Classification and applications of nanomaterials in vitro diagnosis.

With the rapid development of clinical diagnosis and treatment, many traditional and conventional in vitro diagnosis technologies are unable to meet the demands of clinical medicine development. In this situation, nanomaterials are rapidly developing and widely used in the field of in vitro diagnosis. Nanomaterials have distinct size-dependent physical or chemical properties, and their optical, magnetic, electrical, thermal, and biological properties can be modulated at the nanoscale by changing their size, shape, chemical composition, and surface functional groups, particularly because they have a larger specific surface area than macromaterials. They provide an amount of space to modify different molecules on their surface, allowing them to detect small substances, nucleic acids, proteins, and microorganisms. Combining nanomaterials with in vitro diagnosis is expected to result in lower detection limits, higher sensitivity, and stronger selectivity. In this review, we will discuss the classfication and properties of some common nanomaterials, as well as their applications in protein, nucleic acids, and other aspect detection and analysis for in vitro diagnosis, especially on aging-related nanodiagnostics. Finally, it is summarized with guidelines for in vitro diagnosis.

Performance and mechanistic studies of rapid atenolol degradation through peroxymonosulfate activation by V, Co, and bamboo carbon catalyst.

Developing the Co-based catalysts with high reactivity for the sulfate radical (SO4-·)-based advanced oxidation processes (SR-AOPs) has been attracting numerous attentions. To improve the peroxymonosulfate (PMS) activation process, a novel Co-based catalyst simultaneously modified by bamboo carbon (BC) and vanadium (V@CoO-BC) was fabricated through a simple solvothermal method. The atenolol (ATL) degradation experiments in V@CoO-BC/PMS system showed that the obtained V@CoO-BC exhibited much higher performance on PMS activation than pure CoO, and the V@CoO-BC/PMS system could fully degrade ATL within 5 min via the destruction of both radicals (SO4-· and O2-··) and non-radicals (1O2). The quenching experiments and electrochemical tests revealed that the enhancing mechanism of bamboo carbon and V modification involved four aspects: (i) promoting the PMS and Co ion adsorption on the surface of V@CoO-BC; (ii) enhancing the electron transfer efficiency between V@CoO-BC and PMS; (iii) activating PMS with V3+ species; (iv) accelerating the circulation of Co2+ and Co3+, leading to the enhanced yield of reactive oxygen species (ROS). Furthermore, the V@CoO-BC/PMS system also exhibited satisfactory stability under broad pH (3-9) and good efficiency in the presence of co-existing components (HCO3-, NO3-, Cl-, and HA) in water. This study provides new insights to designing high-performance, environment-friendly bimetal catalysts and some basis for the remediation of antibiotic contaminants with SR-AOPs.

Efficient dispersive solid phase extraction of trace nitrophenol pollutants in water with triazine porous organic polymer modified nanofiber membrane.

Detecting trace endocrine disruptors in water is crucial for evaluating the water quality. In this work, a innovative modified polyacrylonitrile@cyanuric chloride-triphenylphosphine nanofiber membrane (PAN@CC-TPS) was prepared by in situ growing triazine porous organic polymers on the polyacrylonitrile (PAN) nanofibers, and used in the dispersive solid phase extraction (DSPE) to enrich trace nitrobenzene phenols (NPs) in water. The resluted PAN@CC-TPS nanofiber membrane consisted of numerous PAN nanofibers cover with CC-TPS solid spheres (∼2.50 µm) and owned abundant functional groups, excellent enrichment performance and good stability. In addition, the method based on PAN@CC-TPS displayed outstanding capacity in detecting the trace nitrobenzene phenols, with 0.50-1.00 µg/L of the quantification, 0.10-0.80 µg/L of the detection limit, 85.35-113.55 % of the recovery efficiency, and 98.08-103.02 of the enrichment factor, which was comparable to most materials. Meanwhile, when PAN@CC-TPS was adopted in the real water samples (sea water and river water), the high enrichment factors and recovery percentages strongly confirmed the feasibility of PAN@CC-TPS for enriching and detecting the trace NPs. Besides, the related mechanism of extracting NPs on PAN@CC-TPS mainly involved the synergistic effect of hydrogen bonding, π-π stacking and hydrophobic effect.

