Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. METHODS: Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. RESULTS: The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. CONCLUSIONS: A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell-cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

The ceRNA Mechanism of lncRNA MEG3/miR-21-5p/SPRY2 in Cell Proliferation and Apoptosis in Bladder Cancer.

Bladder cancer (BC) is the second most common genitourinary malignancy. Long noncoding RNA (lncRNA) is implicated in BC progression. This study delved into the underlying mechanism of lncRNA MEG3 in BC. Bioinformatics analysis predicted the expression of lncRNA MEG3, its association with the survival of BC patients, its subcellular localization, and its binding sites with miR-21-5p. Differentially expressed genes (DEGs) in the GSE13507 chip were analyzed using GEOexplorer, downstream targets of miR-21-5p were predicted from databases, and the overlapping genes were analyzed by the website Venny2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html); their impacts on patient survival were analyzed by the Starbase database. The expression of SPRY2 and TGFBI associated with patient survival was analyzed in TCGA. RT-qPCR and western blot were performed to detect levels of MEG3, miR-21-5p, and SPRY2 in BC/SV-HUC-1 cells. Malignant biological behaviors of BC cells were detected using CCK8, flow cytometry, and Transwell assays. RNA pull-down and dual-luciferase assays were employed to verify the binding relationship of miR-21-5p with MEG3 and SPRY2. MEG3 was found to be lowly expressed in BC cells and mainly distributed in the cytoplasm. Over-expression of MEG3 was found to inhibit BC cell activity, promote apoptosis, and reduce invasion and migration. miR-21-5p was found to be highly expressed in BC cells, and its down-regulation was found to inhibit the malignant behavior of BC cells. Over-expression of miR-21-5p was found to reverse the effect of pcDNA3.1-MEG3 on BC cells. MEG3 was found to competitively bind to miR-21-5p as a ceRNA to promote SPRY2 levels. LncRNA MEG3 promotes SPRY2 expression by competitively binding to miR-21-5p, thereby inhibiting proliferation and promoting apoptosis of BC cells.

Platelet-Rich Plasma for Androgenetic Alopecia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Platelet-rich plasma (PRP) contains a variety of growth factors and has been widely used in maxillofacial surgery, orthopedics, plastic surgery, ophthalmology, and other fields. In recent years, with the increasing morbidity of androgenetic alopecia (AGA), the use of PRP has also increased. The objective of this article was to evaluate the efficacy and safety of PRP for AGA. We searched PubMed, Embase, Web of Science, and Cochrane Library, covering the databases from their earliest records until March 2022. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to explore the effects of PRP for hair density, hair count, and hair diameter in AGA. Nine trials involving 238 patients were included. The meta-analysis showed that PRP for AGA increased hair density at 3 and 6 months with statistically significant differences compared with the placebo (P < .05). PRP also increased hair count and hair diameter compared with the baseline, but there was no significant difference compared with the placebo (P > .05). Two of the 7 studies reported adverse reactions. No serious adverse reactions were found. In conclusion, PRP is an effective and safe treatment for increasing the hair density in AGA. Trial registration: The systematic review was registered with PROSPERO (CRD42022362432).

Osmotic stress-induced localisation switch of CBR1 from mitochondria to the endoplasmic reticulum triggers ATP production via ß-oxidation to respond to osmotic shock.

Drought and high salinity are major environmental factors that reduce plant growth and development, leading to loss of plant productivity in agriculture. Under these stress conditions, photosynthesis is greatly suppressed despite the high cellular energy cost of stress response processes. Currently, the process that allows plants to secure the energy required for osmotic stress responses remains elusive. Here, we provide evidence that cytochrome b5 reductase 1 (CBR1), a cytochrome b5 reductase, plays an important role in ATP production in response to NaCl and dehydration stresses. Overexpression and loss of function of CBR1 led to enhanced resistance and sensitivity, respectively, to osmotic stress. Upon exposure to osmotic stress, CBR1 was localised to the endoplasmic reticulum (ER) instead of to mitochondria, where it was localised under normal conditions. Transgenic plants overexpressing ER-targeted CBR1 showed enhanced resistance to osmotic stress. Moreover, CBR1-ER and CBR1-OX plants, had higher levels of ATP and unsaturated fatty acids under osmotic stress. However, these effects were abrogated by thioridazine and 2-deoxy glucose, inhibitors of ß-oxidation and glycolysis, respectively. Based on these results, we propose that ER-localised CBR1 triggers ATP production via the production and ß-oxidation of polyunsaturated fatty acids under osmotic stress.

