Whole-transcriptome defines novel glucose metabolic subtypes in colorectal cancer.

Colorectal cancer (CRC) is the most prevalent malignancy of the digestive system. Glucose metabolism plays a crucial role in CRC development. However, the heterogeneity of glucose metabolic patterns in CRC is not well characterized. Here, we classified CRC into specific glucose metabolic subtypes and identified the key regulators. 2228 carbohydrate metabolism-related genes were screened out from the GeneCards database, 202 of them were identified as prognosis genes in the TCGA database. Based on the expression patterns of the 202 genes, three metabolic subtypes were obtained by the non-negative matrix factorization clustering method. The C1 subtype had the worst survival outcome and was characterized with higher immune cell infiltration and more activation in extracellular matrix pathways than the other two subtypes. The C2 subtype was the most prevalent in CRC and was characterized by low immune cell infiltration. The C3 subtype had the smallest number of individuals and had a better prognosis, with higher levels of NRF2 and TP53 pathway expression. Secreted frizzled-related protein 2 (SFRP2) and thrombospondin-2 (THBS2) were confirmed as biomarkers for the C1 subtype. Their expression levels were elevated in high glucose condition, while their knockdown inhibited migration and invasion of HCT 116 cells. The analysis of therapeutic potential found that the C1 subtype was more sensitive to immune and PI3K-Akt pathway inhibitors than the other subtypes. To sum up, this study revealed a novel glucose-related CRC subtype, characterized by SFRP2 and THBS2, with poor prognosis but possible therapeutic benefits from immune and targeted therapies.

Immune Response of Plasmacytoid Dendritic Cells Stimulated by Human Papillomavirus (HPV) E6 in an In Vitro System.

BACKGROUND This study aimed to analyze the changes in plasmacytoid dendritic cell (pDC) immunophenotypes when co-cultured with Caski cells and stimulated by human papillomavirus (HPV) E6 in vitro, and thus to discuss the immunoregulatory roles of pDCs in the tumorigenesis of cervical cancer. MATERIAL AND METHODS The immunophenotypic expression of pDCs was analyzed under stimulation of HPV E6 and co-culturing with Caski cells in vitro. RESULTS HPV E6 infection caused significantly increased expression of CD40 in HPV16 M and HPV16 H groups MyD88 in HPV16 M,HPV16 H, and HPV18L groups; and TRAF6 in HPV16 M, HPV16 H, and HPV18L groups. pDCs co-cultured with Caski cells showed significantly lower expression of MyD88 and TRAF6 compared with the control. CONCLUSIONS The expression of MyD88 and TRAF6 might vary in different stages of HPV infection. pDCs might regulate CD40 to participate in the tumorigenesis and progression of cervical cancer, but related mechanisms still need further investigation.

[Early differential diagnosis between COVID-19 and mycoplasma pneumonia with chest CT scan].

OBJECTIVE: To early differentiate between coronavirus disease 2019 (COVID-19) and adult mycoplasma pneumonia with chest CT scan. METHODS: Twenty-six patients with COVID-19 and 21 patients with adult mycoplasma pneumonia confirmed with RT-PCR test were enrolled from Zibo First Hospital and Lanshan People's Hospital during December 1st 2019 and March 14th 2020. The early chest CT manifestations were analyzed and compared between the two groups. RESULTS: The interstitial changes with ground glass density shadow (GGO) were similar in two groups during first chest CT examination (P>0.05). There were more lung lobes involved on the first chest CT in COVID-19 patients, which were mostly distributed in the dorsal outer zone (23/26, 88.5%), and nearly half of them (12/26, 46.2%) were accompanied by crazy-paving sign; while the lesions in adult mycoplasma pneumonia patients were mostly distributed along the bronchi, and the bronchial wall was thickened (19/21, 90.5%), accompanied with tree buds / fog signs (19/21, 90.5%). The above CT signs were significantly different between the two kinds of pneumonia (all P<0.01). COVID-19 had a longer course compared with mycoplasma pneumonia, the disease peaks of COVID-19 patients was on day (10.5±3.8), while the disease on CT was almost absorbed on day (7.9±2.2) in adult mycoplasma pneumonia. The length of hospital stay in COVID-19 patients was significantly longer than that of mycoplasma pneumonia patients [(19.5±4.3) d vs (7.9±2.2) d, P<0.01]. CONCLUSIONS: The lesions of adult mycoplasma pneumonia are mostly distributed along the bronchi with tree buds/fog signs, while the lesions of COVID-19 are mainly distributed in the dorsal outer zone accompanied by crazy-paving sign, which can early distinguish two diseases.

