Amino Acid-Derived Ionic Chiral Catalysts Enable Desymmetrizing Cross-Coupling to Remote Acyclic Quaternary Stereocenters.

Synthetic application of asymmetric catalysis relies on strategic alignment of bond construction to creation of chirality of a target molecule. Remote desymmetrization offers distinctive advantages of spatial decoupling of catalytic transformation and generation of a stereogenic element. However, such spatial separation presents substantial difficulties for the chiral catalyst to discriminate distant enantiotopic sites through a reaction three or more bonds away from a prochirality center. Here, we report a strategy that establishes acyclic quaternary carbon stereocenters through cross-coupling reactions at distal positions of aryl substituents. The new class of amino acid-derived ionic chiral catalysts enables desymmetrizing (enantiotopic-group-selective) Suzuki-Miyaura reaction, Sonogashira reaction, and Buchwald-Hartwig amination between diverse diarylmethane scaffolds and aryl, alkynyl, and amino coupling partners, providing rapid access to enantioenriched molecules that project substituents to widely spaced positions in the three-dimensional space. Experimental and computational investigations reveal electrostatic steering of substrates by the C-terminus of chiral ligands through ionic interactions. Cooperative ion-dipole interactions between the catalyst's amide group and potassium cation aid in the preorganization that transmits asymmetry to the product. This study demonstrates that it is practical to achieve precise long-range stereocontrol through engineering the spatial arrangements of the ionic catalysts' substrate-recognizing groups and metal centers.

Distal Ionic Substrate-Catalyst Interactions Enable Long-Range Stereocontrol: Access to Remote Quaternary Stereocenters through a Desymmetrizing Suzuki-Miyaura Reaction.

Spatial distancing of a substrate's reactive group and nonreactive catalyst-binding group from its pro-stereogenic element presents substantial hurdles in asymmetric catalysis. In this context, we report a desymmetrizing Suzuki-Miyaura reaction that establishes chirality at a remote quaternary carbon. The anionic, chiral catalyst exerts stereocontrol through electrostatic steering of substrates, even as the substrate's reactive group and charged catalyst-binding group become increasingly distanced. This study demonstrates that precise long-range stereocontrol is achievable by engaging ionic substrate-ligand interactions at a distal position.

The diagnostic pitfalls of lumbar disc herniation---- malignant sciatic nerve tumour: two case reports and literature review.

BACKGROUND: Sciatica pain is a typical symptom of lumbar disc herniation (LDH), but some neurogenic and malignant tumours surrounding the sciatic nerve can also cause similar symptoms. These tumours are often misdiagnosed or even mistreated as LDH in clinical practice. CASE PRESENTATION: In our clinical practice, we found two patients with malignant tumours who were misdiagnosed with LDH. One patient complained of pain and numbness in the right lower limb. The primary diagnosis was LDH, and the patient underwent posterior lumbar interbody fusion surgery. After the operation, the symptoms were not alleviated. Then, diffuse large B-cell lymphoma involving the soft tissue and the sciatic nerve was identified. Another patient who manifested with radiating pain in the right lower limb was diagnosed with LDH at Chengde Central Hospital. He received regular conservative treatment for approximately 6 months, but his symptoms were not relieved, and then he was referred to our hospital. A malignant peripheral nerve sheath tumour (MPNST) of the sciatic nerve was diagnosed, and he received cisplatin (DDP) chemohyperthermia. CONCLUSIONS: Descriptions of tumour lesions involving the sciatic nerve and misdiagnosed as LDH in the literature are rare. In the reported literature, 7 patients were misdiagnosed with LDH, and all patients presented with sciatica. Among them, 4 patients only received surgical treatment, 1 patient only underwent neurolysis, and 2 patients received both surgical and chemotherapy treatment. Their low incidence and similar clinical manifestations to LDH make malignant tumours involving the sciatic nerve easy to misdiagnose. When the clinical symptoms and signs are inconsistent with the imaging findings, we need to be aware of non-discogenic sciatica, including tumours involving the sciatic nerve. Furthermore, tumours that grow near the exit of the sciatic notch may be misdiagnosed because of their deeper location and because they are covered with gluteal muscles. Sometimes sciatica caused by sciatic nerve tumours is only distal, without any radicular distribution. This pain is more severe than that caused by LDH, and this pain is not related to the position of the lumbar spine. Thus, it is beneficial to perform a detailed physical examination of the sciatic nerve to avoid this kind of misdiagnosis.

