In-bag extraction of tissue through an incision in the posterior vaginal wall in laparoscopic myomectomy: a large retrospective study.

BACKGROUND: Our purpose was to describe the outcomes of transvaginal in-bag tissue extraction tissue through an incision in the posterior vaginal wall the middle part incision of posterior vagina in laparoscopic myomectomy. METHODS: This was a retrospective study of patients who received laparoscopic myomectomy and in-bag tissue extraction through an incision in the posterior vaginal wall between January 2016 and December 2022. Patient characteristics, intra- and post-operative complications, and outcomes were collected and analyzed. RESULTS: A total of 511women were included in the analysis. The mean largest myoma diameter was 8.44 ± 3.56 cm; mean specimen weight was 789.23 ± 276.97 g; mean operative time was 129.01 ± 53.13minutes; and mean blood loss was 175.99 ± 210.96 mL. Within 30-days of surgery, no fever, infection, or vaginal bleeding was noted in any patient, and the vaginal incisions of all patients had healed well. There were no incisional hernias, pelvic infections, and vaginal adhesions noted at follow-up 3 months after the operation. There were 37 cases of vaginal delivery of the patients after surgery, and there were no lacerations of the posterior wall vaginal incision. CONCLUSIONS: Transvaginal in-bag extraction though an incision in the posterior vaginal wall is feasible and safe for removing tissue after laparoscopic myomectomy.

Machine learning prediction models for different stages of non-small cell lung cancer based on tongue and tumor marker: a pilot study.

OBJECTIVE: To analyze the tongue feature of NSCLC at different stages, as well as the correlation between tongue feature and tumor marker, and investigate the feasibility of establishing prediction models for NSCLC at different stages based on tongue feature and tumor marker. METHODS: Tongue images were collected from non-advanced NSCLC patients (n = 109) and advanced NSCLC patients (n = 110), analyzed the tongue images to obtain tongue feature, and analyzed the correlation between tongue feature and tumor marker in different stages of NSCLC. On this basis, six classifiers, decision tree, logistic regression, SVM, random forest, naive bayes, and neural network, were used to establish prediction models for different stages of NSCLC based on tongue feature and tumor marker. RESULTS: There were statistically significant differences in tongue feature between the non-advanced and advanced NSCLC groups. In the advanced NSCLC group, the number of indexes with statistically significant correlations between tongue feature and tumor marker was significantly higher than in the non-advanced NSCLC group, and the correlations were stronger. Support Vector Machine (SVM), decision tree, and logistic regression among the machine learning methods performed poorly in models with different stages of NSCLC. Neural network, random forest and naive bayes had better classification efficiency for the data set of tongue feature and tumor marker and baseline. The models' classification accuracies were 0.767 ± 0.081, 0.718 ± 0.062, and 0.688 ± 0.070, respectively, and the AUCs were 0.793 ± 0.086, 0.779 ± 0.075, and 0.771 ± 0.072, respectively. CONCLUSIONS: There were statistically significant differences in tongue feature between different stages of NSCLC, with advanced NSCLC tongue feature being more closely correlated with tumor marker. Due to the limited information, single data sources including baseline, tongue feature, and tumor marker cannot be used to identify the different stages of NSCLC in this pilot study. In addition to the logistic regression method, other machine learning methods, based on tumor marker and baseline data sets, can effectively improve the differential diagnosis efficiency of different stages of NSCLC by adding tongue image data, which requires further verification based on large sample studies in the future.

Effect of a two-phase tobacco control regulation on incidence from ischemic stroke and hemorrhagic stroke, Shenzhen, China, 2007-2016.