Discovery of a selective NLRP3-targeting compound with therapeutic activity in MSU-induced peritonitis and DSS-induced acute intestinal inflammation.

The aberrant activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is known to contribute to the pathogenesis of various human inflammation-related diseases. However, to date, no small-molecule NLRP3 inhibitor has been used in clinical settings. In this study, we have identified SB-222200 as a novel direct NLRP3 inhibitor through the use of drug affinity responsive target stability assay, cellular thermal shift assay, and surface plasmon resonance analysis. SB-222200 effectively inhibits the activation of the NLRP3 inflammasome in macrophages, while having no impact on the activation of NLRC4 or AIM2 inflammasome. Furthermore, SB-222200 directly binds to the NLRP3 protein, inhibiting NLRP3 inflammasome assembly by blocking the NEK7 - NLRP3 interaction and NLRP3 oligomerization. Importantly, treatment with SB-222200 demonstrates alleviation of NLRP3-dependent inflammatory diseases in mouse models, such as monosodium urate crystal-induced peritonitis and dextran sulfate sodium-induced acute intestinal inflammation. Therefore, SB-222200 holds promise as a lead compound for the development of NLRP3 inhibitors to combat NLRP3-driven disease and serves as a versatile tool for pharmacologically investigating NLRP3 biology.

Asparanin A exerts cytotoxicity on human endometrial cancer Ishikawa cells via regulating miR-6236-p5_4 expression.

miRNAs are emerging as a novel proto-oncogene or tumor suppressor in the initiation and progression of cancer. Several plants naturally contain asparanin A (AA), which has potent anticancer properties. Previously, we discovered that AA exposure increased the expression of miR-6236-p5_4 and caused cytotoxicity in endometrial carcinoma (EC) Ishikawa cells. Herein, the regulation mechanism of miR-6236-p5_4 in the anticancer activity of AA in EC was investigated. Our results showed that the overexpressed miR-6236-p5_4 contributed to modulating cell viability and cell cycle arrest, triggering cell apoptosis, and suppressing migration. Conversely, down-regulation of miR-6236-p5_4 attenuated the anti-cancer effect of AA. Additionally, the PI3K-Akt, p53, Ras, and Rap1 signaling pathways were demonstrated to be the key pathways, whereas CDK6, PIK3CB, and KRAS were found to be directly functional target genes. Our findings imply that miRNA-6236-p5_4 can act as both a molecular diagnostic for the clinical identification and prognosis of EC and a tumor suppressor in AA against EC.

[Pollution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Agricultural Soils of Different Land Use Types in Nanjing Suburbs].

In order to clarify the pollution characteristics of PAHs in suburban agricultural soils, the content of 16 types of PAHs was measured in agricultural soils with different land use types (paddy fields, vegetable fields, and forest land) in the suburbs of Nanjing. The results showed that acenaphthene (Acy) was not detected in any soil samples. The concentration of 15 PAHs in agricultural soil in suburban Nanjing ranged from 24.49 to 925.54 µg·kg-1, with an average concentration of 259.88 µg·kg-1. In different land use types, the order of PAHs concentration in soil from high to low was:forest land>paddy fields>vegetable fields, and the high-ring PAHs content was dominant in general. The effects of different soil physicochemical properties on PAHs showed that there was a certain correlation between soil organic carbon (TOC) and clay (clay) content and PAHs, whereas pH and total nitrogen (TN) had no significant correlation with PAHs. The toxic equivalence method and CSI index method were used for ecological risk assessment, which showed that the ecological risk of PAHs in agricultural soils in suburban Nanjing was relatively small; however, the ecological risk of PAHs in forest land should be given some attention, and supervision should be strengthened. Health risk assessment using incremental lifetime cancer risk (ILCR) showed that the threat to the health of children was slightly greater than that of adults, and the CR of forest land was significantly higher than that of vegetable and paddy fields, though still within an acceptable range. Uncertain health assessments were performed in adults, showing that risk analyses of deterministic health risks underestimated the health risks of PAHs. The results of sensitivity analysis showed that the input parameter that had the greatest impact on the total variance of the total carcinogenic risk CR was the exposure frequency EF (50.7%), followed by the pollutant concentration CS (43.3%).