One-pot reaction for the preparation of diatom hemostatic particles with effective hemostasis and economic benefits.

Effective hemostatic materials have been in demand for rapid pre-hospital hemostasis in emergency situations, which can significantly reduce accidental deaths. The development of emergency hemostatic materials with rapid hemostasis, biosafety, and economical preparation is a great challenge. In this study, Ca(OH)2-complexed diatom powder hemostatic particles (Ca(OH)2-Php) were prepared based on a one-pot reaction by directly mixing various raw materials and by rotary granulation. High-temperature calcination was able to carbonate and consume the organic matter in the hemostatic particles. The crosslinked hydrogen bonds in those particles were converted to silica-oxygen bonds, the particles became more stable, and the porous structure of diatom biosilica (DBs) was exposed. Ca(OH)2-Php has high porosity, can quickly adsorb the water in blood (water absorption: 75.85 ± 6.93%), and exhibits rapid hemostasis capacity (clotting time was shortened by 43% compared with that of the control group), good biocompatibility (hemolysis rate <7%, no cytotoxicity), and simplicity of handling (conveniently debride, no residues, no tissue inflammation). This study provides a new idea for the preparation of emergency hemostatic materials, and Ca(OH)2-Php prepared by one-pot reaction has various high-quality characteristics including rapid hemostasis, wide applicability, economical preparation, and potential for large-scale production.

[Distribution Characteristics and Health Effects of Bioaerosols in Spring over Xi'an City].

A large amount of fluffy caktins appears in spring in Xi'an that may cause air pollution and lead to health risks such as asthma. In this study, bioaerosol, PM2.5, and fluffy catkins were collected from different sample points (traffic site and campus site) in Xi'an in spring. The variations in bioaerosol, fluffy catkins, and the bacterial community structure were investigated using culture-dependent and high-throughput sequencing methods. The results showed that the concentration of culturable bacteria was significantly higher (P=0.027) at the traffic site. The concentration of culturable bacteria at the traffic site was 2.7 times that of fungi, whereas the concentration of culturable fungi at the campus site was 1.4 times higher than that of bacteria. The peak concentrations of culturable bacteria and fungi appeared at 08:00 a.m. The size distribution of culturable bacteria showed a bimodal pattern, whereas that of culturable fungi showed a unimodal distribution. Soil and vegetation were the main sources of atmospheric microorganisms (85.9%), and Proteobacteria was the most abundant phylum in both fluffy catkins and PM2.5, accounting for 91.3% (traffic site) and 99.1% (campus site) of the fluffy catkins. Actinobacteria, Firmicutes, Bacteroidetes, Cyanobacteria, and Deinococcus-Thermus were the dominant phyla in PM2.5. Some genera were opportunistic pathogen bacteria in the fluffy catkins, such as Enterobacter and Pseudomonas, which can lead to infection and diarrhea risks. These results could provide fundamental data on potential health risks of spring-borne bioaerosols.

Web-based nomogram to predict postresection risk of distant metastasis in patients with leiomyosarcoma: retrospective analysis of the SEER database and a Chinese cohort.