INTRODUCTION: The Shenzhen government is widely considered to be most efficiently implementing smoke-free legislation in China. We evaluated and compared the impact of Shenzhen's two-phase smoke-free regulation on the incidence rates for ischemic and hemorrhagic stroke. METHODS: An interrupted time series design was used to capture immediate and annual incidence changes from 2007 to 2016 for both ischemic and hemorrhagic stroke due to two-phase smoke-free regulation in Shenzhen, China, by using a generalized additive model. The first phase, implemented on 9 March 2010, required five main public places to be smoke-free. In the second phase, the comprehensive law was expanded to the whole city on 1 March 2014. RESULTS: The regulation implementation during phase I was associated with a strong immediate decline in the incidence rate of ischemic stroke (-14.2%, 95% CI: -19.6 - -8.4) and hemorrhagic stroke (-10.1%, 95% CI: -18.2 - -1.2), but without showing the annual changes (p>0.05). Following the implementation of the comprehensive law, the gradual annual effect showed a significant change in ischemic stroke, with a 6.3% (95% CI: 8.9 - -3.6) reduction. Neither the immediate nor gradual decreases in hemorrhagic stroke incidences associated with the comprehensive regulation were statistically significant during phase II (p>0.05). Subgroup analyses indicate that a much larger health effect of the regulation during phase I was greater among those aged ≥65 years than among those aged 35-64 years. CONCLUSIONS: Shenzhen's two-phase smoke-free regulation was well implemented. Even though the regulation did not extend to the whole city, the immediate health benefits on the incidence rates of ischemic stroke and hemorrhagic stroke could be seen. However, the health benefits brought by the implementation of comprehensive smoke-free legislation were attenuated by previous smoke-free regulations in five main public places, which were more evident in hemorrhagic stroke.

A lung cancer risk warning model based on tongue images.

Objective: To investigate the tongue image features of patients with lung cancer and benign pulmonary nodules and to construct a lung cancer risk warning model using machine learning methods. Methods: From July 2020 to March 2022, we collected 862 participants including 263 patients with lung cancer, 292 patients with benign pulmonary nodules, and 307 healthy subjects. The TFDA-1 digital tongue diagnosis instrument was used to capture tongue images, using feature extraction technology to obtain the index of the tongue images. The statistical characteristics and correlations of the tongue index were analyzed, and six machine learning algorithms were used to build prediction models of lung cancer based on different data sets. Results: Patients with benign pulmonary nodules had different statistical characteristics and correlations of tongue image data than patients with lung cancer. Among the models based on tongue image data, the random forest prediction model performed the best, with a model accuracy of 0.679 ± 0.048 and an AUC of 0.752 ± 0.051. The accuracy for the logistic regression, decision tree, SVM, random forest, neural network, and naïve bayes models based on both the baseline and tongue image data were 0.760 ± 0.021, 0.764 ± 0.043, 0.774 ± 0.029, 0.770 ± 0.050, 0.762 ± 0.059, and 0.709 ± 0.052, respectively, while the corresponding AUCs were 0.808 ± 0.031, 0.764 ± 0.033, 0.755 ± 0.027, 0.804 ± 0.029, 0.777 ± 0.044, and 0.795 ± 0.039, respectively. Conclusion: The tongue diagnosis data under the guidance of traditional Chinese medicine diagnostic theory was useful. The performance of models built on tongue image and baseline data was superior to that of the models built using only the tongue image data or the baseline data. Adding objective tongue image data to baseline data can significantly improve the efficacy of lung cancer prediction models.

LncRNA GSCAR promotes glioma stem cell maintenance via stabilizing SOX2 expression.

