Intelligent electromagnetic navigation system for robot-assisted intraoral osteotomy in mandibular tumor resection: a model experiment.

Background: Mandibular tumor surgery necessitates precise osteotomies based on tumor boundaries; however, conventional osteotomies often lack accuracy in predicting osteotomy positions and planes, potentially leading to excessive resection of normal bone tissues or residual tumors, thus compromising postoperative quality of life and clinical outcomes. Robotic-assisted surgery (RAS) augmented with artificial intelligence (AI) offers precise localization capabilities, aiding surgeons in achieving accurate osteotomy positioning. This study aimed to evaluate the feasibility and accuracy of a robotic magnetic navigation system for positioning and osteotomy in an intraoral surgical trial of a mandibular tumor model. Methods: Patient computed tomography (CT) imaging data of mandibular chin and body tumors were utilized to create 3D printed models, serving as study subjects for mandibular tumor resection. Ten pairs of models were printed for the experimental and control groups. The experimental group (EG) underwent osteotomy using a robot-assisted surgical navigation system, performing osteotomy under robotic navigation following alignment based on preoperative design. The control group (CG) underwent traditional surgery, estimating osteotomy position empirically according to preoperative design. Postoperative CT scans were conducted on both models, and actual postoperative results were compared to preoperative design. Osteotomy accuracy was evaluated by positional and angular errors between preoperatively designed and actual osteotomy planes. Results: For ten randomly selected spots on the left and right sides, respectively, the EG group had mean distance errors of 0.338 mm and 0.941 mm. These values were obtained from the EG group. In the EG group, on the left side, the mean angular errors were 14.741 degrees, while on the right side, they were 13.021 degrees. For the 10 randomly selected spots on the left and right sides, respectively, the CG had mean distance errors of 1.776 mm and 2.320 mm. This is in contrast to the results obtained by the EG. It was determined that the left side had a mean angle error of 16.841 degrees, while the right side had an error of 18.416 degrees in the CG group. The above results indicated significantly lower point errors of bilateral osteotomy planes in the experimental group compared to the control group. Conclusion: This study demonstrates the feasibility of electromagnetic navigation robot-assisted intraoral osteotomy for mandibular tumors and suggests that this approach can enhance the precision of clinical surgery.

Developing targeted therapies for neuroblastoma by dissecting the effects of metabolic reprogramming on tumor microenvironments and progression.

Rationale: Synergic reprogramming of metabolic dominates neuroblastoma (NB) progression. It is of great clinical implications to develop an individualized risk prognostication approach with stratification-guided therapeutic options for NB based on elucidating molecular mechanisms of metabolic reprogramming. Methods: With a machine learning-based multi-step program, the synergic mechanisms of metabolic reprogramming-driven malignant progression of NB were elucidated at single-cell and metabolite flux dimensions. Subsequently, a promising metabolic reprogramming-associated prognostic signature (MPS) and individualized therapeutic approaches based on MPS-stratification were developed and further validated independently using pre-clinical models. Results: MPS-identified MPS-I NB showed significantly higher activity of metabolic reprogramming than MPS-II counterparts. MPS demonstrated improved accuracy compared to current clinical characteristics [AUC: 0.915 vs. 0.657 (MYCN), 0.713 (INSS-stage), and 0.808 (INRG-stratification)] in predicting prognosis. AZD7762 and etoposide were identified as potent therapeutics against MPS-I and II NB, respectively. Subsequent biological tests revealed AZD7762 substantially inhibited growth, migration, and invasion of MPS-I NB cells, more effectively than that of MPS-II cells. Conversely, etoposide had better therapeutic effects on MPS-II NB cells. More encouragingly, AZD7762 and etoposide significantly inhibited in-vivo subcutaneous tumorigenesis, proliferation, and pulmonary metastasis in MPS-I and MPS-II samples, respectively; thereby prolonging survival of tumor-bearing mice. Mechanistically, AZD7762 and etoposide-induced apoptosis of the MPS-I and MPS-II cells, respectively, through mitochondria-dependent pathways; and MPS-I NB resisted etoposide-induced apoptosis by addiction of glutamate metabolism and acetyl coenzyme A. MPS-I NB progression was fueled by multiple metabolic reprogramming-driven factors including multidrug resistance, immunosuppressive and tumor-promoting inflammatory microenvironments. Immunologically, MPS-I NB suppressed immune cells via MIF and THBS signaling pathways. Metabolically, the malignant proliferation of MPS-I NB cells was remarkably supported by reprogrammed glutamate metabolism, tricarboxylic acid cycle, urea cycle, etc. Furthermore, MPS-I NB cells manifested a distinct tumor-promoting developmental lineage and self-communication patterns, as evidenced by enhanced oncogenic signaling pathways activated with development and self-communications. Conclusions: This study provides deep insights into the molecular mechanisms underlying metabolic reprogramming-mediated malignant progression of NB. It also sheds light on developing targeted medications guided by the novel precise risk prognostication approaches, which could contribute to a significantly improved therapeutic strategy for NB.

