The efficacy and safety of different does of intravenous tranexamic acid on blood loss in fresh foot and ankle fractures: a prospective, randomized controlled study.

BACKGROUND: There are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety. METHODS: A total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery. RESULTS: There was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE. CONCLUSION: This is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.

Hyaluronan-decorated copper-doxorubicin-anlotinib nanoconjugate for targeted synergistic chemo/chemodynamic/antiangiogenic tritherapy against hepatocellular carcinoma.

Copper-based nanomaterials show considerable potential in the chemodynamic therapy of cancers. However, their clinical application is restricted by low catalytic activity in tumor microenvironment and copper-induced tumor angiogenesis. Herein, a novel copper-doxorubicin-anlotinib (CDA) nanoconjugate was constructed by the combination of copper-hydrazide coordination, hydrazone linkage and Schiff base bond. The CDA nanoconjugate consists of a copper-3,3'-dithiobis(propionohydrazide)-doxorubicin core and an anlotinib-hyaluronan shell. Benefiting from hyaluronan camouflage and abundant disulfide bonds and Cu2+, the CDA nanoconjugate possessed excellent tumor-targeting and glutathione-depleting abilities and enhanced chemodynamic efficacy. Released doxorubicin significantly improved copper-mediated chemodynamic therapy by upregulating nicotinamide adenine dinucleotide phosphate oxidase 4 expression to increase intracellular H2O2 level. Furthermore, the nanoconjugate produced excessive •OH to induce lipid peroxidation and mitochondrial dysfunction, thus greatly elevating doxorubicin-mediated chemotherapy. Importantly, anlotinib effectively inhibited the angiogenic potential of copper ions. In a word, the CDA nanoconjugate is successfully constructed by combined coordination and pH-responsive linkages, and displays the great potential of copper-drug conjugate for targeted synergistic chemo/chemodynamic/antiangiogenic triple therapy against cancers.

KLF7 promotes colon adenocarcinoma progression through the PDGFB signaling pathway.

Colon adenocarcinoma (COAD) is the most common malignancy of the digestive tract, which is characterized by a dismal prognosis. No effective treatment has been established presently, thus there is an urgent need to understand the mechanisms driving COAD progression in order to develop effective therapeutic approaches and enhance clinical outcomes. In this study, we found that KLF7 is overexpressed in COAD tissues and correlated with clinicopathological features of COAD. Both gain-of-function and loss-of-function experiments have unequivocally demonstrated that overexpression of KLF7 promotes the growth and metastasis of COAD in vitro and in vivo, while KLF7 knockdown attenuated these effects. Mechanistically, our findings reveal that KLF7 can specifically bind to the promoter region of PDGFB (TGGGTGGAG), thus promoting the transcription of PDGFB and increasing its secretion. Subsequently, secreted PDGFB facilitates the progression of COAD by activating MAPK/ERK, PI3K/AKT, and JAK/STAT3 signaling pathways through PDGFRß. Additionally, we found that sunitinib can block PDGFB signaling and inhibit COAD progression, offering a promising therapeutic strategy for COAD treatment.

Effects of Heated Infiltration Solutions and Forced-Air Heating Blankets on Intraoperative Hypothermia During Liposuction: A Factorial Randomized Controlled Trial.

BACKGROUND: This study was conducted to compare the effects of heat preservation by two recommended methods, heated infiltration solutions and forced-air heating blankets, in patients undergoing liposuction under general anesthesia. METHODS: Forty patients were divided into four groups based on whether heated infiltration solutions or forced-air heating blankets were used. Group A received general anesthesia liposuction plastic surgery routine temperature care. Based on the care measures of group A, heated infiltration solutions were used in group B; forced-air heating blanket was used in group C; and heated infiltration solutions and forced-air heating blankets were both used in group D. The primary end point was intraoperative and perioperative temperature measured with an infrared tympanic membrane thermometer. Secondary end points included surgical outcomes, subjective experience, and adverse events. RESULTS: Compared with group A, the intraoperative body temperatures of groups B, C, and D were significantly higher, indicating that the two intervention methods were helpful on increasing the core body temperature. Pairwise comparisons of these three groups showed that there was no significant difference between group C and group D. However, using forced-air heating blankets had a marked effect compared with using heated infiltration solutions alone at three time points. The same trend could be seen in other surgical outcomes. CONCLUSIONS: Heated infiltration solutions and forced-air heating blankets could reduce the incidence of intraoperative hypothermia and improve patients' prognosis after liposuction under general anesthesia. Compared with the heated infiltration fluid, the forced-air heating blanket may have a better thermal insulation effect. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prediction Model of Ocular Metastases in Gastric Adenocarcinoma: Machine Learning-Based Development and Interpretation Study.

