Genetic variants in hypoxia-inducible factor pathway are associated with colorectal cancer risk and immune infiltration.

Hypoxia-inducible factor (HIF) pathway genes influence tumorigenesis and immune status. However, the associations between genetic variants in hypoxia-related genes and colorectal cancer risk and the immune status of hypoxia-associated genes in colorectal cancer have not been systematically characterized. The associations between genetic variants and colorectal cancer risk were evaluated in Chinese, Japanese and European populations using logistic regression analysis. The relationships between target genes and tumour immune infiltration were predicted by Tumour Immune Estimation Resource (TIMER). We found that rs34533650 in EPAS1 was associated with colorectal cancer risk (OR = 1.43, 95% CI = 1.20-1.70, P(FDR) = 8.35 × 10-4 ), and this finding was validated in two independent populations (Japanese: OR = 1.07, 95% CI = 1.01-1.15, p = 3.38 × 10-2 ; European: OR = 1.11, 95% CI = 1.03-1.19, p = 6.04 × 10-3 ). EPAS1-associated genes were enriched in immune-related pathways. In addition, we found that EPAS1 copy number variation (CNV) was associated with the degree of infiltration of immune cells and observed correlations between EPAS1 expression and immune cell infiltration levels in colorectal cancer. These results highlight that genetic variants of hypoxia-related genes play roles in colorectal cancer risk and provide new insight that EPAS1 might be a promising predictor of colorectal cancer susceptibility and immune status.

Exploratory Study of a New Technique of Pixelated Chromoendoscopy in the Diagnosis of Early Esophageal Cancer.

BACKGROUND: Chromoendoscopy is an effective method for early screening of esophageal cancer, but diagnosis can depend on subjective judgment. The study aimed to explore a new technique of pixelated chromoendoscopy in the diagnosis of early esophageal cancer. PATIENTS AND METHODS: The study included patients with symptoms of esophageal cancer who attended Jiangyin People's Hospital between January 2015 and July 2021. Chromoendoscopy was performed on each patient. The images then underwent digital analysis; the lesion area (the sensitive region) was pixelated by dividing it into the smallest image unit and the red, green, and blue color components. The diagnostic performance of pixelated chromoendoscopy was evaluated by calculating the area under the receiver operating characteristic. RESULTS: The study finally enrolled 86 patients (aged 51.34 ± 5.82 y), including 54 males and 32 females. Pathologic diagnosis identified 54 cases in the cancer group and 32 cases in the non-cancer group. Traditional judgment had a diagnostic sensitivity of 70.73% and specificity was 75.00%. Pixelated chromoendoscopy sensitivity was 80.49%, and specificity was 83.33%. The area under the receiver operating characteristic was 0.814, at a cutoff value of 0.625, indicating a good prediction effect. CONCLUSIONS: These results showed that pixelated chromoendoscopy might improve the rate of esophageal cancer diagnoses from early screening.

Genetic variants in RNA m5 C modification genes associated with survival and chemotherapy efficacy of colorectal cancer.

BACKGROUND: Colorectal cancer is one of the most common malignant digestive tract tumors with a poor prognosis. RNA 5-methylcytosine (m5 C) is an important posttranscriptional widespread modification involved in many biological processes. However, the association between genetic variations of m5 C modification genes and the prognostic value of colorectal cancer remains unclear. METHODS: We investigated the association between candidate single nucleotide polymorphisms (SNPs) in 13 m5 C modification genes and colorectal cancer overall survival (OS) after chemotherapy by the Cox regression model. The combined effect of selected SNPs on OS, progression-free survival (PFS), and disease control rate (DCR) was assessed by the number of risk alleles (NRA). The GTEx and TCGA database were used to perform expression qualitative trait locus (eQTL) analysis. RESULTS: We identified that two SNPs in YBX1 were associated with OS after chemotherapy (HR = 1.43, p = 0.001 for rs10890208; HR = 1.36, p = 0.025 for rs3862218). A striking dose-response effect between NRA and OS after chemotherapy was found (ptrend  = 0.002). The DCR of patients receiving oxaliplatin chemotherapy in the 3-4 NRA group was markedly reduced in comparison to that in the 0-2 NRA group (OR = 1.49, p = 0.036). Moreover, YBX1 mRNA expression was significantly overexpressed in tumor tissues (p < 0.05) in the TCGA database, and eQTL analysis demonstrated that the two SNPs were associated with YBX1 (p = 0.003 for rs10890208 and p = 0.024 for rs3862218). CONCLUSION: Our study indicates that genetic variants in m5 C modification genes may mediate changes in YBX1 mRNA levels and affect the chemotherapeutic efficacy of colorectal cancer patients.

