The effects of postoperative targeted immunotherapy on peripheral blood cytokines and immune cell profile in lung cancer patients.

Objective: Cytokines and cell subsets are important components of the tumor microenvironment. Previous research has revealed that there are differences in cytokines and cell subsets in the peripheral blood of lung cancer (LCA) patients before and after eradication. The purpose of this study is to explore the monitoring value of cytokines and cellular subpopulations as biomarkers in post-immunotherapy monitoring of patients with LCA after surgery. Methods: We conducted a case-control study using double-antibody sandwich magnetic microsphere flow cytometry with immunofluorescence technology and fluorescent monoclonal antibody multiparameter flow cytometry to detect differences in peripheral blood cytokines and cell subsets between LCA patients after immunotherapy and healthy controls. Results: Our research results show that there are differences in the levels of IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α in the peripheral blood of LCA patients (n=70) after immunotherapy compared to the healthy controls (n=55) (P<0.05), and there are differences in 10 cell subgroups including DP T Cells, AT cells, and NLR in the peripheral blood compared to the healthy controls (n=35) (P<0.05). Further analysis revealed significant differences in the detection data of IL-6, IL-10, IFN-γ, CD56dim NK cells, Total B cells, Total NE cells, CD15+M cells, and NLR between LCA deceased patients (n=25) and LCA surviving patients (n=27) during the same period (P<0.05). The continuous monitoring of cytokines and cell subsets is far more valuable than a single-time test, as abnormal fluctuations in the data of cytokines and cell subsets are often associated with poor prognosis. In addition, IL-6 and NLR showed the strongest discriminative ability between postoperative immunotherapy-treated LCA patients and healthy controls, with AUC values of 0.840 and 0.822, respectively. There was a significant association between IFN-γ and distant metastasis in LCA (P<0.05), as well as between CD56dim NK cells and lymph node infiltration (P<0.05). Conclusion: This research results support peripheral blood cytokines and cell subsets as biomarkers for monitoring the postoperative immune status and predicting the prognosis of LCA patients after immunotherapy. The continuous monitoring of cytokines and cell subsets is far more valuable than a single-time detection.

[Retracted] Fe3O4­solamargine induces apoptosis and inhibits metastasis of pancreatic cancer cells.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the Transwell invasion assay data shown in Fig. 5B on p. 911 were strikingly similar to data that had appeared in a previously published paper written by different authors at a different research institute. In view of the fact that certain of the data in the above article had already appeared in a previously published paper, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 54: 905­915, 2019; DOI: 10.3892/ijo.2018.4637].

A metabolic map and artificial intelligence-aided identification of nasopharyngeal carcinoma via a single-cell Raman platform.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a complex cancer influenced by various factors. This study explores the use of single-cell Raman spectroscopy as a potential diagnostic tool for investigating biomolecular changes associated with NPC carcinogenesis. METHODS: Seven NPC cell lines, one immortalised nasopharyngeal epithelial cell line, six nasopharyngeal mucosa tissues and seven NPC tissue samples were analysed by performing confocal Raman spectroscopic measurements and imaging. The single-cell Raman spectral dataset was used to quantify relevant biomolecules and build machine learning classification models. Metabolomic profiles were investigated using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). RESULTS: By generating a metabolic map of seven NPC cell lines, we identified an interplay of altered metabolic processes involving nucleic acids, amino acids, lipids and sugars. The results from spatially resolved Raman maps and UPLC-MS/MS metabolomics were consistent, revealing an increase of unsaturated fatty acids in cancer cells, particularly in highly metastatic 5-8F and poorly differentiated CNE2 cells. The classification model achieved a nearly perfect classification when identifying NPC and non-NPC cells with an ROC-AUC of 0.99 and a value of 0.97 when identifying 13 tissue samples. CONCLUSION: This study unveils a complex interplay of metabolic network and highlights the potential roles of unsaturated fatty acids in NPC progression and metastasis. This renders further research to provide deeper insights into NPC pathogenesis, identify new metabolic targets and improve the efficacy of targeted therapies in NPC. Artificial intelligence-aided analysis of single-cell Raman spectra has achieved high accuracies in the classification of both cancer cells and patient tissues, paving the way for a simple, less invasive and accurate diagnostic test.

