Incidence and influence factors of venous thromboembolism in traumatic rib fracture patient: a multicenter study.

BACKGROUND: This study aimed to determine the incidence and influencing factors of venous thromboembolism (VTE) in patients with traumatic rib fractures. METHODS: The retrospective study analyzed medical records of patients with traumatic rib fractures from 33 hospitals. RESULTS: The overall incidence of VTE in hospitalized patients with traumatic rib fractures was 8.1%. Patients with isolated traumatic rib fractures had a significantly lower incidence of VTE (4.4%) compared to patients with rib fractures combined with other injuries (12.0%). Multivariate analysis identified the number of rib fractures as an independent risk factor for thrombosis. Surgical stabilization of isolated rib fractures involving three or more ribs was associated with a lower VTE incidence compared to conservative treatment. CONCLUSIONS: Patients with rib fractures have a higher incidence of VTE, positively correlated with the number of rib fractures. However, the occurrence of thrombosis is relatively low in isolated rib fractures. Targeted thromboprophylaxis strategies should be implemented for these patients, and surgical stabilization of rib fractures may be beneficial in reducing the risk of VTE.

Mechanism of Self-Oxidative Copolymerization and its Application with Polydopamine-pyrrole Nano-copolymers.

Currently, the copolymer of dopamine (DA) and pyrrole (PY) via chemical and electrochemical oxidation usually requires additional oxidants, and lacks flexibility in regulating the size and morphology, thereby limiting the broad applications of DA-PY copolymer in biomedicine. Herein, the semiquinone radicals produced by the self-oxidation of DA is ingeniously utilized as the oxidant to initiate the following copolymerization with PY, and a series of quinone-rich polydopamine-pyrrole copolymers (PDAm -nPY) with significantly enhanced absorption in near-infrared (NIR) region without any additional oxidant assistance is obtained. Moreover, the morphology and size of PDAm -nPY can be regulated by changing the concentration of DA and PY, thereby optimizing nanoscale PDA0.05 -0.15PY particles (≈ 150 nm) with excellent NIR absorption and surface modification activity are successfully synthesized. Such PDA0.05 -0.15PY particles show effective photoacoustic (PA) imaging and photothermal therapy (PTT) against 4T1 tumors in vivo. Furthermore, other catechol derivatives can also copolymerize with PY under the same conditions. This work by fully utilizing the semiquinone radical active intermediates produced through the self-oxidation of DA reduces the dependence on external oxidants in the synthesis of composite materials and predigests the preparation procedure, which provides a novel, simple, and green strategy for the synthesis of other newly catechol-based functional copolymers.

Effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with esophageal squamous cell carcinoma: a prospective multicenter observational cohort study.

Background: Camrelizumab has been demonstrated to be a feasible treatment option for locally advanced esophageal squamous cell carcinoma (ESCC) when combined with neoadjuvant chemotherapy. This trial was conducted to investigate the effectiveness and safety of camrelizumab-containing neoadjuvant therapy in patients with ESCC in daily practice. Methods: This prospective multicenter observational cohort study was conducted at 13 tertiary hospitals in Southeast China. Patients with histologically or cytologically confirmed ESCC [clinical tumor-node-metastasis (cTNM) stage I-IVA] who had received at least one dose of camrelizumab-containing neoadjuvant therapy were eligible for inclusion. Results: Between June 1, 2020 and July 13, 2022, 255 patients were enrolled and included. The median age was 64 (range, 27 to 82) years. Most participants were male (82.0%) and had clinical stage III-IVA diseases (82.4%). A total of 169 (66.3%) participants underwent surgical resection; 146 (86.4%) achieved R0 resection, and 36 (21.3%) achieved pathological complete response (pCR). Grades 3-5 adverse events (AEs) were experienced by 14.5% of participants. Reactive cutaneous capillary endothelial proliferation occurred in 100 (39.2%) of participants and all were grade 1 or 2. Conclusions: Camrelizumab-containing neoadjuvant therapy has acceptable effectiveness and safety profiles in real-life ESCC patients.

Pyrrole-Doped Polydopamine-Pyrrole (PDA-nPY) Nanoparticles with Tunable Size and Improved NIR Absorption for Photothermal Therapy.

