Comparative study of imaging and pathology of primary mucinous adenocarcinoma with different imaging manifestations.

BACKGROUND: Pulmonary mucinous adenocarcinoma is a special type of lung cancer. Its imaging manifestations are diverse, which brings challenges to clinical diagnosis. However, its formation mechanism is unclear. OBJECTIVE: The objective of this study is to analyse the relevant mechanisms of the formation of pulmonary mucinous adenocarcinoma by observing its different imaging and pathological manifestations. DATA AND METHODS: Retrospective analysis was conducted on imaging manifestations and pathological data of 103 patients with pulmonary mucinous adenocarcinoma confirmed intraoperatively or pathologically. RESULTS: Forty-three patients had pulmonary mucinous adenocarcinoma with a solitary nodule/mass, 41 patients with localized pneumonia and 19 patients with diffuse pneumonia. Their CT manifestations included 'falling snowflake sign', ground-glass opacity close to the heart, vacuous signs/honeycombing and withered tree branches. Under the microscope, all the three types of pulmonary mucinous adenocarcinoma had visibly formed mucus lakes but were made of tumour cells with totally different shapes, which included the goblet-like shape (tall column-like shape) and quasi-circular shape. Tall column-shaped tumour cells were negative or weakly positive for thyroid transcription factor-1 (TTF-1) and strongly positive for ALK mutation, whereas quasi-circular tumour cells were positive for TTF-1 and less positive for ALK mutation. CONCLUSION: The different imaging manifestations of mucinous adenocarcinoma are possibly due to the different amounts or viscosity of mucus produced, and the mechanisms of its formation may include (1) tumour cells in different shapes have different abilities to produce mucus; (2) tumours in different stages produce different amounts or viscosity of mucus; and (3) the TTF-1 and ALK genes affect the production of mucus.

Indirubin-3'-monoxime exhibits potent antiviral and anti-inflammatory effects against human adenoviruses in vitro and in vivo.

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3'-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.

Generation and characterization of the iPS cell line (SYSUSHi001-A) derived from the peripheral blood mononuclear cells (PBMCs) of a 33-year-old patient with acute myeloid leukemia (AML).

We successfully developed an induced pluripotent stem cell (iPSC) line, SYSUSHi001-A, from the peripheral blood mononuclear cells (PBMC) of a patient with Acute Myeloid Leukemia, harboring two genetic mutations (XPO1: c.591-4_591-3dupTT; PALB2: c.3296C > T; p.T1099M). This iPSC line was facilitated through the use of episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, and human miR-302. The SYSUSHi001-A iPSC line exhibited characteristic embryonic stem cell-like morphology, maintained the XPO1 and PALB2 mutations, expressed key pluripotency markers, preserved a normal karyotype (46, XY), and demonstrated the ability to differentiate into cells from all three germ layers in vitro.

Immune-related adverse events in non-small cell lung cancer: Occurrence, mechanisms and therapeutic strategies.

The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non-small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune-related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ-specific irAEs in patients with NSCLC and provide an in-depth analysis of recent advancements in understanding the mechanisms driving ICI-induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

The radiological characteristics, tertiary lymphoid structures, and survival status associated with EGFR mutation in patients with subsolid nodules like stage I-II LUAD.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules. MATERIALS AND METHODS: The inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis. RESULTS: Finally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037). CONCLUSIONS: In early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation.

[Virtual preoperative planning and 3D-printed templates for pre-contoured plates in treatment of acetabular posterior wall fractures].