Deep learning-based accurate diagnosis and quantitative evaluation of microvascular invasion in hepatocellular carcinoma on whole-slide histopathology images.

BACKGROUND: Microvascular invasion (MVI) is an independent prognostic factor that is associated with early recurrence and poor survival after resection of hepatocellular carcinoma (HCC). However, the traditional pathology approach is relatively subjective, time-consuming, and heterogeneous in the diagnosis of MVI. The aim of this study was to develop a deep-learning model that could significantly improve the efficiency and accuracy of MVI diagnosis. MATERIALS AND METHODS: We collected H&E-stained slides from 753 patients with HCC at the First Affiliated Hospital of Zhejiang University. An external validation set with 358 patients was selected from The Cancer Genome Atlas database. The deep-learning model was trained by simulating the method used by pathologists to diagnose MVI. Model performance was evaluated with accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve. RESULTS: We successfully developed a MVI artificial intelligence diagnostic model (MVI-AIDM) which achieved an accuracy of 94.25% in the independent external validation set. The MVI positive detection rate of MVI-AIDM was significantly higher than the results of pathologists. Visualization results demonstrated the recognition of micro MVIs that were difficult to differentiate by the traditional pathology. Additionally, the model provided automatic quantification of the number of cancer cells and spatial information regarding MVI. CONCLUSIONS: We developed a deep learning diagnostic model, which performed well and improved the efficiency and accuracy of MVI diagnosis. The model provided spatial information of MVI that was essential to accurately predict HCC recurrence after surgery.

Identification and preliminary analysis of hub genes associated with bladder cancer progression by comprehensive bioinformatics analysis.

Bladder cancer (BC) is a crisis to human health. It is necessary to understand the molecular mechanisms of the development and progression of BC to determine treatment options. Publicly available expression data were obtained from TCGA and GEO databases to spot differentially expressed genes (DEGs) between cancer and normal bladder tissues. Weighted co-expression networks were constructed, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Associations in hub genes, immune infiltration, and immune therapy were evaluated separately. Protein-protein interaction (PPI) networks for the genes identified in the normal and tumor groups were launched. 3461 DEGs in the TCGA dataset and 1069 DEGs in the GSE dataset were identified, including 87 overlapping genes between cancer and normal bladder groups. Hub genes in the tumor group were mainly enriched for cell proliferation, while hub genes in the normal group were related to the synthesis and secretion of neurotransmitters. Based on survival analysis, CDH19, RELN, PLP1, and TRIB3 were considerably associated with prognosis (P < 0.05). CDH19, RELN, PLP1, and TRIB3 may play important roles in the development of BC and are potential biomarkers in therapy and prognosis.

A study of machine learning models for rapid intraoperative diagnosis of thyroid nodules for clinical practice in China.

BACKGROUND: In China, rapid intraoperative diagnosis of frozen sections of thyroid nodules is used to guide surgery. However, the lack of subspecialty pathologists and delayed diagnoses are challenges in clinical treatment. This study aimed to develop novel diagnostic approaches to increase diagnostic effectiveness. METHODS: Artificial intelligence and machine learning techniques were used to automatically diagnose histopathological slides. AI-based models were trained with annotations and selected as efficientnetV2-b0 from multi-set experiments. RESULTS: On 191 test slides, the proposed method predicted benign and malignant categories with a sensitivity of 72.65%, specificity of 100.0%, and AUC of 86.32%. For the subtype diagnosis, the best AUC was 99.46% for medullary thyroid cancer with an average of 237.6 s per slide. CONCLUSIONS: Within our testing dataset, the proposed method accurately diagnosed the thyroid nodules during surgery.