Identification of Six Novel Prognostic Gene Signatures as Potential Biomarkers in Small Cell Lung Cancer.

OBJECTIVE: As a subgroup of lung cancer, small cell lung cancer (SCLC) is characterized by a short tumor doubling time, high rates of early occurred distant cancer spread and poor outcomes. Our study aimed to identify novel molecular markers associated with SCLC prognosis. METHODS: Microarray data from the Gene Expression Omnibus (GEO) database of SCLC tumors and paired normal tissues were obtained. In the dataset, Differentially expressed genes (DEGs) which were identified by comparing gene expression between normal lung and SCLC samples, were screened using the R language. The STRING database was used to map protein-protein interaction (PPI) networks, and these were visualized with the Cytoscape software. Go enrichment analysis and prediction were performed using the Metascape database and the results were visualized. Autophagy-related prognostic genes were identified by univariate COX regression analysis. Subsequently, stepwise model selection using the Akaike information criterion (AIC) and multivariate COX regression model was performed to construct DEGs signature. Survival receiver operating characteristic (ROC) analysis was used to assess the performance of survival prediction. At last, we evaluated the differences in drug sensitivity of the two groups of patients to common chemotherapeutic drugs and small-molecule targeted drugs. RESULTS: A total of 441 identified DE genes, including 412 downregulated and 29 upregulated genes were identified. GO enrichment analyses showed that DEGs were significantly enriched in the collagen-containing extracellular matrix and extracellular matrix organization. 16 genes were individually associated with OS in univariate analyses. The high expression of 6 genes (HIST1H4L, RP11-16O9.2, SNORA71A, SELV, FAM66A and BRWD1-AS1)) was associated with the poor prognosis of SCLC patients. To predict patients' outcomes, we developed an individual's risk score model based on the 6 genes. We found that SCLC patients with a low-risk score had significantly better survival than those with a high-risk score. What's more, association analysis between clinicopathological factors and gene signature showed the risk score was higher in patients with higher clinical stage or T stage. What's more, the patients in the high-risk score group had better treatment effects for etoposide and docetaxel. This suggests that our model can guide clinical treatment decisions. CONCLUSION: A novel six-gene signature was determined for prognostic prediction in SCLC. Our findings may provide new insights into the precise treatment and prognosis prediction of SCLC.