FER-PCVT: Facial Expression Recognition with Patch-Convolutional Vision Transformer for Stroke Patients.

Early rehabilitation with the right intensity contributes to the physical recovery of stroke survivors. In clinical practice, physicians determine whether the training intensity is suitable for rehabilitation based on patients' narratives, training scores, and evaluation scales, which puts tremendous pressure on medical resources. In this study, a lightweight facial expression recognition algorithm is proposed to diagnose stroke patients' training motivations automatically. First, the properties of convolution are introduced into the Vision Transformer's structure, allowing the model to extract both local and global features of facial expressions. Second, the pyramid-shaped feature output mode in Convolutional Neural Networks is also introduced to reduce the model's parameters and calculation costs significantly. Moreover, a classifier that can better classify facial expressions of stroke patients is designed to improve performance further. We verified the proposed algorithm on the Real-world Affective Faces Database (RAF-DB), the Face Expression Recognition Plus Dataset (FER+), and a private dataset for stroke patients. Experiments show that the backbone network of the proposed algorithm achieves better performance than Pyramid Vision Transformer (PvT) and Convolutional Vision Transformer (CvT) with fewer parameters and Floating-point Operations Per Second (FLOPs). In addition, the algorithm reaches an 89.44% accuracy on the RAF-DB dataset, which is higher than other recent studies. In particular, it obtains an accuracy of 99.81% on the private dataset, with only 4.10M parameters.

Comprehensive plasma metabolomics and lipidomics of benign and malignant solitary pulmonary nodules.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are commonly found in imaging technologies, but are plagued by high false-positive rates. OBJECTIVE: We aimed to identify metabolic alterations in SPN etiology and diagnosis using less invasive plasma metabolomics and lipidomics. METHODS: In total, 1160 plasma samples were obtained from healthy volunteers (n = 280), benign SPNs (n = 157) and malignant SPNs (stage I, n = 723) patients enrolled from 5 independent centers. Gas chromatography-triple quadrupole mass spectrometry (GC‒MS) and liquid chromatography-Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometry (LC‒MS) were used to analyze the samples for untargeted metabolomics and lipidomics. RESULTS AND CONCLUSION: GC‒MS-based metabolomics revealed 1336 metabolic features, while LC‒MS-based lipidomics revealed 6088 and 2542 lipid features in the positive and negative ion modes, respectively. The metabolic and lipidic characteristics of healthy vs. benign or malignant SPNs exhibited substantial pattern differences. Of note, benign and malignant SPNs had no significant variations in circulating metabolic and lipidic markers and were validated in four other centers. This study demonstrates evidence of early metabolic alterations that can possibly distinguish SPNs from healthy controls, but not between benign and malignant SPNs.

Pralsetinib treatment for multiple RET fusions in lung adenocarcinoma: a case report.

Despite recent advances in treatments and knowledge of biomarkers, patients with metastatic lung cancer have a 5-year survival rate of 5%. Rearranged during transfection (RET) fusions occur in 1% to 2% of lung cancer patients. Pralsetinib has been used to treat non-small cell lung cancer with a single RET fusion; however, there have been no reports regarding its use in patients with multiple RET fusions. Genetic mutations in tumor tissues were tested using Amplification Refractory Mutation System-PCR and next-generation sequencing (NGS). Pleural fluids obtained from a male patient with non-small cell lung cancer were also used to detect genetic aberrations by NGS. Pleural fluid-based NGS revealed three RET rearrangements: CCDC6-RET (C2:R12), RET-NRG3 (R11:N3), and CCDC6-RET (C1:R12). All three rearrangements were targeted by pralsetinib, a RET fusion inhibitor. Pralsetinib drastically improved the patient's condition within 4 days, and a partial response was achieved 1 week after pralsetinib was administered. We report for the first time the important clinical observation of a patient with multiple RET fusions who was effectively treated with pralsetinib.

[Application of metabonomics examination in differential diagnosis of non-small cell lung cancer (NSCLC)].

