Effectiveness of human immunodeficiency virus prevention strategies by mapping the geographic dispersion pattern of human immunodeficiency virus prevalence in Nanning, China.

BACKGROUND: The Guangxi government initiated two rounds of the Guangxi AIDS Conquering Project (GACP) in 2010 (Phase I) and 2015 (Phase II) to control human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemics. However, the effectiveness of GACP in HIV prevention and treatment has rarely been reported. This study aimed to assess the effectiveness of the GACP implemented in Guangxi, China and provide data for strategy and praxis improvements to achieve Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95 targets. METHODS: We used spatial approaches to trace the spatiotemporal distribution properties, epidemic trends, and correlation between macroscopic factors and HIV incidence using data from the Chinese HIV/AIDS case reporting system to explore the effects of the GACP. RESULTS: During the GACP era, the HIV epidemic stabilized in urban centers, showing a downward trend in the Hengzhou and Binyang Counties in the eastern region, whereas it continued to increase in rural areas of the northwest region, such as the Long'an, Mashan, Shanglin, and Wuming Districts. The linear directional mean (LDM) of HIV infection reported cases displayed a southeast-northwest direction, with an LDM value of 12.52°. Compared with that in Phase I, Hengzhou withdrew from the high-high clustering area, and the west-north suburban counties pulled out the low-low clustering area during Phase II. Significant HIV clusters were identified in the eastern region during Phase I, whereas these clusters emerged in the northwestern areas during Phase II. Regarding HIV, socioeconomic status, population mobility, and medical care levels were the key social drivers of heterogeneous spatial distribution. CONCLUSIONS: The GACP assisted in effectively managing the HIV epidemic in urban and eastern areas of Nanning City. However, prevention and control efforts in rural regions, particularly those located in the northwest, may not have yielded comparable outcomes. To address this disparity, allocating additional resources and implementing tailored intervention measures for these rural areas are imperative.

Mining the Prognostic Role of DNA Methylation Heterogeneity in Lung Adenocarcinoma.

Purpose: DNA methylation heterogeneity is a type of tumor heterogeneity in the tumor microenvironment, but studies on the identification of the molecular heterogeneity of the lung adenocarcinoma genome with respect to DNA methylation sites and their roles in lung cancer progression and prognosis are scarce. Methods: Prognosis-associated DNA methylation subtypes were filtered by the Cox proportional hazards model and then established by unsupervised cluster analysis. Association analysis of these subtypes with clinical features and functional analysis of annotated genes potentially affected by methylation sites were performed. The robustness of the model was further tested by a Bayesian network classifier. Results: Over 7 thousand methylation sites were associated with lung adenocarcinoma prognosis. We identified seven molecular methylation subtypes, including 630 methylation sites. The subtypes yielded the most stable results for differentiating methylation profiles, prognosis, and gene expression patterns. The annotated genes potentially affected by these methylation sites are enriched in biological processes such as morphogenesis and cell adhesion, but their individual impact on the tumor microenvironment and prognosis is multifaceted. Discussion. We revealed that DNA methylation heterogeneity could be clustered and associated with the clinical features and prognosis of lung adenocarcinoma, which could lead to the development of a novel molecular tool for clinical evaluation.

Survival nomogram for patients with metastatic siewert type II adenocarcinoma of the esophagogastric junction: a population-based study.

BACKGROUND: The aim of this study was to construct a nomogram to predict the survival of patients with metastatic Siewert Type II adenocarcinomas of the esophagogastric junction (AEG). METHODS: Patients were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression analysis was performed to assess the prognostic factors. A nomogram comprising independent prognostic factors was established and evaluated using C-indexes, calibration curves, and decision curve analyses. RESULTS: In total 1616 eligible patients were enrolled. Race, age, bone metastasis, liver metastasis, lung metastasis, other metastasis sites, and distant lymph nodes metastasis were independent prognostic factors and were integrated to construct the nomogram. The nomogram had a C-index of 0.590 (95% CI: 0.569-0.611) in the training cohort and 0.569 (95% CI: 0.532-0.606) in the validation cohort. The calibration plots for the probabilities of 6-month and 1-year overall survival demonstrated there was an optimum between nomogram prediction and actual observation. CONCLUSION: We developed and validated a nomogram to predict individual prognosis for patients with metastatic Siewert Type II AEG, and the risk stratification system based on the nomogram could effectively stratify the patients into two risk subgroups, which can help clinicians accurately predict mortality risk and recommend personalized treatment modalities.

Sites of distant metastases and the cancer-specific survival of metastatic Siewert type II esophagogastric junction adenocarcinoma: a population-based study.

