Decision Fusion Model for Predicting Microvascular Invasion in Hepatocellular Carcinoma Based on Multi-MR Habitat Imaging and Machine-Learning Classifiers.

RATIONALE AND OBJECTIVES: Accurate prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is crucial for guiding treatment. This study evaluates and compares the performance of clinicoradiologic, traditional radiomics, deep-learning radiomics, feature fusion, and decision fusion models based on multi-region MR habitat imaging using six machine-learning classifiers. MATERIALS AND METHODS: We retrospectively included 300 HCC patients. The intratumoral and peritumoral regions were segmented into distinct habitats, from which radiomics and deep-learning features were extracted using arterial phase MR images. To reduce feature dimensionality, we applied intra-class correlation coefficient (ICC) analysis, Pearson correlation coefficient (PCC) filtering, and recursive feature elimination (RFE). Based on the selected optimal features, prediction models were constructed using decision tree (DT), K-nearest neighbors (KNN), logistic regression (LR), random forest (RF), support vector machine (SVM), and XGBoost (XGB) classifiers. Additionally, fusion models were developed utilizing both feature fusion and decision fusion strategies. The performance of these models was validated using the area under the receiver operating characteristic curve (ROC AUC), calibration curves, and decision curve analysis. RESULTS: The decision fusion model (VOI-Peri10-1) using LR and integrating clinicoradiologic, radiomics, and deep-learning features achieved the highest AUC of 0.808 (95% confidence interval [CI]: 0.807-0.912) in the test cohort, with good calibration (Hosmer-Lemeshow test, P > 0.050) and clinical net benefit. CONCLUSION: The LR-based decision fusion model integrating clinicoradiologic, radiomics, and deep-learning features shows promise for preoperative prediction of MVI in HCC, aiding in patient outcome predictions and personalized treatment planning.

Stepwise Corrected Attention Registration Network for Preoperative and Follow-Up Magnetic Resonance Imaging of Glioma Patients.

The registration of preoperative and follow-up brain MRI, which is crucial in illustrating patients' responses to treatments and providing guidance for postoperative therapy, presents significant challenges. These challenges stem from the considerable deformation of brain tissue and the areas of non-correspondence due to surgical intervention and postoperative changes. We propose a stepwise corrected attention registration network grounded in convolutional neural networks (CNNs). This methodology leverages preoperative and follow-up MRI scans as fixed images and moving images, respectively, and employs a multi-level registration strategy that establishes a precise and holistic correspondence between images, from coarse to fine. Furthermore, our model introduces a corrected attention module into the multi-level registration network that can generate an attention map at the local level through the deformation fields of the upper-level registration network and pathological areas of preoperative images segmented by a mature algorithm in BraTS, serving to strengthen the registration accuracy of non-correspondence areas. A comparison between our scheme and the leading approach identified in the MICCAI's BraTS-Reg challenge indicates a 7.5% enhancement in the target registration error (TRE) metric and improved visualization of non-correspondence areas. These results illustrate the better performance of our stepwise corrected attention registration network in not only enhancing the registration accuracy but also achieving a more logical representation of non-correspondence areas. Thus, this work contributes significantly to the optimization of the registration of brain MRI between preoperative and follow-up scans.

Robot-assisted repair of ureteral stricture.

As robot-assisted laparoscopic techniques continue to advance, becoming increasingly complex and refined, there has been significant progress in the minimally invasive treatment of ureteral strictures. This abstract aims to provide an overview and description of various surgical techniques that utilize robots for repairing ureteral strictures. We have summarized the progression of these surgical methods and highlighted the latest advancements in the procedures. When compared to open surgery, robot-assisted reconstruction techniques demonstrate superior functional outcomes, fewer postoperative complications, and a faster recovery in the treatment of ureteral strictures. This abstract aims to provide an overview and description of various surgical techniques utilizing robots to repair ureteral strictures. Robotic ureteral stricture correction has emerged as a valuable therapeutic option, particularly when endoscopic procedures are not feasible. Compared to traditional open surgery, robotic methods exhibit superior therapeutic effectiveness, fewer postoperative complications, and accelerated recovery. Reconstructive procedures such as reimplantation, psoas hitch, Boari flap, ureter-to-ureter anastomosis, appendix graft, buccal mucosa graft (BMG), ileal transplantation, or kidney autotransplantation can be performed depending on the extent and location of the stricture. Robotic surgical techniques also offer advantages, such as an expanded field of vision and the incorporation of supplementary technologies such as FireflyTM, indocyanine green (ICG), and near-infrared fluorescence (NIRF) imaging. However, further long-term, multicenter investigations are necessary to validate the positive findings reported in existing case series. Compared with open surgery, robot-assisted reconstruction techniques yield superior functional outcomes, fewer postoperative complications, and accelerated recovery for the treatment of ureteral strictures.