Objective To explore the preliminary application of metabonomics in the qualitative diagnosis of non-small cell lung cancer (NSCLC). Methods According to the pathological type, 201 patients with NSCLC were divided into squamous cell carcinoma (SCC) group (n=71) and adenocarcinoma (AC) group (n=130). Immunohistochemistry was used to detect the expression of ki67, cytokeratin 5/6 (CK5/6) and CK7. Ultra-high performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to detect serum metabolomics. Results SCC group showed typical SCC structure; ki67 proliferation index was 21.9%; CK5/6 expression was positive; CK7 expression was negative or weakly positive. The typical adenoid structure was found in the AC group; the proliferation index of ki67 was 17.6%; CK7 was positive; and CK5/6 was negative or weakly positive. UPLC-Q/TOF-MS screened 28 different metabolites, of which 6 were the most significant ones: L-leucine, carnitine, C16 sphinganine, 13, 16, 19-docosatrienoic acie (DA), LysoPE (18:2/0:0), PC (20:4/P-16:0). These metabolites had good diagnostic value, among which L-Leucine had the highest specificity and LysoPE had the highest sensitivity. Conclusion Metabolomic analysis of lung SCC and AC provides a new index for the differential diagnosis of NSCLC.

Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer.

BACKGROUND: The murine double minute-2 gene (MDM2) was originally identified as predicting chemotherapy efficacy. However, little is known regarding the association between single nucleotide polymorphisms (SNPs) in the p53 signaling pathway and prognosis/chemotherapy sensitivity in colorectal cancer. METHODS: We analyzed the association between 111 SNPs in 22 p53 signaling pathway genes and both progression-free survival (PFS) and disease control rate (DCR) using Cox regression and logistics regression analysis. The false discovery rate method was used for correction of multiple testing. Secondary structure was predicted by RNAfold. Expression qualitative trait locus analysis and mRNA expression differences were assessed using the GTEx and TCGA databases. RESULTS: We found that the rs747828 C allele of TP73 was significantly associated with reduced PFS (HR = 1.64, 95% CI = 1.27-2.12, P = 2.00 × 10-4 ) in the additive model. In the stratified analysis, the rs747828 C allele was significantly associated with both reduced PFS (P = 1.40 × 10-3 ) and DCR (P = 1.82 × 10-2 ) in oxaliplatin-based chemotherapy. The secondary structure of TP73 was altered in response to different rs747828 genotypes. Although the rs747828 C allele was not associated with messenger RNA (mRNA) TP73 expression, it was significantly associated with increased mRNA TP73-AS1 expression levels in sigmoid tissues. TP73 mRNA was significantly overexpressed in tumor tissues compared to adjacent normal tissues (P = 2.36 × 10-19 ). CONCLUSION: Our findings indicate that functional genetic variants of TP73 mediate the response to chemotherapy in colorectal cancer.

Sinomenine inhibits proliferation, migration, invasion and promotes apoptosis of prostate cancer cells by regulation of miR-23a.

Background Prostate cancer is an extremely common disease in males, and the mortality of prostate cancer has been rising year by year. Sinomenine has been reported to exhibit anti-tumor effect on various cancers, but the function of Sinomenine in prostate cancer remains unclear. The study aimed to explore the effect of Sinomenine on proliferation, apoptosis, migration and invasion in prostate cancer cells. Methods PC3 cells were stimulated by different concentrations of Sinomenine, then cell proliferation, migration, invasion and apoptosis were examined by CCK-8, BrdU, Transwell and flow cytometry, respectively. Subsequently, miR-23a mimic and miR-23a inhibitor were transfected into PC3 and LNCaP cells, cell proliferation, apoptosis, migration and invasion were reassessed in these transfected cells. The related factors of cell cycle, apoptosis, metastasis and PI3K/AKT and JAK/STAT signal pathways were measured by western blot. Results Sinomenine significantly suppressed cell proliferation, promoted apoptosis and inhibited migration and invasion, as well as down-regulated Cyclin D1, CDK4, Bcl-2, MMP-2, MMP-9, Vimentin protein levels and up-regulated p16 and Bax protein levels in PC3 cells. Additionally, Sinomenine decreased the expression level of miR-23a, and overexpression of miR-23a reversed the effects of Sinomenine on cell proliferation, apoptosis, migration and invasion in PC3 and LNCaP cells. Further, Sinomenine inactivated PI3K/AKT and JAK/STAT signal pathways by regulation of miR-23a. Conclusions The data suggested that Sinomenine could suppress cell proliferation, migration, invasion, and promote apoptosis of prostate cancer cells through regulation of miR-23a. These findings might provide a possible strategy for the clinical treatment of prostate cancer.