[Genetic analysis of a fetus with Meckel syndrome due to variants of TMEM67 gene].

OBJECTIVE: To carry out prenatal diagnosis for a fetus with Meckel syndrome (MKS) and explore its genetic basis. METHODS: A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c.296delA (p.Lys99SerfsTer6) and c.1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.296delA variant was predicted to be pathogenic (PVS1+PM2_Supporting+PP4), whilst the c.1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4). CONCLUSION: The c.296delA and c.1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.

Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis.

BACKGROUND AND AIMS: Survivors of acute coronary syndromes face an elevated risk of recurrent atherosclerosis-related vascular events despite advanced medical treatments. The underlying causes remain unclear. This study aims to investigate whether myocardial infarction (MI)-induced trained immunity in monocytes could sustain proatherogenic traits and expedite atherosclerosis. METHODS: Apolipoprotein-E deficient (ApoE-/-) mice and adoptive bone marrow transfer chimeric mice underwent MI or myocardial ischaemia-reperfusion (IR). A subsequent 12-week high-fat diet (HFD) regimen was implemented to elucidate the mechanism behind monocyte trained immunity. In addition, classical monocytes were analysed by flow cytometry in the blood of enrolled patients. RESULTS: In MI and IR mice, blood monocytes and bone marrow-derived macrophages exhibited elevated spleen tyrosine kinase (SYK), lysine methyltransferase 5A (KMT5A), and CCHC-type zinc finger nucleic acid-binding protein (CNBP) expression upon exposure to a HFD or oxidized LDL (oxLDL) stimulation. MI-induced trained immunity was transmissible by transplantation of bone marrow to accelerate atherosclerosis in naive recipients. KMT5A specifically recruited monomethylation of Lys20 of histone H4 (H4K20me) to the gene body of SYK and synergistically transactivated SYK with CNBP. In vivo small interfering RNA (siRNA) inhibition of KMT5A or CNBP potentially slowed post-MI atherosclerosis. Sympathetic denervation with 6-hydroxydopamine reduced atherosclerosis and inflammation after MI. Classical monocytes from ST-elevation MI (STEMI) patients with advanced coronary lesions expressed higher SYK and KMT5A gene levels. CONCLUSIONS: The findings underscore the crucial role of monocyte trained immunity in accelerated atherosclerosis after MI, implying that SYK in blood classical monocytes may serve as a predictive factor for the progression of atherosclerosis in STEMI patients.

Epstein-Barr Virus-Positive Plasma Cell Neoplasms in Immunocompetent Patients: A Clinicopathological Study of 15 Cases from South China and Literature Review.