Identification and validation of SLCO4C1 as a biological marker in hepatocellular carcinoma based on anoikis classification features.

BACKGROUND: Hepatocellular carcinoma (HCC) exhibits a high degree of invasiveness and is closely associated with rapid disease progression. Multiple lines of evidence indicate a strong correlation between anoikis resistance and tumor progression, invasion, and metastasis. Nevertheless, the classification of anoikis in HCC and the investigation of novel biological target mechanisms in this context continue to pose challenges, requiring further exploration. METHODS: Combined with HCC samples from TCGA, GEO and ICGC databases, cluster analysis was conducted on anoikis genes, revealing novel patterns among different subtypes. Significant gene analysis of different gene subtypes was performed using WCGNA. The anoikis prognostic risk model was established by Lasso-Cox. Go, KEGG, and GSEA were applied to investigate pathway enrichment primarily observed in risk groups. We compared the disparities in immune infiltration, TMB, tumor microenvironment (TME), and drug sensitivity between the two risk groups. RT-qPCR and Western blotting were performed to validate the expression levels of SLCO4C1 in HCC. The biological functions of SLCO4C1 in HCC cells were assessed through various experiments, including CCK8 assay, colony formation assay, invasion migration assay, wound healing assay, and flow cytometry analysis. RESULTS: HCC was divided into 2 anoikis subtypes, and the subtypeB had a better prognosis. An anoikis prognostic model based on 12 (COPZ2, ACTG2, IFI27, SPP1, EPO, SLCO4C1, RAB26, STC2, RAC3, NQO1, MYCN, HSPA1B) risk genes is important for survival and prognosis. Significant differences were observed in immune cell infiltration, TME, and drug sensitivity analysis between the risk groups. SLCO4C1 was downregulated in HCC. SLCO4C1 downregulation promoted the proliferation, invasion, migration, and apoptosis of HCC cells. The tumor-suppressive role of SLCO4C1 in HCC has been confirmed. CONCLUSIONS: Our study presents a novel anoikis classification method for HCC that reveals the association between anoikis features and HCC. The anoikis feature is a critical biomarker bridging tumor cell death and tumor immunity. In this study, we provided the first evidence of SLCO4C1 functioning as a tumor suppressor in HCC.

Prevalence of Syphilis Infections Among Volunteer Blood Donors in Jinan Blood Center, China: A 15-Year Retrospective Study.

Background: Syphilis infections among volunteer blood donors increased rapidly in recent years. It is important to analyze the demographics of seropositive donor groups and help to recruit donors from low-risk population. Objective: The aim of this study was to analyze the syphilis prevalence among volunteer blood donors in Jinan Blood Center and give direction to blood recruitment. Methods and Materials: A cross-sectional study was conducted among blood donors in Jinan, China. Socio-demographic data and blood donation testing data from January 2007 to December 2021 were extracted from the database of blood management software of Jinan Blood Center for analysis. All blood samples were screened by ELISA, and those anti-TP-positive samples were counted and analyzed by sex, age, educational background, occupation and blood donation times. Logistic regression was used to explore risk factors associated with syphilis infection. Results: Totally 700,757 blood samples were collected in the study during 2007 to 2021, 2290 cases were detected anti-TP positive with a positive rate of 0.33%. Female, 35-44 years old, with a lower education degree, farmers and first-time donors were the high-risk subgroups. Conclusion: Consultation and identification of high-risk population groups should be improved. Measures should be taken to make the donor recruitment more professional and detailed.

Association of pretreatment SUVmax of cervix and SCC-antigen with FIGO2018 stage in Stage IIB-IVB squamous cervical cancer and relationship to prognosis.

