Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma

BackgroundPrevious studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC).MethodsBased on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of LPCAT1 knockdown on HCC cell behavior was verified using in vitro experiments.ResultsThis study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene LPCAT1 was upregulated in HCC cell lines. LPCAT1 knockdown markedly decreased HCC cell proliferation and migration.ConclusionPANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment

Microbial denitrification characteristics of typical decentralized wastewater treatment processes based on 16S rRNA sequencing

Despite the widespread application of decentralized wastewater treatment (WWT) facilities in China, relatively few research has used the multi-media biological filter (MMBF) facilities to investigate the microorganism characteristics. This study utilizes 16S rRNA high-throughput sequencing (HTS) technology to examine the microbial biodiversity of a representative wastewater treatment (WWT) system in an expressway service area. The pathways of nitrogen removal along the treatment route were analyzed in conjunction with water quality monitoring. The distribution and composition of microbial flora in the samples were examined, and the dominant flora were identified using LEfSe analysis. The FAPROTAX methodology was employed to investigate the relative abundance of genes associated with the nitrogen cycle and to discern the presence of functional genes involved in nitrogen metabolism. On average, the method has a high level of efficiency in removing COD, TN, NH3-N, and TP from the effluent. The analysis of the microbial community identified a total of 40 phyla, 111 classes, 143 orders, 263 families, and 419 genera. The phyla that were predominantly observed include Proteobacteria, Acidobacteria, Chloroflexi, Actinobacteria, Nitrospirae, Bacteroidetes. The results show that the system has achieved high performance in nitrogen removal, the abundance of nitrification genes is significantly higher than that of other nitrogen cycle genes such as denitrification, and there are six nitrogen metabolism pathways, primarily nitrification, among which Nitrospirae and Nitrospira are the core differentiated flora that can adapt to low temperature conditions and participate in nitrification, and are the dominant nitrogen removal flora in cold regions. This work aims to comprehensively investigate the diversity and functional properties of the bacterial community in decentralized WWT processes

The versatile application of cervicofacial and cervicothoracic rotation flaps in head and neck surgery

<p>Abstract</p> <p>Background</p> <p>The large defects resulting from head and neck tumour surgeries present a reconstructive challenge to surgeons. Although numerous methods can be used, they all have their own limitations. In this paper, we present our experience with cervicofacial and cervicothoracic rotation flaps to help expand the awareness and application of this useful system of flaps.</p> <p>Methods</p> <p>Twenty-one consecutive patients who underwent repair of a variety of defects of the head and neck with cervicofacial or cervicothoracic flaps in our hospital from 2006 to 2009 were retrospectively analysed. Statistics pertaining to the patients' clinical factors were gathered.</p> <p>Results</p> <p>Cheek neoplasms are the most common indication for cervicofacial and cervicothoracic rotation flaps, followed by parotid tumours. Among the 12 patients with medical comorbidities, the most common was hypertension. Defects ranging from 1.5 cm × 1.5 cm to 7 cm × 6 cm were reconstructed by cervicofacial flap, and defects from 3 cm × 2 cm to 16 cm × 7 cm were reconstructed by cervicothoracic flap. The two flaps also exhibited versatility in these reconstructions. When combined with the pectoralis major myocutaneous flap, the cervicothoracic flap could repair through-and-through cheek defects, and in combination with a temporalis myofacial flap, the cervicofacial flap was able to cover orbital defects. Additionally, 95% patients were satisfied with their resulting contour results.</p> <p>Conclusions</p> <p>Cervicofacial and cervicothoracic flaps provide a technically simple, reliable, safe, efficient and cosmetic means to reconstruct defects of the head and neck.</p

Outdoor particulate matter exposure affects metabolome in chronic obstructive pulmonary disease: Preliminary study

IntroductionThe metabolomic changes caused by airborne fine particulate matter (PM2.5) exposure in patients with chronic obstructive pulmonary disease (COPD) remain unclear. The aim of this study was to determine whether it is possible to predict PM2.5-induced acute exacerbation of COPD (AECOPD) using metabolic markers.MethodsThirty-eight patients with COPD diagnosed by the 2018 Global Initiative for Obstructive Lung Disease were selected and divided into high exposure and low exposure groups. Questionnaire data, clinical data, and peripheral blood data were collected from the patients. Targeted metabolomics using liquid chromatography-tandem mass spectrometry was performed on the plasma samples to investigate the metabolic differences between the two groups and its correlation with the risk of acute exacerbation.ResultsMetabolomic analysis identified 311 metabolites in the plasma of patients with COPD, among which 21 metabolites showed significant changes between the two groups, involving seven pathways, including glycerophospholipid, alanine, aspartate, and glutamate metabolism. Among the 21 metabolites, arginine and glycochenodeoxycholic acid were positively associated with AECOPD during the three months of follow-up, with an area under the curve of 72.50% and 67.14%, respectively.DiscussionPM2.5 exposure can lead to changes in multiple metabolic pathways that contribute to the development of AECOPD, and arginine is a bridge between PM2.5 exposure and AECOPD

Water Pollution Prediction in the Three Gorges Reservoir Area and Countermeasures for Sustainable Development of the Water Environment