Epstein-Barr virus (EBV)-positive plasma cell neoplasms (PCNs) in immunocompetent patients are a rare entity, the clinicopathological and prognostic features of which have not been well characterized. Fifteen cases of EBV-positive PCN arising in immunocompetent patients from south China were retrospectively analyzed, and an additional 44 cases from the literature were reviewed. The overall EBV-positive rate defined by EBV-encoded small RNAs (EBERs) in-situ hybridization of PCNs was 12.3% (15/122), and it was significantly higher in plasmacytoma (17.1%, 13/76) than in plasma cell myeloma/multiple myeloma (4.3%, 2/46; P=0.031). The age of the patients ranged from 17 to 79 years, with a median age of 56 years. There was a large preponderance of men, with a male-to-female ratio of 4:1. Solitary plasmacytoma of bone (23.8%, 5/21) had comparable EBV-encoded small RNAs-positive rates with extramedullary plasmacytoma arising in the upper respiratory tract (19.5%, 8/41; P=0.949). Anaplastic and classic cytologic appearance was observed in 61.5% (8/13) and 38.5% (5/13) of EBV-positive plasmacytomas, respectively. Cases with an anaplastic cytologic appearance had a significantly higher Ki-67 proliferation index than those with a classic cytologic appearance (median: 55% vs. 10%, P=0.001). In the combined cohorts, anaplastic/plasmablastic cytologic appearance was significantly more common in extramedullary plasmacytoma arising in the upper respiratory tract (72.0%, 18/25) than outside the upper respiratory tract (11.1%, 1/9; P=0.006). Among the 59 cases of EBV-positive PCN, survival data of 34 cases were available for analysis, including 30 cases of plasmacytoma and 4 cases of plasma cell myeloma/multiple myeloma. There was no statistically significant difference in overall survival between patients with EBV-positive plasmacytomas in the combined cohorts and EBV-negative plasmacytomas in the present cohort. The prevalence of EBV in PCN in immunocompetent patients varies according to histologic subtype and tumor location. Compared with EBV-negative cases, EBV-positive plasmacytomas tend to have an anaplastic/plasmablastic cytologic appearance. No significant impact of EBV infection on clinical outcomes is observed in the limited number of reported cases.

MDM-U-Net: A novel network for renal cancer structure segmentation.

Accurate segmentation of the renal cancer structure, including the kidney, renal tumors, veins, and arteries, has great clinical significance, which can assist clinicians in diagnosing and treating renal cancer. For accurate segmentation of the renal cancer structure in contrast-enhanced computed tomography (CT) images, we proposed a novel encoder-decoder structure segmentation network named MDM-U-Net comprising a multi-scale anisotropic convolution block, dual activation attention block, and multi-scale deep supervision mechanism. The multi-scale anisotropic convolution block was used to improve the feature extraction ability of the network, the dual activation attention block as a channel-wise mechanism was used to guide the network to exploit important information, and the multi-scale deep supervision mechanism was used to supervise the layers of the decoder part for improving segmentation performance. In this study, we developed a feasible and generalizable MDM-U-Net model for renal cancer structure segmentation, trained the model from the public KiPA22 dataset, and tested it on the KiPA22 dataset and an in-house dataset. For the KiPA22 dataset, our method ranked first in renal cancer structure segmentation, achieving state-of-the-art (SOTA) performance in terms of 6 of 12 evaluation metrics (3 metrics per structure). For the in-house dataset, our method achieves SOTA performance in terms of 9 of 12 evaluation metrics (3 metrics per structure), demonstrating its superiority and generalization ability over the compared networks in renal structure segmentation from contrast-enhanced CT scans.

Clinical outcomes after vascular reconstruction using synthetic grafts for limb salvage in patients with lower extremity sarcoma: a single-center retrospective experience.

Introduction: Limb-salvage surgery has become the mainstream approaches for the treatment of sarcoma in the lower extremity. In cases where the sarcoma infiltrates the primary vessel, concurrent resection of the vessels and vascular reconstruction are required to ensure sufficient resection and preservation of limb function. The objective of this study is to assess the clinical outcomes of patients who underwent vascular reconstruction utilizing synthetic grafts for limb salvage, specifically in terms of postoperative complications and limb functional status. Methods: Between September 2016 and October 2021, 15 consecutive patients who underwent 15 arterial and 3 venous reconstruction procedures were included in this retrospective study. Incidence of postoperative morbidity, graft patency, rate of limb salvage, and overall survival of patients were analyzed. Results: The median follow-up was 12.5 months (range, 4.5-72.0). Graft thrombosis occurred in 5 patients (33.3%) and graft occlusion occurred in 3 patients (20.0%). The median overall survival was 28.0 months with the estimated 2-year and 5-year overall survival of 57.8% and 43.4% respectively. The 1-year and 2-year estimated patency rates of arterial reconstructions were 82.3% and 62.1%, respectively. None of the included patients with limb amputation were observed as a consequence of severe vascular complications, while two patients underwent amputation due to the repeat recurrence, resulting in a limb salvage rate of 86.7%. Conclusion: Our results show that the combination of vascular reconstruction and oncologic resection is a feasible option for preserving limbs in cases of musculoskeletal sarcoma with vessel involvement in the lower extremity. When vascular reconstruction surgery is performed, synthetic substitutes can be effectively used with low perioperative morbidity and an acceptable rate of limb salvage.