OBJECTIVE: To evaluate the association of pretreatment maximum standardized 18 F-fluorodeoxyglucose uptake value (SUVmax ) of cervix and serum squamous cell carcinoma antigen (SCC-ag) with FIGO2018 stage and prognosis among women with Stage IIB-IVB squamous cervical cancer. METHODS: Retrospective study of 116 women with FIGO2018 Stage IIB-IVB cervical cancer treated in Hangzhou, China, 2013-2015. The relationship between pretreatment SUVmax or SCC-ag and prognostic factors was evaluated by univariate and multivariate analyses. RESULTS: Women were stratified by mean SUVmax and mean SCC-ag. There was a significant difference between low (<12.9) and high (≥12.9) SUVmax groups in menopause (P = 0.004), FIGO2018 stage (P = 0.015), and survival rate (P < 0.001). The low group had better overall and progress-free survival by Kaplan-Meier evaluation (both P = 0.022). High SCC-ag (≥14.6 ng/mL) was associated with FIGO2018 stage (P = 0.038) and distant metastasis (P = 0.011). There was a significant correlation between SUVmax and serum SCC-ag (P = 0.026). In multivariate Cox regression analyses, FIGO2018 stage (P = 0.019) and SUVmax of cervix (P = 0.015) were independent predictors of poor outcome in squamous cervical cancer. CONCLUSION: Both SUVmax of cervix and SCC-ag were associated with FIGO2018 stage in squamous cervical cancer. Pretreatment high SUVmax of cervix and advanced FIGO2018 stage might indicate a poor prognosis.

Prognostic factors affecting survival and recurrence in patients with early cervical squamous cell cancer following radical hysterectomy.

OBJECTIVE: This study aimed to investigate the clinical and histological features affecting the survival of patients with early cervical squamous cell cancer treated with radical hysterectomy. METHODS: We retrospectively analyzed clinical and histological data for patients with stage IB-IIA cervical cancer treated by radical hysterectomy at Zhejiang Cancer Hospital from August 2008 to January 2013. RESULTS: A total of 1435 patients were included in the study. Cox regression analysis identified tumor size >4 cm, lymphovascular space involvement (LVSI), lymph node ratio (LNR), and squamous cell carcinoma antigen (SCC-Ag) >2.65 ng/mL as independent prognostic risk factors. Among 1096 patients without high pathological risk factors, the 5-year local recurrence rates for SCC-Ag ≤2.65 and >2.65 ng/mL were 6.6% and 25.7%, respectively. Among 332 patients with lymph node positivity, the overall survival rates for LNR ≤0.19 and >0.19 were 87.8% and 55.6%, respectively. CONCLUSIONS: LVSI, tumor size >4 cm, LNR >0.19, and SCC-Ag >2.65 ng/mL may predict a poor prognosis in patients with early cervical squamous cell cancer treated with radical hysterectomy. SCC-Ag >2.65 ng/mL may be a useful prognostic factor guiding the use of postoperative radiotherapy in patients without pathologic risk factors.

GSH and GABA decreases in IDH1-mutated low-grade gliomas detected by HERMES spectral editing at 3 T in vivo.

Isocitrate dehydrogenase 1 (IDH1) mutational status is an important prognostic biomarker in gliomas. γ-aminobutyric acid (GABA) and reduced glutathione (GSH) play an important role in energy production, which is related to tumor progression. Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES) is able to detect GABA and GSH in healthy controls. This study aims to examine GABA and GSH alterations in IDH1-mutated low-grade gliomas using HERMES. We prospectively enrolled 14 suspected low-grade gliomas and 6 healthy control patients in this study, all cases underwent a 3 T MRI scan, including T1-weighted imaging and HERMES acquisition with a volume of interest 3 × 3 × 3 cm3. HERMES detects a "GABA+" signal that includes contributions from macromolecules and homocarnosine. GABA+ and GSH in tumor foci (group 1), contralateral cerebral regions (group 2) and healthy controls (group 3) were quantified using Gannet. The fitting errors and SNR of HERMES for GABA+ and GSH were analyzed; FWHM of the unsuppressed water signal was also recorded. The Wilcoxon signed-rank test was performed to test for differences between contralateral GABA+ and GSH levels, and differences in GABA+, GSH and fitting errors/SNR between the three groups were analyzed using analysis of variance (ANOVA). Eleven IDH1-mutant low-grade gliomas (5 Female and 6 Male, age 33-69) and 6 healthy subjects (2 Female and 4 Male, age 35-60) were finally enrolled this study. The mean water linewidth across all subjects was 9.67 ± 2.28 Hz. The Wilcoxon signed-rank test revealed that GABA+ and GSH were decreased significantly in glioma foci compared with contralateral regions, whereas no differences were seen between the left and right regions in healthy controls. ANOVA showed that GABA+ and GSH levels in tumor were lower than contralaterally and in healthy controls, while no differences were observed between the contralateral healthy tissue and healthy controls. No differences of fitting errors or SNR were found between tumors, contralateral regions or healthy controls. Our results suggest that HERMES is a reliable tool to simultaneously measure GABA and GSH alterations in low-grade gliomas with IDH1 mutations.