Downregulation of microRNA-122 promotes proliferation, migration, and invasion of human hepatocellular carcinoma cells by activating epithelial-mesenchymal transition.

OBJECTIVE: To investigate the effects of microRNA-122 (miR-122) on proliferation, migration, and invasion in human hepatocellular carcinoma (HCC) cells by activating epithelial-mesenchymal transition (EMT) pathways. METHODS: miR-122 mimics, miR-122 inhibitors, relevant control oligonucleotides, and Wnt1 were transfected into HepG2 and huh7 cell lines which were then divided into six groups: miR-122 group, anti-miR-122 group, miR-negative control (NC) group, anti-miR-NC group, miR-122 + Wnt1 group, and miR-122 + vector group. The miR-122 expressions and mRNA expressions of Wnt1 and EMT-related genes (E-cadherin, vimentin, ß-cadherin, and N-cadherin) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression levels of Wnt1, E-cadherin, vimentin, ß-cadherin, and N-cadherin were measured by Western blot. Cell proliferation, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound-healing assay, and Transwell assay, respectively. RESULTS: Dual luciferase reporter gene results showed that Wnt1 is a direct target gene of miR-122 in both HepG2 and huh7 cell lines. Compared to miR-NC, anti-miR-NC, and miR-122 + Wnt1 groups, miR-122 expression was markedly higher in the miR-122 group and miR-122 + vector group, but was sharply decreased in anti-miR-122 group (both P<0.05), and the mRNA and protein levels of Wnt1, vimentin, ß-cadherin, and N-cadherin decreased significantly; also E-cadherin increased, and cell proliferation, migration, and invasion decreased in the miR-122 group and miR-122 + vector group (all P<0.05), but the situation was totally reversed in the anti-miR-122 group (all P<0.05). CONCLUSION: Downregulation of miR-122 promoted proliferation, migration, and invasion of human HCC cells by targeting Wnt1 and regulating Wnt/ß-catenin pathway which activated the EMT pathways.

Associations between polymorphisms of long non-coding RNA MEG3 and risk of colorectal cancer in Chinese.

Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), is involved in cancer development and metastasis. The objective of the present study was to evaluate whether common single nucleotide polymorphisms (SNPs) in MEG3 could be related with colorectal cancer risk in Chinese. We genotyped six tagSNPs of MEG3 in a colorectal cancer case-control study including 518 cases and 527 control subjects. Multivariate logistic regression analysis was applied to calculate adjusted odds ratios (ORs). We found that MEG3 rs7158663 AA genotype, but not GA genotype, had significant increased colorectal cancer risk, compared with GG genotype (OR = 1.96 and P = 0.006 for AA versus GG, and OR = 1.20 and P = 0.171 for GA versus GG). Further stratified analysis indicated that the increased risk was significantly correlated with individuals with age ≤ 60 and family history of cancer. However, there was no significant association between rs7158663 and colorectal tumor site and stage (P = 0.842 for tumor site, and P = 0.601 for tumor stage). These results demonstrate that genetic variants in MEG3 may contribute to the development and risk of colorectal cancer. Further studies are required to confirm these findings.

Hearing loss due to metastasis of gastric cancer to temporal bone: A case report.

Metastatic temporal bone tumors are rare, and tend to be asymptomatic. The clinical symptoms consist of aural discharge, bleeding, hearing loss and facial nerve paresis. The most common origin of the metastasis is breast cancer, and other sites of the primary tumor include the thyroid gland, brain, lungs, prostate and blood. Clinical reports of hearing loss due to gastric cancer metastatic to temporal bone are rare. In the present study, a case of gastric cancer metastasis to temporal bone without other organ involvement is described. The patient presented with the symptom of hearing loss, and the metastatic tumor was diagnosed by radiological imaging, including magnetic resonance imaging, computed tomography and bone scan.

[The Cross-sectional Study on the Influence Factors for Encrustation of Double J Stent in Patients with Urolithiasis].