Integrated miRNA and mRNA omics reveal dioscin suppresses migration and invasion via MEK/ERK and JNK signaling pathways in human endometrial carcinoma in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum sibiricum Redouté (PS, also called Huangjing in traditional Chinese medicine), is a perennial herb as homology of medicine and food. According to the traditional Chinese medicine theory "Special Records of Famous Doctors", its functions include invigorating qi and nourishing yin, tonifying spleen and kidney. Traditionally, qi and blood therapy has been believed as most applicable to the treatment of uterine disease. The current research has focused on the effect and mechanism of dioscin, the main active component of PS, on Endometrial carcinoma (EC). AIM OF THE STUDY: To study the efficacy of dioscin on proliferation and migration of Endometrial carcinoma cell line, we conducted experiments by using xenograft model and Ishikawa cells, and explored the potential molecular mechanism. MATERIALS AND METHODS: mRNA and miRNA omics techniques were employed to investigate the regulatory mechanism of dioscin on EC Ishikawa cells. Based on in vivo and in vitro experiments, cell clone formation, cell scratching, Transwell, H&E staining, immunohistochemistry, q-PCR, and Western blot techniques were used to determine the molecular effects and mechanisms of dioscin on cell migration. RESULTS: Integrated miRNA and mRNA omics data showed that 513 significantly different genes marked enrichment in MAPK signaling pathway. The in vivo data showed that dioscin (24 mg/kg) significantly inhibited tumor growth. The in vitro proliferation and invasiveness of dioscin on Ishikawa cells showed that dioscin could significantly decrease the colony numbers, and suppress the Ishikawa cell wound healing, migration and invasion. Molecular data revealed that dioscin decreased the MMP2 and MMP9 expression in vitro and in vivo. The p-MEK, p-ERK, and p-JNK expression levels were also confirmed to be significantly reduced. Key regulators in the MAPK signaling pathway were further validated in xenograft tumors. CONCLUSION: Our data indicated that dioscin inhibited Ishikawa cell migration and invasion mediated through MEK/ERK and JNK signaling. More importantly, screened hub miRNAs and genes can be regarded as potential molecular targets for future EC treatment.

Anti-hardening effect and mechanism of silkworm sericin peptide in high protein nutrition bars during early storage.

Hardening presents an inevitable challenge during the storage of high protein nutrition bars. Sericin peptide is the product of hydrolysis of sericin, a protein from the silkworm cocoon. Here in, the effects of sericin peptide addition on the hardening of high protein nutrition bars during 72 h of storage were investigated. The addition of sericin peptide to high protein nutrition bars reduced the hardening of the sample during the early storage, The main mechanism was to improve the mobility of water and small hydrophilic molecules, which slowed down the phase separation. As well, after sericin peptide addition, the ζ- potential, the content of secondary structure, and the surface hydrophobicity of the samples were also changed, which prevented the self-aggregation of proteins. These results indicate that SRP can be used as a promising anti-hardening ingredient in the food industry to improve the texture of food products.

Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo.

Endometrial cancer (EC) is a very common female cancer which has attracted more and more attention. According to the individual patient's condition, the current treatment of EC patients is mainly based on surgery, which is supplemented by chemotherapy, radiotherapy, and endocrine intervention. However, these existing treatment strategies also have some inevitable limitations. Therefore, it is particularly important to find an active ingredient with low toxicity and a high safety profile against EC. Isorhamnetin is a flavonoid known to be present in a variety of plants, such as sea buckthorn, dry willow, and wolfberry. In recent years, the anti-tumor effects of isorhamnetin have been reported. In our study, isorhamnetin was shown to induce apoptosis in Ishikawa cells by inducing the endogenous mitochondrial apoptotic pathway and exogenous death receptor pathway, promoting the endoplasmic reticulum stress-related pathway, and activating the corresponding markers of UPR response. In addition, isorhamnetin affected the expression of MMP2 and MMP9-related proteins in vitro and in vivo and eventually repressed metastasis. Therefore, isorhamnetin can be used as a promising medicinal material for the treatment of EC.

Development and Validation of a DNA Methylation-related Classifier of Circulating Tumour Cells to Predict Prognosis and to provide a therapeutic strategy in Lung Adenocarcinoma.

Background: A significant factor influencing the prognosis of lung adenocarcinoma (LUAD) is tumor metastasis. Studies have shown that abnormal DNA methylation in circulating tumor cells (CTCs) is associated with tumour metastasis. Based on the genes expressed in CTCs that play an important role in DNA methylation, we hope to build a risk model to predict prognosis and provide a therapeutic strategy in LUAD. Methods: The CTC sequencing data for LUAD were obtained from GSE74639, which contains 10 CTC samples and 6 primary tumour samples. To carefully assess the clinical value, functional status, involvement of the tumor microenvironment (TME) based on the risk model, and genetic variants based on based on data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), a reliable risk model was successfully built. Results: Three differentially methylated genes (DMGs) of CTCs for LUAD, including mitochondrial ribosomal protein L51 (MRPL51), STE20-like kinase (SLK), and protein regulator of cytokinesis 1(PRC1), were effectively used to construct a risk model. Both the training and validation cohorts' stability and accuracy of the risk model were evaluated. Each patient in the TCGA-LUAD cohort received a risk score, and based on the median score, they were divided into high- and low-risk groups. The tumors in the high-risk group in this study were classified as "cold" and immunosuppressed, which may be linked to a poor prognosis. The tumors in the low-risk group, however, were deemed "hot" and had immune hyperfunction linked to a positive prognosis. Additionally, patients in the low-risk group showed greater sensitivity to immunotherapy than those in the high-risk group. Conclusions: Based on DMGs of CTCs from LUAD, we successfully developed a predictive risk model and discovered differences in biological function, TME, genetic variation, and clinical outcomes between those at high and low risk group.

Physicochemical and antioxidant properties of Lycium barbarum seed dreg polysaccharides prepared by continuous extraction.

Lycium barbarum seed dreg polysaccharides (LBSDPs) were continuously extracted with four different solvents [hot buffer (HBSS), chelating agent (CHSS), dilute alkaline (DASS), and concentrated alkaline (CASS)]. The present study characterized the physicochemical and anti-oxidant based functional properties of different LBSDPs. The monosaccharide analysis revealed xylose (64.63%, 70.00%, 44.71%, and 66.67%) as the main sugar with the molecular weights of 5985, 7062, 5962, and 8762 Da in HBSS, CHSS, DASS, and CASS, respectively. Among the four polysaccharides, CASS had the strongest DPPH radical scavenging ability and reducing power; while, CHSS had the strongest ferrous ions chelating ability and HBSS showed the strongest OH radical scavenging ability. In terms of functional properties, HBSS and CASS had better solubility and oil holding capacity, while, CASS and CHSS had higher foam capacity and foam stability. Altogether, the polysaccharides extracted from L. barbarum seed dreg exhibit a potential application prospect in functional food and cosmetics industries.

Low-cost polymer-film spiral inertial microfluidic device for label-free separation of malignant tumor cells.

We developed a low-cost polymer-film spiral inertial microfluidic device for the effective size-dependent separation of malignant tumor cells. The device was fabricated in polymer films by rapid laser cutting and chemical bonding. After fabricating the prototype device, the separation performance of our device was evaluated using particles and cells. The effects of operational flow rate, cell diameter, and cell concentration on the separation performance were explored. Our device successfully separated tumor cells from polydisperse white blood cells according to their different migration modes and lateral positions. Then, the separation of rare cells was carried out using the high-concentration lysed blood spiked with 200 tumor cells. Experimental results showed that 83.90% of the tumor cells could be recovered, while 99.87% of white blood cells could be removed. We successfully employed our device for processing clinical pleural effusion samples from patients with advanced metastatic breast cancer. Malignant tumor cells with an average purity of 2.37% could be effectively enriched, improving downstream diagnostic accuracy. Our device offers the advantages of label-free operation, low cost, and fast fabrication, thus being a potential tool for effective cell separation.

Development and Validation of an E2F-Related Gene Signature to Predict Prognosis of Patients With Lung Squamous Cell Carcinoma.

BACKGROUND: Lung squamous cell carcinoma (LUSC) generally correlates with poor clinical prognoses due to the lack of available prognostic biomarkers. This study is designed to identify a potential biomarker significant for the prognosis and treatment of LUSC, so as to provide a scientific basis for clinical treatment decisions. METHODS: Genomic changes in LUSC samples before and after radiation were firstly discussed to identify E2 factor (E2F) pathway of prognostic significance. A series of bioinformatics analyses and statistical methods were combined to construct a robust E2F-related prognostic gene signature. Furthermore, a decision tree and a nomogram were established according to the gene signature and multiple clinicopathological characteristics to improve risk stratification and quantify risk assessment for individual patients. RESULTS: In our investigated cohorts, the E2F-related gene signature we identified was capable of predicting clinical outcomes and therapeutic responses in LUSC patients, besides, discriminative to identify high-risk patients. Survival analysis suggested that the gene signature was independently prognostic for adverse overall survival of LUSC patients. The decision tree identified the strong discriminative performance of the gene signature in risk stractification for overall survival while the nomogram demonstrated a high accuracy. CONCLUSION: The E2F-related gene signature may help distinguish high-risk patients so as to formulate personalized treatment strategy in LUSC patients.

Dysregulated ferroptosis-related genes indicate potential clinical benefits for anti-PD-1/PD-L1 immunotherapy in lung adenocarcinoma.

BACKGROUND: Ferroptosis is an iron-dependent programmed cell death mechanism that influences the development of malignancy. Lung adenocarcinoma (LUAD) is the most common type of lung cancer with no known cure. Anti-PD-1/PD-L immunotherapy is effective for patients with partial LUAD. Therefore, there is an immediate requirement of novel markers to predict the individualised benefits of immunotherapy. METHODS: We manually collected the ferroptosis-related gene (FERG) set and employed the Wilcoxon rank-sum test to identify the differentially expressed FERGs. Subsequently, we constructed a recursive partitioning and regression tree (RPART) model to predict the benefits of anti-PD-1/PD-L1 immunotherapy. Subsequently, the ROC curve and AUC were used to evaluate the model efficiency in an independent dataset. RESULTS: In this study, we found that the dysregulated FERGs were closely associated with multiple metabolic processes in LUAD. Furthermore, we identified three ferroptosis-related tumour subtypes (F1, F3 and F3). The F3 subtype exhibited higher immunoactivity and lower tumour purity, mutation count and aneuploidy and had better survival outcomes compared with the other two subtypes, implying that FERGs played an important role in intertumoral immune heterogeneity. We further explored the role of FERGs in the anti-PD-1/PD-L1 immunotherapy. We identified a set of three-FERGs signature (CD44, G6PD and ZEB1) that acted as a promising indicator (AUC = 0.697) for the prediction of the benefits of anti-PD-1/PD-L1 immunotherapy. CONCLUSION: Ferroptosis, as emerging programmed cell death mechanism, was associated with cancer development. We used ferroptosis-related genes to predict the immunotherapy benefits that may facilitate the development of individualised anti-cancer treatment strategies.

[The effect of orthognathic surgery on speech function in patients with skeletal Class â ¢ malocclusion].

PURPOSE: To investigate the influence of the position of the upper and lower jaws on the anatomical structure of pharynx before and after orthognathic surgery in patients with skeletal Class Ⅲ malocclusion. METHODS: Craniofacial CT scan and speech data were collected from 31 patients with skeletal Class Ⅲ malocclusion before and 3 months after surgery. The collected CT data was imported into Dolphin imaging 11.95 software to establish a digital original model, and the anatomical structure of the pharynx was measured and analyzed. Speech data were analyzed objectively and subjectively by Computerized Speech Lab 4500b and professional speech specialists. Statistical analysis was performed using SPSS 24.0 software package. RESULTS: The distance from the lower edge of the soft palate to the posterior pharyngeal wall, the shortest distance from the posterior margin of the tongue to the posterior pharyngeal wall and its corresponding cross-sectional area were significantly different from those before surgery (P<0.05). The changes of SNA, SNB, ANB, OJ, and OBJ before and after surgery were significant in this series. Importantly, the speech intelligibility of orthognathic patients before and after surgery changed significantly subjectively (P<0.05). Objectively, the postoperative vowels /a/B2, B3, B4, /i/B1,B2, /u/B1,B2 and B4 of the patients were significantly different from those before surgery. There was no significant difference in the lower limit frequency of the consonants /x/, /zh/, /s/, the energy value of /zh/ and the grammatical form of /z/ before and after surgery. The maxillary advancement distance was highly correlated or significantly correlated with △S1, △VOP, and voice changes. CONCLUSIONS: Orthognathic surgery moves the upper and lower jaws to cause changes in the anatomy of the pharyngeal cavity, leading to changes of postoperative speech.