OBJECTIVES: This study investigated risk factors and constructed an online tool to predict distant metastasis (DM) risk in patients with leiomyosarcoma (LMS) after surgical resection. METHODS: Data regarding patients with LMS who underwent surgical resection between 2010 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Data were collected regarding patients with LMS who underwent surgical resection at Tianjin Medical University Cancer Hospital and Institute (TJMUCH) between October 2010 and July 2018. Patients were randomly divided into training and validation sets. Logistic regression analyses were performed; a nomogram was established. The area under the curve (AUC) and calibration curve were used to evaluate the nomogram, which served as the basis for a web-based nomogram. RESULTS: This study included 4461 and 76 patients from the SEER database and TJMUCH, respectively. Age, ethnicity, grade, T stage, N stage, radiotherapy, and chemotherapy were associated with DM incidence. C-index values were 0.815 and 0.782 in the SEER and Chinese datasets, respectively; corresponding AUC values were 0.814 and 0.773, respectively. A web-based nomogram (https://weijunqiang-leimyosarcoma-seer.shinyapps.io/dynnomapp/) was established. CONCLUSIONS: Our web-based nomogram is an accurate and user-friendly tool to predict DM risk in patients with LMS; it can aid clinical decision-making.

A web-based nomogram to predict overall survival for postresection leiomyosarcoma patients with lung metastasis.

To investigate the overall survival of post-resection leiomyosarcoma (LMS) patients with lung metastasis, data of post-resection LMS patients with lung metastasis between 2010 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The clinical characteristics and survival data for post-resection LMS patients with lung metastasis at Tianjin Medical University Cancer Hospital & Institute (TJMUCH) between October 2010 and July 2018 were collected. Patients derived from the SEER database and TJMUCH were divided into training and validation cohorts, respectively. Univariate and multivariate Cox regression analyses were performed and a nomogram was established. The area under the curve (AUC) and the calibration curve were used to evaluate the nomogram. A web-based nomogram was developed based on the established nomogram. Eventually, 226 patients from the SEER database who were diagnosed with LMS and underwent primary lesion resection combined with lung metastasis were enrolled in the training cohort, and 17 patients from TJMUCH were enrolled in the validation cohort. Sex, race, grade, tumor size, chemotherapy, and bone metastasis were correlated with overall survival in patients with LMS. The C-index were 0.65 and 0.75 in the SEER and Chinese set, respectively. Furthermore, the applicable AUC values of the ROC curve in the SEER cohort to predict the 1-, 3-, 5- years survival rate were 0.646, 0.682, and 0.689, respectively. The corresponding AUC values in the Chinese cohort were 0.970, 0.913, and 0.881, respectively. The calibration curve showed that the nomogram performed well in predicting the overall survival in post-resection LMS patients with lung metastasis. A web-based nomogram (https://weijunqiang.shinyapps.io/survival_lms_lungmet/) was established. The web-based nomogram (https://weijunqiang.shinyapps.io/survival_lms_lungmet/) is an accurate and personalized tool for predicting the overall survival of post-resection LMS with lung metastasis.

Metformin regulates chondrocyte senescence and proliferation through microRNA-34a/SIRT1 pathway in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common degenerative disease in joints among elderly patients. Senescence is deeply involved in the pathogenesis of osteoarthritis. Metformin is widely used as the first-line drug for Type 2 diabetes mellitus (T2DM), and has great potential for the treatment of other aging-related disorders, including OA. However, the role of metformin in OA is not fully elucidated. Therefore, our aim here was to investigate the effects of metformin on human chondrocytes. METHODS: After metformin treatment, expression level of microRNA-34a and SIRT1 in chondrocyte were detected with quantitative real-time PCR and immunofluorescence staining. Then, microRNA-34a mimic and small interfering RNA (siRNA) against SIRT1 (siRNA-SIRT1) were transfected into chondrocyte. Senescence-associated ß-galactosidase (SA-ß-gal) staining was performed to assess chondrocyte senescence. Chondrocyte viability was illustrated with MTT and colony formation assays. Western blot was conducted to detect the expression of P16, IL-6, matrix metalloproteinase-13 (MMP-13), Collagen type II (COL2A1) and Aggrecan (ACAN). RESULTS: We found that metformin treatment (1 mM) inhibited microRNA-34a while promoted SIRT1 expression in OA chondrocytes. Both miR-34a mimics and siRNA against SIRT1 inhibited SIRT1 expression in chondrocytes. SA-ß-gal staining assay confirmed that metformin reduced SA-ß-gal-positive rate of chondrocytes, while transfection with miR-34a mimics or siRNA-SIRT1 reversed it. MTT assay and colony formation assay showed that metformin accelerated chondrocyte proliferation, while miR-34a mimics or siRNA-SIRT1 weakened this effect. Furthermore, results from western blot demonstrated that metformin suppressed expression of senescence-associated protein P16, proinflammatory cytokine IL-6 and catabolic gene MMP-13 while elevated expression of anabolic proteins such as Collagen type II and Aggrecan, which could be attenuated by transfection with miR-34a mimics. CONCLUSION: Overall, our data suggest that metformin regulates chondrocyte senescence and proliferation through microRNA-34a/SIRT1 pathway, indicating it could be a novel strategy for OA treatment.

