Shenqi Fuzheng injection facilitates skeletal muscle mitophagy mediated by the ubiquitination of HIF-1α to ameliorate cancer-associated fatigue.

Cancer-related fatigue (CRF) significantly impacts the quality of life of cancer patients. This study investigates the therapeutic potential of Shenqi Fuzheng injection (SFI) in managing CRF, focusing on its mechanistic action in skeletal muscle. We utilized a CRF mouse model to examine the effects of SFI on physical endurance, monitoring activity levels, swimming times and rest periods. Proteomic analysis of the gastrocnemius muscle was performed using isobaric tags and liquid chromatography-tandem mass spectrometry to map the muscle proteome changes post-SFI treatment. Mitochondrial function in skeletal muscle was assessed via ATP bioluminescence assay. Furthermore, the regulatory role of the hypoxia inducible factor 1 subunit alpha (HIF-1α) signalling pathway in mediating SFI's effects was explored through western blotting. In CRF-induced C2C12 myoblasts, we evaluated cell viability (CCK-8 assay), apoptosis (flow cytometry) and mitophagy (electron microscopy). The study also employed pulldown, luciferase and chromatin immunoprecipitation assays to elucidate the molecular mechanisms underlying SFI's action, particularly focusing on the transcriptional regulation of PINK1 through HIF-1α binding at the PINK1 promoter region. Our findings reveal that SFI enhances physical mobility, reduces fatigue symptoms and exerts protective effects on skeletal muscles by mitigating mitochondrial damage and augmenting antioxidative responses. SFI promotes cell viability and induces mitophagy while decreasing apoptosis, primarily through the modulation of HIF-1α, PINK1 and p62 proteins. These results underscore SFI's efficacy in enhancing mitochondrial autophagy, thereby offering a promising approach for ameliorating CRF. The study not only provides insight into SFI's potential therapeutic mechanisms but also establishes a foundation for further exploration of SFI interventions in CRF management.

[Evaluation of augmented reality technology in the recognizing of oral and maxillofacial anatomy].

OBJECTIVE: To evaluate the outcome of Augmented reality technology in the recognizing of oral and maxillofacial anatomy. METHODS: This study was conducted on the undergraduate students in Peking University School of Stomatology who were learning oral and maxillofacial anatomy. The image data were selected according to the experiment content, and the important blood vessels and bone tissue structures, such as upper and lower jaws, neck arteries and veins were reconstructed in 3D(3-dimensional) by digital software to generate experiment models, and the reconstructed models were encrypted and stored in the cloud. The QR (quick response) code corresponding to the 3D model was scanned by a networked mobile device to obtain augmented reality images to assist experimenters in teaching and subjects in recognizing. Augmented reality technology was applied in both the theoretical explanation and cadaveric dissection respectively. Subjects' feedback was collected in the form of a post-class questionnaire to evaluate the effectiveness of augmented reality technology-assisted recognizing. RESULTS: In the study, 83 undergraduate students were included as subjects in this study. Augmented reality technology could be successfully applied in the recognizing of oral and maxillofacial anatomy. All the subjects could scan the QR code through a connected mobile device to get the 3D anatomy model from the cloud, and zoom in/out/rotate the model on the mobile. Augmented reality technology could provide personalized 3D model, based on learners' needs and abilities. The results of likert scale showed that augmented reality technology was highly recognized by the students (9.19 points), and got high scores in terms of forming a three-dimensional sense and stimulating the enthusiasm for learning (9.01 and 8.85 points respectively). CONCLUSION: Augmented reality technology can realize the three-dimensional visualization of important structures of oral and maxillofacial anatomy and stimulate students' enthusiasm for learning. Besides, it can assist students in building three-dimensional space imagination of the anatomy of oral and maxillofacial area. The application of augmented reality technology achieves favorable effect in the recognizing of oral and maxillofacial anatomy.

The efficacy of clinicopathological and imaging features in differentiating benign from malignant parotid micro- and minitumors: a retrospective analysis.