Engineering Novel Amphiphilic Platinum(IV) Complexes to Co-Deliver Cisplatin and Doxorubicin.

In this study, we report a novel platinum-doxorubicin conjugate that demonstrates superior therapeutic indices to cisplatin, doxorubicin, or their combination, which are commonly used in cancer treatment. This new molecular structure (1) was formed by conjugating an amphiphilic Pt(IV) prodrug of cisplatin with doxorubicin. Due to its amphiphilic nature, the Pt(IV)-doxorubicin conjugate effectively penetrates cell membranes, delivering both cisplatin and doxorubicin payloads intracellularly. The intracellular accumulation of these payloads was assessed using graphite furnace atomic absorption spectrometry and fluorescence imaging. Since the therapeutic effects of cisplatin and doxorubicin stem from their ability to target nuclear DNA, we hypothesized that the amphiphilic Pt(IV)-doxorubicin conjugate (1) would effectively induce nuclear DNA damage toward killing cancer cells. To test this hypothesis, we used flow the cytometric analysis of phosphorylated H2AX (γH2AX), a biomarker of nuclear DNA damage. The Pt(IV)-doxorubicin conjugate (1) markedly induced γH2AX in treated MDA-MB-231 breast cancer cells, showing higher levels than cells treated with either cisplatin or doxorubicin alone. Furthermore, MTT cell viability assays revealed that the enhanced DNA-damaging capability of complex 1 resulted in superior cytotoxicity and selectivity against human cancer cells compared to cisplatin, doxorubicin, or their combination. Overall, the development of this amphiphilic Pt(IV)-doxorubicin conjugate represents a new form of combination therapy with improved therapeutic efficacy.

Integrated transcriptomics and proteomics analyses reveal the ameliorative effect of hepatic damage in tilapia caused by polystyrene microplastics with chlorella addition.

Fish exhibit varying responses to polystyrene microplastics (MPs) depending on particle size. Previous studies suggested that microorganisms adhering to the surface of MPs can induce toxic effects. In this study, Tilapia were exposed to MPs of control (group A), 75 nm (B), 7.5 µm (C), 750 µm (D), as well as combinations of all sizes (E) and 75 nm MPs with Chlorella vulgaris addition (F) for 7, 10 and 14 days. Histopathological changes in liver of tilapia were assessed using enzyme activities, transcriptomics and proteomics. The results showed that in groups combined MPs of different particle sizes and those supplemented with chlorella, MPs were localized on the surface of goblet cells, leading to vacuoles, constricted hepatic sinuses and nuclei displacement. Exposure to 7.5 and 750 µm MPs significantly increased the contents of fatty acid synthase (FAS), adenosine triphosphate (ATP), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), total cholesterol (TC), total triglyceride (TG) contents at 7 and 10 days. In particular, cytochrome p450 1a1 (EROD), reactive oxygen species (ROS) and superoxide dismutase (SOD) were markedly elevated following exposure to MPs. Apoptotic markers caspase-3, and inflammatory markers, including tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß), had a similar upward trend in comparisons of group C vs A at 7 d, group D vs A at 14 d. The peroxisome proliferator activated receptor (PPAR) signaling pathway, spliceosome, was highly enriched during the 7-day exposure of medium sized MPs, while largest MPs in the comparison of group D vs A at 14 d activated pathways such as phagosome, apoptosis, salmonella infection. Transcriptomic analysis revealed that after 14 days, the kyoto encyclopedia of genes and genomes (KEGG) pathways associated with protein processing in endoplasmic reticulum and the PPAR signaling has been significantly enriched in the Chlorella-supplemented group, which was further confirmed via the proteomic analysis. Overall, the findings highlight the size-dependent effects of MPs on histopathological changes, gene and protein expression in the liver of tilapia, and C. vulgaris effectively attenuated liver damages, likely through modulation of endoplasmic reticulum protein processing and PPAR signaling pathways.