Monitoring of IL-10 in the serum of patients with advanced ovarian cancer: results from a prospective pilot-study.

OBJECTIVES: The fact that ovarian cancer remains confined to the peritoneal cavity even in advanced stages has allowed us to surmise that local immunosuppressive factors could be involved in the tumor biology of ovarian cancer. In this context, IL-10 can be one of the key factors. By studying the kinetics of IL-10 concentrations prior to and after surgery, this study attempts to reveal once more the ability of tumor micro-environment to produce IL-10. Some studies indicate that IL-10 concentration correlates with the tumor burden and can thus predict the surgical outcome. Data concerning this aim from patients with ovarian cancer do not seem to exist. METHODS: In this prospective study, serum blood was collected from 27 patients, one day prior to surgery as well as 24h, 4 and 8 days after surgery. The concentration of IL-10 was determined using ELISA. RESULTS: While IL-10 levels rise within the first day post-OP, they are found to be reduced significantly when measured at later time points. IL-10 levels also correlate statistically significantly with the tumor grade, with lower IL-10 levels observed in well-differentiated and higher IL-10 levels in undifferentiated or only poorly differentiated tumors. CONCLUSION: IL-10 expression levels appear to be a good surrogate marker for tumor grading. If validated, this may in future contribute to the understanding of the biology stage cancers.

Impact of sites versus number of metastases on survival of patients with organ metastasis from newly diagnosed cervical cancer.

OBJECTIVE: The aim of this study was to investigate the potential associations of the sites and the number of specific metastases with survival in patients newly diagnosed with cervical cancer. METHODS: Medical records of patients with organ metastases of newly diagnosed cervical cancer at Zhejiang Cancer Hospital from October 2006 to December 2016 were reviewed retrospectively. Survival times were compared using the Kaplan-Meier method. Variables associated with survival were identified using univariate and multivariate Cox proportional hazards models. RESULTS: A total of 99 patients with newly diagnosed organ metastatic cervical cancer were identified. Median follow-up was 11.6 months (range, 0.5-114.7 months). Median overall survival (OS) time was 11.7 months from diagnosis, with 1, 2, and 5-year OS rates of 48.2%, 22.8%, and 12.6%, respectively. The most common site of organ metastasis was bone (36.8%), followed by lung (32.8%) and liver (24%). In univariate analysis, OS rates were better for bone metastasis than visceral metastasis (P=0.013), oligometastasis than non-oligometastasis (P=0.003) and single organ metastasis than multiple organ metastases (P=0.016), while that for liver metastasis was poorer than non-liver metastases (P<0.001). In multivariate analysis, liver metastasis (hazard ratio [HR] =4.02; 95% confidence interval [CI], 1.15-14.05, P=0.029) was significantly and independently related to poor overall survival. CONCLUSION: Our data revealed the site of metastasis is associated with overall survival of patients with newly diagnosed organ metastatic cervical cancer, with liver metastasis signifying particularly poor overall survival. Individualized treatments should be administered to patients depending on the specific metastatic sites.

[Combined detection of thyroid transcription factor 1 and napsin A in pleural fluid cell blocks facilitates cytopathologic diagnosis of pulmonary adenocarcinoma].