OBJECTIVE: To evaluate the feasibility and accuracy of virtual preoperative planning and 3D-printed templates for pre-contoured plates for the treatment of posterior wall fractures of the acetabulum. METHODS: A retrospective analysis of 29 patients with posterior acetabular wall fractures treated between August 2017 and March 2021 were divided into 2 groups based on whether to use preoperative virtual planning and 3D printed template. In 3D-printing group, there were 14 patients, including 10 males and 4 females； aged from 21 to 53 years old；CT-based virtual surgical planning was done using Mimics and 3-Matic software and 3D-printed templates for pre-contoured plates were adopted. In conventional group, there were 15 patients, including 10 males and 5 females；aged from 19 to 55 years old；conventional method of intra-operative contouring to adapt the plate to the fracture region was adopted. Blood loss, surgical time, radiographic quality of reduction, and hip function were compared between groups. RESULTS: The difference in operation time and intraoperative blood loss was significant（P<0.05）. Twenty-three patients were followed up from 12 to 30 months, and the fractures in both groups healed with a healing time of 3 to 6 months. At the last follow-up, the Merle d'Aubign-Postel score of the 3D printed group was lower than that of the conventional group（P<0.05）, with no significant differences in walking ability, hip mobility and total score（P>0.05）. In 3D printing group, 6 cases were excellent, 5 cases were good, 3 cases were fair；in conventional group, 5 cases were excellent, 5 cases were good, 4 cases were fair, 1 case was worse；no significant difference between two groups（P>0.05）. CONCLUSION: Virtual preoperative planning and 3D-printed templates for pre-contoured plates can reduce operative time and the blood loss of surgery, improve the quality of reduction. This method is efficient, accurate and reliable to treat acetabular posterior wall fractures.

Rapid on-site evaluation improves diagnostic performance of fine-needle aspiration cytology for salivary lesions: Comparison of data from two cancer centers in southern China.

OBJECTIVES: To evaluate the diagnostic performance of Milan system for reporting salivary gland cytopathology (MSRSGC) in two southern China tertiary cancer centers and investigate the impact of rapid on-site evaluation (ROSE) on FNAC performance. MATERIALS AND METHODS: Five hundred and forty-nine patients who underwent FNAC for salivary lesions with surgical follow-up from two centers were enrolled in this retrospective cohort study. All slides were recategorized using MSRSGC after consensus on diagnostic criteria for each category. The diagnostic performance of FNAC for salivary lesions was evaluated and compared and the impact of ROSE on FNAC performance was analyzed. RESULTS: The distribution of cases per category based on the MSRSGC criteria in the whole series was as followed: ND 49 (8.9%), NN 76 (14.4%), BN 262 (47.7%), AUS 20 (3.6%), SUMP 43 (7.8%), SM 21 (3.8%), M 78 (14.2%). The SUMC series had significantly more ND distributions than JXCH did (16.2% vs. 0, p = .000). Risk of malignancy for each category in the total series was as followed: 42.9% for ND, 9.2% for NN, 3.8% for BN, 30.0% for AUS, 23.3% for SUMP, 81.0% for SM, and 94.9% for M. When ND and AUS/SUMP were excluded, the sensitivity, specificity, PPV, NPV, and accuracy were 84.0%, 97.1%, 89.9%, 95.1%, and 94.0%, respectively; sensitivity, specificity, PPV, NPV, and accuracy were comparable between the two centers. CONCLUSIONS: FNAC using MSRSGC provides a good tool in preoperative evaluation for salivary lesions in southern China. ROSE improves its diagnostic performance by reducing the ratio of the ND category.

Cryptococcus gattii strains with a high phagocytosis phenotype by macrophages display high pathogenicity at the early stage of infection in vivo.