BACKGROUND: The effect of distant metastasis on prognosis in patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) remains elusive. METHODS: Patients diagnosed as metastatic Siewert type II AEG were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis and a Cox proportional hazards analysis were performed to assess the effect of distant metastases sites. RESULTS: We analyzed 1616 eligible patients. Liver was the most frequent metastatic site. For patients with isolated distant metastasis, the median survival time was 8, 7, 8, 10, and 11 months for patients with liver, bone, brain, lung, and distant lymph nodal metastasis, respectively (p = 0.011). The number of metastatic sites and the site of distant metastasis were independent prognostic factors for cancer-specific survival (CSS). In patients with isolated distant metastasis, using bone metastasis as reference, lung (p = 0.011) or distant lymph node metastasis (p = 0.030) was associated with better CSS, while patients with liver (p = 0.051) or brain (p = 0.488) metastasis had similar CSS compared to patients with bone metastasis. CONCLUSION: CSS in metastatic Siewert type II AEG is dependent on the metastatic site and the number of metastatic sites.

[Application of flexible bronchoscopy in children with respiratory diseases].

OBJECTIVE: To investigate the significance of flexible bronchoscopy in children with respiratory diseases. METHODS: A retrospective analysis was performed for the clinical data of 80 children who were hospitalized due to respiratory diseases (including severe pneumonia, Mycoplasma pneumoniae pneumonia with atelectasis/lung consolidation/local emphysema, protracted pneumonia, coughing and wheezing of unknown cause, chronic cough of unknown cause, and laryngeal stridor) and who underwent flexible bronchoscopy/alveolar lavage. RESULTS: Bronchoscopy found that all the 80 children had endobronchial inflammation, among whom 28 children had severe airway obstruction by secretion. Twenty-four children had congenital airway dysplasia besides endobronchial inflammation, and three children had bronchial foreign bodies. In the children with coughing and wheezing of unknown cause and laryngeal stridor, some had congenital airway dysplasia or bronchial foreign bodies. Among the 27 children with Mycoplasma pneumoniae pneumonia, 26 had severe airway obstruction/embolization by secretion; 25 children (93%) underwent chest imaging again at 2 weeks after alveolar lavage, and the results showed complete or partial lung recruitment. Among the 80 children who underwent bronchoscopy, 3 had severe hypoxemia during surgery, 1 had epistaxis, 1 had minor bleeding during alveolar lavage, 3 had transient bronchospasm, and 5 had postoperative fever; these children were all improved after symptomatic treatment. CONCLUSIONS: Flexible bronchoscopy is safe and reliable in children with respiratory diseases. Early alveolar lavage under a flexible bronchoscope is recommended for children with severe/refractory Mycoplasma pneumoniae pneumonia to improve prognosis. Flexible bronchoscopy is recommended for children with recurrent coughing and wheezing and persistent laryngeal stridor, in order to directly observe the throat and airway under an endoscope.

UXT-AS1-induced alternative splicing of UXT is associated with tumor progression in colorectal cancer.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) can act as crucial regulators of tumor progression. In the present study, UXT-AS1 was found to be significantly upregulated in colorectal cancer (CRC) and high expression levels of UXT-AS1 were significantly associated with poor prognosis in CRC patients. In addition, upregulation of UXT-AS1 resulted in inhibition of cell apoptosis and the promotion of cell proliferation. Moreover, by regulating the alternative splicing of UXT, upregulation of UXT-AS1 decreased the UXT1 transcript which promoted cell apoptosis and increased the UXT2 transcript which promoted cell proliferation. Thus, aberrant high expression of UXT-AS1 can promote CRC progression by changing the alternative splicing of UXT from the UXT1 transcript to the UXT2 transcript. In conclusion, our findings suggest that the regulation of CRC progression is by UXT-AS1-induced alternative splicing of UXT, and the expression level of UXT-AS1 may be a potential prognostic biomarker and therapy target in CRC patients.

NEK2 serves as a prognostic biomarker for hepatocellular carcinoma.

Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a microtubule-associated protein that regulates spindle assembly in human cells and is overexpressed in various malignancies. However, the role of NEK2 in hepatocellular carcinoma (HCC) remains undetermined. We performed RNA-seq of the HCC cell line SMMC-7721 and the normal liver cell line HL-7702 using the Ion Proton System. NEK2 expression was detected using quantitative reverse transcription polymerase chain reaction in two cell lines and 5 matched HCC and adjacent non-tumorous liver tissues. The correlation between survival and NEK2 expression was analyzed in 359 patients with HCC using RNASeqV2 data available from The Cancer Genome Atlas (TCGA) website (https://tcga-data.nci.nih.gov/tcga/). The expression of NEK2, phospho-AKT and MMP-2 was evaluated by immunohistochemistry in 63 cases of HCC and matched adjacent non-tumorous liver tissues. Relationships between protein expression and clinicopathological parameters were assessed, and the correlations between NEK2 with phospho-AKT and MMP-2 expressions were evaluated. A total of 610 differentially expressed genes (DEGs) were revealed in the transcriptome comparison, 297 of which were upregulated and 313 were downregulated in HCC. NEK2, as the most obviously different DEG in cells and tissues from the RNA-seq data, was listed as an HCC candidate biomarker for further verification. NEK2 was overexpressed in HCC cells and tissues (P=0.002, P=0.013) and HCC patients with a high expression of NEK2 had a poor prognosis (P=0.0145). Clinical analysis indicated that the overexpression of NEK2 in HCC was significantly correlated with diolame complete (P<0.001), tumor nodule number (P=0.012) and recurrence (P=0.004). NEK2 expression was positively correlated with the expression of phospho-AKT (r=0.883, P<0.01) and MMP-2 (r=0.781, P<0.01). Overexpression of NEK2 was associated with clinicopathological characteristics and poor patient outcomes, suggesting that NEK2 serves as a prognostic biomarker for HCC. Alteration of NEK2 protein levels may contribute to invasion and metastasis of HCC, which may occur through activation of AKT signaling and promotion of MMP-2 expression.