Blood Biomarkers Panels for Screening of Colorectal Cancer and Adenoma on a Machine Learning-Assisted Detection Platform.

OBJECTIVE: A mini-invasive and good-compliance program is critical to broaden colorectal cancer (CRC) screening and reduce CRC-related mortality. Blood testing combined with imaging examination has been proved to be feasible on screen for multicancer and guide intervention. The study aims to construct a machine learning-assisted detection platform with available multi-targets for CRC and colorectal adenoma (CRA) screening. METHODS: This was a retrospective study that the blood test data from 204 CRCs, 384 CRAs, and 229 healthy controls was extracted. The classified models were constructed with 4 machine learning (ML) algorithms including support vector machine (SVM), random forest (RF), decision tree (DT), and eXtreme Gradient Boosting (XGB) based on the candidate biomarkers. The importance index was used by SHapely Adaptive exPlanations (SHAP) analysis to identify the dominant characteristics. The performance of classified models was evaluated. The most dominating features from the proposed panel were developed by logistic regression (LR) for identification CRC from control. RESULTS: The candidate biomarkers consisted of 26 multi-targets panel including CEA, AFP, and so on. Among the 4 models, the SVM classifier for CRA yields the best predictive performance (the area under the receiver operating curve, AUC: .925, sensitivity: .904, and specificity: .771). As for CRC classification, the RF model with 26 candidate biomarkers provided the best predictive parameters (AUC: .941, sensitivity: .902, and specificity: .912). Compared with CEA and CA199, the predictive performance was significantly improved. The streamlined model with 6 biomarkers for CRC also obtained a good performance (AUC: .946, sensitivity: .885, and specificity: .913). CONCLUSIONS: The predictive models consisting of 26 multi-targets panel would be used as a non-invasive, economical, and effective risk stratification platform, which was expected to be applied for auxiliary screening of CRA and CRC in clinical practice.

IL-27p28 specifically regulates MHC II expression in macrophages through CIITA.

Antigen-presenting cells (APCs) constantly express major histocompatibility complex II (MHC II), including macrophages and dendritic cells (DCs) which deliver antigens to CD4+ T cells and play an important role in adaptive immunity. The expression of MHC II is controlled by the transcriptional coactivator CIITA. Interleukin-27 (IL-27), a newly discovered IL-12 family cytokine, is composed of p28 and EBI3 subunits. In this study, we used IL-27p28 conditional knock-out mice to investigate the regulatory effects of IL-27p28 on macrophage polarization and the expression of MHC II in macrophages. We found that MHC II expression was upregulated in the bone marrow-derived and peritoneal exudate macrophages (BMDMs; PEMs) from IL-27p28-deficient mice, with their inflammation regulating function unaffected. We also demonstrated that in the APCs, IL-27p28 selectively regulated MHC II expression in macrophages but not in dendritic cells. During Pseudomonas aeruginosa (P. aeruginosa) reinfection, higher survival rate, bacterial clearance, and ratio of CD4+/CD8+ T cells in the spleen during the specific immune phase were observed in IL-27p28 defect mice, as well as an increased MHC II expression in alveolar macrophages (AMs). But these did not occur in the first infection. For the first time we discovered that IL-27p28 specifically regulates the expression of MHC II in macrophages by regulating CIITA, while its absence enhances antigen presentation and adaptive immunity against P. aeruginosa.

The Comparison of Biomolecular Changes of Epstein-Barr Virus Infection in Nasopharyngeal Epithelial Cells Using Confocal Raman Microspectroscopy.