Background: Although gastric adenocarcinoma (GA) related ocular metastasis (OM) is rare, its occurrence indicates a more severe disease. We aimed to utilize machine learning (ML) to analyze the risk factors of GA-related OM and predict its risks. Methods: This is a retrospective cohort study. The clinical data of 3532 GA patients were collected and randomly classified into training and validation sets in a ratio of 7:3. Those with or without OM were classified into OM and non-OM (NOM) groups. Univariate and multivariate logistic regression analyses and least absolute shrinkage and selection operator were conducted. We integrated the variables identified through feature importance ranking and further refined the selection process using forward sequential feature selection based on random forest (RF) algorithm before incorporating them into the ML model. We applied six ML algorithms to construct the predictive GA model. The area under the receiver operating characteristic (ROC) curve indicated the model's predictive ability. Also, we established a network risk calculator based on the best performance model. We used Shapley additive interpretation (SHAP) to identify risk factors and to confirm the interpretability of the black box model. We have de-identified all patient details. Results: The ML model, consisting of 13 variables, achieved an optimal predictive performance using the gradient boosting machine (GBM) model, with an impressive area under the curve (AUC) of 0.997 in the test set. Utilizing the SHAP method, we identified crucial factors for OM in GA patients, including LDL, CA724, CEA, AFP, CA125, Hb, CA153, and Ca2+. Additionally, we validated the model's reliability through an analysis of two patient cases and developed a functional online web prediction calculator based on the GBM model. Conclusion: We used the ML method to establish a risk prediction model for GA-related OM and showed that GBM performed best among the six ML models. The model may identify patients with GA-related OM to provide early and timely treatment.

Ozone exposure affects corneal epithelial fate by promoting mtDNA leakage and cGAS/STING activation.

Ozone is a common air pollutant associated with various human diseases. The human ocular surface is frequently exposed to ozone in the troposphere, but the mechanisms by which ozone affects the ocular surface health remain unclear. This study aimed to establish a mouse model to investigate the effects of ozone exposure on the ocular surface and the corneal epithelium. The findings revealed that ozone exposure disrupted corneal epithelial homeostasis and differentiation, resulting in corneal squamous metaplasia. Further, ozone exposure induced oxidative damage and cytoplasmic leakage of mitochondrial DNA (mtDNA), thereby activating the cGAS/STING signaling pathway. The activation of the cGAS/STING signaling pathway triggered the activation of downstream NF-κB and TRAF6 signaling pathways, causing corneal inflammation, thereby promoting corneal inflammation and squamous metaplasia. Finally, C-176, a selective STING inhibitor, effectively prevented and treated corneal inflammation and squamous metaplasia caused by ozone exposure. This study revealed the role of mtDNA leakage-mediated cGAS/STING activation in corneal squamous epithelial metaplasia caused by ozone exposure. It also depicted the abnormal expression pattern of corneal epithelial keratin using three-dimensional images, providing new targets and strategies for preventing and treating corneal squamous metaplasia and other ocular surface diseases.

A comparison between transforaminal lumbar epidural injection performed under picture archiving and communication systems-based magnetic resonance imaging planning and injection under immediate X-ray guidance.

OBJECTIVES: The study aimed to compare the treatment cost, operation time, clinical effect, and complications between punctures done under magnetic resonance imaging (MRI) planning based on picture archiving and communication systems (PACS) and punctures done under immediate X-ray fluoroscopy guidance in the treatment of lumbar disc herniation by transforaminal lumbar epidural injection. PATIENTS AND METHODS: In this prospective study conducted between October 2016 and June 2021, 128 patients were randomly divided into Groups A and B by the random number table method. In Group A (n=66; 36 males, 30 females; mean age: 64.5±2.4 years, range, 50 to 72 years), puncture was performed by planning with PACS-based MRI; in Group B (n=62; 34 males, 28 females; mean age: 65.3±2.6 years; range, 48 to 73 years), puncture was performed under immediate X-ray guidance. The cost of treatment, duration of procedure, clinical outcome, and complications were compared between the two groups. RESULTS: The difference in treatment cost in Groups A and B was statistically significant (p<0.001), with 755.67±29.45 yuan and 1.158.08±43.92 yuan, respectively. The mean treatment time was statistically significant (p<0.001) between the groups, with 21.16±1.91 min in Group A and 37.26±2 min in Group B. However, there was no significant difference between Group A and Group B in terms of improvement in pain scores and Oswestry disability index (both p>0.05). There was also no significant difference between Group A and Group B in terms of complication rates (both p>0.05). CONCLUSION: Compared to immediate X-ray guided puncture, the puncture method using PACS for MRI planning shortened the transforaminal lumbar epidural injection procedure time and reduced the treatment costs without exposing the physician or patient to additional radiation, while there was no significant difference in the short-term clinical outcome or complication rate.

