Substance P in the medial amygdala regulates aggressive behaviors in male mice.

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.

Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.

Discrimination of Liver Metastases of Digestive System Neuroendocrine Tumors From Neuroendocrine Carcinoma by Computed Tomography-Based Radiomics Analysis.

OBJECTIVE: The aim of the study is to investigate the value of computed tomography (CT) radiomics features to discriminate the liver metastases (LMs) of digestive system neuroendocrine tumors (NETs) from neuroendocrine carcinoma (NECs). METHODS: Ninety-nine patients with LMs of digestive system neuroendocrine neoplasms from 2 institutions were included. Radiomics features were extracted from the portal venous phase CT images by the Pyradiomics and then selected by using the t test, Pearson correlation analysis, and least absolute shrinkage and selection operator method. The radiomics score (Rad score) for each patient was constructed by linear combination of the selected radiomics features. The radiological model was constructed by radiological features using the multivariable logistic regression. Then, the combined model was constructed by combining Rad score and the radiological model into logistic regression. The performance of all models was evaluated by the receiver operating characteristic curves with the area under curve (AUC). RESULTS: In the radiological model, only the enhancement degree (odds ratio, 8.299; 95% confidence interval, 2.070-32.703; P = 0.003) was an independent predictor for discriminating the LMs of digestive system NETs from those of NECs. The combined model constructed by the Rad score in combination with the enhancement degree showed good discrimination performance, with AUCs of 0.893, 0.841, and 0.740 in the training, testing, and external validation groups, respectively. In addition, it performed better than radiological model in the training and testing groups (AUC, 0.893 vs 0.726; AUC, 0.841 vs 0.621). CONCLUSIONS: The CT radiomics might be useful for discrimination LMs of digestive system NECs from NETs.

A Nucleus Accumbens Tac1 Neural Circuit Regulates Avoidance Responses to Aversive Stimuli.

Neural circuits that control aversion are essential for motivational regulation and survival in animals. The nucleus accumbens (NAc) plays an important role in predicting aversive events and translating motivations into actions. However, the NAc circuits that mediate aversive behaviors remain elusive. Here, we report that tachykinin precursor 1 (Tac1) neurons in the NAc medial shell regulate avoidance responses to aversive stimuli. We show that NAcTac1 neurons project to the lateral hypothalamic area (LH) and that the NAcTac1→LH pathway contributes to avoidance responses. Moreover, the medial prefrontal cortex (mPFC) sends excitatory inputs to the NAc, and this circuit is involved in the regulation of avoidance responses to aversive stimuli. Overall, our study reveals a discrete NAc Tac1 circuit that senses aversive stimuli and drives avoidance behaviors.

Dysregulation of AMPK-mTOR signaling leads to comorbid anxiety in Dip2a KO mice.

Autism is often comorbid with other psychiatric disorders. We have previously shown that Dip2a knockout (KO) induces autism-like behaviors in mice. However, the role of Dip2a in other psychiatric disorders remains unclear. In this paper, we revealed that Dip2a KO mice had comorbid anxiety. Dip2a KO led to a reduction in the dendritic length of cortical and hippocampal excitatory neurons. Molecular mechanism studies suggested that AMPK was overactivated and suppressed the mTOR cascade, contributing to defects in dendritic morphology. Deletion of Dip2a in adult-born hippocampal neurons (Dip2a conditional knockout (cKO)) increased susceptibility to anxiety upon acute stress exposure. Application of (2R,6R)-hydroxynorketamine (HNK), an inhibitor of mTOR, rescued anxiety-like behaviors in Dip2a KO and Dip2a cKO mice. In addition, 6 weeks of high-fat diet intake alleviated AMPK-mTOR signaling and attenuated the severity of anxiety in both Dip2a KO mice and Dip2a cKO mice. Taken together, these results reveal an unrecognized function of DIP2A in anxiety pathophysiology via regulation of AMPK-mTOR signaling.

Facilitating Hot Electron Injection from Graphene to Semiconductor by Rectifying Contact for Vis-NIR-Driven H2 O2 Production.