OBJECTIVE: To compare clinicopathological and imaging features of micro- and minitumors of the parotid gland and provide a reference for preoperative prediction of benign vs malignant status. STUDY DESIGN: Patients with parotid gland tumors treated surgically were selected. Relevant clinicopathological and imaging data were collected for patients with maximum tumor diameters ≤20 mm on preoperative computed tomography (CT). The lesions were divided into 2 groups, microtumors and minitumors, based on maximum tumor diameter. CT imaging features of benign and malignant tumors were compared through binary logistic regression analysis. RESULTS: Microtumors and minitumors were categorized by maximum diameters <10 mm (n = 74) and 10-20 mm (n = 611), respectively. Benign and malignant minitumors exhibited significant differences in boundary, tumor density, margin morphology, spiculation margin, and CT values in the plain and arterial phase (P ≤ .027), resembling those found in typical malignant parotid gland tumors. However, no significant differences were observed between benign and malignant microtumors. Logistic regression analysis identified boundary, margin morphology, and spiculation margin as independent predictors of malignancy. The prediction model excelled in identifying benign lesions but was less successful in identifying malignancies. CONCLUSION: Parotid gland minitumors had imaging features similar to typical larger malignant tumors. Active exclusion of the malignant risk and early surgical treatment is recommended for these tumors.

Direct visualization of intraparotid facial nerve assisting in parotid tumor resection.

Precise recognition of the intraparotid facial nerve (IFN) is crucial during parotid tumor resection. We aimed to explore the application effect of direct visualization of the IFN in parotid tumor resection. Fifteen patients with parotid tumors were enrolled in this study and underwent specific radiological scanning in which the IFNs were displayed as high-intensity images. After image segmentation, IFN could be preoperatively directly visualized. Mixed reality combined with surgical navigation were applied to intraoperatively directly visualize the segmentation results as real-time three-dimensional holograms, guiding the surgeons in IFN dissection and tumor resection. Radiological visibility of the IFN, accuracy of image segmentation and postoperative facial nerve function were analyzed. The trunks of IFN were directly visible in radiological images for all patients. Of 37 landmark points on the IFN, 36 were accurately segmented. Four patients were classified as House-Brackmann Grade I postoperatively. Two patients with malignancies had postoperative long-standing facial paralysis. Direct visualization of IFN was a feasible novel method with high accuracy that could assist in recognition of IFN and therefore potentially improve the treatment outcome of parotid tumor resection.

Mixed Reality Combined with Surgical Navigation in Resection of Micro- and Mini-Tumors of the Parotid Gland: A Pilot Study.

OBJECTIVE: This study aimed to evaluate the feasibility and outcomes of mixed reality combined with surgical navigation (MRSN) in the resection of parotid micro- and mini-tumors. METHODS: Eighteen patients who underwent parotid tumor resection between December 2020 and November 2022 were included. Six patients were enrolled in MRSN group, and the surgeons performed the surgery with the help of MRSN technology. The surgical procedures include virtual planning, data transfer between mixed reality and surgical navigation, tumor localization and resection assisted by surgical navigation under mixed reality environment. Twelve patients were enrolled in control group, and intraoperative tumor localization and resection were performed according to the experience of the surgeon. Total surgery time and intraoperative bleeding were recorded. Perioperative complications were recorded during follow-up. RESULTS: The mean surgery time of MRSN group (76.7 ± 14.0 min) and control group (65.4 ± 21.3 min) showed no significant difference (p = 0.220), so did the intraoperative bleeding of MRSN group (16.0 ± 8.0 mL) and control group (16.7 ± 6.6 mL) (p = 0.825). None of the patient in MRSN group underwent any complication, although one patient in control group suffered temporary facial paralysis. The mean deviation between the virtually marked and the intraoperative actual outermost point of tumor was 3.03 ± 0.83 mm. CONCLUSION: MRSN technology can realize real-time three-dimensional visualization of the tumor, and it has the potential of enhancing the safety and accuracy of resection of micro- and mini-tumors of parotid gland. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1670-1678, 2024.

A deep learning and radiomics fusion model based on contrast-enhanced computer tomography improves preoperative identification of cervical lymph node metastasis of oral squamous cell carcinoma.