Upregulation of eIF2α by m6A modification accelerates the proliferation of pulmonary artery smooth muscle cells in MCT-induced pulmonary arterial hypertension rats.

Pulmonary arterial hypertension (PAH) is a malignant cardiovascular disease. Eukaryotic initiation factor 2α (eIF2α) plays an important role in the proliferation of pulmonary artery smooth muscle cells (PASMCs) in hypoxia-induced pulmonary hypertension (HPH) rats. However, the regulatory mechanism of eIF2α remains poorly understood in PAH rats. Here, we discover eIF2α is markedly upregulated in monocrotaline (MCT)-induced PAH rats, eIF2α can be upregulated by mRNA methylation, and upregulated eIF2α can promote PASMC proliferation in MCT-PAH rats. GSK2606414, eIF2α inhibitor, can downregulate the expression of eIF2α and alleviate PASMC proliferation in MCT-PAH rats. And we further discover the mRNA of eIF2α has a common sequence with N 6-methyladenosine (m6A) modification by bioinformatics analysis, and the expression of METTL3, WTAP, and YTHDF1 is upregulated in MCT-PAH rats. These findings suggest a potentially novel mechanism by which eIF2α is upregulated by m6A modification in MCT-PAH rats, which is involved in the pathogenesis of PAH.

Near-Infrared-II Nanoparticles for Vascular Normalization Combined with Immune Checkpoint Blockade via Photodynamic Immunotherapy Inhibit Uveal Melanoma Growth and Metastasis.

Photodynamic therapy (PDT) has been widely employed in tumor treatment due to its effectiveness. However, the tumor hypoxic microenvironment which is caused by abnormal vasculature severely limits the efficacy of PDT. Furthermore, the abnormal vasculature has been implicated in the failure of immunotherapy. In this study, a novel nanoparticle denoted as Combo-NP is introduced, composed of a biodegradable NIR II fluorescent pseudo-conjugate polymer featuring disulfide bonds within its main chain, designated as TPA-BD, and the vascular inhibitor Lenvatinib. Combo-NP exhibits dual functionality by not only inducing cytotoxic reactive oxygen species (ROS) to directly eliminate tumor cells but also eliciting immunogenic cell death (ICD). This ICD response, in turn, initiates a robust cascade of immune reactions, thereby augmenting the generation of cytotoxic T lymphocytes (CTLs). In addition, Combo-NP addresses the issue of tumor hypoxia by normalizing the tumor vasculature. This normalization process enhances the efficacy of PDT while concurrently fostering increased CTLs infiltration within the tumor microenvironment. These synergistic effects synergize to potentiate the photodynamic-immunotherapeutic properties of the nanoparticles. Furthermore, when combined with anti-programmed death-ligand 1 (PD-L1), they showcase notable inhibitory effects on tumor metastasis. The findings in this study introduce an innovative nanomedicine strategy aimed at triggering systemic anti-tumor immune responses for the treatment of Uveal melanoma.

LITAF Promotes Atherosclerotic Plaque Formation by Stimulating the NF-κB Inflammatory Pathway.