Solar-driven production of hydrogen peroxide (H2 O2 ), as an important industrial chemical oxidant with an extensive range of applications, from oxygen reduction is a sustainable alternative to mainstream anthraquinone oxidation and direct hydrogenation of dioxygen methods. The efficiency of solar to hydrogen peroxide over semiconductor-based photocatalysts is still largely limited by the narrow light absorption to visible light. Here, the authors proposed and demonstrate the proof-of-concept application of light-generated hot electrons in a graphene/semiconductor (exemplified with widely used TiO2 ) dyad to largely extend visible light spectra up to 800 nm for efficient H2 O2 production. The well-designed graphene/semiconductor heterojunction has a rectifying interface with a zero barrier for the hot electron injection, largely boosting excited hot electrons with an average lifetime of ≈0.5 ps into charge carriers with a long fluorescent lifetime (4.0 ns) for subsequent H2 O2 production. The optimized dyadic photocatalyst can provide an H2 O2 yield of 0.67 mm g-1  h-1 under visible light irradiation (λ ≥ 400 nm), which is 20 times of the state-of-the-art noble-metal-free titanium oxide-based photocatalyst, and even achieves an H2 O2 yield of 0.14 mm g-1  h-1 upon photoexcitation by near-infrared-region light (≈800 nm).

microRNA-200c-3p suppresses proliferation and invasion of nephroblastoma cells by targeting EP300 and inactivating the AKT/FOXO1/p27 pathway.

miR-200c-3p is aberrantly expressed in numerous cancers, but its underlying mechanisms in nephroblastoma are unknown. In our study, the differentially regulated miRNAs between the nephroblastoma tissues and adjacent non-neoplastic renal tissues were screened based on microarray analysis. The miR-200c-3p expression in nephroblastoma tissues and cells was detected by qRT-PCR. Then, the effects of miR-200c-3p mimic or inhibitor on cell proliferation, invasion, and migration were evaluated by CCK-8 assay, plate colony formation assay, soft agar assay, Transwell, and wound-healing assay in SK-NEP-1 and G401 cells. Afterward, the target gene of miR-200c-3p was predicted by TarBase, miRTarBase, miRDB softwares, and then verified by dual-luciferase reporter gene assay. The in vivo effects of miR-200c-3p on pathological changes and tumor volume were investigated in tumor xenograft mice by H&E staining and in vivo fluorescence imaging. ChIP assay was used to evaluate the relationship between histone acetyltransferase E1A-binding protein p300 (EP300) and P27, and the relationship of the role of miR-200c-3p in nephroblastoma and the AKT/FOXO1/p27 signaling pathways was evaluated by western blotting. Our study shows that miR-200c-3p was downregulated in nephroblastoma tissues and cells, and EP300 was a target gene of miR-200c-3p. Furthermore, miR-200c-3p mimic decreased cell proliferation and inhibited cell migration and invasion in nephroblastoma. Mechanistically, miR-200c-3p could inhibit p-AKT activity and enhance p-FOXO1 and p27 expression. Notably, the transcription factor P27 could bind to the EP300 promoter. This study demonstrates a new approach to treat nephroblastoma.

Soluble Triggering Receptors Expressed on Myeloid Cells-1 as a Neonatal Ventilator-Associated Pneumonia Biomarker.

BACKGROUND: Neonatal ventilator-associated pneumonia (NVAP) is one of the main infections acquired in hospitals, and soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) are a TREM-1 subtype that can be released into the blood or bodily fluids during an infection. METHODS: The patients included in the present study were divided into three groups: the NVAP group, the first control group, and the second control group (n = 20, each). Children requiring respiratory treatment were assigned to the NVAP group, newborns who received mechanical ventilation and had neonatal respiratory distress syndrome were assigned to the first control group, and newborns with normal X-ray and electrocardiogram results but no non-pulmonary infection was assigned to the second control group. The blood and bronchoalveolar lavage fluid (BALF) sTREM-1 levels in all newborns were analyzed. RESULTS: The acute-phase blood and BALF sTREM-1 levels were significantly higher in the NVAP group than in the first control group, and the blood sTREM-1 expression level was lower in the second control group than in the NVAP group. CONCLUSION: The present results suggest that sTREM-1 might be a useful biomarker for NVAP prediction in the Department of Pediatrics.