BACKGROUND: Due to its unique fingerprinting properties, Confocal Raman microscopy (CRM) can be used to examine the biomolecular changes of viruses invading and manipulating host cells. Recently, the biochemical changes due to the invasion and infection of B lymphocyte cells, nerve cells, and epithelial cells by Epstein-Barr virus (EBV) have been reported. However, biomolecular changes in nasopharyngeal epithelial cells that result from EBV infection are still poorly understood. METHODS: In continuation of our prior investigation of EBV infection in nasopharyngeal epithelial cells, we tried to expound on biomolecular changes in EBV-infected nasopharyngeal epithelial cells using Raman microspectroscopy. EBV has two life cycles, latent infection and lytic replication. We have established latent and lytic infection models at the cellular level. In order to understand the characteristics of the two patterns of EBV infection, we used Raman spectroscopy to identify the changes in biomolecules of EBV latent cells (CNE2, CNE2-EBV) and lytic cells (NPEC1-BMI1-CN, NPEC1-BMI1-EBV). RESULTS: During latent infection, levels of glycogen, protein, and lipid molecules in the cell increased while levels of nucleic acid and collagen molecules decreased. Molecular levels of glycogen, proteins, and nucleic acids are reduced during lytic infection. We found that molecular levels of nucleic acid decreased during two different periods of infection, whereas levels of other biomolecules showed the opposite trend. Glycogen, proteins, lipids, nucleic acids, and other molecules are associated with alterations in cellular biochemical homeostasis. These changes correspond to unique Raman spectra in infected and uninfected cells associated with specific biomolecules that have been proven. These molecules are mainly responsible for cellular processes such as cell proliferation and apoptosis. The Raman signatures of these biomolecular changes depend on the different phases of viral infection. CONCLUSIONS: Therefore, by using CRM, it is possible to discern details in the progression of EBV infection in nasopharyngeal epithelial cells at the molecular level.

Bone marrow sparing oriented multi-model image registration in cervical cancer radiotherapy.

Cervical cancer poses a serious threat to the health of women and radiotherapy is one of the primary treatment methods for this condition. However, this treatment is associated with a high risk of causing acute hematologic toxicity. Delineating the bone marrow (BM) for sparing based on computer tomography (CT) images before radiotherapy can effectively avoid this risk. Unfortunately, compared to magnetic resonance (MR) images, CT images lack the ability to express the activity of BM. Therefore, medical practitioners currently manually delineate the BM on CT images by corresponding to MR images. However, the manual delineation of BM is time-consuming and cannot guarantee accuracy due to the inconsistency of the CT-MR multimodal images. This study proposes a multimodal image-oriented automatic registration method for pelvic BM sparing. The proposed method includes three-dimensional (3D) bone point clouds reconstruction and an iterative closest point registration based on a local spherical system for marking BM on CT images. By introducing a joint coordinate system that combines the global Cartesian coordinate system with the local point clouds' spherical coordinate system, the increasement of point descriptive dimension avoids the local optimal registration and improves the registration accuracy. Experiments on the dataset of patients demonstrate that our proposed method can enhance the multimodal image registration accuracy and efficiency for medical practitioners in BM-sparing of cervical cancer radiotherapy. The method proposed in this contribution might also provide a solution to multimodal registration, especially in multimodal sequential images in other clinical applications, such as the diagnosis of cervical cancer and the preservation of normal organs during radiotherapy.

Pseudoprogression in the era of immunotherapy-based strategies for recurrent head and neck squamous cell carcinoma achieving complete response: A case report.