Regulatory T cells subgroups in the tumor microenvironment cannot be overlooked: Their involvement in prognosis and treatment strategy in melanoma.

BACKGROUND: Melanoma, the most lethal form of skin cancer, presents substantial challenges despite effective surgical interventions for in situ lesions. Regulatory T cells (Tregs) wield a pivotal immunomodulatory influence within the tumor microenvironment, yet their impact on melanoma prognosis and direct molecular interactions with melanoma cells remain elusive. This investigation employs single-cell analysis to unveil the intricate nature of Tregs in human melanoma. METHODS: Single-cell RNA and bulk sequencing data, alongside clinical information, were obtained from public repositories. Initially, GO and GSEA analyses were employed to delineate functional disparities among distinct cell subsets. Pseudotime and cell-cell interconnection analyses were conducted, followed by an endeavor to construct a prognostic model grounded in Treg-associated risk scores. This model's efficacy was demonstrated via PCA and K-M analyses, with multivariate Cox regression affirming its independent prognostic value in melanoma patients. Furthermore, immune infiltration analysis, immune checkpoint gene expression scrutiny, and drug sensitivity assessments were performed to ascertain the clinical relevance of this prognostic model. RESULTS: Following batch effect correction, 80 025 cells partitioned into 31 clusters, encompassing B cells, plasma cells, endothelial cells, fibroblasts, melanoma cells, monocytes, macrophages, and T_NK cells. Within these, 4240 CD4+ T cells were subclassified into seven distinct types. Functional analysis underscored the immunomodulatory function of Tregs within the melanoma tumor microenvironment, elucidating disparities among Treg subpopulations. Notably, the ITGB2 signaling pathway emerged as a plausible molecular nexus linking Tregs to melanoma cells. Our prognostic signature exhibited robust predictive capacities for melanoma prognosis and potential implications in evaluating immunotherapy response. CONCLUSION: Tregs exert a critical role in immune suppression within the melanoma tumor microenvironment, revealing a potential molecular-level association with melanoma cells. Our innovative Treg-centered signature introduces a promising prognostic marker for melanoma, holding potential for future clinical prognostic assessments.

Efficacy of navigation system-assisted distraction osteogenesis for hemifacial microsomia based on artificial intelligence for 3 to 18 years old: study protocol for a randomized controlled single-blind trial.