Gliomas are the most aggressive type of malignant brain tumors. Recent studies have demonstrated that the existence of glioma stem cells (GSCs) is critical for glioma recurrence, metastasis, and chemo- or radio-therapy resistance. Temozolomide (TMZ) has been used as an initial therapy for gliomas. However, the overall survival time is still limiting due to the lack of effective targets and treatment options. Therefore, identifying novel biomarkers for gliomas, especially for GSCs, is important to improve the clinical outcome in the future. In this study, we identify a human-specific long non-coding RNA (lncRNA, ENSG00000250377), termed GSCAR (glioma stem cell associated lncRNA), which is highly expressed in glioma cancerous tissues and cell lines. We reveal that GSCAR positively correlates with tumor grade. Glioma patients with GSCAR high expression exhibit shortened overall survival time, compared to patients with GSCAR low expression. Furthermore, we show that GSCAR knockdown by shRNAs or antisense oligonucleotide (ASO) reduces tumor cell proliferation, migration and xenograft tumor formation abilities. Mechanistic study shows that GSCAR acts as a ceRNA (competing endogenous RNA) for miR-6760-5p to promote the expression of oncogene SRSF1 (serine and arginine rich splicing factor 1). In addition, GSCAR mediates the protein complex formation between DHX9 (DExH-Box helicase 9) and IGF2BP2 (insulin-like growth factor 2 mRNA-binding protein 2), leading to the stabilization of SOX2 (sex-determining region Y-box 2) mRNA and then the transcriptional activation of GSCAR. Depleting GSCAR reduces SOX2 expression and GSC self-renewal ability, but promotes tumor cell responses to TMZ. These findings uncover that GSCAR/miR-6760-5p/SRSF1 axis and GSCAR/DHX9-IGF2BP2/SOX2 positive feedback loop are critical for glioma progression, which could be used as prognostic biomarkers and therapeutic targets in the future.

A digital workflow to predict facial aesthetics in patients with maxillofacial trauma with implant retained prostheses.

Purpose To introduce a digital workflow for the prediction of facial aesthetics, especially in patients with dentation deformity caused by maxillofacial trauma.Methods Cone-beam computed tomography (CBCT) and three-dimensional facial scans of patients with radiographic prostheses were collected. The aforementioned data were uploaded to ProPlan CMF software and merged to generate a virtual patient with craniofacial hard tissue, realistic facial soft tissue, and remaining dentition. The radiographic prostheses were scanned to form a digital cast, which was fitted with its CBCT image to create the virtual prostheses. Postoperative facial soft tissue was simulated according to the movement of the virtual prostheses. An appropriate virtual diagnostic prosthesis plan was selected by the patient and dentist. Subsequently, prosthetically driven implant guide and restoration were designed and fabricated.Conclusions A virtual patient was successfully constructed. A 4-mm protrusion of the virtual prosthesis was chosen. Subsequently, implant surgery was performed, and dental prostheses were fabricated based on this location. The fusion of the postoperative facial scan and preoperative facial prediction was found to be coincident. This technique can effectively predict facial aesthetic features of patients with maxillofacial trauma, facilitate communication with patients, reduce chairside time, and guide the multidisciplinary design of implant placement and restoration fabrication.

Generation of Oxygen Vacancies in Metal-Organic Framework-Derived One-Dimensional Ni0.4Fe2.6O4 Nanorice Heterojunctions for ppb-Level Diethylamine Gas Sensing.

Metal-organic frameworks (MOFs) are ideal sensing materials due to their distinctive morphologies, high surface area, and simple calcination to remove sacrificial MOF scaffolds. Oxygen vacancies (Ovs) can be efficiently generated by the thermal annealing of metal oxides in an inert atmosphere. Herein, MIL-53-based Fe and Fe/Ni-MOFs nanorices (NRs) were first prepared by using a solvothermal method, and then one-dimensional (1D) Fe2O3 and Ni0.4Fe2.6O4 NRs were derived from the MOFs after calcination at 350 °C in an air and argon (Ar) atmosphere, respectively. It was found that Ar-annealed Ni0.4Fe2.6O4 NRs have higher Ovs concentrations (82.11%) and smaller NRs (24.3 nm) than air-annealed NRs (65.68% & 31.5 nm). Beneficially, among the synthesized NRs, the Ar-Ni0.4Fe2.6O4 NRs show a higher sensitivity to diethylamine (DEA) (Ra/Rg = 23 @ 5 ppm, 175 °C), low detection limit (Ra/Rg = 1.2 @ 200 ppb), wide dynamic response (Ra/Rg = 93.5@ 30 ppm), high stability (30 days), and faster response/recovery time (4 s/38 s). Moreover, the 1D nanostructure containing heterostructures offers excellent sensing selectivity and a wide detection range from 200 ppb to 30 ppm in the presence of DEA. The outstanding gas sensing behavior can be attributable to synergistic impact, structural advantages, high concentration of Ovs, and the heterojunction interface, which can have profound effects on gas sensor performance. This study provides a unique technique for constructing high-performance gas sensors for ppb-level DEA detection and the formation of Ovs in metal oxides without the need for any additives.