OBJECTIVES: In this study, we constructed and validated models based on deep learning and radiomics to facilitate preoperative diagnosis of cervical lymph node metastasis (LNM) using contrast-enhanced computed tomography (CECT). MATERIALS AND METHODS: CECT scans of 100 patients with OSCC (217 metastatic and 1973 non-metastatic cervical lymph nodes: development set, 76 patients; internally independent test set, 24 patients) who received treatment at the Peking University School and Hospital of Stomatology between 2012 and 2016 were retrospectively collected. Clinical diagnoses and pathological findings were used to establish the gold standard for metastatic cervical LNs. A reader study with two clinicians was also performed to evaluate the lymph node status in the test set. The performance of the proposed models and the clinicians was evaluated and compared by measuring using the area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). RESULTS: A fusion model combining deep learning with radiomics showed the best performance (ACC, 89.2%; SEN, 92.0%; SPE, 88.9%; and AUC, 0.950 [95% confidence interval: 0.908-0.993, P < 0.001]) in the test set. In comparison with the clinicians, the fusion model showed higher sensitivity (92.0 vs. 72.0% and 60.0%) but lower specificity (88.9 vs. 97.5% and 98.8%). CONCLUSION: A fusion model combining radiomics and deep learning approaches outperformed other single-technique models and showed great potential to accurately predict cervical LNM in patients with OSCC. CLINICAL RELEVANCE: The fusion model can complement the preoperative identification of LNM of OSCC performed by the clinicians.

Biomechanical behavior of the three-dimensionally printed surgical plates for mandibular defect reconstruction: a finite element analysis.

The aim of the study was to investigate the biomechanical behavior of three-dimensionally (3D)-printed surgical plates used for mandibular defect reconstruction, compare them with conventional surgical plates, and provide experimental evidence for their clinical application. Three-dimensional models were created for the normal mandible and for mandibular body defects reconstructed using free fibula and deep circumflex iliac artery flaps. Three-dimensional finite element models of reconstructed mandibles fixed using 3D-printed and conventional surgical plates were established. Vertical occlusal forces were applied to the remaining teeth and the displacement and Von Mises stress distributions were studied using finite element analysis. The normal and reconstructed mandibles had similar biomechanical behaviors. The displacement distributions for the surgical plates were similar, and the maximum total deformation occurred at the screw hole of the anterior segment of the surgical plates. However, there were differences in the Von Mises stress distributions for the surgical plates. In reconstructed mandibles fixed using 3D-printed surgical plates, the maximum equivalent Von Mises stress occurred at the screw hole of the posterior segment, while in those fixed using conventional surgical plates, the maximum equivalent Von Mises stress was at the screw hole of the anterior segment. In the mandible models reconstructed with the same free flap but fixed with different surgical plates, the plates had similar biomechanical behaviors. The biomechanical behavior of 3D-printed surgical plates was similar to conventional surgical plates, suggesting that 3D-printed surgical plates used to reconstruct mandibular body defects with vascularized autogenous bone grafts could lead to secure and stable fixation.

Reduction in gefitinib resistance mediated by Yi-Fei San-Jie pill in non-small cell lung cancer through regulation of tyrosine metabolism, cell cycle, and the MET/EGFR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herbal prescription Yi-Fei San-Jie pill (YFSJ) has been used for adjuvant treatment in patients with lung cancer for a long time. AIM OF THE STUDY: Reports have indicated that the combination of gefitinib (Gef) with YFSJ inhibits the proliferation of EGFR-TKI-resistant cell lines by enhancing cellular apoptosis and autophagy in non-small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the effect of YFSJ on EGFR-TKI resistance and related metabolic pathways remain to be explored. MATERIALS AND METHODS: In our report, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), metabolomics, network pharmacology, bioinformatics, and biological analysis methods were used to investigate the mechanism. RESULTS: The UPLC-MS/MS data identified 42 active compounds of YFSJ extracts. YFSJ extracts can enhance the antitumor efficacy of Gef without hepatic and renal toxicity in vivo. The analysis of the metabolomics pathway enrichment revealed that YFSJ mainly affected the tyrosine metabolism pathway in rat models. Moreover, YFSJ has been shown to reverse Gef resistance and improve the effects of Gef on the cellular viability, migration capacity, and cell cycle arrest of NSCLC cell lines with EGFR mutations. The results of network pharmacology and molecular docking analyses revealed that tyrosine metabolism-related active compounds of YFSJ affect EGFR-TKIs resistance in NSCLC by targeting cell cycle and the MET/EGFR signaling pathway; these findings were validated by western blotting and immunohistochemistry. CONCLUSIONS: YFSJ inhibits NSCLC by inducing cell cycle arrest in the G1/S phase to suppress tumor growth, cell viability, and cell migration through synergistic effects with Gef via the tyrosine metabolic pathway and the EGFR/MET signaling pathway. To summarize, the findings of the current study indicate that YFSJ is a prospective complementary treatment for Gef-resistant NSCLC.

Identification of the active compounds in the Yi-Fei-San-Jie formula using a comprehensive strategy based on cell extraction/UPLC-MS/MS, network pharmacology, and molecular biology techniques.

BACKGROUND: Chinese herbal formulae has multiple active constituents and targets, and the good clinical response is encouraging more scientists to explore the bio-active ingredients in such complex systems. Yi-Fei-San-Jie formula (YFSJF) is commonly used to treat patients with lung cancer in South China; however, its bio-active ingredients remain unknown. PURPOSE: We investigated the bio-active ingredients of the YFSJF using a novel comprehensive strategy. METHODS: A549 cell extraction coupled with ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was used for the screening of potential bio-active ingredients. Network pharmacology approach and molecular dynamics simulation were performed for the screening of targets. Surface plasmon resonance (SPR) assay and molecular biology techniques were used to verify the targets. RESULTS: Nine A549 cell membrane-binding compounds were identified through cell extraction/UPLC-MS/MS. Five compounds, namely ginsenoside Ro, ginsenoside Rb1, ginsenoside Rc, peimisine, and peimine were cytotoxic to A549 cells, and they were considered the bio-active ingredients of the YFSJF in vitro. Network pharmacology analysis revealed that TGFBR2 is the key target and the TGFß pathway is the key pathway targeted by YFSJF in non-small cell lung cancer. Peimisine showed an affinity to TGFBR2 using molecular docking and dynamic stimulation, which was confirmed using surface plasmon resonance spectroscopy. The molecular biology-based analysis further confirmed that peimisine targets TGFBR2 and can reverse A549 epithelial-mesenchymal transition by inhibiting the TGFß pathway. CONCLUSION: Taken together, cell extraction/UPLC-MS/MS, network pharmacology, and molecular biology-based analysis comprise a feasible strategy to explore active ingredients in YFSJF.

Transarterial chemoembolization (TACE) plus tyrosine kinase inhibitors versus TACE in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC. METHODS: We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio's random-effects model. Quality assessments were performed using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs). RESULTS: The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65-0.80), OS (combined HR 0.57, 95% CI 0.49-0.67), and objective response rate (OR 2.13, 95% CI 1.23-3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88-177.23), diarrhea (OR 18.13%, 95%CI 9.32-35.27), and hypertension (OR 12.24%, 95%CI 5.89-25.42). CONCLUSIONS: Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings. TRIAL REGISTRATION: PROSPERO registration number: CRD42022298003.

A Mechanism Exploration for the Yi-Fei-San-Jie Formula against Non-Small-Cell Lung Cancer Based on UPLC-MS/MS, Network Pharmacology, and In Silico Verification.

Non-small-cell lung cancer (NSCLC) is one of the most prevalent cancers worldwide. A Yi-Fei-San-Jie formula (YFSJF), widely used in NSCLC treatment in south China, has been validated in clinical studies. However, the pharmacological mechanism behind it remains unclear. In this study, 73 compounds were identified using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), with 58 enrolled in network pharmacology. The protein-protein interaction network, functional enrichment analysis, and compound-target-pathway network were constructed using 74 overlapping targets from 58 drugs and NSCLC. YFSJF has many targets and pathways in the fight against NSCLC. PIK3R1, PIK3CA, and AKT1 were identified as key targets, and the PI3K/AKT pathway was identified as the key pathway. According to the Human Protein Atlas (THPA) database and the Kaplan-Meier Online website, the three key targets had varying expression levels in normal and abnormal tissues and were linked to prognosis. Molecular docking and dynamics simulations verified that hub compounds have a strong affinity with three critical targets. This study revealed multiple compounds, targets, and pathways for YFSJF against NSCLC and suggested that YFSJF might inhibit PIK3R1, PIK3CA, and AKT1 to suppress the PI3K/AKT pathway and play its pharmacological role.

Factors influencing the accuracy of multimodal image fusion for oral and maxillofacial tumors: a retrospective study.

BACKGROUND: Ensuring high accuracy in multimodal image fusion for oral and maxillofacial tumors is crucial before further application. The aim of this study was to explore the factors influencing the accuracy of multimodal image fusion for oral and maxillofacial tumors. METHODS: Pairs of single-modality images were obtained from oral and maxillofacial tumor patients, and were fused using a proprietary navigation system by using three algorithms (automatic fusion, manual fusion, and registration point-based fusion). Fusion accuracy was evaluated including two aspects-overall fusion accuracy and tumor volume fusion accuracy-and were indicated by mean deviation and fusion index, respectively. Image modality, fusion algorithm, and other characteristics of multimodal images that may have potential influence on fusion accuracy were recorded. Univariate and multivariate analysis were used to identify relevant affecting factors. RESULTS: Ninety-three multimodal images were generated by fusing 31 pairs of single-modality images. The interaction effect of image modality and fusion algorithm (P = 0.02, P = 0.003) and thinner slice thickness (P = 0.006) were shown to significantly influence the overall fusion accuracy. The tumor volume (P < 0.001), tumor location (P = 0.007), and image modality (P = 0.01) were significant influencing factors for tumor volume fusion accuracy. CONCLUSIONS: To ensure high overall fusion accuracy, manual fusion was not preferred in CT/MRI image fusion, and neither was automatic fusion in image fusion containing PET modality. Using image sets with thinner slice thickness could increase overall fusion accuracy. CT/MRI fusion yielded higher tumor volume fusion accuracy than fusion containing PET modality. The tumor volume fusion accuracy should be taken into consideration during image fusion when the tumor volume is small and the tumor is located in the mandible.

Cuproptosis-Related Signature Predicts the Prognosis, Tumor Microenvironment, and Drug Sensitivity of Hepatocellular Carcinoma.

Background: Copper (Cu) metabolism is strongly associated with liver disease. Cuproptosis is a novel format of cell death, and cuproptosis-related genes (CRGs) were identified. However, the role of CRGs in Hepatocellular Carcinoma (HCC) remains unknown. Method: The mRNA transcriptome profiling data, somatic mutation data, and copy number gene level data of The Cancer Genome Atlas-Liver Hepatocellular Carcinoma project (TCGA-LIHC) were downloaded for subsequent analysis. Molecular characterization analysis of CRGs, including differential gene expression analysis, mutation analysis, copy number variation (CNV) analysis, Kaplan-Meier analysis, and immune regulator prioritization analysis, was implemented. The nonnegative matrix factorization (NMF) approach was used to identify the CRG-related molecular subtypes. Principal component analysis was adopted to verify the robustness and reliability of the molecular subtype. The least absolute shrinkage and selection operator regression analysis was performed to construct the prognostic signature based on differentially expressed genes between molecular subtypes. The survival characteristics of the molecular subtype and the signature were analyzed. The Gene Set Variation Analysis was performed for functional annotation. The immune landscape analysis, including immune checkpoint gene analysis, single sample gene set enrichment analysis, tumor immune dysfunction and exclusion (TIDE) analysis, immune infiltration cell, and tumor mutation burden analysis (TMB), was conducted. The ability of the signature to predict conventional anti-HCC agent responses was evaluated. The signature was validated in the LIRI-JP cohort and the IMvigor210 cohort. Result: A total of 13 CRGs are differentially expressed between the tumor and normal samples, while the mutation of CRGs in HCC is infrequent. The expression of CRGs is associated with the CNV level. Fourteen CRGs are associated with the prognosis of HCC. Two clusters were identified and HCC patients were divided into 2 groups with a cutoff risk score value of 1.570. HCC patients in the C1 cluster and high-risk have a worse prognosis. The area under the receiver operating characteristic curve for predicting 1-, 2-, and 3-year overall survival is 0.775, 0.768, and 0.757 in the TCGA-LIHC cohort, and 0.811, 0.741, and 0.775 in the LIRI-JP cohort. Multivariate Cox regression analysis indicates that the signature is an independent prognostic factor. Pathways involved in metabolism and gene stability and immune infiltration cells are significantly enriched. Immune checkpoint genes are highly expressed in the C1 cluster. TMB is positively correlated with the risk score. HCC patients in the high-risk group are more likely to benefit from conventional anti-HCC agents and immune checkpoint inhibitor therapies. Conclusion: The molecular characterization of CRGs in HCC is presented in this study, and a successful prognostic signature for HCC based on the cuproptosis-related molecular subtype was constructed.