Polydopamine (PDA) as a melanin-like biomimetic material with excellent biocompatibility, full spectrum light absorption capacity and antioxidation property has been extensively applied in the biomedical field. Based on the high reactivity of dopamine (DA), exploiting new strategies to fabricate novel PDA-based nano-biomaterials with controllable size and improved performance is valuable and desirable. Herein, we reported a facile way to synthesize pyrrole-doped polydopamine-pyrrole nanoparticles (PDA-nPY NPs) with tunable size and enhanced near-infrared (NIR) absorption capacity through self-oxidative polymerization of DA with PY in an alkaline ethanol/H2O/NH4OH solution. The PDA-nPY NPs maintain excellent biocompatibility and surface reactivity as PDA. By regulating the volume of added PY, PDA-150PY NPs with a smaller size (<100 nm) and four-fold higher absorption intensity at 808 nm than that of PDA can be successfully fabricated. In vitro and in vivo experiments effectively further demonstrate that PDA-150PY NPs can effectively inhibit tumor growth and completely thermally ablate a tumor. It is believed that these PY doped PDA-nPY NPs can be a potential photothermal (PT) agent in biomedical application.

The Chinese consensus for surgical treatment of traumatic rib fractures 2021 (C-STTRF 2021).

Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

Constructing a Risk Prediction Model for Lung Cancer Recurrence by Using Gene Function Clustering and Machine Learning.

OBJECTIVE: A significant proportion of patients with early non-small cell lung cancer (NSCLC) can be cured by surgery. The distant metastasis of tumors is the most common cause of treatment failure. Precisely predicting the likelihood that a patient develops distant metastatic risk will help identify patients who can further intervene, such as conventional adjuvant chemotherapy or experimental drugs. METHODS: Current molecular biology techniques enable the whole genome screening of differentially expressed genes, and rapid development of a large number of bioinformatics methods to improve prognosis. RESULTS: The genes associated with metastasis do not necessarily play a role in the pathogenesis of the disease, but rather reflect the activation of specific signal transduction pathways associated with enhanced migration and invasiveness. CONCLUSION: In this study, we discovered several genes related to lung cancer resistance and established a risk model to predict high-risk patients.

The influences of red wine in phenotypes of human cancer cells.

Alcohol intake increases the risk of cancer development. Approximately 3.6% human cancers worldwide derive from chronic alcohol drinking, including oral, liver, breast and other organs. Our studies in vivo and in vitro have demonstrated that diluted ethanol increase RNA Pol III gene transcription and promotes cell proliferation and transformation, as well as tumor formation. However, it is unclear about the effect of red wines on the human cancer cells. In present study, we investigated the roles of red wine in human cancer cell growth, colony formation and RNA Pol III gene transcription. Low concentration (12.5 mM to 25 mM) of ethanol enhances cell proliferation of breast and esophageal cancer lines, whereas its higher concentration (100 mM to 200 mM) slightly decreases the rates. In contrast, red wines significantly repress cell proliferation of different human cancer lines from low dose to high dose. The results reveal that the red wine also inhibits colony formation of human breast cancer and esophageal carcinoma cells. The effects of repression on different human cancer lines are in a dose-dependent manner. Further analysis indicates that ethanol increases RNA Pol III gene transcription, whereas the red wines significantly reduce transcription of the genes. Interestingly, the effects of mature wine (brick red) on cancer cell phenotypes are much stronger than young wine (intense violet). Together, these new findings suggest that red wines may contain some bioactive components, which are able to inhibit human cancer cell growth and colony formation.

Role of Brf1 interaction with ERα, and significance of its overexpression, in human breast cancer.