Identifying suitable candidates for pancreaticoduodenectomy with extended lymphadenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: To evaluate long-term quality of life and survival in pancreatic ductal adenocarcinoma (PDAC) patients after pancreatoduodenectomy with extended lymphadenectomy (PDEL) and identify candidates. METHODS: Patients with resectable PDAC with ≥1 examined lymph node (LN) during pancreatoduodenectomy (PD), and were divided into the PD with standard lymphadenectomy (PDSL) and PDEL groups. Perioperative data, long-term quality of life and survival were compared, and the prognostic effect of LNs ± in every peripancreatic station were analysed. RESULTS: Screening 446 PDAC patients, 237 and 126 were included in the PDSL and PDEL groups, respectively. The PDEL group showed a longer operation time, greater intraoperative blood loss, severe diarrhoea, a higher incidence of grade III complications. Notably, the PDEL patients experienced significant relief from low back pain and diarrhoea, with an obvious survival advantage (p = 0.037), especially in patients with preoperative tumor contact with vascular and pathological N0; however, LNs+ in any station (No. 8p, 12, 14, or 16) were associated with a poorer prognosis. The vascular reconstruction, T and N stage were independent risk factors for survival. CONCLUSION: PDEL can relieve symptoms and prolong the survival of PDAC patients with acceptable complications, and EL should be performed regardless of preoperative LN enlargement.

14-3-3 Family of Proteins: Biological Implications, Molecular Interactions, and Potential Intervention in Cancer, Virus and Neurodegeneration Disorders.

The 14-3-3 family of proteins are highly conserved acidic eukaryotic proteins (25-32 kDa) abundantly present in the body. Through numerous binding partners, the 14-3-3 is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to the onset of critical illnesses such as cancers, neurodegenerative diseases and viral infections. Interestingly, explorative studies have revealed an inverse correlation of 14-3-3 protein in cancer and neurodegenerative diseases, and the direct manipulation of 14-3-3 by virus to enhance infection capacity has dramatically extended its significance. Of these, COVID-19 has been linked to the 14-3-3 proteins by the interference of the SARS-CoV-2 nucleocapsid (N) protein during virion assembly. Given its predisposition towards multiple essential host signalling pathways, it is vital to understand the holistic interactions between the 14-3-3 protein to unravel its potential therapeutic unit in the future. As such, the general structure and properties of the 14-3-3 family of proteins, as well as their known biological functions and implications in cancer, neurodegeneration, and viruses, were covered in this review. Furthermore, the potential therapeutic target of 14-3-3 proteins in the associated diseases was discussed.

Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.

Circadian rhythm is a self-regulating 24-hour system that synchronizes with the day and night cycle in organisms. The regulation of this system is controlled by clock genes, which function to harmoniously express molecular levels that facilitate the orderly coordination of various cellular processes, such as sleep, metabolism, endocrine function, cell proliferation and immunity. The root cause of tumorigenesis is that the body loses its normal regulation of cell growth at the genetic level. Long-term disruptions in circadian rhythms caused by factors such as shift work, jet lag, and unstable sleep patterns can impact cellular health, leading to various health problems, including cancer. Circadian rhythm controls most cellular functions related to cancer progression, which has a significant impact on the ability of immune cells to detect cancer cells and promote their clearance and has crucial implication for future tumor immunotherapy. This article aims to review the crosstalk between dysregulation of circadian rhythm and tumorigenesis, tumor metabolism, and immune response. Additionally, we discuss the role of circadian rhythm disruption in tumor therapy, highlighting its potential to optimize treatment timing and improve therapeutic outcomes.

Establishment and evaluation of a prognostic model for patients with unresectable gastric cancer liver metastases.