Network pharmacology-based research on the effect of Radix Astragali on osteosarcoma and the underlying mechanism.

To explore the anti-tumor effects of Radix Astragali on osteosarcoma and its mechanism. We analyzed the PPI network of Radix Astragali's potential targets for treating osteosarcoma and got the hub targets. We used KM curves to screen hub targets that could prolong sarcoma patients' survival time. We performed GO and KEGG enrichment analysis of Radix Astragali's potential targets and predicted Radix Astragali's molecular mechanism and function in treating osteosarcoma. The binding process between the hub targets, which could prolong sarcoma patients' survival time, and Radix Astragali was simulated through molecular docking. PPI network analysis of potential therapeutic targets discriminated 25 hub targets. The KM curves of the hub targets showed there were 13 hub targets that were effective in improving the 5-year survival rate of sarcoma patients. GO and KEGG enrichment demonstrated that Radix Astragali regulates multiple signaling pathways of osteosarcoma. Molecular docking results indicated that Radix Astragali could bind freely to the hub target, which could prolong the sarcoma patient's survival time. Radix Astragali act on osteosarcoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways. Radix Astragali has the potential to become a drug for treating osteosarcoma and prolonging the sarcoma patient's survival time.

Network pharmacology-based research on the effect of angelicin on osteosarcoma and the underlying mechanism.

To explore the antitumor effects of angelicin on osteosarcoma and the underlying mechanism. We aimed to elucidate the mechanism by network pharmacology, molecular docking, and in vitro experiments. We analyzed a PPI network of potential angelicin targets in the treatment of osteosarcoma and identified hub targets. We systematically performed GO and KEGG enrichment analyses of the potential targets of angelicin, and we predicted it function in osteosarcoma treatment and the underlying molecular mechanism. Through molecular docking, the interactions between hub targets and angelicin were simulated, and then, the hub targets of angelicin were identified. Based on these results, we validated the effects of angelicin on osteosarcoma cells by conducting in vitro experiments. The PPI network analysis of potential therapeutic targets identified four apoptosis-related hub targets, namely, BCL-2, Casp9, BAX and BIRC 2. GO and KEGG enrichment analyses demonstrated that angelicin regulates osteosarcoma cell apoptosis. Molecular docking results indicated that angelicin can freely bind to the hub targets listed above. In vitro experiments showed that angelicin promoted osteosarcoma cell apoptosis in a dose-dependent manner and inhibited osteosarcoma cell migration and proliferation in a time- and dose-dependent manner. The RT-PCR results showed that angelicin simultaneously promoted the mRNA expression of Bcl-2 and Casp9 and inhibited the mRNA expression of BAX and BIRC 2. Angelicin promotes osteosarcoma cell apoptosis and inhibits osteosarcoma cell proliferation and migration by activating a signaling network that is composed of hub targets that link multiple signaling pathways. Angelicin could become an alternative drug for the treatment of osteosarcoma.