OBJECTIVE: Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) protein is a newly discovered inflammatory protein. This study aims to study the role of LITAF in the formation of atherosclerosis. METHODS: A total of 10 C57BL/6J mice and 10 C57BL/6J mice with knockout of LITAF gene (C57BL/6J-LITAF-) were divided into two groups: the control group and the LITAF-/- group. The animals were accommodated for 16 weeks and then euthanized with their hearts and aortas isolated thereafter. Next, the roots of the mouse aorta were cryosectioned and stained with Oil Red O staining and immunohistochemical staining (CD68, α-SMA, and Masson), respectively. The area of Oil Red O staining and the proportion of positive expression after immunohistochemical staining were then compared between the control and LITAF-/- groups. At the same time, the blood of mice was collected for the extraction of proteins and RNA. The proteins and RNA were used to detect the expression of major molecules of the NF-κB inflammatory pathway in mice in the control group and the LITAF-/- group by Western blotting and RT-PCR. RESULTS: Oil Red O staining of the aortic root sections of the mice in each group revealed that the area of atherosclerotic plaques in the LITAF-/- group was substantially lower than that in the control group (P<0.05). Moreover, immunohistochemical staining determined that the expression level of α-SMA and CD68 in the LITAF-/- group was significantly lower than that in the control group, whereas the results were reversed following Masson staining (P<0.05). The expression levels of P65 and caspase 3 were significantly lower in the LITAF-/- group than in the control group (P<0.05), whereas the expression level of IκB was higher in the LITAF-/- group. CONCLUSION: LITAF might participate in the formation of atherosclerotic plaque through the NF-κB pathway and play a promoting role in the formation of atherosclerosis.

Prediction model of ocular metastasis from primary liver cancer: Machine learning-based development and interpretation study.

BACKGROUND: Ocular metastasis (OM) is a rare metastatic site of primary liver cancer (PLC). The purpose of this study was to establish a clinical predictive model of OM in PLC patients based on machine learning (ML). METHODS: We retrospectively collected the clinical data of 1540 PLC patients and divided it into a training set and an internal test set in a 7:3 proportion. PLC patients were divided into OM and non-ocular metastasis (NOM) groups, and univariate logistic regression analysis was performed between the two groups. The variables with univariate logistic analysis p < 0.05 were selected for the ML model. We constructed six ML models, which were internally verified by 10-fold cross-validation. The prediction performance of each ML model was evaluated by receiver operating characteristic curves (ROCs). We also constructed a web calculator based on the optimal performance ML model to personalize the risk probability for OM. RESULTS: Six variables were selected for the ML model. The extreme gradient boost (XGB) ML model achieved the optimal differential diagnosis ability, with an area under the curve (AUC) = 0.993, accuracy = 0.992, sensitivity = 0.998, and specificity = 0.984. Based on these results, an online web calculator was constructed by using the XGB ML model to help clinicians diagnose and treat the risk probability of OM in PLC patients. Finally, the Shapley additive explanations (SHAP) library was used to obtain the six most important risk factors for OM in PLC patients: CA125, ALP, AFP, TG, CA199, and CEA. CONCLUSION: We used the XGB model to establish a risk prediction model of OM in PLC patients. The predictive model can help identify PLC patients with a high risk of OM, provide early and personalized diagnosis and treatment, reduce the poor prognosis of OM patients, and improve the quality of life of PLC patients.

Solanum nigrum Linn.: Advances in anti-cancer activity and mechanism in digestive system tumors.

Cancer has currently become a serious public health issue in many countries worldwide, and tumors of the digestive system have attracted an increasing number of researchers' due to their numerous types, high proportion and wide area of occurrence. While tumors of the digestive system suffer from high mortality rates, leading to untimely diagnosis and a poor prognosis, making it necessary to update current treatment approaches such as surgery, radiation therapy, and chemotherapy. This highlights the importance of exploring novel therapeutic ideas and targets. Traditional Chinese medicine has a long history of clinical use due to its low toxicity and multi-factor targeting of multiple pathways. As a kind of traditional Chinese herb, S. nigrum Linn. is highly regarded for its proven antitumor activity. The aim of this study was to comprehensively recapitulate and analyze the anti-cancer effects and molecular mechanisms of treatment of gastrointestinal tumors with S. nigrum Linn. extracts and related compounds, including classical signaling pathways mediated by them as well as noncoding RNA pathways associated with tumor suppression. Components that have been found to be responsible for the anti-cancer activity of S. nigrum Linn. include solanine, solasonine, solamargine, a-L-rhhamnopyranose, uttroside B, degalactotigonin, glycoprotein, and other compounds. The underlying mechanisms of anti-cancer activity reflected in this study include apoptosis, cell cycle arrest, autophagy, anti-angiogenesis, suppression of metastasis and invasion, immune escape, and increased sensitivity to radiotherapy. S. nigrum Linn. has great potential in the treatment of tumors of the digestive system, and through further clinical trials and pharmacological mechanisms it has the potential to become a uniform and standardized anti-tumor drug.