Cryptococcus gattii (Cg) is a facultative intracellular pathogen that can replicate and disseminate in mammalian macrophages, causing life-threatening cryptococcosis in both immunocompetent and immunocompromised individuals. Cryptococcus-macrophage interactions are crucial for cryptococcosis prognosis. However, the relationship between Cg pathogenicity and phagocytosis by macrophages has not yet been investigated in depth. In this study, a series of in vitro and in vivo experiments were conducted to investigate the interaction between macrophages and Cg. Flow cytometry was used to detect the phagocytic phenotypes of the Cg strains within macrophages. Scanning electron microscopy, transmission electron microscopy, and immunofluorescence were used to observe phagocytosis and proliferation, respectively. Survival and lung fungal burden tests were also performed. Our results show that Cg cells display different phagocytosis phenotypes, which are independent of the molecular type. Within macrophages, the high phagocytosis phenotype (HP) strains obtain higher intracellular proliferation than the low phagocytosis phenotype (LP) strains. At the early stage of infection in vivo, HP-inducing permissive granulomas within the lungs seldom limit the dissemination of cryptococci. In addition, HP strains could inhibit the formation of M1-type macrophages, proliferate intracellularly and disseminate extracellularly, and cause hypoxia induced by mucus and acidic polysaccharide accumulation in pulmonary alveoli much earlier than LP strains in vivo. Our work reveals that Cg displays diverse interactions with macrophages, which may enhance our understanding of the pathogenicity of this life-threatening pathogen.

Osthole inhibits GSK-3ß/AMPK/mTOR pathway-controlled glycolysis and increases radiosensitivity of subcutaneous transplanted hepatocellular carcinoma in nude mice.

PURPOSE: Osthole possesses anti-tumor activities. However, whether osthole can have a radiosensitization effect on hepatic cancer remains unclear. Here, an HCC-LM3 cells-inoculated subcutaneous transplanted tumor was adopted to explore the effect of osthole. METHODS: The tumor-bearing mice were treated with 100 mg/kg osthole for 12 days, 4 Gy irradiation twice, or their combination. The tumor volume and weight, lactic acid content, glycolytic enzyme activities, and protein expression of glycogen synthase kinase 3ß (GSK-3ß), p­GSK-3ß, mammalian target of rapamycin (mTOR), p­mTOR, AMP-activated protein kinase (AMPK), p­AMPK, glucose transporter 1/3, and pyruvate kinase M2 were determined. The GSK-3ß-overexpressed HCC-LM3 or SK-Hep­1 cell models were also adopted to verify the effects of osthole on expression of these proteins. RESULTS: The tumor volume and weight, lactic acid content, and glycolytic enzyme activities in tumor tissues were lower in the osthole + radiation group than in the radiation group. Moreover, osthole could reverse the radiation-induced increments of p­GSK-3ß/GSK-3ß and p­mTOR/mTOR protein ratios and the expression of glucose transporter 1/3 and pyruvate kinase M2 proteins in tumor tissues, and increase the protein ratio of p­AMPK/AMPK. The effects of osthole on these glycolysis-related proteins were also observed in GSK-3ß-overexpressed HCC-LM3 or SK-Hep­1 cell models. CONCLUSION: Osthole has a radiosensitizing effect on subcutaneous transplanted hepatocellular carcinoma, and its mechanism may be related to inhibition of GSK-3ß/AMPK/mTOR pathway-controlled glycolysis.

Circ_0004140 promotes lung adenocarcinoma progression by upregulating NOVA2 via sponging miR-330-5p.

BACKGROUND: Circular RNAs (circRNAs) play a significant role in the tumorigenesis and progression of diverse human cancers, including lung adenocarcinoma. A previous study suggested that circ_0004140 expression was increased in lung adenocarcinoma cells. However, the molecular mechanism of circRNA circ_0004140 involved in lung adenocarcinoma is poorly defined. METHODS: Circ_0004140, microRNA-330-5p (miR-330-5p), and NOVA alternative splicing regulator 2 (NOVA2) expression were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, invasion, and angiogenesis ability were assessed using 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, transwell, and capillary-like network formation assays. Proliferating cell nuclear antigen (PCNA), cyclin D1, and NOVA2 protein levels were detected using Western blot assay. The interaction between miR-330-5p and circ_0004140 or NOVA2 was verified by dual-luciferase reporter assay. Xenograft tumor model was utilized to assess the role of circ_0004140 in tumor growth in vivo. RESULTS: Circ_0004140 was upregulated in lung adenocarcinoma tissues and cell lines. Circ_0004140 silencing suppressed cell proliferation, migration, invasion and tube formation ability, and triggered the apoptosis of lung adenocarcinoma cells. Circ_0004140 acted as a molecular sponge for miR-330-5p, and miR-330-5p silencing largely reversed circ_0004140 knockdown-induced effects in lung adenocarcinoma cells. NOVA2 was a target of miR-330-5p, and NOVA2 overexpression might largely overturn miR-330-5p overexpression-induced influences in lung adenocarcinoma cells. Circ_0004140 upregulated NOVA2 expression via sponging miR-330-5p in lung adenocarcinoma cells. Circ_0004140 silencing restrained xenograft tumor growth in vivo. CONCLUSION: Circ_0004140 knockdown might suppress the malignant biological behaviors of lung adenocarcinoma cells via miR-330-5p-dependent regulation of NOVA2.