BACKGROUND: Liver metastases (LM) is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer (GC). The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis, thereby enhancing the ability to evaluate patient outcomes. AIM: To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis, thereby enhancing patient outcome assessment. METHODS: Retrospective analysis was conducted on clinical data pertaining to GCLM (type III), admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018. The dataset was divided into a development cohort and validation cohort in a ratio of 2:1. In the development cohort, we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients. Subsequently, we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis, calibration curves, and clinical decision curves. A nomogram was created to visually represent the prediction model, which was then externally validated using the validation cohort. RESULTS: A total of 372 patients were included in this study, comprising 248 individuals in the development cohort and 124 individuals in the validation cohort. Based on Cox analysis results, our final prediction model incorporated five independent risk factors including albumin levels, primary tumor size, presence of extrahepatic metastases, surgical treatment status, and chemotherapy administration. The 1-, 3-, and 5-years Area Under the Curve values in the development cohort are 0.753, 0.859, and 0.909, respectively; whereas in the validation cohort, they are observed to be 0.772, 0.848, and 0.923. Furthermore, the calibration curves demonstrated excellent consistency between observed values and actual values. Finally, the decision curve analysis curve indicated substantial net clinical benefit. CONCLUSION: Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model, demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.

[Research progress in the regulation of autophagy and mitochondrial homeostasis by AMPK signaling channels].

AMP-activated protein kinase (AMPK) is a widely distributed and evolutionarily conserved serine/threonine protein kinase present in eukaryotic cells. In regulating cellular energy metabolism, AMPK plays an extremely important role as an energy metabolic kinase. When the body is in a low energy state, AMPK is activated in response to changes in intracellular adenine nucleotide levels and is bound to adenosine monophosphate (AMP) or adenosine diphosphate (ADP). Activated AMPK regulates various metabolic processes, including lipid and glucose metabolism and cellular autophagy. AMPK directly promotes autophagy by phosphorylating autophagy-related proteins in the mammalian target of rapamycin complex 1 (mTORC1), serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1) and type III phosphatidylinositol 3-kinase-vacuolar protein-sorting 34 (PIK3C3-VPS34) complexes. AMPK also indirectly promotes autophagy by regulating the expression of downstream autophagy-related genes of transcription factors such as forkhead box O3 (FOXO3), lysosomal function transcription factor EB (TFEB) and bromodomain protein 4 (BRD4). AMPK also regulates mitochondrial autophagy, induces the division of damaged mitochondria and promotes the transfer of the autophagic response to damaged mitochondria. Another function of AMPK is to regulate mitochondrial health by stimulating mitochondrial biogenesis and participating in various aspects of mitochondrial homeostasis regulation. This review discusses the specific regulation of mitochondrial biology and internal environmental homeostasis by AMPK signaling channels as central to the cellular response to energy stress and regulation of mitochondria, highlighting the key role of AMPK in regulating cellular autophagy and mitochondrial autophagy, as well as advances in research on the regulation of mitochondrial homeostasis.

Gene-environment transactions between peer cigarette use, parental supervision, and Chinese adolescent cigarette smoking initiation.

INTRODUCTION: The initiation and continued use of tobacco products constitute an ongoing source of preventable disease that continues to pose a significant risk to global adolescent health. Scarce research has sought to explore the influences of two well-known environmental risk factors, parental supervision and peer cigarette use, on genetic and environmental contributions to adolescent cigarette use, especially in non-Western populations. METHODS: Following 602 Chinese twin pairs (52% female, N = 1204) from early to middle adolescence at two-time points (Mage = 12 and 15) from 2006 to 2009 and using multivariate biometric modeling, this study examined gene-environment interplay (i.e., gene-environment correlation and interaction) between perceived parental supervision, peer cigarette use, and adolescent cigarette smoking initiation. RESULTS: From early to middle adolescence, genetic influences on cigarette smoking initiation became more pronounced, whereas shared environmental influences that promote similarity between family members diminished. Genetic factors primarily explained the links between parental supervision and cigarette smoking initiation in mid-adolescence. Peer cigarette use displayed stronger associations with and moderating potential in adolescent cigarette smoking initiation than parental supervision. High levels of peer cigarette use amplified genetic risk for cigarette smoking initiation in mid-adolescence. CONCLUSIONS: Chinese adolescent cigarette smoking initiation involves dynamic gene-environment transactions primarily with peer processes over development. Mid-adolescence constitutes a developmental period wherein underlying genetic risk for cigarette smoking initiation is particularly sensitive to peer influences. Targeted interventions aimed at reducing Chinese adolescent cigarette smoking initiation should focus on peer processes during this developmental period.