OBJECTIVE: To study the influence factors for encrustation of double J stent in patients with urolithiasis. METHODS: In this study, there were 84 urolithiasis patients with double J stent included from February to July 2014 in our hospital. The encrustation on double J stent was evaluated by a PC stereo microscope. The nterrelated clinical data were obtained, then the factors which may affect the encrustation were studied by logistic regression analysis. RESULTS: The mean indwelling time was (17. 0±6. 0) d, and a thin encrustation formed on the stents for most cases [67/84(79. 8%)]. Compared with the cases who did not form a thin encrustation, those having a thin encrustation formation on the stent were younger [(44. 9±11. 5) vs. (54. 4±12. 6), P=0. 004]; The patients with proteinuria got a higher rate of encrustation [62/73(84. 9%) vs. 5/11 (45. 5%), P=0. 002]. The patients with urinary tract infection had a higher rate of encrustation [26/28(92. 9%) vs. 41/56(73. 2%), P 3. 035]. The patients with hematuriaalso got a higher rate of encrustation [67/80(83. 8%) vs. 0/4, P=0. 001]. Different sex, retention time,serum calcium,inorganic phosphorus, uric acid, urine pH,lithiasis component had no effects on encrustation (P>0. 05). Logistic regression analysis showed that age and proteinuria was retained as idependent correlated factors with encrustation (P<0. 05), while hematuria and urinary tract infections had a low ntensity correlation with encrustation (P>0. 05). CONCLUSION: For encrustation of double J stentin patients with urolithiasis, younger age, increased urinary protein, hematuria and infections are important risk-factors.

Simvastatin downregulates HER2 via upregulation of PEA3 to induce cell death in HER2-positive breast cancer cells.

Simvastatin is a widely used cholesterol-adjusting drug that selectively inhibits the 3-hyrdoxy-3-methylglutaryl-coenzyme A reductase, leading to decreased cholesterol biosynthesis. Notably, through this activity, simvastatin exerts antiproliferative and proapoptotic effects on various cancer cells, including non-small cell lung and breast cancer. Although statin-induced breast cancer cell death is nitric oxide inducible and arginase dependent, we report alternative mechanisms relative to the antitumor function of simvastatin in breast cancer cells. Simvastatin induced cell death in MDA-MB-361, SK-Ov3, and SKBR3, HER2-overexpressing cell lines, in both time- and dose-dependent manners, but did not exert cytotoxicity in MCF10A and MDA-MB-231, HER2 low/negative cell lines. The protein expression of HER2 decreased after the cells were treated with simvastatin; however, HER2 protein and mRNA stabilities were not changed. Furthermore, simvastatin inhibited the activity of the HER2 promoter. Simvastatin-induced cytotoxicity and promoter activity repression were reversed by mevalonate and GGPP, the immediate metabolic products of the acetyl CoA/3-hyrdoxy-3-methylglutaryl CoA reductase reaction and the isoprenoid of the mevalonate cascade, respectively. In addition, simvastatin treatment induced the expression of PEA3, which is a HER2 promoter inhibitor. The use of siRNA to downregulate expression of PEA3 inhibited the simvastin-induced HER2 repression and cell death. These findings provide alternative mechanisms for the antitumor effects of simvastatin, suggesting that simvastatin could also be used as a combination therapy with other chemotherapy agents in HER2-positive patients.

CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis.

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case-control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy-Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16-2.33; GA versus GG, OR = 1.42, 95% CI = 1.18-1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21-1.72). Furthermore, Egger's test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.

MDM2 SNP309 polymorphism and colorectal cancer risk: a meta-analysis.

MDM2 is a phosphoprotein that interacts with p53 and inhibits its activity. Recently, a T to G substitution (SNP309) in the promoter of MDM2 was identified and associated with increased MDM2 expression and a significantly earlier age of onset of several tumors, including colorectal cancer. Several studies evaluated the association between SNP309 and colorectal cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of association between MDM2 SNP309 and risk of colorectal cancer, we performed a meta-analysis of 3347 colorectal cancer cases and 3102 controls from eight published case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The results suggested that the variant genotype was associated with a significantly increased colorectal cancer risk (GT vs. TT: OR=1.19, 95% CI=1.06-1.35; p=0.005). In the stratified analyses, significantly increased risks were found among Asian populations (OR=1.28, 95% CI=1.10-1.50; p=0.002) and population-based studies (OR=1.18, 95% CI=1.03-1.34; p=0.016). Although some bias could not be eliminated, this meta-analysis suggested that the MDM2 SNP309 polymorphism is a low-penetrance risk factor for the development of colorectal cancer, particularly among Asians.