Computed tomography (CT) characteristics and pathologic basis of ciliated muconodular papillary tumors of the lung.

Background: Ciliated muconodular papillary tumor (CMPT) is a rare pulmonary tumor with papillary architecture. Most studies have focused on the clinicopathological features of CMPT, while computed tomography (CT) characteristics have rarely been systematically described. Methods: A cohort of 27 patients with surgically resected CMPT were identified. Clinical and demographic features were recorded. Preoperative CT images of the CMPTs and the corresponding histopathological basis were also retrospectively analyzed. Results: All of the tumors appeared as solitary nodules. Pure ground glass, part-solid nodules and solid nodules were detected in 2/27 (7.4%), 17/27 (63.0%), and 8/27 (29.6%) patients, respectively. Twenty-one tumors (77.8%) were located in the lower lobe. The average tumor size was 1.21±0.74 (range, 0.44-3.46) cm. Eighteen (66.7%) of the 27 patients had tumors with well-defined margins and lobulated contours. Fifteen patients (55.6%) had air bronchograms in the tumor, and 19 patients (70.4%) had air-containing space. There were two patients whose tumor size was enlarged and accompanied by an increase in solid components, and one patient simply had an increase in tumor size at the preoperative follow-up duration. Notably, one patient with solid tumor components was finally diagnosed with CMPT accompanied by adenocarcinoma. Conclusions: CMPTs of the lung mostly manifest as solitary, lobulated, well-defined tumors with air-containing spaces on CT and often occur in the periphery of the pulmonary lower lobe. When CT findings meet these criteria, the possibility of CMPT should be considered. Additionally, CMPT can coexist with adenocarcinoma. Further investigation will contribute significantly to the biological properties of CMPT and its relationship to the potential for malignant transformation.

A digital microfluidic platform coupled with colorimetric loop-mediated isothermal amplification for on-site visual diagnosis of multiple diseases.

Traditional diagnosis of infectious diseases relies on advanced analyzers in central hospitals, which is not sufficient for rapid control of epidemics, especially in resource-limited areas, raising the importance of the development of diagnostic systems for point-of-care testing (POCT). Here, we developed a simple and cost-effective digital microfluidic (DMF) platform in combination with colorimetric loop-mediated isothermal amplification (LAMP) for simple on-site diagnosis of diseases by the naked eye. The DMF chip contained four parallel units for the simultaneous detection of multiple genes and samples at a time. After amplification, the results were visualized by endpoint detection with concentrated dry neutral red on the chip. The whole process could be completed within 45 min and the on-chip LAMP reaction was shortened to 20 min. The analytical performance of this platform was evaluated by the detection of Enterocytozoon hepatopenaei, infectious hypodermal and hematopoietic necrosis virus, and white spot syndrome virus genes of shrimp. The DMF-LAMP assay showed a detection limit of 101 copies per µl for each target, exhibiting comparable sensitivity to the conventional LAMP assay but was more efficient. The sensitivity was also competitive with that of microfluidic-based LAMP assays using other POCT devices such as centrifugal discs regarding the detection of the same targets. Moreover, the proposed device possessed a simple chip structure and high flexibility to integrate multiplex analysis, which was beneficial for further widespread use in POCT. The practicability of the DMF-LAMP assay was verified by the testing of field shrimp. The result of the DMF-LAMP assay indicated a good agreement with the qPCR method, with Cohen's kappa values ranging from 0.91 to 1.00 depending on different targets. For the first time, an image processing method was established based on RGB analysis under different lighting conditions, and a universally adaptable positive threshold was determined regardless of lighting conditions. Paired with a smartphone, the objective analytical method was facile to implement in the field. Moreover, the DMF-LAMP system is easy to extend for a broad range of bioassays, with the advantages of low-cost, rapid detection, ease of use, good sensitivity, and easy readout.