Versican core protein aids in the diagnosis and grading of breast phyllodes tumor.

Phyllodes tumors (PTs) are biphasic fibroepithelial lesions that occur in the breast. Diagnosing and grading PTs remains a challenge in a small proportion of cases, due to the lack of reliable specific biomarkers. We screened a potential marker versican core protein (VCAN) through microproteomics analysis, validated its role for the grading of PTs by immunohistochemistry, and analyzed the correlation between VCAN expression and clinicopathological characteristics. Cytoplasmic immunoreactivity for VCAN was identified in all benign PT samples, among which 40 (93.0 %) showed VCAN-positive staining in ≥50 % of tumor cells. Eight (21.6 %) borderline PT samples showed VCAN-positive staining in ≥50 % of the cells with weak to moderate staining intensity, whereas 29 samples (78.4 %) showed VCAN-positive staining in <50 % of the cells. In malignant PTs, 16 (84.2 %) and three (15.8 %) samples showed VCAN-positive staining in <5 % and 5-25 % of stromal cells, respectively. Fibroadenomas showed a similar expression pattern to benign PTs. Fisher's exact test showed that the percentages of positive cells (P < .001) and staining intensities (P < .001) of tumor cells were significantly different between the five groups. VCAN positivity was associated with tumor categories (P < .0001) and CD34 expression (P < .0001). The expression of VCAN gradually decreases as the tumor categories increases, following recurrence. To the best of our knowledge, our results are the first in the literature to reveal that VCAN is useful for diagnosing and grading PTs. The expression level of VCAN appeared to be negatively associated with PT categories, suggesting that dysregulation of VCAN may be involved in the tumor progression of PTs.

Global thyroid cancer incidence trend and age-period-cohort model analysis based on Global Burden of Disease Study from 1990 to 2019.

Background: In view of the rapid increase in the incidence of thyroid cancer (TC) and the spread of overdiagnosis around the world, the quantitative evaluation of the effect of age, period and birth cohort on the incidence of TC, and the analysis of the role of different factors in the incidence trend can provide scientific basis and data support for the national health departments to formulate reasonable prevention and treatment policies. Methods: The study collated the global burden disease study data of TC incidence from 1990 to 2019, and used APC model to analyze the contribution of age, period and birth cohort to the incidence trend of TC. Results: There was an obvious unfavorable upward trend in terms of age and cohort effect all over the world. Since 2007, the growth rate of risk slowed down and the risk in female even decreased since 2012, which mainly contributed to the developed countries. In all SDI countries, 2002 is the dividing point of risk between male and female. In 2019, The global age-standardized incidence rate (ASIR) of TC in the 5 SDI countries all showed a significant upward trend, with the largest upward trend in the middle SDI countries. Conclusion: The trend of rapid increase in the incidence of TC has begun to slow down, but the global incidence of TC has obvious gender and regional/national heterogeneity. Policy makers should tailor specific local strategies to the risk factors of each country to further reduce the burden of TC.

DFR-U-Net: Dual residual and feature fusion network for ulna and radius segmentation on dual-energy X-ray absorptiometry images.