A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice.

It has been reported that Netrin-1 is involved in neuroprotection following injury to the central nervous system. However, the minimal functional domain of Netrin-1 which can preserve the neuroprotection but avoid the major side effects of Netrin remains elusive. Here, we investigated the neuroprotective effect of a peptide E1 derived from Netrin-1's EGF3 domain (residues 407-422). We found that it interacts with deleted colorectal carcinoma (DCC) to activate focal adhesion kinase phosphorylation exhibiting neuroprotection. The administration of the peptide E1 was able to improve functional recovery through reduced apoptosis in an experimental murine model of intracerebral hemorrhage (ICH). In summary, we reveal a functional sequence of Netrin-1 that is involved in the recovery process after ICH and identify a candidate peptide for the treatment of ICH.

DIP2A is involved in SOD-mediated antioxidative reactions in murine brain.

Autism spectrum disorders (ASDs) are highly associated with oxidative stress. We have recently shown that Disconnected-interacting protein homolog 2 A (DIP2A) functions in ASD pathophysiology by regulating cortactin acetylation for spine development and synaptic transmission. However, its role is not fully understood in the context of its abundant expression in mitochondria. In this paper, we found that DIP2A was involved in superoxide dismutase (SOD)-mediated antioxidative reactions. In mice, DIP2A knockout inhibited SOD activity and increased reactive oxygen species (ROS) levels in the cerebral cortex. In vitro gain-of-function experiments further confirmed the positive role of DIP2A in scavenging ROS upon oxidative stress. Moreover, DIP2A knockout caused irregular mitochondrial morphology in the cerebral cortex and impaired mitochondrial metabolism with an over consumption of lipids for energy supply. Taken together, these results revealed unrecognized functions of DIP2A in antioxidative protection, providing another possible explanation for DIP2A-mediated ASD pathophysiology.

Nucleus Accumbens Tac1-Expressing Neurons Mediate Stress-Induced Anhedonia-like Behavior in Mice.

Major depressive disorder (MDD) presents with two primary symptoms: depressed mood and anhedonia, which suggests that distinct neuronal circuits may regulate MDD. However, the underlying circuits of these individual symptoms linked to depression remain elusive. Herein, we identify a discrete circuit of tachykinin precursor 1 (Tac1)-expressing neurons in the nucleus accumbens (NAc) lateral shell, which project to ventral pallidum and contribute to stress-induced anhedonia-like behavior. Selective inhibition and activation of Tac1NAc neurons bidirectionally modulate stress susceptibility, revealing that Tac1 neurons in the NAc are critical for regulating anhedonia-like behaviors. We find that a subpopulation of VP neurons receives inhibitory inputs from Tac1NAc neurons and exhibits decreased excitability in susceptible mice. Furthermore, the inhibition of the neurokinin 1 receptor promotes susceptibility to social stress. Overall, our study reveals a discrete circuit regulating anhedonia-like behavior in mice.