Clinical characteristics and therapeutic effects of checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer.

BACKGROUND: With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects. METHODS: The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized. RESULTS: 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs. CONCLUSION: We found that glucocorticoid 1-2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.

Comparisons of lymphocytes profiles and inflammatory cytokines levels in blood of patients with differed severity of infection by human adenovirus type 7.

BACKGROUND: Human adenovirus (HAdV) infection outbreak causes community-acquired pneumonia. Cellular immune dysfunction and hypercytokinemia play important roles in the pathogenesis of adenovirus respiratory infection. Some soluble factors in peripheral blood can assist in judging the virus-induced disease severity. The expression levels of inflammatory cytokines differ among patients with different disease severity. However, whether and how HAdV-7 infection influences the composition of blood immune cells and serum cytokine levels in patients at different disease stages, as well as the diagnosis values of these parameters, have rarely been intensively studied. We aimed to investigate lymphocytes profiles and cytokines levels in blood of patients at different disease stages upon human adenovirus type 7 (HAdV-7) infections, and explored the diagnosis values of the investigated parameters. METHODS: Patients from two outbreaks of HAdV-7 in military of China were categorized into upper respiratory infection (URI) group, common pneumonia (CP) group and severe pneumonia (SP) group according to disease severity. Peripheral blood samples were subjected to routine laboratory tests, while flow cytometry and ELISA were used to measure the lymphocyte subsets and cytokines in blood, respectively. The receiver operating characteristic (ROC) curves were performed to examine the diagnostic of these blood parameters. RESULTS: Signs of imbalanced lymphocytes composition and hypercytokinemia were observed in HAdV-7-infected patients. The percentages of CD3+ T cells and NK cells were significantly decreased along with the aggravation of the disease, particularly for NK cells and CD4+ T cells. The neutrophil to lymphocyte ratio (NLR) increased significantly in patients with more severe disease. In addition, the levels of serum CXCL10, IL-2 and TNF-α were positively correlated with disease severity, while reduced levels of IFN-γ and IL-10 were found in SP patients. Furthermore, analysis of ROC showed that multiple parameters including the percentage of blood CD3+ cells and serum CXCL10 level could predict the progression of HAdV-7 infection. CONCLUSION: Imbalance of immune state with hypercytokinemia occurred during HAdV-7 infection. The percentages of blood immune cells such as CD3+ T cells and the levels of serum cytokines such as CXCL10 showed potential diagnosis values in HAdV-7 infection.

Osthole increases the radiosensitivity of hepatoma cells by inhibiting GSK-3ß/AMPK/mTOR pathway-controlled glycolysis.