OBJECTIVE: To investigate the value of detecting thyroid transcription factor 1 (TTF-1) and Noval aspartic proteinase of pepsin family A (napsin A) in pleural fluid cell blocks in cytopathologic diagnosis of pulmonary adenocarcinoma. METHODS: Conventional cell smears of pleural effusions were obtained from 48 patients with a history of lung adenocarcinoma for cytological analysis. The cell blocks were prepared using the cytological specimens and examined with immunohistochemistry for TTF-1 and napsin A. The rates of a positive diagnosis of pulmonary adenocarcinoma were compared between the two methods, and the diagnositic value of TTF-1 and napsin A in pleural fluid cell blocks was evaluated. RESULTS: Immuno- histochemistry of the cell block sections yielded a significantly higher positive rate of diagnosis than cytological analysis of conventional cell smear (84.44% vs 55.56%, P<0.05). Most of the pleural fluid cell blocks showed positive expressions of TTF-1 (36/38, 94.74%) and napsin A (30/38, 78.95%), and none of samples showed TTF-1 or napsin A expression in the mesothelial cells (P<0.05). The combination detection of TTF-1 and napsin A in pleural fluid cell blocks had a high diagnosis value with a diagnostic sensitivity of 97.37% and a specificity of 100% for pulmonary adenocarcinoma. CONCLUSIONS: The combined detection of TTF-1 and napsin A in pleural fluid cell blocks facilitates cytopathologic diagnosis of pulmonary adenocarcinoma.

Distribution of HPV Genotype in Invasive Cervical Carcinoma and Cervical Intraepithelial Neoplasia in Zhejiang Province, Southeast China: Establishing the Baseline for Surveillance.

Human papillomavirus (HPV) are firmly established as the principal causative agent for cervical carcinoma. Current vaccines may provide some protection for women from cervical carcinoma linked to HPV genotype 16 and 18. This may be the best vaccine for Western women, but the geographical variation in HPV distributions may not make it the most appropriate vaccine for China or Asia. This study provided an observational, retrospective, hospital-based cross-sectional study on the distribution of HPV genotypes among 5410 women with invasive cervical cancer (ICC) or cervical intraepithelial neoplasia (CIN). Overall, the positive rates of the four HPV types included in current prophylactic vaccines were counted, the two high-risk types (HPV-16 and -18) covered by current vaccines represented 66.9% of women with squamous cancer, 55.0% with adenocarcinoma, 64.9% with adenosquamous carcinoma and 77.4% of other type ICC, as well as 59.5% of CIN III, 45.0% of CIN II and 38.1% of CIN I cases. As expected, two low-risk types (HPV-6 and -11) included in the quadrivalent vaccine did not show good coverage data. Particularly worth mentioning is the fact that the addition of HPV-52 and -58 to the vaccine cocktail would increase cancer protection in our population, potentially preventing up to beyond 16% of squamous/adenosquamous carcinoma and other type of cervical cancers, and 7.75% of adenocarcinomas. It might also potentially reduce the rate of CIN III by a further 28.6% and CIN II and I by a third. This study established the baseline for surveillance in Zhejiang Province, and provides data for further vaccine designs: a quadrivalent HPV vaccine covering HPV-16/-58/-18/-52, would be more welcome in our region in the forthcoming year compared to the currently available vaccine.

[Detection of multiple loci in single cell by primer extension preamplification and nest PCR]

OBJECTIVE: To investigate the feasibility of multiple loci detection in single cell by primer extension preamplification (PEP) followed by nest PCR. METHODS: Using PEP, the whole genomic DNA in single lymphocyte or single blastomere was amplified. In addition, CD17, nt-28 and linked ATTTT repeat for beta-thalassemia, F508 and linked GATT repeat for cystic fibrosis, DMD exon 17 and 48 for Duchenne muscular dystrophy, short tandem repeats of D18S51, D21S11 and D21S1411, and sex-determination gene SRY of the Y chromosome were all detected using nest-PCR from a small aliquot of the PEP reaction. RESULTS: The rate of successful single lymphocyte amplification was 89.5%(false positive 0.48%false negative 2.5%). The rate of successful single blastomere amplification was 85.56%(false positive 3%). CONCLUSION: The PEP technique followed by nest PCR analysis of single cell is very useful for simultaneous detection of multiple gene loci. It may be applicable for preimplantation genetic diagnosis.