High-Throughput Electrosynthesis of Gradient Polypyrrole Film Using a Single-Electrode Electrochemical System.

As an effective approach for materials synthesis, bipolar electrochemistry has been earning a renewed interest nowadays thanks to its unique features compared to conventional electrochemistry. Indeed, the wireless mode of electrode reactions and the generation of a gradient potential distribution above the bipolar electrode are among the most appealing qualities of bipolar electrochemistry. In particular, the gradient potential distribution is a highly attractive characteristic for the fabrication of surfaces with gradients in their chemical properties or molecular functionalities. Herein, we report the high-throughput electrosynthesis of gradient polypyrrole films by means of a new electrochemical cell design named the single-electrode electrochemical system (SEES). SEESs are made by attaching an inert plastic board with holes onto an indium tin oxide electrode, constructing multiple microelectrochemical cells on the same electrode. This type of arrangement enables parallel electrochemical reactions to be carried out simultaneously and controlled in a contactless manner by a single electrode. Several experimental conditions for polypyrrole film growth were extensively investigated. Furthermore, the gradient property of the polymer films was evaluated by thickness determination, surface morphology analysis, and contact angle measurements. The use of SEES has been demonstrated as a convenient and cost-effective strategy for high-throughput electrosynthesis and electroanalytical applications and has opened up a new door for gradient film preparation via a rapid condition screening process.

miR-141-3p Promotes the Cisplatin Sensitivity of Osteosarcoma Cell through Targeting the Glutaminase [GLS]-Mediated Glutamine Metabolism.

AIMS: This study aimed to evaluate the roles and molecular targets of miRNA-141-3p in the cisplatin sensitivity of osteosarcoma. BACKGROUND: Osteosarcoma is one of the most common-type bone tumors, occurring mainly in children and adolescents. Cancer cells display dysregulated cellular metabolism, such as the abnormally elevated glutamine metabolism. OBJECTIVE: Non-coding RNA miRNA-141-3p has been reported to act as a tumor suppressor in osteosarcoma. Currently, the precise molecular mechanisms for the miR- 141-3p-mediated chemosensitivity through regulating glutamine metabolism remain unclear. METHODS: We collected thirty paired OS tumors and their adjacent normal tissues. The osteosarcoma cell lines [Saos-2] and normal osteoblast cells, hFOB1.19, were used for in vitro experiments. RT-qPCR and Western blot were applied for gene expression detections. Targets of miR-141-3p were predicted from starBase. The MTT and flow cytometric assays were performed to determine cell growth and apoptosis rates. The cellular glutamine metabolism was monitored by glutamine uptake assay and the glutaminase [GLS] activity assay. RESULTS: We reported that miR-141-3p were significantly downregulated in osteosarcoma tissues and cells. Overexpression of miR-141-3p suppressed OS cell growth and sensitized OS cells to cisplatin. In addition, glutamine metabolism was significantly increased in osteosarcoma. We characterized that GLS played oncogenic roles in osteosarcoma and validated GLS was a direct target of miR-141-3p in OS cells. Rescue experiments consistently demonstrated that miR-141-3p-promoted cisplatin sensitivity was achieved by targeting GLS directly. CONCLUSION: Overall, our findings revealed new molecular mechanisms of the miR-141- 3p-modulated cisplatin sensitization through targeting the GLS-glutamine metabolism pathway. This study will contribute to developing new therapeutic approaches for the treatments of chemoresistant osteosarcoma.

Facial changes in patients with skeletal class III deformity after bimaxillary surgery: an evaluation based on three-dimensional photographs registered with computed tomography.