RATIONALE: In the last few years, treatment of head and neck squamous cell carcinoma (HNSCC) has been enhanced by the emergence of immunotherapy. A biological phenomenon unique to immunotherapy is pseudoprogression, an increase in tumor burden or the appearance of a new lesion subsequently followed by tumor regression. PATIENT CONCERNS: A 78-year-old man complaining of a lump (6*4 cm) gradually swelling on the right side of his neck with recurrent buccal mucosa squamous cell carcinoma presented to our institution. Two months prior, he received resection of the buccal lesion but refused suggested adjuvant chemoradiotherapy after the operation. DIAGNOSES: Recurrent buccal mucosa squamous cell carcinoma. INTERVENTIONS: Induction immunotherapy was initiated, followed by a new node appearing on the surface of the neck mass. We considered the presence of pseudoprogression and continued with immunotherapy. The patient received immunotherapy combined with chemotherapy and intensity-modulated radiation therapy (IMRT) consecutively. OUTCOMES: The patient experienced an excellent recovery with the disappearance of pain and the lump, along with return of a healthy appetite, weight gain and positive outlook. Complete response (CR) was also noted by magnetic resonance imaging (MRI) scan, with the upper right neck mass significantly retreated to unclear display. The patient is still alive with stable, asymptomatic disease at the time of this writing. LESSONS: These results provide confidence in the safety and efficacy of radical chemo-radio-immunotherapy for the treatment of recurrent, unresectable or metastatic HNSCC.

Imaging features of primary hepatic sarcomatoid carcinoma: Differentiation from hepatocellular carcinoma and intrahepatic cholangiocarcinoma on CT: A preliminary study.

Purpose: Primary hepatic sarcomatoid carcinoma (PHSC) is a rare type of malignant tumor in the liver. Nevertheless, few studies have focused on the imaging diagnosis of PHSC. In this study, we collected clinical and computed tomography (CT) imaging data of PHSC from two institutions, aiming to investigate the clinical and radiological characteristics of PHSC. Methods: We retrospectively investigated the clinical characteristics and CT features of 22 PHSC patients (19 males and 3 females; mean age, 63.4 years; range, 49 to 76 years), 95 hepatocellular carcinoma (HCC) patients and 50 intrahepatic cholangiocarcinoma (ICC) patients. Two radiologists independently evaluated the CT features of the three groups. Subsequently, we analyzed the differences in the clinical characteristics and CT features between the PHSC and control groups. Results: Most PHSCs were larger than 5 cm (72.7%). PHSC mainly showed irregular (81.8%), heterogeneous (100%) masses with ill-defined (72.7%) borders with necrosis (86.4%) on CT, which are more common CT features versus HCC (p < 0.001). In the arterial phase, PHSC always showed noticeable heterogeneous enhancement (100.0%), mainly manifesting as partial arterial phase hyperenhancement (APHE) (86.4%). The enhancement patterns of PHSC mainly included delayed progressive enhancement (72.7%), nonperipheral washout (22.7%), and unclassified enhancement (4.5%), which were significantly different from the HCC enhancement pattern but similar to the enhancement pattern of ICC. In addition, vein tumor thrombus (18.2%), intrahepatic metastasis (27.3%), and lymphadenopathy (27.3%) were relatively common in PHSC. Furthermore, most PHSC tumors classified as LR-M (66.7%) were similar to ICC. Conclusions: PHSC generally presents as irregularly large masses with necrosis, intrahepatic metastasis, and lymphadenopathy. The CT enhancement of PHSC is mainly part of APHE and delayed progressive enhancement.

Unsaturated phospholipid modified FeOCl nanosheets for enhancing tumor ferroptosis.

Iron-dependent accumulation of reactive oxygen species (ROS) and lipid peroxidation play key roles in ferroptosis, which has been an attractive strategy to kill tumor cells. However, the rapid annihilation of hydroxyl radicals (˙OH) produced from the Fenton reaction has become a major obstacle in inducing lipid peroxidation in cells. In this study, we develop a nano-delivery system of unsaturated phospholipid (Lip) and polyacrylic acid (PAA) functionalized FeOCl nanosheets (FeOCl@PAA-Lip). In this system, the ˙OH radicals produced from the Fenton reaction between FeOCl nanosheets and endogenous H2O2 of tumor cells attack Lip on the nanosheets in situ to initiate the lipid peroxidation chain reaction, which not only realizes free radical conversion but also leads to the amplification of ROS and lipid peroxides, thus enhancing tumor ferroptosis. The in vitro and in vivo results confirmed that FeOCl@PAA-Lip nanosheets exhibited specific tumor cell-killing effects, good biocompatibility, long circulation time, low side effects, high tumor targeting and an excellent tumor inhibition rate (73%). The Lip functionalization strategy offers a paradigm of enhancing ferroptosis treatment by conversion of ˙OH/phospholipid radicals/lipid peroxyl radicals and strengthening lipid peroxidation.

Comprehensive analysis of aberrantly expressed circRNAs, mRNAs and lncRNAs in patients with nasopharyngeal carcinoma.

BACKGROUND: The location of nasopharyngeal cancer is hidden, so it is difficult to diagnose at an early stage. In this study, we aimed to investigate the expression profiles of circRNAs, mRNAs and IncRNAs and to provide some basis for further studies. METHODS: Expression profiles of circRNAs, mRNAs, and lncRNAs were analyzed using microarray techniques. The differentially expressed ncRNA was calculated by bioinformatics. RESULTS: A total of 3048 circRNAs, 2179 lncRNAs, and 2015 mRNAs were detected to be significantly differentially expressed in NPC. The most upregulated circRNAs, lncRNAs, and mRNAs were hsa-circ-0067562, NONHSAT232922.1, and HOXB13, respectively. And, the most downregulated circRNAs, lncRNAs, and mRNAs were hsa_circ_0078837, lnc-TTC8-4:3, and LTF, respectively. The number of upregulated DE lncRNAs was more than twice than those downregulated. Our data showed that 80.44% of pairs of lncRNAs and cis-mRNAs demonstrated positive correlations. For lncRNAs and trans-mRNAs pairs, 53.7% of pairs showed positive correlation. LncRNA-mediated cis regulation is a prevalent regulatory mode in the development of nasopharyngeal carcinoma. CR1, LRMP and SORBS2 are predicted to be mediated not only by cis-acting lncRNA modes of action, but also by trans-acting lncRNA mechanisms. Additionally, we constructed a diagnostic prediction model with a high sensitivity and specificity. CONCLUSION: Our study characterized the landscape of circRNAs, mRNAs and lncRNAs in NPC tissue and provided novel insights into the molecular mechanisms of NPC.

Clinical application of spectral CT perfusion scanning in evaluating the blood supply source of portal vein tumor thrombus in hepatocellular carcinoma.

Purpose: To evaluate the characteristic of blood supply of liver portal vein tumor thrombus (PVTT) using perfusion indexes and spectral parameters. Methods: Between July 2020 and December 2022, the study enrolled 25 liver cancer patients completed with PVTT (male=20, female=5; age 41-74 years (59.48 ± 9.12)) from the Interventional Department of Jiangsu Cancer Hospital. There were 11 cases of type III PVTT, 12 of type II PVTT, and 2 of type I PVTT (Cheng's classification). All patients underwent spectral perfusion scans through dual-layer spectral detector computed tomography. The PVTTs were divided into proximal and distal groups based on the distance between the tumor thrombus and the main portal vein. The perfusion analysis was performed on the 120-kVp conventional images to generate hepatic perfusion index (HPI). The spectral based images (SBIs) during the artery and venous peak phases were extracted from the perfusion data. The iodine map and 40&100-keV virtual monoenergetic image (VMI) were generated from SBI data. HPI, iodine concentration (IC), CT value at 40 and 100-keV, and spectral slope (40-100keV) of the primary lesion, proximal and distal PVTT, and liver parenchyma were measured and compared. The correlation between the primary lesion and proximal and distal PVTT was analyzed. Results: The IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT, and distal PVTT were highly correlated (P<0.001). The differences between the IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT were statistically significant (P<0.001). The differences between the IC during venous peak phase and HPI of primary lesion, distal PVTT were statistically significant (P<0.001), and there was no statistically significant difference in arterial phase IC, arterial and venous phase spectral slopes. Conclusion: The IC, slope, and HPI of the distal and proximal PVTT were highly correlated with the primary lesion, indicating that PVTT was similar to the primary lesion in the liver that they were both mainly supplied by the hepatic artery. However, there was still significant heterogeneity between the proximal PVTT and the primary lesion, while the difference in the distal PVTT was relatively small.

Case report: Hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune-mediated disease that affects patients with known genetic defects and is increasingly found among those with autoimmune diseases and persistent infections. Talaromyces marneffei (TM) is a human opportunistic fungus that commonly infects immunodeficient or immunosuppressed individuals. Few TM-associated secondary HLH cases resulting from autoimmune deficiency have been reported previously. The current case study describes a pediatric patient hospitalized with recurrent fever and lymphadenopathy. The child had abnormal blood cell classification, and microscopy revealed mature granulocytes that phagocytized fungal spores. It was speculated that the patient was infected with TM. The pathogen was detected earlier than the blood culture and confirmed by metagenomic next-generation sequencing. Whole-exome sequencing revealed that the patient had complex mutations associated with immunodeficiency. This included a mutation in exon 3 of the CD40LG gene, c.346G>A, which may be linked to hyper-IgM syndrome, a primary immunodeficiency disease with immunoglobulin conversion recombination defects that could explain the patient's increased susceptibility to serious opportunistic infections. In addition, a heterozygous frameshift variant, c.820dup (p.Asp274GlyfsTer61), was detected in exon 6 of CARD9, a key gene associated with fungal immune surveillance. After 4 days of fungal treatment, the abnormal blood cell clusters disappeared, but other infections occurred in succession for 6 months after rehabilitation. The patient was followed with the aim of providing subsequent immunotherapy. This study found that infection can trigger HLH in HIV-negative individuals, highlighting the importance of early definitive identification of the causative agent and investigation of potential immunodeficiency.

Classification prediction of pancreatic cystic neoplasms based on radiomics deep learning models.

BACKGROUND: Preoperative prediction of pancreatic cystic neoplasm (PCN) differentiation has significant value for the implementation of personalized diagnosis and treatment plans. This study aimed to build radiomics deep learning (DL) models using computed tomography (CT) data for the preoperative differential diagnosis of common cystic tumors of the pancreas. METHODS: Clinical and CT data of 193 patients with PCN were collected for this study. Among these patients, 99 were pathologically diagnosed with pancreatic serous cystadenoma (SCA), 55 were diagnosed with mucinous cystadenoma (MCA) and 39 were diagnosed with intraductal papillary mucinous neoplasm (IPMN). The regions of interest (ROIs) were obtained based on manual image segmentation of CT slices. The radiomics and radiomics-DL models were constructed using support vector machines (SVMs). Moreover, based on the fusion of clinical and radiological features, the best combined feature set was obtained according to the Akaike information criterion (AIC) analysis. Then the fused model was constructed using logistic regression. RESULTS: For the SCA differential diagnosis, the fused model performed the best and obtained an average area under the curve (AUC) of 0.916. It had a best feature set including position, polycystic features (≥6), cystic wall calcification, pancreatic duct dilatation and radiomics-DL score. For the MCA and IPMN differential diagnosis, the fused model with AUC of 0.973 had a best feature set including age, communication with the pancreatic duct and radiomics score. CONCLUSIONS: The radiomics, radiomics-DL and fused models based on CT images have a favorable differential diagnostic performance for SCA, MCA and IPMN. These findings may be beneficial for the exploration of individualized management strategies.

Self-assembling Bioadhesive Inspired by the Fourth Repetitive Sequence of Balanus albicostatus Cement Protein 20 kDa (Balcp-20 k).

Barnacle cement proteins are multi-protein complexes composed of a series of functionally related synergistic proteins that enable barnacles to adhere strongly and consistently to various underwater substrates. There is no post-translational modification of barnacle cement proteins, which provides a possibility for the synthesis of similar adhesive materials. Balcp-20 k has four repetitive sequences with multiple conserved cysteine groups. Whether these repeats are separate functional units and the role of cysteine in adhesion is not clear. In order to investigate the adhesion properties of Balcp-20 k, we amplified and expressed R4 (DHLACNAKHPCWHKHCDCFC)4, which is a quadruple repeat of Balcp-20 k's fourth repetitive sequence, and S0R4 (DHLASNAKHPSWHKHSDSFS)4, all cysteine of R4 replaced by serine. Analysis showed that R4 had a similar structure to Balcp-20 k, and the amyloid fibrils structure formed by self-assembly of R4 played an important role in improving the adhesion strength. The absence of disulfide bonds in S0R4 prevents self-assembly, and the failure of self-assembly after the reduction of disulfide bonds of R4 by DTT indicates that disulfide bonds play an important role in self-assembly. With adhesion and coating analysis, it was found that R4 has good adhesion on different materials surfaces, which is better than Balcp-20 k, while S0R4 has weak adhesion, which is only better than BSA.

Long-term survival of gastric mixed neuroendocrine-non-neuroendocrine neoplasm: Two case reports.

BACKGROUND: Gastric mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), which consists of neuroendocrine and non-neuroendocrine components, is quite rare. Until now, most data on gastric MiNEN come from clinical cases, without large-scale retrospective studies or controlled clinical trials. Consequently, no consensus regarding the origin, molecular characteristics, or appropriate treatment of MiNEN has been reached so far. We conducted chemotherapy of irinotecan plus cisplatin (IP regimen) and surgery in two patients with gastric MiNEN, which had never been used in treating this kind of tumor, leading to their long-term survival for more than 3 and 7 years, respectively. CASE SUMMARY: We present two patients (one male and one female) with gastric MiNEN, with the primary manifestation of recurrent upper abdominal pain. After they were referred to our hospital, a diagnosis of gastric MiNEN was defined with the help of CT scan, and histopathological and immunohistochemical examinations on the samples of gastrointestinal endoscopy or radical surgery. The male patient (case 1) were found to have metastases in the reginal lymph nodes and the left liver. He received four cycles of IP regimens first, then the gastrectomy and partial left liver resection, followed by additional two cycles of IP chemotherapy. The female patient (case 2) underwent a laparoscopic gastrectomy, and received six cycles of IP regimen. She was found to have metastatic lesions in the right lung 2 years after that, and underwent video-assisted thoracoscopic surgery (VATS) of the lower lobe of the right lung. The two patients have now survived for more than 3 years and 7 years, respectively, without any evidence of recurrence or metastases. CONCLUSION: IP regimen, combined with curative-intent surgery if feasible, could be considered as the priority in the choice of front-line chemotherapy for gastric MiNEN.

Epstein-Barr virus-associated leiomyosarcoma of the larynx in an adult patient with human immunodeficiency virus infection: Case report and review of the literature.

We investigated the clinical features, treatment, and prognosis of laryngeal leiomyosarcoma (LLMS) and Epstein-Barr virus-associated (EBV-associated) LMS. We report a case of EBV-associated LLMS in an adult patient with HIV infection. We also conducted a review of the English-language literature on LLMS and EBV-associated leiomyosarcoma. To the best of our knowledge, 62 cases of LLMS and EBV-associated leiomyosarcoma have been reported to date. Of patients with LLS, 18.9% had distant metastases and 17.0% had local recurrence. The overall 5-year survival rate was 64.0%. Distant metastases affected the survival of patients with LLMS (p = 0.04). EBV-positive patients had a low survival rate (p = 0.01). Among patients with EBV-associated LMS, 8.2% had distant metastases and recurrence and the overall 5-year survival rate was 50.0%. EBV-associated LLMS is rare. The EBV infection might be a poor prognostic factor of LLMS.