Osthole is a natural coumarin substance that has an inhibitory effect on hepatic cancer, but its radiosensitization effect on hepatoma cells has not been reported. This study aimed to investigate the effect of osthole. Human HCC-LM3 and SK-Hep-1 hepatoma cells were used and treated with or without osthole, irradiation, or their combination; the cell survival, migration, colony formation, DNA damage repair, intracellular lactic acid content, and glycolysis-related glycogen synthase kinase-3ß (GSK-3ß), p-GSK-3ß, AMP-activated protein kinase (AMPK), p-AMPK, mammalian target of rapamycin (mTOR), p-mTOR, glucose transporter-1 (GLUT-1), GLUT-3, and pyruvate kinase isozyme type M2 (PKM2) protein expressions were determined. Compared with the irradiation group, the osthole plus irradiation group could further decrease the survival rate, migration, colony formation, and DNA damage repair of both hepatoma cells, indicating a synergistic effect of the combination treatment. Moreover, the combination of osthole and irradiation could decrease the content of intracellular lactic acid, ratios of intracellular p-GSK-3ß/GSK-3ß and p-mTOR/mTOR proteins, and expressions of intracellular GLUT-1/3 and PKM2 proteins, and increase the ratio of intracellular p-AMPK/AMPK proteins. Osthole can increase the radiosensitivity of hepatoma cells, and its radiosensitization mechanisms may be related to glycolytic inhibition by attenuating the GSK-3ß/AMPK/mTOR pathway.

HMMR associates with immune infiltrates and acts as a prognostic biomaker in lung adenocarcinoma.

BACKGROUND: To explore the expression of hyaluronan mediated motility receptor (HMMR) in lung adenocarcinoma (LUAD) and its relationship with clinicopathological features and tumor-infiltrating is not clear. METHODS: The expression of HMMR in Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA)-LUAD. TCGA was employed to examine the relationship between the clinicopathological characteristics and HMMR expression and the LUAD patients' prognosis. Tumor Immune Estimation Resource (TIMER)database was employed to analyze the relationship between immune infiltration and HMMR. Gene Set Enrichment Analysis was explored through gene enrichment. Gene Expression Omnibus (GEO) data and our hospital data were utilized to confirm the findings. RESULTS: The expression level of HMMR in lung adenocarcinoma tissue and cells was greater than that in the normal group, which was linked to clinical stage, smoking history, and recurrence, and could increase the progression or recurrence of LUAD. Patients in the pathological grade had a significant expression of HMMR in moderately differentiated LUAD tissues. In addition, HMMR has an impact on LUAD patients' overall survival rate [P = 9.5e-06; hazard ratio (HR) = 2]. The level of HMMR expression in LUAD was significantly linked to neutrophils, CD8+T, and CD4+T cells. TMB analysis showed that HMMR could also affect the tumor microenvironment in LUAD. HMMR might be employed as an independent predictive biomarker of LUAD, according to a multivariate COX regression analysis. The findings of GSEA analysis showed that the samples with high HMMR expression levels were rich in cell cycle, cell metabolism, and DNA replication. The analysis results of GSE31210 data are basically consistent with those of TCGA-LUAD. CONCLUSIONS: It is suggested that HMMR has an effect on the occurrence and development of lung adenocarcinoma. Besides, HMMR is also linked to the level of immune infiltration of neutrophils, CD8+T cells, and CD4+T cells and LUAD patients' prognosis. HMMR was suggested to be utilized as a biomarker or therapeutic target to judge the prognosis and immune infiltration of LUAD.

PIWI-interacting RNAs in cancer: Biogenesis, function, and clinical significance.

PIWI-interacting RNAs (piRNAs) are a less-studied class of small non-coding RNAs approximately 24-31 nucleotides in length. They express in germline and somatic cells and form complexes with PIWI proteins to exert regulatory effects. New studies show that piRNAs are aberrantly expressed in various cancers. In this review, we focus on those piRNAs that are associated with cancer hallmarks such as proliferation, invasion, and chemoresistance and discuss their potential as biomarkers for cancer diagnosis and prognosis.

Research Progress on the Microregulatory Mechanisms of Fertilization: A Review.