Alpha-Fetoprotein Regulates the Expression of Immune-Related Proteins through the NF-κB (P65) Pathway in Hepatocellular Carcinoma Cells.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) is poor, with 60% to 70% of patients developing recurrence and metastasis within five years of radical resection. Alpha-fetoprotein (AFP) plays a significant role in predicting the recurrence and metastasis of HCC after surgery. However, its role in modulating tumor immunity has not been investigated. Our objective was to examine the effect of AFP on the expression of B7 family and activation of the NF-κB (P65) pathway in HCC. METHODS: We generated human hepatoma SMMC-7721 cell lines with or without recombinant AFP transfection (AFPup and control groups). Colony formation assay, Transwell invasion assay, and wound healing assay were used to detect the function of AFP. Liver cancer xenografts were made in BALB/c nude male mice (N = 6 per group). After 28 days of inoculation, the expression of immune genes in the HCC tissues, including PD-L (B7-H1), B7-H3, B7-H4, and P65, was evaluated by quantitative real-time PCR (qPCR) and western blot. In addition, immunofluorescence was used to determine the subcellular localization of the P65 protein, a key factor in the NF-κB pathway. An online HCC patients' dataset was also used to detect the connection between AFP and P65. RESULTS: Overexpression of AFP could enhance proliferation, invasion, and migration of HCC cells. Both qPCR and western blot results demonstrated that the expressions of PD-L1, B7-H4, and P65 were significantly higher in the AFP group compared to the controls (P < 0.05). Immunofluorescence results indicated that the majority of the P65 protein was located in the cytoplasm in the control group but was translocated to the nucleus in the AFPup group. The Spearman correlation coefficient confirms that AFP has a positive correlation with P65 in HCC patients (R = 0.33, P=0.05). CONCLUSION: AFP could enhance proliferation, invasion, and migration in HCC cells. The upregulation of AFP would increase the PD-L1 and B7-H4 mRNA and protein expression in HCC tissues through the upregulation and activation of the P65 protein.

Integrative Analysis of Siglec-15 mRNA in Human Cancers Based on Data Mining.

Objective: Cancer is expected to be the leading cause of death worldwide within the 21st century and is the single most important obstacle to extending life expectancy. Unfortunately, the most effective approach to combating cancers remains a complex and unsolved problem. Siglec-15 is a member of the Siglec family and plays a conserved regulatory role in the immune system of vertebrates. Previous studies on Siglec-15 have focused on its function in osteoclast regulation. The purpose of this study was to explore the significance of Siglec-15 mRNA in human cancer mainly based on information obtained from online databases. Method: Data were collected from several online databases. Serial analysis of gene expression (SAGE) and Virtual Northern, UALCAN Database Analysis, Catalog of Somatic Mutations in Cancer (COSMIC) analysis, the cBio cancer genomics portal, Cancer Regulome tools and data, Kaplan-Meier Plotter Analysis and the UCSC Xena website were used to analyze the data. Results: Compared with normal tissues, Siglec-15 up-regulation was widely observed in tuomrs. Differences in Siglec-15 expression were associated with different prognoses. Siglec-15 mutations are widely observed in tumors and interact with different genes in different cancer types. Conclusion: Siglec-15 is a potential target for the expansion of cancer immunotherapy.

Higher Serum C-Reactive Protein Levels in Catatonic Patients: A Comparison to Non-catatonic Patients and Healthy Controls.

Catatonia is a psychomotor syndrome defined by a constellation of predominantly motor symptoms. The aim of the present study was to determine whether recently admitted psychiatric patients with catatonia exhibited higher serum C-reactive protein (hs-CRP) levels compared to non-catatonic psychiatric patients and healthy controls (HCs). Recently admitted psychiatric patients were screened and evaluated for the catatonia syndrome using the Bush-Francis Catatonia Rating Scale and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The study sample was formed by 150 individuals (39 male and 111 female), including 51 catatonic patients, 55 non-catatonic patients, and 44 HCs. Serum hs-CRP levels were processed with the enzyme-linked immunosorbent assay. Serum levels of creatine kinase (CK), adrenocorticotropic hormone (ACTH), immunoglobulin G (IgG), complement component 3 (C3), and complement component 4 (C4) were also determined. There was a significantly higher percentage of patients with high inflammatory levels (hs-CRP > 3000ng/ml) in the catatonic (43.1%) than in the non-catatonic (14.5%) or HCs group (9.1%) (χ 2 =18.9, P < .001). Logistic regression showed that catatonic patients had significantly higher hs-CRP levels compared to non-catatonic patients even after controlling for other clinical and laboratory variables (OR = 3.52, P = .015, 95% CI 1.28-9.79). Multiple linear regression analysis revealed that log-transformed hs-CRP was independently predicted by body mass index and log-transformed C4, ACTH, and Cortisol in catatonic patients. Findings of the present study suggest that catatonia is specifically linked to a higher level of systemic inflammation, not merely attributable to the overall psychopathology, or alterations in the stress level and complement system.