BACKGROUND: Mandibular distraction osteogenesis (MDO) is a major part of the treatment for hemifacial microsomia patients. Due to the narrow surgical field of the intraoral approach, osteotomy accuracy is highly dependent on the surgeons' experience. Electromagnetic (EM) tracking systems can achieve satisfying accuracy to provide helpful real-time surgical navigation. Our research team developed an EM navigation system based on artificial intelligence, which has been justified in improving the accuracy of osteotomy in the MDO in animal experiments. This study aims to clarify the effect of the EM navigation system in improving the MDO accuracy for hemifacial microsomia patients. METHODS: This study is designed as a single-centered and randomized controlled trial. Altogether, 22 hemifacial microsomia patients are randomly assigned to the experiment and control groups. All patients receive three-dimensional CT scans and preoperative surgical plans. The EM navigation system will be set up for those in the experiment group, and the control group will undergo traditional surgery. The primary outcome is the surgical precision by comparing the osteotomy position of pre- and postoperative CT scan images through the Geomagic Control software. The secondary outcomes include mandibular symmetry (occlusal plane deviation angle, mandibular ramus height, and body length), pain scale, and complications. Other indications, such as the adverse events of the system and the satisfactory score from patients and their families, will be recorded. DISCUSSION: This small sample randomized controlled trial intends to explore the application of an EM navigation system in MDO for patients, which has been adopted in other surgeries such as orthognathic procedures. Because of the delicate structures of children and the narrow surgical view, accurate osteotomy and protection of nearby tissue from injury are essential for successful treatment. The EM navigation system based on artificial intelligence adopted in this trial is hypothesized to provide precise real-time navigation for surgeons and optimally improve patient outcomes, including function and aesthetic results. The results of this trial will extend the application of new navigation technology in pediatric plastic surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200061565. Registered on 29 June 2022.

Single-cell sequencing analysis related to sphingolipid metabolism guides immunotherapy and prognosis of skin cutaneous melanoma.

Background: We explore sphingolipid-related genes (SRGs) in skin melanoma (SKCM) to develop a prognostic indicator for patient outcomes. Dysregulated lipid metabolism is linked to aggressive behavior in various cancers, including SKCM. However, the exact role and mechanism of sphingolipid metabolism in melanoma remain partially understood. Methods: We integrated scRNA-seq data from melanoma patients sourced from the GEO database. Through the utilization of the Seurat R package, we successfully identified distinct gene clusters associated with patient survival in the scRNA-seq data. Key prognostic genes were identified through single-factor Cox analysis and used to develop a prognostic model using LASSO and stepwise regression algorithms. Additionally, we evaluated the predictive potential of these genes within the immune microenvironment and their relevance to immunotherapy. Finally, we validated the functional significance of the high-risk gene IRX3 through in vitro experiments. Results: Analysis of scRNA-seq data identified distinct expression patterns of 4 specific genes (SRGs) in diverse cell subpopulations. Re-clustering cells based on increased SRG expression revealed 7 subgroups with significant prognostic implications. Using marker genes, lasso, and Cox regression, we selected 11 genes to construct a risk signature. This signature demonstrated a strong correlation with immune cell infiltration and stromal scores, highlighting its relevance in the tumor microenvironment. Functional studies involving IRX3 knockdown in A375 and WM-115 cells showed significant reductions in cell viability, proliferation, and invasiveness. Conclusion: SRG-based risk signature holds promise for precise melanoma prognosis. An in-depth exploration of SRG characteristics offers insights into immunotherapy response. Therapeutic targeting of the IRX3 gene may benefit melanoma patients.

Experimental Study of Skin Contraction Induced by Bipolar Radiofrequency.

Background: Facial skin relaxation has become an important part in solving the problem of facial rejuvenation. Minimally invasive or noninvasive skin-tightening procedures have become a trend for facial rejuvenation. Bipolar radiofrequency (RF) is a new option for treating skin relaxation and is more effective than noninvasive surgery without surgical incision. Objective: To explore the effect of different bipolar RF powers on the area of the original box, changes of skin and subcutaneous tissue thickness and numbers of fibroblasts in rabbits. Design: The research team performed an animal study. Setting: This study took place in Affiliated Hospital of Nanjing University of Chinese Medicine. Participants: Eighteen common-grade adult New Zealand rabbits (female, 2.5-3.0 kg). Methods: Bipolar radiofrequency therapy was given to a girl rabbit on the left side of the treatment area. Standard HE and Masson staining were performed to assess the pathological changes, area of the original box and the number of fibroblasts in skin and subcutaneous tissues. Outcome Measures: (1) The area of the original box, changes of skin and subcutaneous tissue thickness, and numbers of fibroblasts under different bipolar RF temperatures or under different bipolar RF powers immediately after surgery, 1 month after surgery and 3 months after surgery were observed. (2) Standard HE and Masson staining results. Results: Under the condition of certain instrument power, at 36de 38d and 40nd the area of the original box shrank to different degrees immediately after surgery (16.54±0.37, 17.78±0.03, 17.19±0.01), 1 month after surgery (16.59±0.31, 17.82±0.01, 18.34±0.30) and 3 months after surgery (16.89±0.12, 18.16±0.14, 19.23±0.32) compared with that before surgery (P < .05). Under specific temperature conditions, at 16 W, 18 W, 20 W, and 22 W, the area of the original box shrank to different degrees immediately after surgery (16.40±0.49, 15.55±0.57, 17.54±0.12, 16.19±0.27), 1 month after surgery (16.88±0.12, 17.46±0.02, 18.05±0.35, 19.41±0.08) and 3 months after surgery (19.09±1.01, 18.30±0.69, 20.00±0.29, 21.20±0.90) compared with that before surgery (P < .05). When the power was fixed, the thickness of skin and subcutaneous tissue decreased immediately after surgery (6.7, 6.8, 7), 1 month after surgery (6, 6.1, 6.3) and 3 months after surgery (6.4, 6.5, 6.2) at different temperatures (P < .05). When the temperature was fixed, the thickness of skin and subcutaneous tissue decreased immediately after surgery (6.1, 6.08, 6.03), 1 month after surgery (6.2, 6.15, 6.13), and 3 months after surgery (6.2, 6.23, 6.03) under different powers (P < .05). Under the condition of certain instrument power, at 36de 38d and 40n, the number of fibroblasts increased to different degrees immediately after surgery (26.54±2.37, 30.78±3.03, 37.19±4.01), 1 month after surgery (28.59±2.31, 34.82±3.01, 40.34±4.30), and 3 months after surgery (30.89±0.12, 38.16±0.14, 42.23±0.32) compared with that before surgery, and all were statistically significant (P < .05). Under specific temperature conditions, at 16 W, 18 W, 20 W, and 22 W, the number of fibroblasts increased to different degrees immediately after surgery (28.29±2.49, 30.97±3.57, 38.74±3.12, 45.68±4.27), 1 month after surgery (30.88±3.12, 32.46±4.02, 41.05±0.35, 50.41±0.08), and 3 months after surgery (29.99±2.01, 33.30±2.69, 39.00±3.29, 23.20±2.90) compared with that before surgery, and all were statistically significant (P < .05). Conclusions: Our study clarifies that bipolar RF can decrease the skin and subcutaneous tissue thickness and increase the numbers of fibroblasts at the temperature of 36°C, 38°C, and 40°C and frequency of 16-22 W, which has a therapeutical effect on skin contraction. Our study might effectively improve the skin slack of patients, and the postoperative maintenance rate is high, and will not cause obvious complications. This study may provide a theoretical direction for clinicians to tighten the skin of patients using bipolar RF.

Platelet-rich plasma combined with lyophilizing thrombin powder for the treatment of complicated enterocutaneous fistula: a case report.

Background: Enterocutaneous fistula is one of the most challenging problems facing surgeons. In severe cases, a large amount of fluid loss can lead to problems such as water and electrolyte acid-base imbalance, malnutrition, infection, and organ dysfunction. Here we reported a case of platelet-rich plasma combined with lyophilizing thrombin powder for the treatment of complicated enterocutaneous fistula. Case presentation: A 48-year-old male, more than 2 years after the operation of abdominal trauma, the leakage of the fistula in the right upper abdominal wall was accompanied by fever for 3 days. The Contrast Fistulography and upper abdomen CT accurately depicted the entry of the meglumine diatrizoate into the small intestine through the small fistula. The patient had a large abdominal wall defect and severe intestinal adhesions. Reoperation may lead to more serious ECF. Therefore, we decided to seal the fistulas with PRP combined with lyophilizing thrombin powder. Conclusions: The findings in this case report suggest that the combination of PRP and lyophilized thrombin powder holds promise as a viable approach for managing ECF in patients with chronic abdominal wall fistulas, as it appears to facilitate fistula closure, reduce healing time, and improve patient outcomes.

Targeted genome mining for microbial antitumor agents acting through DNA intercalation.

Microbial natural products have been one of the most important sources for drug development. In the current postgenomic era, sequence-driven approaches for natural product discovery are becoming increasingly popular. Here, we develop an effective genome mining strategy for the targeted discovery of microbial metabolites with antitumor activities. Our method employs uvrA-like genes as genetic markers, which have been identified in the biosynthetic gene clusters (BGCs) of several chemotherapeutic drugs of microbial origin and confer self-resistance to the corresponding producers. Through systematic genomic analysis of gifted actinobacteria genera, identification of uvrA-like gene-containing BGCs, and targeted isolation of products from a BGC prioritized for metabolic analysis, we identified a new tetracycline-type DNA intercalator timmycins. Our results thus provide a new genome mining strategy for the efficient discovery of antitumor agents acting through DNA intercalation.

Innovative breakthroughs facilitated by single-cell multi-omics: manipulating natural killer cell functionality correlates with a novel subcategory of melanoma cells.

Background: Melanoma is typically regarded as the most dangerous form of skin cancer. Although surgical removal of in situ lesions can be used to effectively treat metastatic disease, this condition is still difficult to cure. Melanoma cells are removed in great part due to the action of natural killer (NK) and T cells on the immune system. Still, not much is known about how the activity of NK cell-related pathways changes in melanoma tissue. Thus, we performed a single-cell multi-omics analysis on human melanoma cells in this study to explore the modulation of NK cell activity. Materials and methods: Cells in which mitochondrial genes comprised > 20% of the total number of expressed genes were removed. Gene ontology (GO), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and AUCcell analysis of differentially expressed genes (DEGs) in melanoma subtypes were performed. The CellChat package was used to predict cell-cell contact between NK cell and melanoma cell subtypes. Monocle program analyzed the pseudotime trajectories of melanoma cells. In addition, CytoTRACE was used to determine the recommended time order of melanoma cells. InferCNV was utilized to calculate the CNV level of melanoma cell subtypes. Python package pySCENIC was used to assess the enrichment of transcription factors and the activity of regulons in melanoma cell subtypes. Furthermore, the cell function experiment was used to confirm the function of TBX21 in both A375 and WM-115 melanoma cell lines. Results: Following batch effect correction, 26,161 cells were separated into 28 clusters and designated as melanoma cells, neural cells, fibroblasts, endothelial cells, NK cells, CD4+ T cells, CD8+ T cells, B cells, plasma cells, monocytes and macrophages, and dendritic cells. A total of 10137 melanoma cells were further grouped into seven subtypes, i.e., C0 Melanoma BIRC7, C1 Melanoma CDH19, C2 Melanoma EDNRB, C3 Melanoma BIRC5, C4 Melanoma CORO1A, C5 Melanoma MAGEA4, and C6 Melanoma GJB2. The results of AUCell, GSEA, and GSVA suggested that C4 Melanoma CORO1A may be more sensitive to NK and T cells through positive regulation of NK and T cell-mediated immunity, while other subtypes of melanoma may be more resistant to NK cells. This suggests that the intratumor heterogeneity (ITH) of melanoma-induced activity and the difference in NK cell-mediated cytotoxicity may have caused NK cell defects. Transcription factor enrichment analysis indicated that TBX21 was the most important TF in C4 Melanoma CORO1A and was also associated with M1 modules. In vitro experiments further showed that TBX21 knockdown dramatically decreases melanoma cells' proliferation, invasion, and migration. Conclusion: The differences in NK and T cell-mediated immunity and cytotoxicity between C4 Melanoma CORO1A and other melanoma cell subtypes may offer a new perspective on the ITH of melanoma-induced metastatic activity. In addition, the protective factors of skin melanoma, STAT1, IRF1, and FLI1, may modulate melanoma cell responses to NK or T cells.

Accuracy and safety of robotic navigation-assisted distraction osteogenesis for hemifacial microsomia.