Identification of a clinical web-based nomogram to predict overall survival in elderly retroperitoneal sarcoma patients: A population-based study.

The purpose of this study was to develop a web-based nomogram and risk stratification system to predict overall survival (OS) in elderly patients with retroperitoneal sarcoma (RPS). Elderly patients diagnosed with RPS between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox analysis to identify independent prognostic factors. We plotted the nomogram for predicting the OS of elderly RPS patients at 1, 3, and 5 years by integrating independent prognostic factors. The nomograms were subsequently validated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). By calculating the Nomogram score for each patient, we build a risk stratification model to evaluate the survival benefit of elderly RPS patients. A total of 722 elderly RPS patients were included in our study. The nomogram includes 5 clinicopathological variables as independent prognostic factors: age, histological subtype, grade, metastasis status, and surgery. Through the validation, we found that the nomogram has excellent prediction performance. Then web-based nomograms were established. We performed a web-based nomogram and a risk stratification model to assess the prognosis of elderly RPS patients, which are essential for prognostic clustering and decision-making about treatment.

Size distribution, community composition, and influencing factors of bioaerosols on haze and non-haze days in a megacity in Northwest China.

Bioaerosols have become a major environmental concern in recent years. In this study, the diurnal variations and size distributions of bioaerosols, as well as airborne bacterial community compositions and their influencing factors on haze and non-haze days in Xi'an, China, were compared. The results indicated that the mean bacteria and fungi concentrations on non-haze days were 1.7 and 1.4 times of those on haze days, respectively, whereas the mean total airborne microbe (TAM) concentration was higher on haze days. Bacteria concentrations were the lowest in the afternoon, and the TAM concentration exhibited a bimodal distribution with two peaks coinciding with traffic rush hours. On haze days airborne fungi was mainly attached to PM2.5, whereas bacteria and TAM were mainly distributed in coarse PM. The relative abundance of Chao1, Shannon and Simpson indices of bacterial communities were higher in the non-haze day samples, for the reason that high PM2.5 levels with a large specific surface area may absorb more toxic and harmful substances on haze days, which should affect microbial growth. At the generic level, the relative abundance of Rhodococcus, Paracoccus, Acinetobacter, and Kocuria on haze days was higher than that on non-haze days, indicating a higher risk of contracting pathogenic pneumonia. The results of the redundancy analysis revealed that PM2.5 and water-soluble inorganic ions (WSIIs, NO3-, SO42+, and NH4+) strongly affected the bacterial communities on non-haze days, especially Acinetobacter. The atmospheric oxidation capacity (Ox) had a significant effect on bacterial communities during haze episodes, which were positively correlated with Paracoccus, Deinococcus, Sphingomonas, and Rubellimicrobium and were negatively correlated with Rhodococcus. These results provide valuable data to elucidate the formation and evolution of bioaerosol between haze and non-haze events and its potential threats to human health.

Immune-related lncRNA pairs as novel signature to predict prognosis and immune landscape in melanoma patients.

ABSTRACT: To investigate immune-related long non-coding RNA (irlncRNA) signatures for predicting survival and the immune landscape in melanoma patients.We retrieved gene expression files from The Cancer Genome Atlas and the Genotype-Tissue Expression database and extracted all the long non-coding RNAs from the original data. Then, we selected immune-related long non-coding RNAs (irlncRNAs) using co-expression networks and screened differentially expressed irlncRNAs (DEirlncRNAs) to form pairs. We also performed univariate analysis and Least absolute shrinkage and selection operator (LASSO) penalized regression analysis to identify prognostic DEirlncRNA pairs, constructed receiver operating characteristic curves, compared the areas under the curves, and calculated the optimal cut-off point to divide patients into high-risk and low-risk groups. Finally, we performed multivariate Cox regression analysis, Kaplan-Meier (K-M) survival analysis, clinical correlation analysis, and investigated correlations with tumor-infiltrating immune cells, chemotherapeutic effectiveness, and immunogene biomarkers.A total of 297 DEirlncRNAs were identified, of which 16 DEirlncRNA pairs were associated with prognosis in melanoma. After grouping patients by the optimal cut-off value, we could better distinguish melanoma patients with different survival outcomes, clinical characteristics, tumor immune status changes, chemotherapeutic drug sensitivity, and specific immunogene biomarkers.The DEirlncRNA pairs showed potential as novel biomarkers to predict the prognosis of melanoma patients. Furthermore, these DEirlncRNA pairs could be used to evaluate treatment efficacy in the future.