Accuracy of globe-sparing orbital reconstruction using individually bent titanium mesh: A comparative study.

Accurate reconstruction of orbital and midfacial defects following extensive globe-sparing maxillectomy is challenging, due to the complex anatomy of facial skeleton. The aim of this study is to evaluate the outcomes of individually bent titanium mesh in navigation-assisted reconstruction of post-ablative orbits in comparison with that without intraoperative navigation. Forty-one patients undergone globe-sparing maxillectomy and orbital floor reconstruction using individually bent titanium mesh with or without intraoperative navigation were assessed. Pre- and postoperative orbital projection and volume measurements were performed on both orbits. The unaffected orbit was used as a control for comparison. True-to-original orbital reconstruction was achieved in this study. The average difference of globe projection and orbital volume between unaffected and reconstructed orbits was 0.8 ± 0.5 mm and 0.9 ± 1.2cm3, respectively, in navigation-assisted group. In non-navigation-assisted group, the average difference of globe projection and orbital volume of unaffected and reconstructed orbit was 0.7 ± 0.5 mm and 1.3 ± 1.3cm3, respectively. There was no statistical significance in mean differences between unaffected and affected globe projection (P = 0.744) and orbital volume (P = 0.677) in both groups. There was also no significant difference observed when comparing the mean differences between pre- and postoperative globe projection (P = 0.659) and orbital volume (P = 0.582) in both groups. While intraoperative navigation system was shown to be effective in orbital reconstruction in the past decade, equal satisfactory post-ablative orbital reconstruction can be achieved with individually bent titanium mesh with or without intraoperative navigation.

Comprehensive analysis of an immune infiltrate-related competitive endogenous RNA network reveals potential prognostic biomarkers for non-small cell lung cancer.

Globally, non-small cell lung cancer (NSCLC) is the most common malignancy and its prognosis remains poor because of the lack of reliable early diagnostic biomarkers. The competitive endogenous RNA (ceRNA) network plays an important role in the tumorigenesis and prognosis of NSCLC. Tumor immune microenvironment (TIME) is valuable for predicting the response to immunotherapy and determining the prognosis of NSCLC patients. To understand the TIME-related ceRNA network, the RNA profiling datasets from the Genotype-Tissue Expression and The Cancer Genome Atlas databases were analyzed to identify the mRNAs, microRNAs, and lncRNAs associated with the differentially expressed genes. Weighted gene co-expression network analysis revealed that the brown module of mRNAs and the turquoise module of lncRNAs were the most important. Interactions among microRNAs, lncRNAs, and mRNAs were prognosticated using miRcode, miRDB, TargetScan, miRTarBase, and starBase databases. A prognostic model consisting of 13 mRNAs was established using univariate and multivariate Cox regression analyses and validated by the receiver operating characteristic (ROC) curve. The 22 immune infiltrating cell types were analyzed using the CIBERSORT algorithm, and results showed that the high-risk score of this model was related to poor prognosis and an immunosuppressive TIME. A lncRNA-miRNA-mRNA ceRNA network that included 69 differentially expressed lncRNAs (DElncRNAs) was constructed based on the five mRNAs obtained from the prognostic model. ROC survival analysis further showed that the seven DElncRNAs had a substantial prognostic value for the overall survival (OS) in NSCLC patients; the area under the curve was 0.65. In addition, the high-risk group showed drug resistance to several chemotherapeutic and targeted drugs including cisplatin, paclitaxel, docetaxel, gemcitabine, and gefitinib. The differential expression of five mRNAs and seven lncRNAs in the ceRNA network was supported by the results of the HPA database and RT-qPCR analyses. This comprehensive analysis of a ceRNA network identified a set of biomarkers for prognosis and TIME prediction in NSCLC.