BACKGROUND: Ulna and radius segmentation of dual-energy X-ray absorptiometry (DXA) images is essential for measuring bone mineral density (BMD). OBJECTIVE: To develop and test a novel deep learning network architecture for robust and efficient ulna and radius segmentation on DXA images. METHODS: This study used two datasets including 360 cases. The first dataset included 300 cases that were randomly divided into five groups for five-fold cross-validation. The second dataset including 60 cases was used for independent testing. A deep learning network architecture with dual residual dilated convolution module and feature fusion block based on residual U-Net (DFR-U-Net) to enhance segmentation accuracy of ulna and radius regions on DXA images was developed. The Dice similarity coefficient (DSC), Jaccard, and Hausdorff distance (HD) were used to evaluate the segmentation performance. A one-tailed paired t-test was used to assert the statistical significance of our method and the other deep learning-based methods (P < 0.05 indicates a statistical significance). RESULTS: The results demonstrated our method achieved the promising segmentation performance, with DSC of 98.56±0.40% and 98.86±0.25%, Jaccard of 97.14±0.75% and 97.73±0.48%, and HD of 6.41±11.67 pixels and 8.23±7.82 pixels for segmentation of ulna and radius, respectively. According to statistics data analysis results, our method yielded significantly higher performance than other deep learning-based methods. CONCLUSIONS: The proposed DFR-U-Net achieved higher segmentation performance for ulna and radius on DXA images than the previous work and other deep learning approaches. This methodology has potential to be applied to ulna and radius segmentation to help doctors measure BMD more accurately in the future.

The facilitation of constructional meaning in the processing of Mandarin innovative Bei construction.

The processing of Mandarin innovative Bei construction in the form of "Bei + X" is different from that of the traditional Bei construction in that the former activates the constructional meaning which is intrinsically negative. This study thus investigates whether the processing of Mandarin innovative Bei construction is facilitated by the access of such emergent negative associations in a self-paced reading experiment with a priming paradigm. In this study, participants firstly read lexical primes in three conditions including construction-related phrases (i.e. phrases expressing the negative constructional meaning of the innovative Bei construction), component-related phrases (i.e. phrases expressing the partial literal meaning of the innovative Bei construction), and unrelated phrases (i.e. phrases expressing unrelated meaning to the innovative Bei construction). They then read sentences where the innovative Bei construction was fitted into and finally answered questions. Results showed that the lexical primes conveying the constructional meaning of the innovative Bei construction significantly shortened participants' reading time duration as compared with another two priming conditions. To conclude, the processing of Mandarin innovative Bei construction is facilitated by the priming of its constructional meaning, which provides some psychological evidence for the construction-based processing of Mandarin innovative Bei construction.

Giant cell tumor of bone with H3F3B mutation: A case report.

RATIONALE: Giant cell tumor of bone is a locally aggressive and rarely metastasizing neoplasm that typically affects the ends of long bones or the axial skeleton of young to middle-aged adults. As many as 69% to 100% of giant cell tumors harbor H3F3A gene mutations, while H3F3B gene mutations have rarely been reported. PATIENT CONCERNS: A 53-year-old male patient who underwent right distal femoral tumor resection. DIAGNOSES: Preoperative CT plain scan indicated giant cell tumor of bone with pathological fracture. Laboratory findings were as follows: serum calcium was 2.23 mmol/L (reference range: 2.1-2.55 mmol/L) and serum phosphorus was 1.35 mmol/L (reference range: 0.81-1.45 mmol/L). INTERVENTIONS: The histological morphology showed the typical features of a conventional GCT. The immunoprecipitation analysis results were as follows: H3.3G34W(-), H3.3G34R(-), H3.3G34V(-), and H3K36M(-). Sanger sequencing showed that the H3F3A and H3F3B gene mutations were wild type. The high-throughput gene sequencing results revealed the H3F3B gene mutations H3.3p.Gly35Trp and H3.3p.Val36Leu. OUTCOMES: The patient was stable with no recurrence in 12 months follow-up. LESSONS: Giant cell tumor of bone with H3F3B gene mutations is extremely rare. In the pathological diagnosis of bone tumors, we need to analyze clinical presentation, imaging features, histology, immunophenotype, and cytogenetic/molecular alterations, in order to get a correct diagnosis.

SOX9 and HMGB3 co-operatively transactivate NANOG and promote prostate cancer progression.