The Three Gorges Project was implemented in 1994 to promote sustainable water resource use and development of the water environment in the Three Gorges Reservoir Area (hereafter “Reservoir Area”). However, massive discharge of wastewater along the river threatens these goals; therefore, this study employs a grey prediction model (GM) to predict the annual emissions of primary pollution sources, including industrial wastewater, domestic wastewater, and oily and domestic wastewater from ships, that influence the Three Gorges Reservoir Area water environment. First, we optimize the initial values of a traditional GM (1,1) model, and build a new GM (1,1) model that minimizes the sum of squares of the relative simulation errors. Second, we use the new GM (1,1) model to simulate historical annual emissions data for the four pollution sources and thereby test the effectiveness of the model. Third, we predict the annual emissions of the four pollution sources in the Three Gorges Reservoir Area for a future period. The prediction results reveal the annual emission trends for the major wastewater types, and indicate the primary sources of water pollution in the Three Gorges Reservoir Area. Based on our predictions, we suggest several countermeasures against water pollution and towards the sustainable development of the water environment in the Three Gorges Reservoir Area

New genetic biomarkers from transcriptome RNA-sequencing for Mycobacterium tuberculosis complex and Mycobacterium avium complex infections by bioinformatics analysis

Abstract The study aims to accurately identify differentially expressed genes (DEGs) and biological pathways in mycobacterial infections through bioinformatics for deeper disease understanding. Differentially expressed genes (DEGs) was explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Unique DEGs were submitted on least absolute shrinkage and selection operator (LASSO) regression analysis. 1,057 DEGs from two GSE datasets were identified, which were closely connected with NTM/ latent TB infection (LTBI)/active TB disease (ATB). It was demonstrated that these DEGs are mainly associated with detoxification processes, and virus and bacterial infections. Moreover, the METTL7B gene was the most informative marker for distinguishing LTBI and ATB with an area under the curve (AUC) of 0.983 (95%CI: 0.964 to 1). The significantly upregulated HBA1/2 genes were the most informative marker for distinguishing between individuals of IGRA-HC/NTM and LTBI (P < 0.001). Moreover, the upregulated HBD gene was also differ between IGRA-HC/NTM and ATB (P < 0.001). We have identified gene signatures associated with Mycobacterium infection in whole blood, which could be significant for understanding the molecular mechanisms and diagnosis of NTM, LTBI, or ATB

Long-term trends and regional variations of hypertension incidence in China: a prospective cohort study from the China Health and Nutrition Survey, 1991–2015

Objective The aim is to explore the trends of hypertension incidence and regional variations in China from 1991 to 2015.Design A dynamic prospective cohort study.Setting China Health and Nutrition Survey 1991–2015.Participants 12 952 Chinese adults aged 18+ years.Primary outcome measures Incident hypertension from 1993 to 2015.Results Age-standardised hypertension incidence increased from 40.8 per 1000 person-years (95% CI 38.3 to 43.4) between 1993 and 1997 to 48.6 (95% CI 46.1 to 51.0) between 2011 and 2015. The increasing trends were further supported by results from subsequent extended Cox proportional hazard model. In addition, results from the modelling analysis showed that individuals in eastern, central and northeastern China had greater risks of hypertension occurrence in comparison with their counterparts in western China.Conclusion Hypertension incidence increased during the study period. The growth called for more attention on the health education and health promotion of individuals with great risks

TIGIT regulates CD4+ T cell immunity against polymicrobial sepsis

BackgroundSepsis is one of the major causes of death and increased health care burden in modern intensive care units. Immune checkpoints have been prompted to be key modulators of T cell activation, T cell tolerance and T cell exhaustion. This study was designed to investigate the role of the negative immune checkpoint, T cell immunoglobulin and ITIM domain (TIGIT), in the early stage of sepsis.MethodAn experimental murine model of sepsis was developed by cecal ligation and puncture (CLP). TIGIT and CD155 expression in splenocytes at different time points were assessed using flow cytometry. And the phenotypes of TIGIT-deficient (TIGIT-/-) and wild-type (WT) mice were evaluated to explore the engagement of TIGIT in the acute phase of sepsis. In addition, the characteristics were also evaluated in the WT septic mice pretreated with anti-TIGIT antibody. TIGIT and CD155 expression in tissues was measured using real-time quantitative PCR and immunofluorescence staining. Proliferation and effector function of splenic immune cells were evaluated by flow cytometry. Clinical severity and tissue injury were scored to evaluate the function of TIGIT on sepsis. Additionally, tissue injury biomarkers in peripheral blood, as well as bacterial load in peritoneal lavage fluid and liver were also measured.ResultsThe expression of TIGIT in splenic T cells and NK cells was significantly elevated at 24 hours post CLP.TIGIT and CD155 mRNA levels were upregulated in sepsis-involved organs when mice were challenged with CLP. In CLP-induced sepsis, CD4+ T cells from TIGIT-/- mice shown increased proliferation potency and cytokine production when compared with that from WT mice. Meanwhile, innate immune system was mobilized in TIGIT-/- mice as indicated by increased proportion of neutrophils and macrophages with potent effector function. In addition, tissue injury and bacteria burden in the peritoneal cavity and liver was reduced in TIGIT-/- mice with CLP induced sepsis. Similar results were observed in mice treated with anti-TIGIT antibody.ConclusionTIGIT modulates CD4+ T cell response against polymicrobial sepsis, suggesting that TIGIT could serve as a potential therapeutic target for sepsis