Efficacy of Osimertinib in NSCLC Harboring Uncommon EGFR L861Q and Concurrent Mutations: Case Report and Literature Review.

The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on the efficacy of osimertinib in NSCLC patients with uncommon mutations. Here, we report the case of a 68-year-old man with advanced NSCLC with concurrent EGFR L861Q mutation as well as TP53 and RB1 mutations. The patient was treated with osimertinib as first-line therapy and achieved a remarkable progression-free survival of 15 months. His symptoms were significantly alleviated and the dose was well tolerated. The findings of the present study indicate that osimertinib might be a good treatment option for NSCLC patients with the L861Q mutation.

Ginsenoside Rg3 Promotes Cell Growth Through Activation of mTORC1.

Ginsenoside Rg3 is a steroidal saponin isolated from Panax ginseng. Previous studies have shown that Rg3 treatment downregulates the activity of rapamycin complex 1 (mTORC1) activity and inhibits the growth of cancer cells. However, the inhibitory effect of Rg3 on cancer cells is associated with high concentrations of Rg3 that are difficult to achieve in vivo. The human cervix adenocarcinoma HeLa cells were treated with Rg3. The protein levels of AMP-activated protein kinase alpha (AMPKα), protein kinase B(Akt), ribosomal S6 protein(S6), and Erk were determined by immunoblotting analyses. We used a fluorescent probe to detect reactive oxygen species (ROS) production in living cells. The oxygen consumption rate (OCR) was examined by the Seahorse Extracellular Flux Analyzer. The content of adenosine triphosphate (ATP) was measured by ATPlite kit and Mitotracker was applied to detect the mitochondria. We showed that at lower concentrations, Rg3 activates mTORC1 independent of AKT and AMP-activated protein kinase (AMPK). Rg3 promotes mitochondrial biogenesis and function, increases the oxygen consumption of mitochondria and the content of ATP. This effect is in contrast to that of high concentrations of Rg3, which inhibits cell growth. These findings demonstrate a pro-growth activity of Rg3 that acts through mTORC1 and mitochondrial biogenesis and suggest a dose-dependent effect of Rg3 on tumor cell growth.

Comprehensive TCM treatments combined with chemotherapy for advanced non-small cell lung cancer: A randomized, controlled trial.

OBJECTIVE: We conducted this study to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in advanced non-small cell lung cancer (NSCLC) patients who underwent chemotherapy. DESIGN: This was a prospective, open-label, randomized controlled trial. NSCLC patients at stage IIIA, IIIB, or IV were randomly assigned to either TCM plus chemotherapy or chemotherapy alone. The comprehensive TCM treatment consisted of Kang Ai injection, herbal decoction, and Zhenqifuzheng capsules. The primary endpoint was quality of life (QOL) measured by the Functional Assessment of Cancer Therapy-Lung version 4.0. The secondary endpoints were chemotherapy completion rate, tumor response, and adverse events. All assessments were done at baseline, the third week, and the sixth week. RESULTS: Thirty-nine participants were randomly assigned to the treatment group and 36 to the control group. The QOL scores were significantly improved in the treatment group compared with those of the control group in social well-being (cycle 1, P = .048; cycle 2, P = .015), emotional well-being (cycle 1, P = .047; cycle 2, P = 4.29E-05), and functional well-being (cycle 1, P = .030; cycle 2, P = .003), while the QOL scores in the above 3 domains declined in the control group (P < .05). Both groups had a decline in the physical well-being score (cycle 1, P = .042; cycle 2, P = .017) and lung cancer symptom score (cycle 1, P = .001; cycle 2, P = .001) after 2 courses of intervention. The deterioration in physical well-being and lung cancer symptoms was noticeably smaller in the treatment group (P < .05). There were significant differences between the 2 groups in social well-being, emotional well-being, functional well-being, lung cancer symptom domain, and the total score (P < .05). Patients in the treatment group had a significantly lower incidence of platelet reduction than the control group (P = .028) after 2 cycles of treatment. No significant difference in nonhematological adverse events (AEs) was observed. CONCLUSION: This study illustrated that comprehensive TCM treatment could promote the QOL of NSCLC patients, alleviate symptoms, and reduce the AEs caused by chemotherapy, verifying the synergistic and attenuating effects of TCM in NSCLC patients undergoing chemotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR-TRC-13003637.

Accuracy of Mixed Reality Combined With Surgical Navigation Assisted Oral and Maxillofacial Tumor Resection.

OBJECTIVE: To evaluate the feasibility and accuracy of mixed reality combined with surgical navigation in oral and maxillofacial tumor surgery. METHODS: Retrospective analysis of data of seven patients with oral and maxillofacial tumors who underwent surgery between January 2019 and January 2021 using a combination of mixed reality and surgical navigation. Virtual surgical planning and navigation plan were based on preoperative CT datasets. Through IGT-Link port, mixed reality workstation was synchronized with surgical navigation, and surgical planning data were transferred to the mixed reality workstation. Osteotomy lines were marked with the aid of both surgical navigation and mixed reality images visualized through HoloLens. Frozen section examination was used to ensure negative surgical margins. Postoperative CT datasets were obtained 1 week after the surgery, and chromatographic analysis of virtual osteotomies and actual osteotomies was carried out. Patients received standard oncological postoperative follow-up. RESULTS: Of the seven patients, four had maxillary tumors and three had mandibular tumors. There were total of 13 osteotomy planes. Mean deviation between the planned osteotomy plane and the actual osteotomy plane was 1.68 ± 0.92 mm; the maximum deviation was 3.46 mm. Chromatographic analysis showed error of ≤3 mm for 80.16% of the points. Mean deviations of maxillary and mandibular osteotomy lines were approximate (1.60 ± 0.93 mm vs. 1.86 ± 0.93 mm). While five patients had benign tumors, two had malignant tumors. Mean deviations of osteotomy lines was comparable between patients with benign and malignant tumors (1.48 ± 0.74 mm vs. 2.18 ± 0.77 mm). Intraoperative frozen pathology confirmed negative resection margins in all cases. No tumor recurrence or complications occurred during mean follow-up of 15.7 months (range, 6-26 months). CONCLUSION: The combination of mixed reality technology and surgical navigation appears to be feasible, safe, and effective for tumor resection in the oral and maxillofacial region.

Accuracy of multimodal image fusion for oral and maxillofacial tumors: A revised evaluation method and its application.

OBJECTIVE: To develop a revised evaluation method for accuracy of multimodal image fusion for oral and maxillofacial tumors and explore its application for comparing the accuracy of three commonly used fusion algorithms, automatic fusion, manual fusion, and registration point-based fusion. MATERIALS AND METHODS: Image sets of patients with oral and maxillofacial tumor were fused using the iPlan 3.0 navigation system. Fusion accuracy included two aspects: (1) overall fusion accuracy: represented by the mean value of the coordinate differences along the x-, y-, and z- axes (Δx, Δy, and Δz), mean deviation (MD), and root mean square (RMS) of six pairs of landmarks on the two image sets; (2) tumor volume fusion accuracy: represented by Fusion Index (FI), which was calculated based on the volume of tumor delineated on the two image sets. RESULTS: Eighteen pairs of image sets of 17 patients were enrolled in this study. The Δx and Δy values for the three algorithms were less than 1.5 mm. The Δz values for automatic fusion, manual fusion and registration point-based fusion was 1.049 mm, 1.864 mm and 1.254 mm. The MD for automatic fusion, manual fusion and registration point-based fusion was 1.978 mm, 2.788 mm and 1.926 mm. Significant differences existed in Δz for manual fusion and that for automatic fusion (P = 0.058), in MD for manual fusion and that for automatic fusion (P = 0.087), and in MD for manual fusion and that for registration point-based fusion (P = 0.069). The FI for automatic fusion, manual fusion, and registration point-based fusion was 0.594, 0.520, and 0.549; the inter-algorithm differences were not significant (P = 0.290). CONCLUSION: The automatic fusion and the registration point-based fusion were more accurate than manual fusion, and therefore were recommended to be used in multimodal image fusion for oral and maxillofacial tumors.