BACKGROUND: The homeodomain-containing transcription factor NANOG is overexpressed in prostate adenocarcinoma (PCa) and predicts poor prognosis. The SOX family transcription factor SOX9, as well as the transcription co-activator HMGB3 of the HMGB family, are also overexpressed and may play pivotal roles in PCa. However, it is unknown whether SOX9 and HMGB3 interact with each other, or if they regulate NANOG gene transcription. METHODS: We identified potential SOX9 responsive elements in NANOG promoter, and investigated if SOX9 regulated NANOG transcription in co-operation with HMGB3 by experimental analysis of potential SOX9 binding sites in NANOG promoter, reporter gene transcription assays with or without interference or artificial overexpression of SOX9 and/or HMGB3, and protein-binding assays of SOX9-HMGB3 interaction. Clinicopathologic and prognostic significance of SOX9-HMGB3 overexpression in PCa was analyzed. RESULTS: SOX9 activated NANOG gene transcription by preferentially binding to a highly conserved consensus cis-regulatory element (-573 to -568) in NANOG promoter, and promoted the expression of NANOG downstream oncogenic genes. Importantly, HMGB3 functioned as a partner of SOX9 to co-operatively enhance transactivation of NANOG by interacting with SOX9, predominantly via the HMG Box A domain of HMGB3. Overexpression of SOX9 and/or HMGB3 enhanced PCa cell survival and cell migration and were significantly associated with PCa progression. Notably, Cox proportional regression analysis showed that co-overexpression of both SOX9 and HMGB3 was an independent unfavorable prognosticator for both CRPC-free survival (relative risk [RR] = 3.779，95% confidence interval [CI]: 1.159-12.322, p = 0.028) and overall survival (RR = 3.615，95% CI: 1.101-11.876, p = 0.034). CONCLUSIONS: These findings showed a novel SOX9/HMGB3/NANOG regulatory mechanism, deregulation of which played important roles in PCa progression.

Primary lymphoma of the uterine cervix: a clinicopathologic study of 13 cases with review of additional 54 cases in the literature.

Primary lymphoma of the uterine cervix (LUCX) is extremely rare, and its diagnosis is challenging. However, its clinicopathological features have not been well characterized. Thirteen primary LUCX patients were retrospectively studied, and 54 patients from the literature were reviewed. Primary LUCX was identified in 0.22% (13/6000) of patients with uterine cervical malignancies in our institution. The patients' median age was 51 years (range: 22-85 years). All patients had a bulk of neoplasms in the uterine cervix. The median tumour diameter was 6 cm (range: 1.5-10 cm). Approximately 78.0% (39/50) of the patients initially presented with irregular vaginal bleeding or discharge. Moreover, 86.7% (39/45) had Ann Arbor stage I or II. Diffuse large B-cell lymphoma, not otherwise specified, was the most common type, accounting for 85.0% (57/67) of primary LUCX cases. Follicular lymphoma (7.5%, 5/67), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (4.5%, 3/67), mantle cell lymphoma (MCL), blastoid variant (1.5%, 1/67), and peripheral T-cell lymphoma (1.5%, 1/67) were occasionally observed. Three patients (7.1%, 3/42) with DLBCL, NOS died from the disease during the follow-up period. Their 5-year overall survival (OS) rate was 93.5%. The patient with MCL, blastoid variant in our present cohort died of the disease 33 months after diagnosis. Primary LUCX is an extremely rare condition. The clinical symptoms are non-specific. DLBCL, NOS is the most common histologic type, showing a favourable outcome with accurate diagnosis and timely and optimal treatment.

Primary intraosseous Rosai-Dorfman disease: An analysis of clinicopathologic characteristics, molecular genetics, and prognostic features.