Neuroprotective effect of green tea extract (-)-epigallocatechin-3-gallate in a preformed fibril-induced mouse model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). The main bioactive component of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) exerts protective effects against diseases such as neurodegenerative diseases and cancer. Therefore, this study investigated the effect of EGCG on the amelioration of neural damage in a chronic PD mouse model induced by α-synuclein preformed fibrils (α-syn-PFFs). A total of 20 C57BL/6J female mice were randomly divided into 3 groups: control group (saline, n = 6), model group (PFFs, n = 7), and prevention group (EGCG+PFFs, n = 7). A chronic PD mouse model was obtained by the administration of α-syn-PFFs by stereotaxic localization in the striatum. Behavioral tests were performed to evaluate PD-related anxiety-like behavior and motor impairments in the long-term PD progression. Tyrosine hydroxylase (TH) immuno-positive neurons and Ser129-phosphorylated α-syn (p-α-syn) were identified by immunohistochemistry. Pro-inflammatory and anti-inflammatory cytokines were measured by real-time quantitative PCR. EGCG pretreatment reduced anxiety-like behavior and motor impairments as revealed by the long-term behavioral test (2 weeks, 1 month, 3 months, and 6 months) on PD mice. EGCG also ameliorated PFF-induced degeneration of TH immuno-positive neurons and accumulation of p-α-syn in the SN and striatum at 6 months. Additionally, EGCG reduced the expression of pro-inflammatory cytokines while promoting the release of anti-inflammatory cytokines. EGCG exerts a neuroprotective effect on long-term progression of the PD model.

Evolution of Endogenous Retroviruses in the Subfamily of Caprinae.

The interest in endogenous retroviruses (ERVs) has been fueled by their impact on the evolution of the host genome. In this study, we used multiple pipelines to conduct a de novo exploration and annotation of ERVs in 13 species of the Caprinae subfamily. Through analyses of sequence identity, structural organization, and phylogeny, we defined 28 ERV groups within Caprinae, including 19 gamma retrovirus groups and 9 beta retrovirus groups. Notably, we identified four recent and potentially active groups prevalent in the Caprinae genomes. Additionally, our investigation revealed that most long noncoding genes (lncRNA) and protein-coding genes (PC) contain ERV-derived sequences. Specifically, we observed that ERV-derived sequences were present in approximately 75% of protein-coding genes and 81% of lncRNA genes in sheep. Similarly, in goats, ERV-derived sequences were found in approximately 74% of protein-coding genes and 75% of lncRNA genes. Our findings lead to the conclusion that the majority of ERVs in the Caprinae genomes can be categorized as fossils, representing remnants of past retroviral infections that have become permanently integrated into the genomes. Nevertheless, the identification of the Cap_ERV_20, Cap_ERV_21, Cap_ERV_24, and Cap_ERV_25 groups indicates the presence of relatively recent and potentially active ERVs in these genomes. These particular groups may contribute to the ongoing evolution of the Caprinae genome. The identification of putatively active ERVs in the Caprinae genomes raises the possibility of harnessing them for future genetic marker development.

Detecting MRI-Invisible Prostate Cancers Using a Weakly Supervised Deep Learning Model.