TFIIB-related factor 1 (Brf1) modulates the transcription of RNA Pol III genes (polymerase-dependent genes). Upregulation of Pol III genes enhances tRNA and 5S RNA production and increases the translational capacity of cells to promote cell transformation and tumor development. However, the significance of Brf1 overexpression in human breast cancer (HBC) remains to be investigated. Here, we investigate whether Brf1 expression is increased in the samples of HBC, and we explore its molecular mechanism and the significance of Brf1 expression in HBC. Two hundred and eighteen samples of HBC were collected to determine Brf1 expression by cytological and molecular biological approaches. We utilized colocalization, coimmunoprecipitation, and chromatin immunoprecipitation methods to explore the interaction of Brf1 with estrogen receptor alpha (ERα). We determined how Brf1 and ERα modulate Pol III genes. The results indicated that Brf1 is overexpressed in most cases of HBC, which is associated with an ER-positive status. The survival period of the cases with high Brf1 expression is significantly longer than those with low levels of Brf1 after hormone treatment. ERα mediates Brf1 expression. Brf1 and ERα are colocalized in the nucleus. These results indicate an interaction between Brf1 and ERα, which synergistically regulates the transcription of Pol III genes. Inhibition of ERα by its siRNA or tamoxifen reduces cellular levels of Brf1 and Pol III gene expression and decreases the rate of colony formation of breast cancer cells. Together, these studies demonstrate that Brf1 is a good biomarker for the diagnosis and prognosis of HBC. This interaction of Brf1 with ERα and Brf1 itself are potential therapeutic targets for this disease.

Exploring a common mechanism of alcohol-induced deregulation of RNA Pol III genes in liver and breast cells.

Alcohol intake is associated with numbers of different human cancers, such as hepatocellular carcinoma (HCC) and breast cancer. However, the molecular mechanism remains to be elucidated. RNA polymerase III-dependent genes (Pol III genes) deregulation elevates cellular production of tRNAs and 5S rRNA, resulting in an increase in translational capacity, which promote cell transformation and tumor formation. To explore a common mechanism of alcohol-associated human cancers, we have comparably analyzed that alcohol causes deregulation of Pol III genes in liver and breast cells. Our results reveal that alcohol enhances RNA Pol III gene transcription in both liver and breast cells. The induction of Pol III genes caused by alcohol in ER+ breast cancer lines or liver tumor lines are significantly higher than in their non-tumor cell lines. Alcohol increases cellular levels of Brf1 mRNA and protein, (which depeted) Brf1 is a key transcription factor and specifically regulate Pol III gene activity. Alcohol activates JNK1 to upregulate transcription of Brf1 and Pol III genes, whereas inhibition of JNK1 by SP600125 or its siRNA significantly decreases the induction of these genes. Furthermore, alcohol increases the rates of transformation of liver and breast cells, repressed JNK1 and Brf1 expression decrease transcription of Pol III genes and reduce the rates of colony formation of AML-12 and MCF-10 cells. Together, these studies support the idea that alcohol induces deregulation of Brf1 and RNA Pol III genes in liver and breast cells, which share a common signaling pathway to promote cell transformation. Through the common mechanism, alcohol-induced deregulation of RNA Pol III genes brings about greater phenotypic changes.

Downregulated miR-486-5p acts as a tumor suppressor in esophageal squamous cell carcinoma.

microRNAs (miRNAs/miRs) are crucial regulators of gene expression at the post-translational level through promoting mRNA degradation or the repression of translation of target genes. miRs have been confirmed to serve a dominant role in tumor biology. miR-486-5p has been ascertained to be involved in non-small-cell lung cancer, breast cancer and hepatocellular carcinoma; however, the expression and function of miR-486-5p in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. The present study aimed to analyze the expression levels of miR-486-5p in ESCC tissues and paired normal adjacent tissues, and determine the effects of miR-486-5p on esophageal cancer cells using MTT, wound scratch and apoptosis assays. The current results showed that miR-486-5p was significantly downregulated in ESCC specimens. Ectopic expression of miR-486-5p by synthetic mimics reduced cell proliferation and migration and induced increased cell apoptosis. The results indicated miR-486-5p may function as a tumor suppressor in ESCC. The present study demonstrated that miR-486-5p was downregulated in ESCC and served a anti-oncogene role in ESCC via affecting cellular migration.

lncRNA-UCA1 enhances cell proliferation through functioning as a ceRNA of Sox4 in esophageal cancer.

Esophageal cancer (EC) is one of the most common gastrointestinal cancers, which leads to the sixth ranking of cancer-related death. Long non-coding RNAs (lncRNAs) play pivotal roles in many biological processes. lncRNA human urothelial carcinoma associated 1 (UCA1) is significantly upregulated and functions as an important oncogene in many types of human cancers. However, the role of UCA1 in EC and its underlying mechanism remains unclear. In the present study, we demonstrated that UCA1 was significantly upregulated in EC tissues and associated with poor prognosis. