Manganese-mediated potentiation of antitumor immune responses by enhancing KLRG1+ Macrophage function.

Manganese (Mn) play a crucial role in various biological processes in the body. Studies have primarily focused on their ability to enhance immune cell function and activation against tumors, particularly in dendritic cells (DCs), macrophages, and T cells. Tumor-associated macrophages (TAMs) are often the most abundant immune cell population present in the tumor microenvironment (TME). Thus, it would be valuable to investigate the mechanism by which Mn2+ regulates TAMs' involvement in anti-tumor immunity, as it be crucial for advancing our understanding of cancer biology and developing new treatments for cancer. Here, in the present study we discovered that Mn2+ treatment led to a significant increase in KLRG1+ macrophages (KLRG1+ Mφ) in tumor tissues, and most of these cells exhibited an M1 phenotype. Knocking down KLRG1 in macrophages not only impaired their ability to induce downstream anti-tumor immunity of adaptive immune cells, but also impaired their direct cytotoxicity against tumor cells. Moreover, the changes in the polarization phenotype of KLRG1+ macrophages further lead to T cell proliferation and the polarization of CD4+ T cells towards a Th1 phenotype, thereby establishing a foundation for the antitumor immune response. Our study expands the understanding of the anti-tumor mechanism of Mn2+ and demonstrates, for the first time, that Mn2+ can regulate the function of KLRG1+ Mφ to participate in anti-tumor activities. These findings suggest that KLRG1 may represent a promising target for developing new tumor therapy.

The evolutionary and molecular history of a chikungunya virus outbreak lineage.

In 2018-2019, Thailand experienced a nationwide spread of chikungunya virus (CHIKV), with approximately 15,000 confirmed cases of disease reported. Here, we investigated the evolutionary and molecular history of the East/Central/South African (ECSA) genotype to determine the origins of the 2018-2019 CHIKV outbreak in Thailand. This was done using newly sequenced clinical samples from travellers returning to Sweden from Thailand in late 2018 and early 2019 and previously published genome sequences. Our phylogeographic analysis showed that before the outbreak in Thailand, the Indian Ocean lineage (IOL) found within the ESCA, had evolved and circulated in East Africa, South Asia, and Southeast Asia for about 15 years. In the first half of 2017, an introduction occurred into Thailand from another South Asian country, most likely Bangladesh, which subsequently developed into a large outbreak in Thailand with export to neighbouring countries. Based on comparative phylogenetic analyses of the complete CHIKV genome and protein modelling, we identified several mutations in the E1/E2 spike complex, such as E1 K211E and E2 V264A, which are highly relevant as they may lead to changes in vector competence, transmission efficiency and pathogenicity of the virus. A number of mutations (E2 G205S, Nsp3 D372E, Nsp2 V793A), that emerged shortly before the outbreak of the virus in Thailand in 2018 may have altered antibody binding and recognition due to their position. This study not only improves our understanding of the factors contributing to the epidemic in Southeast Asia, but also has implications for the development of effective response strategies and the potential development of new vaccines.

Isolation and characterization of a novel rodent hepevirus in long-tailed dwarf hamsters (Cricetulus longicaudatus) in China.

Hepeviruses have been identified in a broad range of animal hosts, including mammals, birds, and fish. In this study, rodents (n=91) from seven different species and ten pikas (Ochotona curzoniae) were collected in Qinghai Province, China. Using transcriptomic sequencing and confirmatory molecular testing, hepeviruses were detected in 27 of 45 (60 %) long-tailed dwarf hamsters (Cricetulus longicaudatus) and were undetected in other rodents and pika. The complete genome sequences from 14 representative strains were subsequently obtained, and phylogenetic analyses suggested that they represent a novel species within the genus Rocahepevirus, which we tentatively designated as Cl-2018QH. The virus was successfully isolated in human hepatoma (Huh-7) and murine fibroblast (17 Cl-1) cell lines, though both exhibited limited replication as assayed by detection of negative-sense RNA intermediates. A129 immunodeficient mice were inoculated with Cl-2018QH and the virus was consistently detected in multiple organs, despite relatively low viral loads. In summary, this study has described a novel rodent hepevirus, which enhances our knowledge of the genetic diversity of rodent hepeviruses and highlights its potential for cross-species transmission.

Hypoxia promotes metastasis by relieving miR-598-3p-restricted glycolysis in gastric cancer.

The activation of glycolysis, particularly in the context of reprogrammed energy metabolism, is increasingly recognized as a significant characteristic of cancer. However, the precise mechanisms by which glycolysis is promoted in metastatic gastric cancer cells under normal oxygen conditions remain poorly understood. MicroRNAs (miRNAs) play a crucial role in the development of malignant phenotypes in gastric cancer. Nevertheless, our understanding of the specific involvement of miRNAs in hypoxia-induced metabolic shifting and the subsequent metastatic processes is limited. Hypoxia-induced downregulation of miR-598-3p mechanistically leads to the upregulation of RMP and IGF1r, thereby promoting glycolysis. Either overexpression of miR-598-3p or R406 treatment effectively suppresses the metastasis of gastric cancer cells both in vitro and in vivo. Collectively, the depletion of miR-598-3p alters glucose metabolism from oxidative phosphorylation to glycolysis, thereby exacerbating the malignancy of gastric cancer cells. The present findings indicate a potential target for the development of therapeutics against gastric cancers with increased miR-598-3p expression.

Identification of novel mammalian viruses in tree shrews ( Tupaia belangeri chinensis).

The Chinese tree shrew ( Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.

Combination of IL-33 with PD-1 blockade augment mILC2s-mediated anti-tumor immunity.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) represent one of the main tissue-specific innate lymphoid cell populations, which are key drivers of cytokine secretion in their occupational niche. However, the precise involvement of ILC2s in cancer immunity and their potential impact on immunotherapeutic approaches remain poorly understood. METHODS: The proportion of ILC2s originating from various tissue sources were quantified through flow cytometry, along with the determination of CD4+ T cell and CD8+ T cell percentages. Flow cytometry was also employed to assess IFN-γ production and programmed cell death protein-1 (PD-1) expression in T cells. Immunohistochemistry was utilized to detect IL-33 expression in tumor tissues, while immunofluorescence was employed to confirm the infiltration of ILC2s in both murine and human tumor tissues. RESULTS: In this study, we provide evidence that intra-tumoral ILC2s in lung adenocarcinoma (LUAD) exist in a quiescent state. However, the activation of intra-tumoral ILC2s is induced by IL-33 specifically in a natural ILC2s (nILC2, ST2+KLRG1-) phenotype. Considering the pivotal role of PD-1 in cancer immunotherapy and its immunoregulatory functions, we investigated the synergistic effects of IL-33 and anti-PD-1 and found that their combination enhances anti-tumor immunity and improves the efficacy of immunotherapy. Moreover, this combination leads to the upregulation of activated mature ILC2s (mILC2, ST2+KLRG1+) phenotype, thereby highlighting the activated ILC2s as a novel enhancer of the immunoregulatory properties of anti-PD-1. CONCLUSIONS: Collectively, these findings underscore the significance of ILC2s and their contribution to the anti-tumor response in the context of cancer immunotherapy. Consequently, the simultaneous targeting of ILC2s and T cells represents a potentially promising and widely applicable strategy for immunotherapeutic interventions.

Novel prognostic signature for lung adenocarcinoma based on immune-related mRNA pairs.

Lung adenocarcinoma (LUAD) is a highly lethal malignant tumor. While the involvement of multiple mRNAs in the progression of LUAD is well established, the potential diagnostic value of immune-related mRNAs (irmRNAs) in LUAD remains largely unexplored. In this study, we utilized RNA-seq, clinical data, and immune-related gene information from LUAD patients to identify differentially expressed immune-related mRNAs (DEirmRNAs) and developed a predictive risk model based on specific DEirmRNA pairs closely linked with patient prognosis. We classified patients into high-risk and low-risk groups and analyzed factors such as survival rate, clinical characteristics, gene enrichment, immune cell infiltration, tumor mutation load, and drug susceptibility. We confirmed the expression levels of these DEirmRNAs in tumor tissues using qRT-PCR assay. Our results showed that the low-risk group had a longer survival time and lower tumor mutation burden (TMB) and microsatellite instability (MSI) compared to the high-risk group. The high-risk group also had a significant reduction in the number of certain immune cells and a lower half-maximum inhibitor concentration (IC50). We identified specific DEirmRNA pairs that were up-regulated or down-regulated in tumor tissues compared to adjacent tissues. Our prognostic risk model based on DEirmRNA pairs could be used to predict the prognosis of LUAD patients and provide reference for better treatment.

Diversity and connectedness of brine shrimp viruses in global hypersaline ecosystems.

Brine shrimp (Artemia) has existed on Earth for 400 million years and has major ecological importance in hypersaline ecosystems. As a crucial live food in aquaculture, brine shrimp cysts have become one of the most important aquatic products traded worldwide. However, our understanding of the biodiversity, prevalence and global connectedness of viruses in brine shrimp is still very limited. A total of 143 batches of brine shrimp (belonging to seven species) cysts were collected from six continents including 21 countries and more than 100 geographic locations worldwide during 1977-2019. In total, 55 novel RNA viruses were identified, which could be assigned to 18 different viral families and related clades. Eleven viruses were dsRNA viruses, 16 were +ssRNA viruses, and 28 were-ssRNA viruses. Phylogenetic analyses of the RNA-directed RNA polymerase (RdRp) showed that brine shrimp viruses were often grouped with viruses isolated from other invertebrates and fungi. Remarkably, most brine shrimp viruses were related to those from different hosts that might feed on brine shrimp or share the same ecological niche. A notable case was the novel brine shrimp noda-like virus 3, which shared 79.25% (RdRp) and 63.88% (capsid proteins) amino acid identity with covert mortality nodavirus (CMNV) that may cause losses in aquaculture. In addition, both virome composition and phylogenetic analyses revealed global connectedness in certain brine shrimp viruses, particularly among Asia and Northern America. This highlights the incredible species diversity of viruses in these ancient species and provides essential data for the prevalence of RNA viruses in the global aquaculture industry. More broadly, these findings provide novel insights into the previously unrecognized RNA virosphere in hypersaline ecosystems worldwide and demonstrate that human activity might have driven the global connectedness of brine shrimp viruses.

Ubiquitin E3 ligase SPOP is a host negative regulator of enterovirus 71-encoded 2A protease.

IMPORTANCE: EV71 poses a significant health threat to children aged 5 and below. The process of EV71 infection and replication is predominantly influenced by ubiquitination modifications. Our previous findings indicate that EV71 prompts the activation of host deubiquitinating enzymes, thereby impeding the host interferon signaling pathway as a means of evading the immune response. Nevertheless, the precise mechanisms by which the host employs ubiquitination modifications to hinder EV71 infection remain unclear. The present study demonstrated that the nonstructural protein 2Apro, which is encoded by EV71, exhibits ubiquitination and degradation mediated by the host E3 ubiquitin ligase SPOP. In addition, it is the first report, to our knowledge, that SPOP is involved in the host antiviral response.

Prognostic significance of index (LANR) composed of preoperative lymphocytes, albumin, and neutrophils in patients with stage IB-IIA cervical cancer.

BACKGROUND: The purpose of this study was to investigate the role of preoperative lymphocytes, albumin, neutrophils, and LANR in the prognosis of patients with stage IB-IIA cervical cancer (CC). METHODS: We made a retrospective analysis of the clinical information and related materials of 202 patients with stage IB-IIA primary cervical cancer who had undergone a radical hysterectomy in the Department of Gynecology at the Affiliated Hospital of Jiangnan University between January 2017 and December 2018. The definition of LANR was as follows: LANR, lymphocyte × albumin / neutrophil. The receiver operating characteristic curve (ROC) was generated to determine the best cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting recurrence and survival. The Kaplan-Meier method was employed to draw survival curves in our survival analysis. Univariate analysis, multifactorial analysis, and subgroup analysis were used to evaluate the prognostic significance of LANR in overall and progression-free survival. RESULTS: The median follow-up time of the study was 55 months. In overall survival, the area under the curve for LANR was 0.704 (95% CI: 0.590-0.818, p<0.05). And in progression-free survival, the area under the curve for LANR was 0.745 (95% CI: 0.662-0.828, p<0.05). Univariate and multivariate analyses showed that the value of LANR was associated with both overall survival and progression-free survival (p< 0.05). Kaplan-Meier analysis demonstrated that OS (p< 0.001) and PFS (p< 0.001) in patients with high LANR levels were significantly higher than those with low LANR levels. CONCLUSIONS: Our findings suggested that LANR might serve as a clinically reliable and effective independent prognostic indicator in patients with stage IB-IIA cervical cancer.

[Imbalance of lymphoid cells in peripheral blood maintains the immunosuppression and promotes the development of lung adenocarcinoma].

Objectives Objectives To investigate how the imbalance of innate lymphoid cells (ILCs)in the peripheral blood of patients with lung adenocarcinoma affects the balance of downstream mononuclear macrophages and T helper (Th) cells, and to identify the impact of the imbalance of ILCs on the immune status and prognosis of lung adenocarcinoma. Methods The peripheral blood of 20 patients with lung adenocarcinoma and normal controls were collected. The percentage of ILCs, mononuclear macrophages and T lymphocyte in peripheral blood were analyzed by flow cytometry. The characteristic cytokine secretion levels of various types of immune cells in peripheral blood were detected by real-time fluorescence quantitative PCR. Results Compared with the normal controls, the proportion of M2 mononuclear macrophages, ILC1 and ILC2 in patients with lung adenocarcinoma was up-regulated, while the proportion of M1 mononuclear macrophages, CD4+ T and CD8+ T was down-regulated. The mRNA expression of related cytokines of M1 mononuclear macrophages and ILC1 were decreased; while the mRNA expression of related cytokines of M2 mononuclear macrophages and ILC2 were increased. Along with the decreased CD4+T cells-associated cytokine T-bet mRNA expression, and the increased GATA3 mRNA expression. Moreover, the expression of PD-1 in CD8+ T cells was also up-regulated. Conclusion The imbalance of ILCs in peripheral blood of patients with lung adenocarcinoma promotes the imbalance of mononuclear macrophages and Th cells, which altogether maintains the immunosuppression in patients with lung adenocarcinoma, and promotes the development of lung adenocarcinoma.

SFTSV infection is associated with transient overproliferation of monoclonal lambda-type plasma cells.

The impairment of antibody-mediated immunity is a major factor associated with fatal cases of severe fever with thrombocytopenia syndrome (SFTS). By collating the clinical diagnosis reports of 30 SFTS cases, we discovered the overproliferation of monoclonal plasma cells (MCP cells, CD38+cLambda+cKappa-) in bone marrow, which has only been reported previously in multiple myeloma. The ratio of CD38+cLambda+ versus CD38+cKappa+ in SFTS cases with MCP cells was significantly higher than that in normal cases. MCP cells presented transient expression in the bone marrow, which was distinctly different from multiple myeloma. Moreover, the SFTS patients with MCP cells had higher clinical severity. Further, the overproliferation of MCP cells was also observed in SFTS virus (SFTSV)-infected mice with lethal infectious doses. Together, SFTSV infection induces transient overproliferation of monoclonal lambda-type plasma cells, which have important implications for the study of SFTSV pathogenesis, prognosis, and the rational development of therapeutics.

Prognostic Significance of Preoperative Lactate Dehydrogenase to Albumin Ratio in Breast Cancer: A Retrospective Study.

Purpose: We explored the relationship between platelet count to lymphocyte count ratio (PLR), monocyte count to lymphocyte count ratio (MLR), lactate dehydrogenase to albumin ratio (LAR), and long-term survival in patients with breast cancer. Patients and Methods: We retrospectively analyzed the clinical and follow-up data of 134 patients with breast cancer. The receiver operating characteristic curve (ROC curve) was used to distinguish between the low and high ratio groups. The chi-square test or Fisher's exact test was used to calculate the differences among the investigation factors. The Kaplan-Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. A P value of <0.05 was considered statistically significant. Results: The median follow-up time was 45 months. The PFS rates in the low group (LAR≤3.4066) at 18 months, 24 months, and 36 months were 100%, 100%, and 97.6%, and those in the high group (LAR > 3.4066) were 97.7%, 94.3%, and 87.3%, respectively. LAR was associated with Age (P=0.002) and BMI (body mass index) (P=0.002). Univariate analysis showed that Tumor size (P=0.027), Node positivity (P<0.001), TNM (tumor-node-metastasis) stage (P<0.001), PLR (P=0.034), MLR (P=0.038), and LAR (P=0.035) were significantly associated with PFS (progression-free survival) in breast cancer patients. Multivariate analysis showed that Node positivity (P<0.001) and LAR (P=0.035) were associated with PFS, while PLR and MLR were not independent prognostic indicators. Conclusion: Preoperative high LAR will be an independent predictor of prognosis in patients with breast cancer.

Methotrexate and Triptolide regulate Notch signaling pathway by targeting the Nedd4-Numb axis.

Methotrexate (MTX) is used to treat rheumatoid arthritis, acute leukemia, and psoriasis. MTX can cause certain side effects, such as myelosuppression, while the exact mechanism of myelosuppression caused by MTX is unknown. Notch signaling pathway has been considered to be essential to regulate hematopoietic stem cell (HSC) regeneration and homeostasis, thus contributing to bone marrow hematopoiesis. However, whether MTX affects Notch signaling remains unexplored. Here, our study provides evidence that MTX strongly suppresses the Notch signaling pathway. We found that MTX inhibited the interaction between Nedd4 with Numb, thus restricting K48-linked polyubiquitination of Numb and stabilizing Numb proteins. This in turn inhibited the Notch signaling pathway by reducing Notch1 protein levels. Interestingly, we found that a monomeric drug, Triptolide, is capable of alleviating the inhibitory effect of MTX on Notch signaling pathway. This study promotes our understanding of MTX-mediated regulation of Notch signaling and could provide ideas to alleviate MTX-induced myelosuppression.

Pathogenicity and Structural Basis of Zika Variants with Glycan Loop Deletions in the Envelope Protein.

The glycan loop of Zika virus (ZIKV) envelope protein (E) contains the glycosylation site and has been well documented to be important for viral pathogenesis and transmission. In the present study, we report that deletions in the E glycan loop, which were recorded in African ZIKV strains previously, have re-emerged in their contemporary Asian lineages. Here, we generated recombinant ZIKV containing specific deletions in the E glycan loop by reverse genetics. Extensive in vitro and in vivo characterization of these deletion mutants demonstrated an attenuated phenotype in an adult A129 mouse model and reduced oral infections in mosquitoes. Surprisingly, these glycan loop deletion mutants exhibited an enhanced neurovirulence phenotype, and resulted in a more severe microcephalic brain in neonatal mouse models. Crystal structures of the ZIKV E protein and a deletion mutant at 2.5 and 2.6 Å, respectively, revealed that deletion of the glycan loop induces encephalitic flavivirus-like conformational alterations, including the appearance of perforations on the surface and a clear change in the topology of the loops. Overall, our results demonstrate that the E glycan loop deletions represent neonatal mouse neurovirulence markers of ZIKV. IMPORTANCE Zika virus (ZIKV) has been identified as a cause of microcephaly and acquired evolutionary mutations since its discovery. Previously deletions in the E glycan loop were recorded in African ZIKV strains, which have re-emerged in the contemporary Asian lineages recently. The glycan loop deletion mutants are not glycosylated, which are attenuated in adult A129 mouse model and reduced oral infections in mosquitoes. More importantly, the glycan loop deletion mutants induce an encephalitic flavivirus-like conformational alteration in the E homodimer, resulting in a significant enhancement of neonatal mouse neurovirulence. This study underscores the critical role of glycan loop deletion mutants in ZIKV pathogenesis, highlighting a need for global virological surveillance for such ZIKV variants.

Host inflammatory response is the major factor in the progression of Chlamydia psittaci pneumonia.

Purpose: Chlamydia psittaci (C. psittaci) has caused sporadic, but recurring, fatal community-acquired pneumonia outbreaks worldwide, posing a serious threat to public health. Our understanding of host inflammatory responses to C. psittaci is limited, and many bronchitis cases of psittaci have rapidly progressed to pneumonia with deterioration. Methods: To clarify the host inflammatory response in psittacosis, we analyzed clinical parameters, and compared transcriptomic data, concentrations of plasma cytokines/chemokines, and changes of immune cell populations in 17 laboratory-confirmed psittacosis cases, namely, 8 pneumonia and 9 bronchitis individuals, in order to assess transcriptomic profiles and pro-inflammatory responses. Results: Psittacosis cases with pneumonia were found to have abnormal routine blood indices, liver damage, and unilateral pulmonary high-attenuation consolidation. Transcriptome sequencing revealed markedly elevated expression of several pro-inflammatory genes, especially interleukins and chemokines. A multiplex-biometric immunoassay showed that pneumonia cases had higher levels of serum cytokines (G-CSF, IL-2, IL-6, IL-10, IL-18, IP-10, MCP-3, and TNF-α) than bronchitis cases. Increases in activated neutrophils and decreases in the number of lymphocytes were also observed in pneumonia cases. Conclusion: We identified a number of plasma biomarkers distinct to C. psittaci pneumonia and a variety of cytokines elevated with immunopathogenic potential likely inducing an inflammatory milieu and acceleration of the disease progression of psittaci pneumonia. This enhances our understanding of inflammatory responses and changes in vascular endothelial markers in psittacosis with heterogeneous symptoms and should prove helpful for developing both preventative and therapeutic strategies.

Temporal Proteomic and Phosphoproteomic Analysis of EV-A71-Infected Human Cells.

Human enterovirus A71 (EV-A71), a member of the Picornaviridae family, is one of the main etiological viruses that lead to hand, foot, and mouth disease (HFMD). We utilized a multiplex tandem mass tag-based quantitative proteomic technique to monitor the alternation of the whole cell proteome and phosphoproteome of human rhabdomyosarcoma cells over the course of EV-A71 infection. We successfully quantified more than 7000 host proteins and 17,000 phosphosites, of which 80 proteins and nearly 1700 phosphosites were significantly regulated upon viral infection. We found that Myc proto-oncogene protein level decreased significantly, benefiting EV-A71 replication. Multiple signaling pathways were regulated in phosphorylation events that converge for protein translation, cell cycle control, and cell survival. Numerous host factors targeted by virus proteins are phosphoproteins. These factors are involved in host translational initiation, unfolded protein response, endoplasmic reticulum stress, and stress granule formation, and their phosphorylation may play key roles in the virus life cycle. Notably, we identified three conserved phosphorylation sites on viral polyproteins that have not been previously reported. Our study provides valuable resources for a systematic understanding of the interaction between the host cells and the EV-A71 at the protein and the post-translational level.

An Integrative Transcriptomic Analysis Reveals EGFR Exon-19 E746-A750 Fragment Deletion Regulated miRNA, circRNA, mRNA and lncRNA Networks in Lung Carcinoma.

Introduction: Competing endogenous RNA (ceRNA) appears to be an important post-transcriptional manner that regulates gene expression through a miRNA-mediated mechanism. Mutations in exon-19 of EGFR were frequently observed in lung cancer genes, which were associated with EGFR activity and EGFR-targeted therapies. Methods: We explored the transcriptome regulated by mutation in EGFR exon-19 E746-A750 fragment via using a network modeling strategy. We applied transcriptome sequencing to detect the deletion process of EGFR exon-19 E746-A750 fragment. Bio-informatics analyses were used to predict the gene target pairs and explain their potential roles in tumorigenesis and progression of lung cancer. Results: We conducted an explorative lncRNA/miRNA/circRNA and mRNA expression study with two groups of lung adenocarcinoma tissues, including EGFR exon-19 E746-A750 deletion group and EGFR exon-19 wild-type group. Meanwhile, we screen out the hub genes related to the EGFR-19-D patient. Significant pathways and biological functions potentially regulated by the deregulated 128 non-coding genes were enriched. Conclusion: Our work provides an important theoretical, experimental and clinical foundation for further research on more effective targets for the diagnosis, therapy and prognosis of lung cancer.

Minimally invasive pedicle screw fixation, including the fractured vertebra, combined with percutaneous vertebroplasty for treatment of acute thoracolumbar osteoporotic compression fracture in middle-age and elderly individuals: A prospective clinical study.

ABSTRACT: To evaluate the feasibility, efficacy, and safety of minimally invasive pedicle screw (MIPS) fixation, including the fractured vertebra, combined with percutaneous vertebroplasty (PVP) for the treatment of acute thoracolumbar osteoporotic compression fracture in middle-age and elderly individuals.Between January 2016 and August 2019, a total of 30 patients, with a mean age of 69.4 years (range, 58-75 years), who experienced thoracic or lumbar fracture without neurological deficits, underwent the MIPS procedure combined with PVP. Preoperative and postoperative pain were assessed using a visual analog scale and Oswestry Disability Index. Cobb angles and anterior column height were measured on lateral radiographs before surgery and at 3 days, 1, 3, and 6 months, and 1 and 2 years at final follow-up after surgery.All patients underwent surgery successfully, with a mean follow-up of 18.2 ±â€Š5.7 months (range, 12-45 months). Mean preoperative visual analog scale score decreased from 7.3 ±â€Š2.2 to 1.4 ±â€Š0.3 at the final follow-up (P < .05). Mean preoperative Oswestry Disability Index decreased from 84.2 ±â€Š10.3 to 18.8 ±â€Š7.5 (P < .05) at the final follow-up. The Kyphosis angle of operative segment was improved from preoperative (21.38 ±â€Š1.68)° to (4.01 ±â€Š1.38)° 3 days postoperatively and (5.02 ±â€Š1.09)° at final follow-up (P < .05). The anterior vertebral height was improved from preoperative (49.86 ±â€Š6.50)% to (94.01 ±â€Š1.79)% 3 days postoperatively and (91.80 ±â€Š1.88)% at final follow-up (P < .05). No significant changes in vertebral body height restoration were observed during 2 years of follow-up after surgery. In addition, there were no instrumentation failures or complications in any of the patients.MIPS, including the fractured vertebra, combined with PVP, was a reliable and safe procedure, with satisfactory clinical and radiological results for the treatment of thoracolumbar osteoporotic compression fracture in patients without neurological deficits.