Faster Return to Daily Activities and Better Pain Control: A Prospective Study of Enhanced Recovery After Surgery Protocol in Breast Augmentation.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been proven to decrease the amount of opioid use and reduce postoperative pain for a variety of surgeries, including breast reconstruction. However, data on ERAS in breast augmentation is lacking. OBJECTIVES: This study aims to investigate the effectiveness and safety of ERAS for breast augmentation. METHODS: A standardized ERAS protocol was established with full consideration of all aspects of perioperative care. Patients undergoing implant-based breast augmentation were prospectively recruited between December 2020 and January 2023, and assigned to either the ERAS or non-ERAS group randomly. The primary outcome was the activity of daily living after surgery. The secondary was postoperative pain and other outcomes included time to freely elevation, vomiting frequency, the use of analgesics, and complications. RESULTS: A total of 122 patients were included, with 70 in the ERAS group and 52 in the non-ERAS group. Compared to non-ERAS patients, ERAS patients had a shorter time to freely elevation of upper limbs (2.3 d vs. 5.5 d, P < 0.001). For ERAS patients, the pain scores were significantly lower on postoperative days 1 to 3, the activity of daily living index was significantly higher on postoperative days 1 to 3 and the opioids consumption was decreased (7.1 mg vs. 46.2 mg, P = 0.018). No difference was observed in complication and hospital costs between the two groups. CONCLUSION: The ERAS protocol significantly reduced postoperative pain and the use of opioids and promoted a return to daily activities without increasing complications in breast augmentation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The connotation between perioperative glycemic control approach and sternal wound infection in individuals with diabetes mellitus experiencing cardiac surgery: A meta-analysis.

A meta-analysis investigation to measure the connotation between perioperative glycemic control (GC) approach and sternal wound infection (SWI) in individuals with diabetes mellitus (DM) experiencing cardiac surgery (CS). A comprehensive literature inspection till February 2023 was applied and 2654 interrelated investigations were reviewed. The 12 chosen investigations enclosed 1564 individuals with DM and CS in the chosen investigations' starting point, 790 of them were using strict GC, and 774 were using moderate GC. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the Connotation between the perioperative GC approach and SWI in individuals with DM experiencing CS by the dichotomous and continuous approaches and a fixed or random model. Strict GC had significantly lower SWI (OR, 0.33; 95% CI, -0.22-0.50, P < .001) compared with those with moderate GC in individuals with DM and CS. Strict GC had significantly lower SWI compared with those with moderate GC in individuals with DM and CS. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

LINC00511, a future star for the diagnosis and therapy of digestive system malignant tumors.

The digestive system malignant tumors (DSMTs), mainly consist of digestive tract and digestive gland tumors, become an inescapable culprit to hazard human health worldwide. Due to the huge hysteresis in the cognitive theories of DSMTs occurrence and progression, advances in medical technology have not improved the prognosis. Therefore, more studies on a variety of tumor-associated molecular biomarkers and more detailed disclosure on potential regulatory networks are urgently needed to facilitate the diagnostic and therapeutic strategies of DSMTs. With the development of cancer bioinformatics, a special type of endogenous RNA involved in multi-level cellular function regulation rather than encoding protein, is categorized as non-coding RNAs (ncRNAs) and becomes a hotspot issue in oncology. Among them, long non-coding RNAs (lncRNAs), transcription length > 200 nt, show obvious superiority in both research quantity and dimension compared to microRNAs (miRNAs) and circular RNAs (circRNAs). As a recently discovered lncRNA, LINC00511 has been confirmed to be closely associated with DSMTs and might be exploited as a novel biomarker. In the present review, the comprehensive studies of LINC00511 in DSMTs are summarized, as well as the underlying molecular regulatory networks. In addition, deficiencies in researches are point out and discussed. The Cumulative oncology studies provide a fully credible theoretical basis for identifying the regulatory role of LINC00511 in human DSMTs. LINC00511, proved to be an oncogene in DSMTs, might be defined as a potential biomarker for diagnosis and prognosis evaluation, as well as a rare therapeutic target.

Prediction models for chronic postsurgical pain in patients with breast cancer based on machine learning approaches.