The objective of this study was to evaluate facial soft and hard tissue changes, individually and relative to each other, in patients with skeletal class III deformity after bimaxillary surgery using three-dimensional (3D) photos obtained by white light scanning. Thirty patients with skeletal class III deformity who underwent bimaxillary surgery were selected. Each patient underwent white light scanning and spiral computed tomography (CT) within two weeks before (T0) and six months after surgery (T1). The 3D photos were registered with CT soft tissue models for T0 and T1, and the skeletal area unaffected by treatment (cranial base) was used to register T0 and T1. Then, the 3D colour-coded map was analysed to assess both skeletal and soft tissue changes between T0 and T1. Changes in the 3D coordinates of each anatomical landmark were analysed using the Student's t-test. Maxillary advancement by 2-3 mm and mandibular recession by 5-6 mm were observed; the mandible was shortened in the vertical direction. Compared with the preoperative values, the nasal columella was 0.51 mm shorter, the upper lip was 0.71 mm longer, the base of the alar cartilage was 1.38 mm wider, and the nasolabial angle became larger. The ratio of change in the position of soft tissue point Sn to hard tissue point A was 0.73:1, and that of soft tissue point Pg to hard tissue point Pog was 0.86:1. Images obtained by structured white light scanning registered with CT can be used as an alternative to study facial changes after orthognathic surgery.

Oxygen Vacancies Induced by Pd Doping in Ni-P2O5/MoO3 Hollow Polyhedral Heterostructures for Highly Efficient Diethylamine Gas Sensing.

Semiconductor metal-oxide materials have a high surface-to-volume ratio and many active sites, making them potentially useful for gas sensing. Dopants introduced into the lattice can improve the catalytic activity of oxides and promote the formation of oxygen vacancies, hence improving the sensing performance of the materials. However, the simple preparation of materials with high sensitivity, selectivity, and a low detection limit remains a challenge. Herein, we report on the synthesis of Ni-P2O5/MoO3 and Pd-doped Ni-P2O5/MoO3 hollow polyhedral heterostructures (HPHSs) and their application in diethylamine (DEA) sensing for the first time. The Pd-doped Ni-P2O5/MoO3 HPHS was synthesized by doping different proportions of palladium-containing precursors using hydrothermal and solid-state reaction techniques. The concentration of oxygen vacancies in the HPHS composite increased by increasing Pd doping from 2 to 6 weight percent (wt %) but later reduced, according to X-ray photoelectron spectroscopy (XPS) measurements. Pd6%Ni-P2O5/MoO3 has the highest sensitivity to DEA (Ra/Rg = 42.5) and is 5.0 times and 42.5 times more sensitive than the pure Ni-P2O5/MoO3 HPHS (Ra/Rg = 8.5) and commercial ammonium phosphomolybdate (Ra/Rg = 1) at 175 °C toward 10 ppm DEA. Moreover, the DEA sensor exhibits a low detection limit (Ra/Rg = 3.5@1 ppm) with a wide dynamic response (Ra/Rg = 145.5@50 ppm). The remarkable improvement in DEA sensitivity is attributed to the hollow polyhedral structure, heterostructures, and oxygen vacancies formed by Pd doping. This study confirms that developing Pd-doped Ni-P2O5/MoO3 HPHSs provides an innovative approach for DEA sensors.

A multi-step approach for tongue image classification in patients with diabetes.