p75NTR promotes survival of breast cancer resistant cells by regulating Bcl-2/Bax and MAPK pathway.

In breast cancer, the neurotrophin receptor p75NTR is a critical factor that promotes resistance to the drug, however, its mechanism of action remains unclear. In our study, the 10 cases of positive expressions of p75NTR were detected in 86 cases of breast cancer tissues, accounting for 11.6% of cases detected. The immunohistochemistry detection of p75NTR was in the cytoplasm and cell membrane. The expression of p75NTR was significantly associated with histological grade (P<0.01), however, not with the menopause, tumor size and lymph node metastasis. Western blot result showed that p75NTR protein was induced by overexpression in the multidrug-resistant breast cancer cell lines. After transfection of pcDNA3.1-p75NTR, MDA-MB-231/ADR-p75NTR cell cycle was arrested in G0/G1 phase. However, the number of cells in G0/G1 phase increased and decreased in S phase cells (P<0.05). Additionally, apoptosis rate decreased (P<0.05). The p75NTR overexpression increased the expression of MDR related protein and activated MAPK signaling pathway.

Transcriptomic and Proteomic Investigation of HSP90A as a Potential Biomarker for HCC.

BACKGROUND Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death in adults. Despite recent advances in the clinical technologies, the screening and diagnostic efficacy for HCC remains poor. Discovering novel and reliable HCC biomarkers is urgently needed. MATERIAL AND METHODS We performed a transcriptome-proteome integrated assay to track the possible HCC biomarkers from the process of HCC-derived gene expression in malignant cells to its protein product released into serum. RESULTS Our screening results demonstrated that heat shock protein 90A (HSP90A), which participates in the PI3K-Akt signaling pathway and many other cancer-related pathways, warrants further investigation. The expression of HSP90A was increased in the HCC cells, serum, and tissues. Immunohistochemistry analysis on 76 clinical tissue samples also suggested the relevance between HSP90A expression and HCC metastatic behavior. CONCLUSIONS These findings suggest a role for HSP90A in HCC pathogenesis and the potential use of HSP90A for the screening and diagnosis of this malignancy.

Cellular transcriptomics: gelsolin negatively regulates the expression of apoptosis-associated genes and inhibits apoptosis in hepatocarcinoma cells.

Gelsolin (GSN), which is a Ca(2+)-dependent actin filament severing and capping protein, plays a critical role in the cancer progress and has the potential for providing a novel thread for cancer therapy. In current study, we demonstrate the roles of GSN on anti-apoptosis of hepatocarcinoma cells by transcriptome RNA-seq method. Then flow cytometry (FCM), in-cell immunoblotting and transmission electron microscopy (TEM) were used to examine the GSN regulatory cell apoptosis. The results revealed GSN significantly suppresses apoptosis-associated functional categories through down-regulating apoptosis-associated genes in 5 apoptosis terms and 6 relevant KEGG pathways. FCM showed a significant lower apoptotic rate in GSN-SMMC7721 (P<0.05). In-cell immunoblotting detected discrepant expression of the apoptosis factors among GSN expressed/shRNA transfectants (P<0.05). TEM observed the discernible apoptosis morphology. Above results suggest a negative relationship between GSN expression and hepatocarcinoma cell apoptosis. GSN overexpression suppresses apoptosis while down-regulated GSN promotes apoptosis. The possible mechanism could be associated with the regulation of GSN on the apoptosis-associated pathways and the apoptosis factors caspase 3 and bcl-2.

[Effects of elevated CO2 on the Cd uptake and root morphology of different rice varieties under cadmium stress].

A hydroponic experiment was conducted to study the effects of elevated CO2 on the Cd uptake and root morphology of rice varieties Rongyou-398 (RY) and Yueza-889 (YZ) under different levels of Cd stress. Low levels (5, 10, and 20 micromol x L(-1)) Cd stress increased the biomass of the two rice varieties significantly, while high levels (> 50 micromol x L(-1)) Cd stress was in adverse. Elevated CO2 increased the varieties dry biomass significantly, and increased the stem Cd concentration of YZ but decreased that of RY. Under the stress of 5-200 micromol Cd x L(-1), elevated CO2 increased the proportion of active root length in total root length of YZ but decreased that of RY, which could be one of the main reasons for the difference in the Cd uptake of the two varieties under Cd stress.