Human antigen R-regulated mRNA metabolism promotes the cell motility of migrating mouse neurons.

Neocortex development during embryonic stages requires the precise control of mRNA metabolism. Human antigen R (HuR) is a well-studied mRNA-binding protein that regulates mRNA metabolism, and it is highly expressed in the neocortex during developmental stages. Deletion of HuR does not impair neural progenitor cell proliferation or differentiation, but it disturbs the laminar structure of the neocortex. We report that HuR is expressed in postmitotic projection neurons during mouse brain development. Specifically, depletion of HuR in these neurons led to a mislocalization of CDP+ neurons in deeper layers of the cortex. Time-lapse microscopy showed that HuR was required for the promotion of cell motility in migrating neurons. PCR array identified profilin 1 (Pfn1) mRNA as a major binding partner of HuR in neurons. HuR positively mediated the stability of Pfn1 mRNA and influenced actin polymerization. Overexpression of Pfn1 successfully rescued the migration defects of HuR-deleted neurons. Our data reveal a post-transcriptional mechanism that maintains actin dynamics during neuronal migration.

KCNN4 promotes invasion and metastasis through the MAPK/ERK pathway in hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is one of the most common malignancies in the world, and is well-known for its bad prognosis. Potassium calcium-activated channel subfamily N member 4 (KCNN4) is a type of intermediate conductance calcium-activated potassium channel, and increasing evidence suggests that KCNN4 contributes to the regulation of invasion and metastasis in a number of cancers. However, its clinical significance and biological function remain unclear in the HCC disease process. In this study, the expression levels of KCNN4 in 86 HCC samples were compared with corresponding paracancerous tissues. sh-RNA was used to reduce the expression of KCNN4 in Hep3B HCC cells in vitro; this was confirmed by Real time-PCR and western blotting. Wound healing, transwell assays and high content analysis were performed to investigate the tumor-promoting characteristics of KCNN4 in Hep3B HCC cells. As results, KCNN4 expression was significantly associated with preoperative serum alpha-fetoprotein level (p=0.038) and TNM stage (p=0.039). Additionally, patients with high KCNN4 amplification in HCC tissue exhibited shorter disease-free survival, whereas there was no statistical significance between KCNN4 amplification and overall survival. Wound healing and transwell assays showed that knockdown of KCNN4 expression could reduce migration and invasion abilities of HCC cells. High content analysis result showed that down-regulated KCNN4 could inhibit the ability of HCC cell proliferation. The mitogen-activated protein kinase (MAPK) pathway is active in cell proliferation, differentiation, migration, senescence, and apoptosis. Matrix metallopeptidase 9 and extracellular signal regulated kinase 1/2 (ERK1/2) were important biomarkers of MAPK/ERK pathway, knockdown of KCNN4 reduced the expression of MMP9 and ERK1/2. These findings showed that KCNN4 promotes HCC invasion and metastasis through the MAPK/ERK pathway.

Clinical analysis of a case of neonatal exfoliative esophagitis in an 18-day-old neonate.

BACKGROUND: This study aims to provide guidance for clinical work through analysis of the clinical characteristics, endoscopic and pathological manifestations, diagnosis, and treatment of an 18-day-old neonate with exfoliative esophagitis. CASE PRESENTATION: The patient presented with vomiting but the parents did not pay too much attention. The pathological report revealed numerous fibrinous exudative necrotic, and inflammatory cells, as well as a small amount of squamous epithelium. Furthermore, milk allergy factors were considered. Conservative treatments, such as fasting, acid suppression, mucosal protection, parenteral nutrition, and the replacement of anti-allergic milk powder were given. Thereafter, endoscopic examination revealed that the patient returned to normal, and was discharged after 21 days. CONCLUSIONS: Exfoliative esophagitis has multiple causes; and has characteristic clinical and endoscopic manifestations. Endoscopic examination after 18 days presentation and conservative therapy revealed that the esophagus had returned to a normal appearance and the patient was discharged. Following discharge, the parents were advised to feed the patient ALFERE powder. Attention should be given to the timely detection of complications and corresponding treatment.