BACKGROUND: In China, diabetes is a common, high-incidence chronic disease. Diabetes has become a severe public health problem. However, the current diagnosis and treatment methods are difficult to control the progress of diabetes. Traditional Chinese Medicine (TCM) has become an option for the treatment of diabetes due to its low cost, good curative effect, and good accessibility. OBJECTIVE: Based on the tongue images data to realize the fine classification of the diabetic population, provide a diagnostic basis for the formulation of individualized treatment plans for diabetes, ensure the accuracy and consistency of the TCM diagnosis, and promote the objective and standardized development of TCM diagnosis. METHODS: We use the TFDA-1 tongue examination instrument to collect the tongue images of the subjects. Tongue Diagnosis Analysis System (TDAS) is used to extract the TDAS features of the tongue images. Vector Quantized Variational Autoencoder (VQ-VAE) extracts VQ-VAE features from tongue images. Based on VQ-VAE features, K-means clustering tongue images. TDAS features are used to describe the differences between clusters. Vision Transformer (ViT) combined with Grad-weighted Class Activation Mapping (Grad-CAM) is used to verify the clustering results and calculate positioning diagnostic information. RESULTS: Based on VQ-VAE features, K-means divides the diabetic population into 4 clusters with clear boundaries. The silhouette, calinski harabasz, and davies bouldin scores are 0.391, 673.256, and 0.809, respectively. Cluster 1 had the highest Tongue Body L (TB-L) and Tongue Coating L (TC-L) and the lowest Tongue Coating Angular second moment (TC-ASM), with a pale red tongue and white coating. Cluster 2 had the highest TC-b with a yellow tongue coating. Cluster 3 had the highest TB-a with a red tongue. Group 4 had the lowest TB-L, TC-L, and TB-b and the highest Per-all with a purple tongue and the largest tongue coating area. ViT verifies the clustering results of K-means, the highest Top-1 Classification Accuracy (CA) is 87.8%, and the average CA is 84.4%. CONCLUSIONS: The study organically combined unsupervised learning, self-supervised learning, and supervised learning and designed a complete diabetic tongue image classification method. This method does not rely on human intervention, makes decisions based entirely on tongue image data, and achieves state-of-the-art results. Our research will help TCM deeply participate in the individualized treatment of diabetes and provide new ideas for promoting the standardization of TCM diagnosis.

The N6-Methylandenosine-Related Gene BIRC5 as a Prognostic Biomarker Correlated With Cell Migration and Immune Cell Infiltrates in Low Grade Glioma.

Gliomas account for 75% of all primary malignant brain tumors in adults and are associated with high mortality. Emerging evidence has demonstrated that baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays a critical role in cell apoptosis and the progression of diverse cancers. However, no studies have yet focused on the immunological function and mechanisms of upstream BIRC5 regulation in the progression of low-grade gliomas (LGG). Here, we evaluated BIRC5 expression and clinical characteristics in people with LGG using the Chinese Glioma Genome Atlas, The Cancer Genome Atlas, Gene Expression Omnibus, Rembrandt, and Gravendeel databases. We used Kaplan-Meier statistics and receiver operating characteristic (ROC) curves to analyze the prognostic value of BIRC5 in LGG. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment terms were also explored to identify functional roles of BIRC5. The Tumor Immune Estimation Resource (TIMER) and Tumor Immune System Interaction (TISIDB) databases were used to examine the correlation between BIRC5 expression and immune cell infiltration in LGG. The Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal (CTRP) databases were used to examine the potential drugs targeting BIRC5. We used transwell and wound healing assays to determine the biological functions of BIRC5 in glioma cell migration. Our results demonstrated that BIRC5 was highly expressed in LGG and the expression level correlated with tumor grade, prognosis, histological subtype, isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q chromosomal co-deletion, chemotherapy status, and O[6]-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. GO and KEGG analysis showed that BIRC5 is primarily involved in cell proliferation and immune response-related signaling pathways. We also found that BIRC5 was significantly correlated with m6A modification and diverse drug sensitivity. TIMER and TISIDB database analysis showed that BIRC5 expression is associated with infiltration of diverse immune cells and immune modulation in LGG. BIRC5 knockdown inhibited LGG cell migration. Collectively, our results demonstrate that BIRC5 is correlated with cell migration and immune infiltration in LGG and may be a useful prognostic biomarker.

NCAPG as a Novel Prognostic Biomarker in Glioma.