The new horizon of biomarker in melanoma patients: A study based on autophagy-related long non-coding RNA.

ABSTRACT: Autophagy-related long non-coding RNAs (arlncRNAs) play a crucial role in the pathogenesis and development of the tumor. However, there is a lack of systematic analysis of arlncRNAs in melanoma patients.Melanoma data for analysis were obtained from The Cancer Genome Atlas (TCGA) database. By establishing a co-expression network of autophagy-related mRNAs-lncRNAs, we identified arlncRNAs in melanoma patients. We evaluated the prognostic value of arlncRNAs by univariate and multivariate Cox analysis and constructed an arlncRNAs risk model. Patients were divided into high- and low-risk groups based on the arlncRNAs risk score. This model was evaluated by Kaplan-Meier (K-M) analysis, univariate-multivariate Cox regression analysis, and receiver operating characteristic (ROC) curve analysis. Characteristics of autophagy genes and co-expressive tendency were analyzed by principal component analysis and Gene Set Enrichment Analysis (GSEA) functional annotation.Nine arlncRNAs (USP30-AS1, LINC00665, PCED1B-AS1, LINC00324, LINC01871, ZEB1-AS1, LINC01527, AC018553.1, and HLA-DQB1-AS1) were identified to be related to the prognosis of melanoma patients. Otherwise, the 9 arlncRNAs constituted an arlncRNAs prognostic risk model. K-M analysis and ROC curve analysis showed that the arlncRNAs risk model has good discrimination. Univariate and multivariate Cox regression analysis showed that arlncRNAs risk model was an independent prognostic factor in melanoma patients. Principal component analysis and GSEA functional annotation showed different autophagy and carcinogenic status in the high- and low-risk groups.This novel arlncRNAs risk model plays an essential role in predicting of the prognosis of melanoma patients. The model reveals new prognosis-related biomarkers for autophagy, promotes precision medicine, and provides a lurking target for melanoma's autophagy-related treatment.

Development, validation, and visualization of a web-based nomogram for predicting the incidence of leiomyosarcoma patients with distant metastasis.

BACKGROUND: Leiomyosarcoma (LMS) is one of the most common soft tissue sarcomas. LMS is prone to distant metastasis (DM), and patients with DM have a poor prognosis. AIM: In this study, we investigated the risk factors of DM in LMS patients and the prognostic factors of LMS patients with DM. METHODS AND RESULTS: LMS patients diagnosed between 2010 and 2016 were extracted from the Surveillance, Epidemiology, and End Result (SEER) database. Patients were randomly divided into the training set and validation set. Univariate and multivariate logistic regression analyses were performed, and a nomogram was established. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. Based on the nomogram, a web-based nomogram is established. The univariate and multivariate Cox regression analyses were used to assess the prognostic risk factors of LMS patients with DM. Eventually, 2184 patients diagnosed with LMS were enrolled, randomly divided into the training set (n = 1532, 70.14%) and validation set (n = 652, 29.86%). Race, primary site, grade, T stage, and tumor size were correlated with DM incidence in LMS patients. The AUC of the nomogram is 0.715 in training and 0.713 in the validation set. The calibration curve and DCA results showed that the nomogram performed well in predicting the DM risk. A web-based nomogram was established to predict DM's risk in LMS patients (https://wenn23.shinyapps.io/riskoflmsdm/). Epithelioid LMS, in uterus, older age, giant tumor, multiple organ metastasis, without surgery, and chemotherapy had a poor prognosis. CONCLUSIONS: The established web-based nomogram (https://wenn23.shinyapps.io/riskoflmsdm/) is an accurate and personalized tool to predict the risks of LMS developing DM. Advanced age, larger tumor, multiple organ metastasis, epithelioid type, uterine LMS, no surgery, and no chemotherapy were associated with poor prognosis in LMS patients with DM.