Autism candidate gene DIP2A regulates spine morphogenesis via acetylation of cortactin.

Dendritic spine development is crucial for the establishment of excitatory synaptic connectivity and functional neural circuits. Alterations in spine morphology and density have been associated with multiple neurological disorders. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. However, the role of DIP2A in the brain remains largely unknown. In this study, we found that deletion of Dip2a in mice induced defects in spine morphogenesis along with thin postsynaptic density (PSD), and reduced synaptic transmission of pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. Furthermore, Dip2a knockout (KO) mice exhibited autism-like behaviors, including excessive repetitive behaviors and defects in social novelty. Importantly, acetylation mimetic cortactin restored the impaired synaptic transmission and ameliorated repetitive behaviors in these mice. Altogether, our findings establish an initial link between DIP2A gene variations in autism spectrum disorder (ASD) and highlight the contribution of synaptic protein acetylation to synaptic processing.

Comparison and screening of different risk assessment models for deep vein thrombosis in patients with solid tumors.

To increase the detection rate of deep vein thrombosis (DVT) and to compare the predictive value of four different risk assessment scales (Caprini, Autar, Pauda, and Khorana scales) for DVT in patients with solid tumors by the receiver operating curve (ROC). A total of 361 patients with all kinds of malignant solid tumors, who accepted anti-tumor therapy in the cancer center between March 3, 2015 to April 13, 2018, were assigned to a group of 230 cases diagnosed with DVT and a control group of 131 cases without DVT. Data were recorded and summarized, and the predictive value of the above four risk assessment scales for DVT in solid tumor patients was compared based on the area under the ROC curve (AUC). The AUC values determined for the Caprini, Autar, Pauda, and Khorana scales were (0.631 ± 0.030), (0.686 ± 0.028), (0.654 ± 0.029), and (0.599 ± 0.032), respectively; maximum sensitivity, specificity, and Youden index were 80.9% for Khorana, 86.3% for Caprini, and 29.6% for Autar scale, respectively. We found no statistically significant differences in the AUC values between Autar and Caprini, Autar and Khorana, as well as Khorana and Pauda (p > 0.05). However, the AUC differences between Autar and Pauda, Caprini and Khorana, as well as Caprini and Pauda were statistically significant (p < 0.05). All four risk assessment models showed some value in the risk prediction of DVT in patients with solid tumors, but every model also exhibited its own restrictions; maximum sensitivity, specificity, and Youden index were 80.9% for Khorana, 86.3% for Caprini, and 29.6% for Autar scale, respectively. We confirmed that the detection rate can be improved by modifying the BMI cut-off value of the scale or by combining appropriate scales.

Research on circadian clock genes in non-small-cell lung carcinoma.

Circadian clock genes have become a hot topic in cancer research in recent years, and more and more studies are showing that clock genes are involved in regulating cell proliferation cycle and apoptosis of malignant tumors, neuroendocrine and immune function, and other processes. Lung cancer is a malignant tumor with increasing incidence worldwide. The pathogenesis of lung cancer is extremely complicated and includes genetic factors, living environment, and smoking, and the occurrence of lung cancer is related to the regulation of many oncogenes and tumor suppressor genes. But there are few studies on clock genes in lung cancer. Studies on clock genes may help to better understand the mechanism of lung cancer development for an improved treatment. The expressions of all 14 kinds of clock genes in adenocarcinoma (ADC) and squamous cell carcinoma (SCC), two main kinds of non-small-cell lung cancer (NSCLC), were studied based on integration and analysis of data from The Cancer Genome Atlas (TCGA) to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that overexpression of Cry2, BMAL1, and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis of ADC, and the expression of NPAS2 was associated with the time of patient survival. Additionally, the expression of Cry2 was related to TNM stage. In SCC, high expression of DEC1 was correlated with poor overall survival in patients and the expression of Timeless was associated with the time of patient survival. In NSCLC, circadian clock genes constitute cancer circadian rhythm by interacting with each other, showing that asynchrony with normal tissues, which collectively controlling the occurrence and development of NSCLC.