Introduction: This study aimed to verify the accuracy and safety of distraction osteogenesis for hemifacial microsomia assisted by a robotic navigation system based on artificial intelligence. Methods: The small sample early-phase single-arm clinical study, available at http://www.chictr.org.cn/index.aspx, included children aged three years and older diagnosed with unilateral hemifacial microsomia (Pruzansky-Kaban type II). A preoperative design was performed, and an intelligent robotic navigation system assisted in the intraoperative osteotomy. The primary outcome was the accuracy of distraction osteogenesis, including the positional and angular errors of the osteotomy plane and the distractor, by comparing the preoperative design plan with the actual images one week postoperatively. Perioperative indicators, pain scales, satisfaction scales, and complications at one week were also analyzed. Results: Four cases (mean 6.5 years, 3 type IIa and 1 type IIb deformity) were included. According to the craniofacial images one week after surgery, the osteotomy plane positional error was 1.77 ± 0.12 mm, and the angular error was 8.94 ± 4.13°. The positional error of the distractor was 3.67 ± 0.23 mm, and the angular error was 8.13 ± 2.73°. Postoperative patient satisfaction was high, and no adverse events occurred. Discussion: The robotic navigation-assisted distraction osteogenesis in hemifacial microsomia is safe, and the operational precision meets clinical requirements. Its clinical application potential is to be further explored and validated.

Advances in Robot-Assisted Surgery for Facial Bone Contouring Surgery.

Since our team reported the application of robot-assisted surgery in facial contouring surgery in 2020, further clinical trials with large samples have been conducted. This paper will report the interim results of a single-center, large-sample randomized controlled trial of the first robot developed by our team for facial contouring surgery. Meanwhile, this research field will be systematically reviewed and prospected.

The Predictive Value of Changes in the Absolute Counts of Peripheral Lymphocyte Subsets for Progression and Prognosis in Breast Cancer Patients.

Background: As the number and proportion of lymphocyte subsets are an important indicator of the immune function, an in depth understanding of the immune function of patients with malignant tumor has important clinical values for the treatment, prognosis, and evaluation of the disease. This retrospective study was to evaluate the clinical value of the absolute counts of lymphocyte subsets as potential blood biomarkers for progression and prognosis in breast cancer patients. Methods: A total of 237 BC patients and 55 age-matched female normal healthy donors were included in this study. Flow cytometry was used to determine the absolute counts and the percentages of CD3+, CD4+, CD8+, B, and NK cells. The receiver operating characteristic curve (ROC) was used to evaluate the accuracy of absolute count of lymphocyte subsets in the curative efficacy assessment. The clinicopathological parameters influencing the disease progression were determined by Cox proportional hazards regression. Progression-free survival (PFS) was estimated using the Kaplan-Meier method with the log-rank test. Results: Compared with the healthy donors, the absolute counts of lymphocyte subsets in patients decreased significantly. ROC analysis showed that the area under the curve of the CD4+ absolute count was 90% (95% confidence interval 0.859-0.940), and the sensitivity and specificity were 80.9% and 85.3%, respectively. The analysis of Cox regression showed that the cutoff value of the CD4+ absolute count ≥451 cells/µL might be a favorable prognostic factor. Multivariate analysis of prognostic factors of PFS showed that the CD4+ and CD8+ absolute count were independent factors for predicting PFS. Conclusions: The remarkably impaired absolute counts of the CD3+, CD4+, CD8+, B, and NK cells in patients with breast cancer can be used as potential susceptible biomarkers to evaluate the patient's immune status. The higher level of CD4+ and CD8+ absolute counts probably contributed to the longer PFS and favorable outcome of BC patients.

Individualized CT image-guided free-hand catheter technique: A new and reliable method for minimally invasive evacuation of basal ganglia hematoma.

Objective: To validate the clinical reliability of an individualized CT image-guided' free-hand catheter technique (CTGFC) for basal ganglia hematoma (BGH) evacuation. Methods: From January 2017 to December 2020, 58 cases of patients with BGH who underwent catheter evacuation were enrolled. The surgery was conducted using the CTGFC (n = 31) or stereotactic catheter technique (STC, n = 27). The authors evaluated the baseline characteristics, operation-related indicators, postoperative complications, hospitalization-related indicators, short-term and long-term functional outcomes, and mortality rate 1 year after surgery. Results: All patients underwent BGH evacuation under non-general anesthesia in the CTGFC group. The operative time (p < 0.01) and operation costs (p < 0.05) were significantly shorter in the CTGFC group than that in the STC group (p < 0.01). Comparable results were found in the catheter indwelling duration, residual hematoma volume, hematoma evacuation rate, incidence of postoperative complications, hospital ICU stay, and hospital costs between these two groups (p > 0.05). The duration of hospital stay was remarkably shorter in the CTGFC group than that in the STC group (p < 0.01). There were no differences in terms of the short-time functional outcomes score at discharge, including the Glasgow outcome scale (GOS) score, the activities of daily living (ADL) score, and the Karnofsky performance score (KPS). Moreover, comparable findings were also found in the 1-year postoperative GOS score, ADL score, KPS score, and mortality rate between these two groups. Conclusion: The simple CTGFC-assisted surgery was a safe and reliable option for BGH evacuation, especially in primary medical institutes and emergency situations with limited medical resources.

m7G Methylation-Related Genes as Biomarkers for Predicting Overall Survival Outcomes for Hepatocellular Carcinoma.

Aim: The search for prognostic biomarkers and the construction of a prognostic risk model for hepatocellular carcinoma (HCC) based on N7-methyladenosine (m7G) methylation regulators. Methods: HCC transcriptomic data and clinical data were obtained from The Cancer Genome Atlas database and Shanghai Ninth People's Hospital, respectively. m7G methylation regulators were extracted, differential expression analysis was performed using the R software "limma" package, and one-way Cox regression analysis was used to screen for prognostic associations of m7G regulators. Using multi-factor Cox regression analysis, a prognostic risk model for HCC was constructed. Each patient's risk score was calculated using the model, and patients were divided into high- and low-risk groups according to the median risk score. Cox regression analysis was used to verify the validity of the model in the prognostic assessment of HCC in conjunction with clinicopathological characteristics. Results: The prognostic model was built using the seven genes, namely, CYFIP1, EIF4E2, EIF4G3, GEMIN5, NCBP2, NUDT10, and WDR4. The Kaplan-Meier survival analysis showed poorer 5-years overall survival in the high-risk group compared with the low-risk group, and the receiver-operating characteristic (ROC) curve suggested good model prediction (area under the curve AUC = 0.775, 0.820, and 0.839 at 1, 3, and 5 years). The Cox regression analysis included model risk scores and clinicopathological characteristics, and the results showed that a high-risk score was the only independent risk factor for the prognosis of patients with HCC. Conclusions: The developed bioinformatics-based prognostic risk model for HCC was found to have good predictive power.

Using the hybrid EMD-BPNN model to predict the incidence of HIV in Dalian, Liaoning Province, China, 2004-2018.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is a malignant infectious disease with high mortality caused by HIV (human immunodeficiency virus, and up to now there are no curable drugs or effective vaccines. In order to understand AIDS's development trend, we establish hybrid EMD-BPNN (empirical modal decomposition and Back-propagation artificial neural network model) model to forecast new HIV infection in Dalian and to evaluate model's performance. METHODS: The monthly HIV data series are decomposed by EMD method, and then all decomposition results are used as training and testing data to establish BPNN model, namely BPNN was fitted to each IMF (intrinsic mode function) and residue separately, and the predicted value is the sum of the predicted values from the models. Meanwhile, using yearly HIV data to established ARIMA and using monthly HIV data to established BPNN, and SARIMA (seasonal autoregressive integrated moving average) model to compare the predictive ability with EMD-BPNN model. RESULTS: From 2004 to 2017, 3310 cases of HIV were reported in Dalian, including 101 fatal cases. The monthly HIV data series are decomposed into four relatively stable IMFs and one residue item by EMD, and the residue item showed that the incidence of HIV increases firstly after declining. The mean absolute percentage error value for the EMD-BPNN, BPNN, SARIMA (1,1,2) (0,1,1)12 in 2018 is 7.80%, 10.79%, 9.48% respectively, and the mean absolute percentage error value for the ARIMA (3,1,0) model in 2017 and 2018 is 8.91%. CONCLUSIONS: The EMD-BPNN model was effective and reliable in predicting the incidence of HIV for annual incidence, and the results could furnish a scientific reference for policy makers and health agencies in Dalian.

Disruption of Rich-Club Connectivity in Cushing Disease.

OBJECTIVE: Cushing disease (CD) is a rare clinical disease in which brain structural and function are impaired as the result of excessive cortisol. However, little is known whether rich-club organization changes in patients with CD, as visualized on resting-state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aimed to investigate whether the functional connectivity of rich-club organization is affected and whether any abnormal changes may reverse after TSS. METHODS: In this study, 38 patients with active CD, 33 with patients with CD in remission, and 41 age-, sex-, and education-matched healthy control participants underwent resting-state fMRI. Brain functional connectivity was constructed based on fMRI and rich club was calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich-club connectivity based on fMRI. RESULTS: We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich-club connectivity was significantly lower in patients with active CD (P < 0.001). Moreover, abnormal rich-club connectivity improved to normal after TSS. CONCLUSIONS: Our results show rich-club organization was disrupted in patients with active CD with excessive cortisol production. TSS can reverse abnormal rich-club connectivity. Rich club may be a new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in patients with CD.

Texture recognition of pulmonary nodules based on volume local direction ternary pattern.

In recent years, the incidence of lung cancer has been increasing. Lung cancer detection is based on computed tomography (CT) imaging of the lung area to determine whether there are pulmonary nodules. And then judge what's good and what's bad. However, due to the traditional way of manual reading and lack of experience and other problems. This leads to visual fatigue and misdiagnosis and missed diagnosis. In order to detect pulmonary nodules early and accurately, a new assistant diagnosis method for pulmonary nodules is proposed. Firstly, the image is preprocessed and denoised by median filter, the lung parenchyma is segmented by random walk algorithm and the region of interest is extracted, and then, according to the continuity of the CT slices, the texture feature extraction method of pulmonary nodules based on volume local direction ternary pattern is used to extract the features. Finally, the pulmonary nodules are identified and classified by the assistant diagnosis model of pulmonary nodules based on Stacking algorithm. In order to illustrate the validity of the diagnosis model, the experiments are carried out by cross-validation of ten folds. Experiments using data from LIDC database show that the accuracy, sensitivity and specificity of the proposed method are 82.2%, 85.7%, and 78.8%, respectively. Texture Recognition method based on volume vocal direction ternary pattern is feasible for the identification of pulmonary nodules and provides a reference value for doctor-assisted diagnosis.

[Comprehensive Evaluation of Biological Activity in Different Passage Populations of Mesenchymal Stem Cells Derived from Bone Marrow in Ovariectomy Osteoporotic Rats].

This study aimed to comprehensively evaluate the biological activity in different passage populations of mesenchymal stem cells(BMSCs)derived from bone marrow in ovariectomy osteoporotic rats(named OVX-rBMSCs),providing experimental basis for new osteoporotic drug development and research.OVX-rBMSCs were isolated and cultured in vitro by the whole bone marrow adherent screening method.The morphological observation,cell surface markers(CD29,CD45,CD90)detection,cell proliferation,induced differentiation experimental detection were performed to evaluate the biological activity of Passage 1,2,3,4populations(P1,P2,P3,P4)OVX-rBMSCs.The results showed that whole bone marrow adherent culture method isolated and differentially subcultured OVXrBMSCs.The morphology of P4 OVX-rBMSCs was identical fibroblast-like and had the characteristics of ultrastructure of stem cells.The CD29 positive cells rate,CD90 positive cells rate,cell proliferation index,and the osteogenic,adipogenic,chondrogenic differentiation capacities of P4 OVX-rBMSCs were significantly better than those of other populations(P<0.05).OVX-rBMSCs purity and biological activity were gradually optimized with the passaged,and among them P4 cells were superior to all the other populations.Based on these results,we report that the P4OVX-rBMSCs model developed in this study can be used to develop a new and effective medical method for osteoporotic drug screening.