Background: MRI is an important tool for accurate detection and targeted biopsy of prostate lesions. However, the imaging appearances of some prostate cancers are similar to those of the surrounding normal tissue on MRI, which are referred to as MRI-invisible prostate cancers (MIPCas). The detection of MIPCas remains challenging and requires extensive systematic biopsy for identification. In this study, we developed a weakly supervised UNet (WSUNet) to detect MIPCas. Methods: The study included 777 patients (training set: 600; testing set: 177), all of them underwent comprehensive prostate biopsies using an MRI-ultrasound fusion system. MIPCas were identified in MRI based on the Gleason grade (≥7) from known systematic biopsy results. Results: The WSUNet model underwent validation through systematic biopsy in the testing set with an AUC of 0.764 (95% CI: 0.728-0.798). Furthermore, WSUNet exhibited a statistically significant precision improvement of 91.3% (p < 0.01) over conventional systematic biopsy methods in the testing set. This improvement resulted in a substantial 47.6% (p < 0.01) decrease in unnecessary biopsy needles, while maintaining the same number of positively identified cores as in the original systematic biopsy. Conclusions: In conclusion, the proposed WSUNet could effectively detect MIPCas, thereby reducing unnecessary biopsies.

Chlorella alleviates the intestinal damage of tilapia caused by microplastics.

Polyethylene microplastics (MPs) of the different sizes may result in different response in fish. Studies showed microorganisms adhered to the surface of MPs have toxicological effect. Juveniles tilapia (Oreochromis niloticus, n = 600, 26.5 ± 0.6 g) were dispersed into six groups: the control group (A), 75 nm MP exposed group (B), 7.5 µm group (C) and 750 (D) µm group, 75 nm + 7.5 µm+750 µm group (E) and 75 nm + Chlorella vulgaris group (F), and exposed for 10 and 14 days. The intestinal histopathological change, enzymic activities, and the integrated "omics" workflows containing transcriptomics, proteomics, microbiota and metabolomes, have been performed in tilapia. Results showed that MPs were distributed on the surface of goblet cells, Chlorella group had severe villi fusion without something like intestinal damage, as in other MPs groups. The intestinal Total Cholesterol (TC, together with group E) and Tumor Necrosis Factor α (TNFα, except for group B) contents in group F were significantly increased, cytochrome p450 1a1 (EROD, group B and E) significantly increased, adenosine triphosphate (ATP), lipoprotein lipase (LPL) and caspase 3 (except group B) also significantly increased at 14 d. At 14 days, group E saw considerably higher regulation of the actin cytoskeleton, focal adhesion, insulin signaling pathway, and AGE-RAGE signaling pathway in diabetes complications. Whereas, chlorella enhanced the focal adhesion, cytokine-cytokine receptor interaction, and MAPK signaling pathways. PPAR signaling pathway has been extremely significantly enriched via the proteomics method. Candidatus latescibacteria, C. uhrbacteria, C. abyssubacteria, C. cryosericota significantly decreased caused by MPs of different particle sizes. Carboxylic acids and derivatives, indoles and derivatives, organooxygen compounds, fatty acyls and organooxygen compounds significantly increased with long-term duration, especially PPAR signaling pathway. MPs had a size-dependent long-term effect on histopathological change, gene and protein expression, and gut microbial metabolites, while chlorella alleviates the intestinal histopathological damage via the integrated "omics" workflows.

Is Ancient Medical Treatment an Option for Curating Osteosarcoma Combined with Chemotherapy? A Basic Analysis of Clinic Pharmacy.

BACKGROUND: As a malignant tumor, osteosarcoma (OS) ranks first place among adolescent cancers and is susceptible to developing resistance to chemotherapeutic agents. Differently, Traditional Chinese medicine (TCM) has multiple pharmacodynamic targets and complex biological components, which can inhibit tumor survival and drug resistance and gradually play an important role in the treatment of sarcoma. METHODS: This study is to systematically evaluate the safety and efficacy of TCM combined with chemotherapy performed in the clinical treatment of OS. Based on multiple mainstream databases, eleven articles on the relationship between natural products and chemotherapy involving 656 patients were selected from all the literature published as of June 2022. Revman 5.4 software was used for a comprehensive search analysis, supplemented by established exclusion criteria, the Jadad scale, and the evaluation methods provided by Cochrane. RESULTS: The efficiency of TCM combined with chemotherapy was significantly increased compared with chemical drugs alone [OR=2.56, 95% CI (1.36,4.79), Z=2.92, P=0.003]. Meanwhile, the adverse reactions such as nausea and vomiting, hepatotoxicity, and hematological changes caused by chemical drugs were alleviated correspondingly. CONCLUSION: This study indicates that the mode of TCM combined with chemotherapy sheds light on the clinical treatment of OS, which is much better than the one-way mode.

m6A-modified circARHGAP12 promotes the aerobic glycolysis of doxorubicin-resistance osteosarcoma by targeting c-Myc.

Chemotherapy resistance accompanied by energy metabolism abnormality functions as one of the main reasons for treatment failure and poor prognosis. However, the function of N6-methyladenosine (m6A)-modified circular RNA (circRNA) on osteosarcoma (OS) is still unclear. Here, present research investigated the potential role and mechanism of circARHGAP12 on OS doxorubicin (Dox) resistance and aerobic glycolysis. Results indicated that circARHGAP12 was a novel m6A-modified circRNA, which was up-regulated in OS cells. Overexpression of circARHGAP12 promoted the Dox resistance half-maximal inhibitory concentration (IC50) and aerobic glycolysis (glucose uptake, lactate and ATP production) in OS cells (Saos-2/Dox, MG63/Dox). Mechanistically, m6A-modified circARHGAP12 could bind with c-Myc mRNA through m6A-dependent manner, thereby enhancing the c-Myc mRNA stability. Thus, these findings revealed the critical function of circARHGAP12 on OS Dox-resistance and aerobic glycolysis. Taken together, our study demonstrated a critical function of circARHGAP12 on OS chemotherapy resistance and energy metabolism abnormality, providing critical roles on OS treatment.

The accuracy and reliability of different midsagittal planes in the symmetry assessment using cone-beam computed tomography.

Symmetry is an essential component of esthetic assessment. Accurate assessment of facial symmetry is critical to the treatment plan of orthognathic surgery and orthodontic treatment. However, there is no internationally accepted midsagittal plane (MSP) for orthodontists and orthognathic surgeons. The purpose of this study was to explore a clinically friendly MSP, which is more accurate and reliable than what is commonly used in symmetry assessment. Forty patients with symmetric craniofacial structures were analyzed on cone-beam computed tomography (CBCT) scans. The CBCT data were exported to the Simplant Pro software to build four reference planes that were constructed by nasion (N), basion (Ba), sella (S), odontoid (Dent), or incisive foramen (IF). A total of 31 landmarks were located to determine which reference plane is the most optimal MSP by comparing the asymmetry index (AI). The mean value of AI showed a significant difference (p < 0.05) among four reference planes. Also, the mean value of AI for all landmarks showed that Plane 2 (consisting of N, Ba, and IF) and Plane 4 (consisting of N, IF, and Dent) were more accurate and stable. In conclusion, the MSP consisting of N, Dent, and IF shows more accuracy and reliability than the other planes. Further, it is more clinically friendly because of its significant advantage in landmarking.

Transferrin-inspired iron delivery across the cell membrane using [(L2Fe)2(µ-O)] (L = chlorquinaldol) to harness anticancer activity of ferroptosis.

Although iron is a bio-essential metal, dysregulated iron acquisition and metabolism result in production of reactive oxygen species (ROS) due to the Fenton catalytic reaction, which activates ferroptotic cell death pathways. The lipophilic Fe(III)-chelator chlorquinaldol (L; i.e., 5,7-dichloro-8-hydroxy-2-methylquinoline) strongly favors the formation of a highly stable binuclear Fe(III) complex [(L2Fe)2(µ-O)] (1) that can mimic the function of the Fe(III)-transferrin complex in terms of the strong binding to Fe(III) and facile release of Fe(II) when the metal center is reduced. It should be noted that the cellular uptake of 1 is not transferrin receptor-mediated but enhanced by the high lipophilicity of chlorquinaldol. Once 1 is transported across the cell membrane, Fe(III) can be reduced by ferric reductase or other cellular antioxidants to be released as Fe(II), which triggers the Fenton catalytic reaction, thus harnessing the anticancer activity of iron. As the result, this transferrin-inspired iron-delivery strategy significantly reduces the cytotoxicity of 1 in normal human embryonic kidney cells (HEK 293) and the hemolytic activity of 1 in human red blood cells (hRBCs), giving rise to the unique tumor-specific anticancer activity of this Fe(III) complex.