Background: Non-SMC condensin I complex subunit G (NCAPG) is expressed in various human cancers, including gliomas. However, its biological function in glioma remains unclear. The present study was designed to determine the biological functions of NCAPG in glioma and to evaluate the association of NCAPG expression with glioma progression. Methods: Clinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), and the Rembrandt and Gravendeel databases. The correlations among NCAPG expression, pathological characteristics, and clinical outcome were evaluated. In addition, the correlations of NCAPG expression with immune cell infiltration and glioma progression were analyzed. Results: NCAPG expression was higher in gliomas than in adjacent normal tissues. Higher expression of NCAPG in gliomas correlated with poorer prognosis, unfavorable histological features, absence of mutations in the isocitrate dehydrogenase gene (IDH), absence of chromosome 1p and 19q deletions, and responses to chemoradiotherapy. Univariate and multivariate Cox analysis demonstrated, in addition to patient age, tumor grade, absence of IDH mutations, and absence of chromosome 1p and 19q deletions, NCAPG expression was independently prognostic of overall survival, disease-free survival, and progression-free survival in patients with glioma. In addition, high expression of NCAPG correlated with tumor infiltration of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Gene set enrichment analysis (GSEA) indicated that high NCAPG expression was associated with cell proliferation and immune response-related signaling pathways. NCAPG knockdown in glioma cell lines significantly reduced cell survival, proliferation, and migration. Conclusion: NCAPG expression correlates with glioma progression and immune cell infiltration, suggesting that NCAPG expression may be a useful prognostic biomarker for glioma.

Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation.

Gliomas are the most aggressive primary brain tumors. However, no significant improvement in survival has been achieved with the addition of temozolomide (TMZ) or radiation as initial therapy, although many clinical efforts have been carried out to target various signaling pathways or putative driver mutations. Here, we report that glycosyltransferase 8 domain containing 1 (GLT8D1), induced by HIF-1α under a hypoxic niche, significantly correlates with a higher grade of glioma, and a worse clinical outcome. Depletion of GLT8D1 inhibits self-renewal of glioma stem cell (GSC) in vitro and represses tumor growth in glioma mouse models. GLT8D1 knockdown promotes cell cycle arrest at G2/M phase and cellular apoptosis with or without TMZ treatment. We reveal that GLT8D1 impedes CD133 degradation through the endosomal-lysosomal pathway by N-linked glycosylation and protein-protein interaction. Directly blocking the GLT8D1/CD133 complex formation by CD133N1~108 (referred to as FECD133), or inhibiting GLT8D1 expression by lercanidipine, suppresses Wnt/ß-catenin signaling dependent tumorigenesis both in vitro and in patient-derived xenografts mouse model. Collectively, these findings offer mechanistic insights into how hypoxia promotes GLT8D1/CD133/Wnt/ß-catenin signaling during glioma progression, and identify GLT8D1 as a potential therapeutic target in the future.

The effects and mechanism of paeoniflorin in promoting osteogenic differentiation of MC3T3-E1.

BACKGROUND: The incidence of osteoporosis and osteoporotic fractures is increasing every year. Traditional Chinese Medicine (TCM) can shed new light on the treatment of osteoporosis. This study aimed to explore the role and mechanism of paeoniflorin in promoting osteogenic differentiation of an osteoblast precursor cell line (MC3T3-E1). METHODS: MC3T3-E1 cells were cultured in osteogenic induction medium (OIM) and OIM combined with different concentrations of paeoniflorin. The optimal dose of paeoniflorin was assessed by a cell counting kit-8 (CCK-8) assay. Then, alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining were performed to assess the osteogenic capacity of paeoniflorin. The transcription of osteogenic genes and the expression of osteogenic proteins were assessed by RT-PCR and Western blotting, respectively. The transcription of Wnt/ß-catenin signaling pathway genes and proteins was assessed by RT-PCR and Western blotting, respectively. Finally, Dickkopf-1 (DKK-1), a Wnt/ß-catenin signaling pathway inhibitor, was used to identify whether the Wnt/ß-catenin signaling pathway was involved in the osteogenic differentiation of paeoniflorin. Osteoclastogenesis in RAW264.7 cells was identified by tartrate-resistant acid phosphatase (TRAP) staining. RESULTS: At concentrations ranging from 0.1 to 100 µM, paeoniflorin was not cytotoxic to MC3T3-E1 cells. Paeoniflorin significantly increased the osteogenic differentiation of MC3T3-E1 cells in a dose-dependent manner. Moreover, paeoniflorin significantly increased osteogenic differentiation gene and protein expression. Through bioinformatic analysis, paeoniflorin-affected genes were found to be involved in different signaling pathways, such as the Wnt/ß-catenin signaling pathway. Paeoniflorin enhanced ß-catenin and CyclinD1 expression compared with that of the control groups. DKK-1 partially reversed the promoting effects of paeoniflorin in promoting osteogenic differentiation of MC3T3-E1 cells. Moreover, paeoniflorin inhibited the osteoclastogenesis of RAW264.7 cells. CONCLUSION: Paeoniflorin promotes osteogenic differentiation in MC3T3-E1 cells by regulating the Wnt/ß-catenin pathway. Paeoniflorin is a potential therapeutic agent for the treatment of osteoporosis.

RETSAT Mutation Selected for Hypoxia Adaptation Inhibits Tumor Growth.

Hypoxia occurs not only in natural environments including high altitude, underground burrows and deep sea, but also in human pathological conditions, such as hypoxic solid tumors. It has been well documented that hypoxia related signaling pathway is associated with a poor clinical outcome. Our group has recently identified multiple novel genes critical for solid tumor growth comparing the genome-wide convergent/parallel sequence evolution of highland mammals. Among them, a single mutation on the retinol saturase gene (RETSAT) containing amino acid switch from glutamine (Q) to arginine (R) at the position 247 was identified. Here, we demonstrate that RETSAT is mostly downregulated in multiple types of human cancers, whose lower expression correlates with worse clinical outcome. We show that higher expression of RETSAT is positively associated with immune infiltration in different human cancers. Furthermore, we identify that the promoter region of RETSAT is highly methylated, which leads to its decreased expressions in tumor tissues comparing to normal tissues. Furthermore, we show that RETSAT knockdown promotes, while its overexpression inhibits, the cell proliferation ability of mouse embryonic fibroblasts (MEFs) and B16 in vitro. In addition, the mice carrying homozygous Q247R mutation (RETSATR/R) is more resistant to xenograft tumor formation, as well as DMBA/TPA induced cutaneous keratinocyte carcinoma formation, compared to littermate wild-type (RETSATQ/Q) mice. Mechanistic study uncovers that the oncogenic factor, the prolyl isomerase (PPIase) Pin1 and its related downstream signaling pathway, were both markedly repressed in the mutant mice compared to the wild-type mice. In summary, these results suggest that interdisciplinary study between evolution and tumor biology can facilitate identification of novel molecular events essential for hypoxic solid tumor growth in the future.

A New Method for Syndrome Classification of Non-Small-Cell Lung Cancer Based on Data of Tongue and Pulse with Machine Learning.

OBJECTIVE: To explore the data characteristics of tongue and pulse of non-small-cell lung cancer with Qi deficiency syndrome and Yin deficiency syndrome, establish syndrome classification model based on data of tongue and pulse by using machine learning methods, and evaluate the feasibility of syndrome classification based on data of tongue and pulse. METHODS: We collected tongue and pulse of non-small-cell lung cancer patients with Qi deficiency syndrome (n = 163), patients with Yin deficiency syndrome (n = 174), and healthy controls (n = 185) using intelligent tongue diagnosis analysis instrument and pulse diagnosis analysis instrument, respectively. We described the characteristics and examined the correlation of data of tongue and pulse. Four machine learning methods, namely, random forest, logistic regression, support vector machine, and neural network, were used to establish the classification models based on symptom, tongue and pulse, and symptom and tongue and pulse, respectively. RESULTS: Significant difference indices of tongue diagnosis between Qi deficiency syndrome and Yin deficiency syndrome were TB-a, TB-S, TB-Cr, TC-a, TC-S, TC-Cr, perAll, and the tongue coating texture indices including TC-CON, TC-ASM, TC-MEAN, and TC-ENT. Significant difference indices of pulse diagnosis were t4 and t5. The classification performance of each model based on different datasets was as follows: tongue and pulse < symptom < symptom and tongue and pulse. The neural network model had a better classification performance for symptom and tongue and pulse datasets, with an area under the ROC curves and accuracy rate which were 0.9401 and 0.8806. CONCLUSIONS: It was feasible to use tongue data and pulse data as one of the objective diagnostic basis in Qi deficiency syndrome and Yin deficiency syndrome of non-small-cell lung cancer.