[Pollution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in a Suburban Farmland Soil].

In order to assess the pollution of polycyclic aromatic hydrocarbons(PAHs) in a suburban farmland soil, 29 sampling sites were collected around Nanjing according to the grid method, and the contents of 15 different PAHs were determined. Acenaphthene(Ace) was not detected in any of the samples. The total content of PAHs in farmland soil ranged from 24.49 to 750.04 µg·kg-1, with an average of 226.64 µg·kg-1. The spatial distribution of high-ring PAHs, the main PAHs in the farmland soil, was similar to that of total PAHs. There was no significant correlation between PAHs and soil organic matter(SOM), pH, cation exchange capacity(CEC), and total nitrogen(TN), whereas bulk density and low ring PAHs were significantly correlated. The results of source apportionment show that the main source of PAHs in the farmland soil is a mixture of combustion and petroleum. The contamination severity index(CSI) index shows that the PAHs does not pose an ecological risk. The results of the health risk assessment show that there is no potential carcinogenic risk to children or adults, and the main sequence of exposure is skin contact>ingestion>inhalation.

Immune-related eight-lncRNA signature for improving prognosis prediction of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths worldwide. Therefore, the identification of a novel prediction signature for predicting the prognosis risk and survival outcomes is urgently demanded. METHODS: We integrated a machine-learning frame by combing the Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression model to identify the LUAD-related long non-coding RNA (lncRNA) survival biomarkers. Subsequently, the Spearman correlation test was employed to interrogate the relationships between lncRNA signature and tumor immunity and constructed the competing endogenous RNA (ceRNA) network. RESULTS: Herein, we identified an eight-lncRNA signature (PR-lncRNA signature, NPSR1-AS1, SATB2-AS1, LINC01090, FGF12-AS2, AC005256.1, MAFA-AS1, BFSP2-AS1, and CPC5-AS1), which contributes to predicting LUAD patient's prognosis risk and survival outcomes. The PR-lncRNA signature has also been confirmed as the robust signature in independent datasets. Further parsing of the LUAD tumor immune infiltration showed the PR-lncRNAs were closely associated with the abundance of multiple immune cells infiltration and the expression of MHC molecules. Furthermore, by constructing the PR-lncRNA-related ceRNA network, we interrogated more potential anti-cancer therapy targets. CONCLUSION: lncRNAs, as emerging cancer biomarkers, play an important role in a variety of cancer processes. Identification of PR-lncRNA signatures allows us to better predict patient's survival outcomes and disease risk. Finally, the PR-lncRNA signatures could help us to develop novel LUAD anti-cancer therapeutic strategies.

[Evaluation of digital technology for orthognathic surgery in 25 patients].

PURPOSE: To use three-dimensional reconstruction measurement, preoperative diagnosis, surgical design, surgical simulation, guide plate production, navigation verification and effect evaluation of orthognathic surgery assisted by digital technology, in order to explore more scientific and reasonable programs and procedures of orthognathic surgery. METHODS: Twenty-five patients with congenital dental and maxillofacial deformity were selected as the experimental subjects, craniofacial spiral CT was conducted before surgery and CT data were imported into Mimics 20.0 software to establish a 3D head digital model. The bone landmarks in three-dimensional reconstruction digital model were selected, measured, analyzed and diagnosed, and the design of the surgical plan and the production of the guide plates were performed. Surgical navigation system was used to confirm the maxillary position, verify the bone retention and guide precise bone grinding during operation. Craniofacial spiral CT was conducted 1 week after surgery for postoperative validation of the surgical design protocol. Statistical analysis was performed using SPSS 24.0 software package. RESULTS: All 25 patients were operated according to the digital orthognathic surgery design and procedure.There were no significant differences in X, Y and Z three-dimensional directions in 10 actual landmarks between the postoperative actual head model and the preoperative predictive head model（P>0.05）. CONCLUSIONS: Orthognathic surgery assisted by digital technology has the advantages of precision and minimal invasiveness.