Background: Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder of uncertain pathogenesis. Most patients present with proliferation in the lymph nodes manifesting as adenopathy; however, RDD may primarily arise in a variety of extranodal sites, including the bone, which is a great challenge in the diagnosis. The clinicopathological characteristics and prognostic features of primary intraosseous RDD have not been well characterized. Methods: We retrospectively analyzed the clinicopathologic and prognostic features of four cases of primary intraosseous RDD during the past 10 years in our hospital, with a review of an additional 62 cases with complete follow-up data from the literature. Results: Primary intraosseous RDD was identified in 0.14% (4/2,800) of total bone biopsies performed at our institution over the study period. According to our retrospective analysis, a total of 18 cases of primary lymph node, skin, or other non-osseous site-based RDD were diagnosed in our hospital. The ages of the 66 total patients ranged from 1.5 to 76 years, with a median age of 25 years. There were 31 male and 35 female patients, with a male-to-female ratio of 0.89:1. Primary intraosseous RDD occurred most often in the bones of the extremities (60.6%, 40/66), with the proximal tibia being the most common location; 39.4% (26/66) of the cases arose in the axial skeleton, predominantly in the vertebra and craniofacial bones. Solitary masses and multiple tumors were present in 84.8% (56/66) and 15.2% (10/66) of the cases, respectively. Pain of the affected area was the most common presenting symptom. Radiographically, the lesions were lytic with well-defined and usually sclerotic margins. Immunohistochemistry showed that large histiocytes from patients with RDD were positive for OCT2, in addition to S100 and CD68. Molecular tests were performed in seven reported cases and four of our cases. All the 11 cases were non-decalcified. PCR results showed that there were no BRAF-V600E, KRAS, or NRAS mutations in primary intraosseous RDD; only one case with both RDD and Langerhans cell histiocytosis showed BRAF-V600E mutation. The survival data showed that 22.7% (15/66) of the patients experienced recurrences or developed RDD at distant sites during the follow-up period (median follow-up, 13 months; range, 1-106 months). The 5-year progression-free survival (PFS) of the patients with primary intraosseous RDD was 57.5%. We found that there was a significant difference in PFS between female and male patients (p = 0.031). However, there was no statistically significant difference in PFS between patients with solitary masses and multiple tumors (p = 0.698). Similarly, no statistically significant differences in PFS were found between the different age groups (p = 0.908) or tumor locations (p = 0.728). Conclusion: Primary intraosseous RDD is an extremely rare disease. The diagnosis of RDD may be quite challenging because of its non-specific clinical presentation and imaging. Immunohistochemistry showed that large histiocytes were positive for OCT2 in addition to S100 and CD68, which may be helpful for differential diagnosis. Molecular detection showed that RDD may be related to the MAPK pathway, though these results are also ultimately not specific. The pathogenesis of RDD is yet to be elucidated, but recent studies suggest possible clonality of hyperproliferative histiocytes.

Receptor-ligand pair typing and prognostic risk model for papillary thyroid carcinoma based on single-cell sequencing.

The papillary thyroid carcinoma (PTC) microenvironment consists of various cancer and surrounding cells, and the communication between them is mainly performed through ligand-receptor (LR) interactions. Single-cell RNA sequencing (scRNA-seq) has been performed to investigate the role of intercellular communication networks in tumor progression. In addition, scRNA-seq can accurately identify the characteristics of immune cell subsets, which is of great significance for predicting the efficacy of immunotherapy. In this study, the cell-cell communication network was analyzed through LR pairs, and a new PTC molecular phenotype was developed based on LR pairs. Furthermore, a risk model was established to predict patient response to PD-1 blockade immunotherapy. The scRNA-seq dataset was obtained from GSE184362, and the bulk tumor RNA-seq dataset was obtained from The Cancer Genome Atlas. CellPhoneDB was used for cellular communication analysis. LR pair correlations were calculated and used to identify molecular subtypes, and the least absolute shrinkage and selection operator (Lasso) Cox regression was used to develop a risk model based on LR pairs. The IMvigor210 and GSE78220 cohorts were used as external validations for the LR.score to predict responses to PD-L1 blockade therapy. A total of 149 LR pairs with significant expression and prognostic correlation were included, and three PTC molecular subtypes were obtained from those with significant prognostic differences. Then, five LR pairs were selected to construct the risk scoring model, a reliable and independent prognostic factor in the training set, test set, and whole dataset. Furthermore, two external validation sets confirmed the predictive efficacy of the LR.score for response to PD-1 blockade therapy.

