or HSF1 inhibits LPS induced expression of SOCS3 mRNA; HSF1 might inhibit LPS-induced expression of SOCS3 mRNA by binding to HSE in the promoter of SOCS3 gene.

[Dynamic pattern of gene expression in rat hearts responding to transient ischemia/reperfusion detected by cDNA microarray and cluster analysis].

OBJECTIVE: To analyze the pattern of gene expression programs during rat myocardial ischemia/reperfusion at multiple time points. METHODS: Rat model of myocardial ischemia/reperfusion was established by repeating the occlusion and relaxation of left coronary artery. cDNA microarray was used to analyze the pattern of gene expression programs in rat myocardium at 1, 3, 6, 12, 24 hours after reperfusion. SOM cluster analysis was used to identify different cluster of genes in which each cluster had similar expression pattern. RESULTS: Altogether 75, 779, 205, 155, and 166 genes were differentially expressed at 1, 3, 6, 12, 24 hours after the reperfusion respectively. Clusters analysis identified 12 clusters of genes in which each cluster had similar expression pattern. CONCLUSION: Analysis of gene expression pattern revealed sequential induction of subsets of genes that characterize each response.

[Effect of heat shock response on the cleavage of nucleolin induced by oxidative stress].

OBJECTIVE: To observe the cleavage of nucleolin (C23) during apoptosis induced by oxidative stress and to clarify the effect of heat shock response (HSR) on the cleavage of nucleolin and its possible molecular mechanism. METHODS: We added 0.5 mmol/L peroxide hydrogen (H2O2 ) into cultured cells to mimic oxidative stress. Apoptosis and cleavage of C23 were detected using caspase-3 colorimetric assay and Western blotting respectively. HSR was performed to observe the effect of HSR on cleavage of C23 induced by oxidative stress, and over-expressions of HSP70 and HSP25 were detected by Western blotting. RESULTS: Activity of caspase-3 increased significantly after 2 hours of 0.5 mmol/L H2O2 treatment, and reached the peak after 12 hours. The cleavage of C23 appeared 30 minutes to 1 hour after the treatment of H2O2 as indicated by a cleaved fragmentation of 80 kD, which was significantly inhibited by HSR. Moreover, HSR could induce HSP70 and HSP25 over-expressions. CONCLUSION: Oxidative stress can induce the activation of caspase-3, cleavage of C23, and apoptosis. HSR can significantly inhibit the cleavage of C23 induced by oxidative stress, which is related to the over-expressions of HSP70, HSP25, and other stress proteins.