The process of fertilization includes sperm capacitation, hyperactivation, an acrosome reaction and the release of acrosome enzymes, membrane fusion and channel formation, the release of the sperm nucleus, and gamete fusion. This process is closely related to the shape and vitality of the sperm, acrosome enzyme release, and the zona pellucida structure of the egg, as well as the opening and closing of various ion (e.g., calcium) channels, the regulation of signaling pathways such as cyclic adenosine monophosphate-protein kinase A, the release of progesterone, and the coupling of G-proteins. The interaction among multiple factors and their precise regulation give rise to multiple cascading regulatory processes. Problems with any factor will affect the success rate of fertilization. Recent studies have shown that with rapid societal development, the incidence of male infertility is increasing and occurs at younger ages. According to World Health Organization statistics, 15% of couples of childbearing ages have infertility problems, of which 50% are caused by male factors. Additionally, the cause of infertility cannot be identified in as many as 60% to 75% of male infertility patients. In this article, we review the research progress on the microregulation of fertilization and mechanisms underlying this process to identify causes and develop novel prevention and treatment strategies for male infertility.

Consolidation radiographic morphology can be an indicator of the pathological basis and prognosis of partially solid nodules.

BACKGROUND: Part-solid nodules (PSNs) have gradually shifted to defining special clinical subtypes. Commonly, the solid portions of PSNs show various radiological morphologies, of which the corresponding pathological basis and prognosis are unclear. We conducted a radiological-pathological evaluation to determine the histopathologic basis of different consolidation radiographic morphologies related to prognosis. MATERIALS AND METHODS: A cohort of 275 patients with a surgical pathological diagnosis of lung adenocarcinoma were enrolled. Preoperative computed tomography (CT) images of the PSNs were recorded and assessed. A panel of 103 patients with complete pathological specimens was selected to examine the radiological-pathological associations, and follow-up was performed to identify the prognosis. RESULTS: Of the 275 patients, punctate consolidation was observed radiologically in 43/275 (15.7%), stripe consolidation in 68/275 (24.7%), and irregular consolidation in 164/275 (59.6%) patients. The radiological morphology of the solid components was significantly associated with the histopathological subtypes (P < 0.001). Visual punctate solid components on CT correlated with tertiary lymphoid structures, stripe solid components on CT correlated with fibrotic scar, and irregular solid components on CT correlated with invasion. PSNs with regular consolidation had a better prognosis than those with irregular consolidation. CONCLUSION: Radiological morphology of solid components in PSNs can indicate the pathological basis and is valuable for prognosis. In particular, irregular solid components in PSNs usually indicate serious invasive growth, which should be taken with caution during assessment.

The prognosis of different types of pleural tags based on radiologic-pathologic comparison.

OBJECTIVES: There are increasing numbers of studies of pleural tags (PTs). The purpose of this case series was to classify the PTs in patients with peripheral pulmonary adenocarcinoma based on radiologic-pathologic comparison and to study the prognosis. METHODS: The clinical, imaging, pathological and prognostic data of 161 patients with peripheral pulmonary adenocarcinoma in three hospitals were analyzed retrospectively. We classified PTs using computed tomography (CT) for pathologic comparison. RESULTS: According to the relationship between tumors and pleural on CT images, PTs were classified into four types: type 1, one or more linear pleural tag; type 2, one or more linear pleural tag with soft tissue component at the pleural end; type 3, one soft tissue cord-like pleural tag; type 4, directly abutting the visceral pleura, pulling or pushing the visceral pleura. In these PTs, the incidence of visceral pleural invasion (VPI) was high in type 2 (46.88%) and type 3 (56.41%) of PTs. Our prognostic analysis showed that micropapillary or solid histological subtype (HR = 5.766, 95% CI: 1.435-23.159, P = 0.014) and type 3 of PTs (HR = 11.058, 95% CI: 1.349-90.623, P = 0.025) were two independent risk factors for tumor progression. CONCLUSIONS: PT is a risk factor for poor prognosis in patients with peripheral pulmonary adenocarcinoma, the presence of which on CT images can remind us to provide patients with a more reasonable treatment.