Rational Design of a Robust Flexible Triblock Polyurea Copolymer Protective Layer for High-Performance Lithium Metal Batteries.

Dendrite growth and volume expansion in lithium metal are the most important obstacles affecting the actual applications of lithium metal batteries. Herein, we design a robust flexible artificial solid electrolyte interphase layer based on a triblock copolymer polyurea film, which promotes uniform lithium deposition on the surface of the lithium metal electrode and has a high lithium-ion transference number. The high elasticity and close contact of polyurea compounds effectively suppress lithium dendrite growth and volume expansion in the Li anode, which are effectively confirmed by electrochemical characterization and optical microscopy observation. The symmetrical batteries with the PU-Li metal anode can achieve stable and reversible Li plating/stripping over 500 h at a current density of 5 mA cm-2. Matched with the high-mass-loaded S cathode and the commercial NCM523 cathode, this film significantly improves the cycle life of lithium metal batteries.

Construction, validation and, visualization of a web-based nomogram to identify the best candidates for primary tumor resection in advanced cutaneous melanoma patients.

Background: Existing studies have shown whether primary site resection (PSR) in cutaneous melanoma (CM) patients with stage IV is controversial. Our study aimed to identify the clinical characteristics of CM patients with stage IV who benefited from PSR on a population-based study. Methods: We retrospectively reviewed stage IV CM patients in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were divided into surgical and non-surgical groups according to whether PSR was performed or not. According to the median cancer-specific survival (CSS) time of the non-surgery group, the surgical group was divided into the surgery-benefit group and the non-surgery-benefit group. Multivariate cox regression analysis was used to explore independent CSS prognostic factors in the surgical group. Then, based on the independent prognostic factors of the surgical group, we established a web-based nomogram based on logistics regression. Results: A total of 574 stage IV CM patients were included in our study, and 491 (85.60%) patients were included in the surgical group. The clinical characteristics (benefit group and non-benefit group) included age, M stage, lesion location, and ulceration status. These independent prognostic factors were includeed to construct a web-based nomogram. Conclusions: We constructed a web-based nomogram. This model was suitable for identifying the best candidates suitable for PSR in stage IV CM patients.

Network pharmacology, molecular docking and bioinformatics reveal the mechanism of Tripterygii Wilfordii against Osteosarcoma.

Osteosarcoma (OS) is a malignant bone tumor of mesenchymal origin. Tripterygii Wilfordii (TW) is a traditional Chinese medicine widely used for its anti-inflammatory and immunomodulatory effects. Various components of TW have been shown to have antitumor effects, however, no systematic study has been conducted to prove the anti-OS effects of TW. This study aimed to investigate the effects of TW on OS and its mechanism based on network pharmacology and molecular docking. The web pharmacology section includes the gathering of the active components of TW, the collection of predicted targets of TW and OS-related targets, the analysis of therapeutic targets of TW, the enrichment of gene ontology (GO), and the enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG). The Veen diagram showed 451 targets for OS treatment in TW. The therapeutic target enrichment analysis results showed that TW treated OS via multiple targets and pathways. TW can affect OS proliferation, apoptosis, migration, infiltration, and angiogenesis through a signaling network formed by hub genes that cascade through numerous signaling pathways. In addition, molecular docking results showed that triptolide, kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin have relatively high potential to become drugs for patients with OS and improve the 5-year survival rate of patients with OS. Network pharmacology and molecular docking suggest that TW affects the biological behavior of OS through multiple pathways involving multiple targets, such as proliferation, apoptosis, migration, and infiltration. Upregulation of the cellular tumor antigen p53 (TP53) gene and downregulation of peroxisome proliferator-activated receptor gamma (PPARG) and signal transducer and activator of transcription 1-alpha/beta (STAT1) genes can prolong the survival time of patients with OS. Triptolide, kaempferol, and 5,8-Dihydroxy-7-(4-hydroxy-5 methyl-coumarin-3)-coumarin have a relatively high potential to become a treatment for patients with OS and improve 5-year survival of OS patients.