Purpose: This study aimed to develop prediction models for chronic postsurgical pain (CPSP) after breast cancer surgery using machine learning approaches and evaluate their performance. Methods: The study was a secondary analysis based on a high-quality dataset from a randomized controlled trial (NCT00418457), including patients with primary breast cancer undergoing mastectomy. The primary outcome was CPSP at 12 months after surgery, defined as modified Brief Pain Inventory > 0. The dataset was randomly split into a training dataset (90%) and a testing dataset (10%). Variables were selected using recursive feature elimination combined with clinical experience, and potential predictors were then incorporated into three machine learning models, including random forest, gradient boosting decision tree and extreme gradient boosting models for outcome prediction, as well as logistic regression. The performances of these four models were tested and compared. Results: 1152 patients were finally included, of which 22.1% developed CPSP at 12 months after breast cancer surgery. The 6 leading predictors were higher numerical rating scale within 2 days after surgery, post-menopausal status, urban medical insurance, history of at least one operation, under fentanyl with sevoflurane general anesthesia, and received axillary lymph node dissection. Compared with the multivariable logistic regression model, machine learning models showed better specificity, positive likelihood ratio and positive predictive value, helping to identify high-risk patients more accurately and create opportunities for early clinical intervention. Conclusions: Our study developed prediction models for CPSP after breast cancer surgery based on machine learning approaches, which may help to identify high-risk patients and improve patients' management after breast cancer.

The safety and efficiency of photodynamic therapy for the treatment of osteosarcoma: A systematic review of in vitro experiment and animal model reports.

BACKGROUND: Osteosarcoma (OS) is an aggressive malignant bone tumour with high mortality. A poor prognosis is noted in patients with distal metastases or multidrug resistance. As an emerging antitumor strategy, photodynamic therapy (PDT) mediated by visible and near infrared light has attracted intensive attention given its target selectivity, remote controllability, minimal or non-invasive features. However, PDT also has obvious limitations. Specifically, due to the limited penetration of light, it is mainly used in the clinical treatment of superficial malignant tumours, such as musculoskeletal sarcomas and melanoma, but it has not been applied to the clinical treatment of deep malignant bone tumours except for a very small number of experiments on deep canine OS models. MATERIALS AND METHODS: We searched for studies that focused on the effectiveness and safety of PDT for OS based on in vitro experiments and animal models in the last decade. A systematic search was conducted using electronic databases, including PubMed, ClinicalTrials.gov, and the Cochrane Library. INCLUSION CRITERIA: (1) original research articles about PDT for OS; (2) articles in English; (3) in vitro or animal model research; and (4) detailed information, including cell name, fluence, irradiation wavelength, time of incubation with PS, duration between PS treatment and irradiation, and duration between irradiation and viability assays. EXCLUSION CRITERIA: (1) study was a review/systemic review article, patent, letter, or conference abstract/paper; (2) articles were not published in English; (3) studies containing overlapping or insufficient data. RESULTS: We identified 201 publications, and 44 articles met the inclusion criteria and were included in the synthesis. Unfortunately, there are no relevant clinical reports of the use of PDT in the treatment of human OS. In these studies, 8 studies only employed in vivo experiments to evaluate the efficiency of PDT in an OS animal model, 19 studies exclusively performed in vitro viability assays of cells treated with PDT under different conditions, and 17 studies included in vitro cell experiments and in vivo animal OS models to evaluate the effect of PDT on OS in vivo and in vitro. All studies have shown that PDT is cytotoxic to OS cells or can inhibit the growth of OS in heterologous or homologous animal OS models but exhibits minimal cytotoxicity at a certain range of dosages. CONCLUSION: Based on this systematic review, PDT can eradicate OS cells in cell culture and there is some evidence for efficacy in animal models. However, the ability for PDT to control human OS is unclear, the animal and human reports do not show evidence of human OS control, they just do show feasibility. The major issues concerning the potential for treatment of osteosarcoma with PDT are that adequate light should be transmitted to tumor loci and if the disease is caught before metastasis and irradiation of tumor sites is feasible, curative potential is there. Otherwise, PDT may be mainly palliative. To determine whether PDT can safely and efficiently be used in the clinical treatment of OS, many preclinical orthotopic animal OS models and OS models of multiple systemic metastases must be performed and interstitial PDT or intraoperative PDT may be a good and potential candidate for human OS treatment. If these problems can be well solved, PDT may be a potentially effective strategy for the treatment of OS patients.

EMT-Related Gene Signature Predicts the Prognosis in Uveal Melanoma Patients.