Prognostic value of LODDS in medullary thyroid carcinoma based on competing risk model and propensity score matching analysis.

Log odds of positive lymph nodes (LODDS) is an independent prognostic factor for patients with medullary thyroid carcinoma (MTC). However, the optimal cutoff value for LODDS needs to be further confirmed, and previous studies have ignored the prevalent competing events of non-cancer deaths among patients with MTC, thus possibly overestimating the risk of death from cancer. The information of patients with MTC who underwent total thyroidectomy was collected from SEER database. Restricted cubic splines (RCS) were used to determine the optimal cutoff for LODDS. Moreover, patients' overall survival (OS) and disease-specific survival (DSS) were determined using Kaplan-Meier and Cox proportional-hazards model. The competing risk models (CRM) were used to reduce the effect of competing events, and propensity score matching was performed to balance the confounding factors between groups. The cutoff value of LODDS determined by RCS was - 1.004, and a total of 2314 patients with MTC were recruited. In the CRM after PSM, factors such as age over 55 years at diagnosis, being male, treatment with chemotherapy or radiotherapy, unknown tumor size, and LODDS > - 1.004 were significantly associated with poor prognosis of patients both in univariate and multivariate analyses, while the presence of multifocal tumor indicated better prognosis. Patients with MTC who were over 55 years old at diagnosis, were male, received chemotherapy or radiation, had an unclear initial tumor size, and had LODDS > - 1.004 had a worse prognosis than patients with multifocal tumor.

Fibrinogen-like protein 2 deficiency inhibits virus-induced fulminant hepatitis through abrogating inflammatory macrophage activation.

BACKGROUND: Heterogeneous macrophages play an important role in multiple liver diseases, including viral fulminant hepatitis (VFH). Fibrinogen-like protein 2 (FGL2) is expressed on macrophages and regulates VFH pathogenesis; however, the underlying mechanism remains unclear. AIM: To explore how FGL2 regulates macrophage function and subsequent liver injury during VFH. METHODS: Murine hepatitis virus strain 3 (MHV-3) was used to induce VFH in FGL2-deficient (Fgl2-/-) and wild-type (WT) mice. The dynamic constitution of hepatic macrophages was examined. Adoptive transfer of Fgl2-/- or WT bone marrow-derived macrophages (BMDMs) into WT recipients with macrophages depleted prior to infection was carried out and the consequent degree of liver damage was compared. The signaling cascades that may be regulated by FGL2 were detected in macrophages. RESULTS: Following MHV-3 infection, hepatic macrophages were largely replenished by proinflammatory monocyte-derived macrophages (MoMFs), which expressed high levels of FGL2. In Fgl2-/- mice, the number of infiltrating inflammatory MoMFs was reduced compared with that in WT mice after viral infection. Macrophage depletion ameliorated liver damage in WT mice and further alleviated liver damage in Fgl2-/- mice. Adoptive transfer of Fgl2-/- BMDMs into macrophage-removed recipients significantly reduced the degree of liver damage. Inhibition of monocyte infiltration also significantly ameliorated liver damage. Functionally, Fgl2 deletion impaired macrophage phagocytosis and the antigen presentation potential and attenuated the proinflammatory phenotype. At the molecular level, FGL2 deficiency impaired IRF3, IRF7, and p38 phosphorylation, along with NF-κB activation in BMDMs in response to viral infection. CONCLUSION: Infiltrated MoMFs represent a major source of hepatic inflammation during VFH progression, and FGL2 expression on MoMFs maintains the proinflammatory phenotype via p38-dependent positive feedback, contributing to VFH pathogenesis.