A novel inflammatory signature for evaluating immune microenvironment status in soft tissue sarcoma.

Background: Tumorigenesis and progression are intimately associated with inflammation. However, the inflammatory landscape in soft tissue sarcoma (STS) and its clinical consequences are yet unknown, and more investigation is needed. Methods: RNA-seq expression data for STS and corresponding normal tissues were downloaded from The Cancer Genome Atlas database and the Genotype-Tissue Expression Portal. Differential and prognostic analyses were performed based on known inflammatory response genes from Gene Set Enrichment Analysis (GSEA). We utilized LASSO-Cox analysis to determine hub genes and built an inflammatory score (INFscore) and risk stratification model. Furthermore, a nomogram, including the risk stratification model, was established to predict the prognosis. We further elucidated the characteristics among different risk STS patients by GSEA, gene set variation analysis, and detailed immune infiltration analysis. Finally, the INFscore and risk stratification model in predicting prognosis and depicting immune microenvironment status were verified by pan-cancer analysis. Results: Five hub genes (HAS2, IL1R1, NMI, SERPINE1, and TACR1) were identified and were used to develop the INFscore. The risk stratification model distinguished the immune microenvironment status and evaluated the efficacy of immunotherapy and chemotherapy in STS. The novel nomogram had good efficacy in predicting the prognosis of STS patients. Finally, a pan-cancer investigation verified the association of INFscore with prognosis and immunity. Conclusions: According to the present study, the risk stratification model can be used to evaluate STS prognosis, tumor microenvironment status, immunotherapy, and chemotherapy efficacy. The novel nomogram has an excellent predictive value. Thus, the INFscore and risk stratification model has potential value in assessing the prognosis and immune status of multiple malignancies.

m6A regulator-mediated methylation modification patterns and tumor immune microenvironment in sarcoma.

BACKGROUND: Studies have shown that the RNA N6-methyladenosine (m6A) modification patterns are extensively involved in the development of multiple tumors. However, the association between the m6A regulator expression patterns and the sarcoma tumor immune microenvironment (TIME) remains unclear. METHODS: We systematically evaluated the m6A regulator expression patterns in patients with sarcoma based on known 23 m6A regulators. Different m6A regulator expression patterns were analyzed using gene set variation analysis and a single-sample gene set enrichment analysis algorithm. According to the results of consensus clustering, we classified the patients into four different clusters. Next, we subjected the four clusters to differential genetic analysis and established m6A-related differentially expressed genes (DEGs). We then calculated the m6A-related DEGs score and constructed the m6A-related gene signature, named m6A score. Finally, the 259 sarcoma samples were divided into high- and low-m6A score groups. We further evaluated the TIME landscape between the high- and low-m6A score groups. RESULTS: We identified four different m6A modification clusters and found that each cluster had unique metabolic and immunological characteristics. Based on the 19 prognosis-related DEGs, we calculated the principal component analysis scores for each patient with sarcoma and classified them into high- and low-m6A score groups. CONCLUSIONS: The m6A regulator expression patterns and complexity of the sarcoma TIME landscape are closely related to each other. Systematic evaluation of m6A regulator expression patterns and m6A scores in patients with sarcoma will enhance our understanding of TIME characteristics.