Background: Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. Epithelial-mesenchymal transition (EMT) is an essential regulator of the UVM's immune microenvironment. However, the precise role of EMT in UVM remains to be explored and the development of a related treatment strategy is urgently needed. Methods: Multiomics data and clinical information for TCGA-UVM were used to identify the EMT subtypes and analyze their regulatory role in the immune microenvironment in UVM. A machine-learning method based on the identified subtypes was utilized to construct the EMT feature-based prognostic model. External validation cohorts GSE84976 and GSE22138 were employed to validate the model's robustness. Immunotherapy cohort IMvigor210 was used to explore the model's potential to predict immunotherapy responsiveness. Results: Two EMT subtypes were identified in UVM. The role of EMT in shaping the immune microenvironment and regulating cancer-immunity circle of UVM was analyzed. A robust prognostic model was presented and validated to predict patient prognosis. The model also predicted patient's immune features and immunotherapy responsiveness. Conclusion: The EMT-mediated immune features in UVM were illustrated, providing a reliable model to facilitate precise UVM treatment. This research may assist in decision-making during clinical UVM therapy.

Deoxyelephantopin Suppresses Pancreatic Cancer Progression In Vitro and In Vivo by Targeting linc00511/miR-370-5p/p21 Promoter Axis.

Objectives: Deoxyelephantopin (DET) is a kind of natural active ingredient extracted from the Chinese herbal medicine Elephantopus scaber L. Many studies have revealed the potential antitumor effect on multiple malignancies. However, the detailed mechanism of its antitumor effect in pancreatic cancer remains unclear. Recently, studies have confirmed that noncoding RNA (ncRNA) plays an important regulatory role in malignancies. This research was performed to explore the relationship between ncRNA and DET-induced tumor inhibition in pancreatic cancer. Methods: Microarray profiling was applied to identify the candidate ncRNAs associated with DET-induced tumor inhibition. Quantitative real-time PCR was used to evaluate the expression of linc00511 in pancreatic cancer cells and tissues. The influence of DET on the cell proliferation, migration, and invasion was assessed by CCK-8, colony formation, wound healing, and Transwell assays. The relationship between lncRNAs, miRNAs, and p21 promoter region was analyzed by bioinformatics and verified by luciferase reporter gene and western blotting. The effect of linc00511 on nuclear translocation of miR-370-5p was explored by cytoplasmic and nuclear RNA purification. Moreover, the effect of DET on tumor growth and metastasis, and the prophylactic effect were investigated by establishing subcutaneous and lung metastatic tumor models. Results: Microarray assay indicated linc00511 was a potential target gene. The antitumor effect of DET in pancreatic cancer depended on downregulating linc00511 expression, and linc00511 might be an oncogene in pancreatic cancer. Silencing linc00511 enhanced the antitumor function of DET; conversely, linc00511 overexpression antagonized the DET cytotoxic effect. Additionally, miR-370-5p could bind to p21 promoter to exert the RNA activation and then promote p21 expression. P21 was a downstream gene of linc00511 and associated with pancreatic cancer progression. Linc00511 regulated p21 expression by blocking miR-370-5p nuclear translocation. Conclusions: To sum up, the present finding confirmed that DET suppressed the malignant biological behavior of pancreatic cancer via linc00511/miR-370-5p/p21 promoter axis.

The efficacy and safety of intravenous tranexamic acid on blood loss during total ankle replacement: a retrospective study.

Only a few of studies have reported whether Tranexamic acid (TXA) has the same benefits during total ankle replacement as hip and knee replacements. In our study, we hypothesized that TXA was effective in reducing the perioperative blood loss without increasing the risk of symptomatic venous thromboembolism of patients during total ankle replacement. We retrospectively reviewed 71 patients who underwent total ankle replacement at the foot and ankle surgery center of our institution between January 2017 and May 2021. Patients were divided into two groups according to whether they received intravenous tranexamic acid or not. Patients who received intravenous TXA showed significantly lower estimated intraoperative blood loss, hidden blood loss and total blood loss. The early AOFAS score and ROM at the first month follow up of TXA group were better than the NO-TXA group and the incidence of early wound infection and poor healing (< 1 month postoperative) was significant lower than NO-TXA group. Use of TXA was not associated with significant changes in the incidence of postoperative symptomatic venous thromboembolism. We conclude that intravenous TXA can safely and effectively reduce perioperative blood loss and the incidence of early wound infection and poor healing in total ankle replacement, without increasing the risk of symptomatic venous thromboembolism.The application of TXA following total ankle replacement helped improve ankle function and patient quality of life during the early stage.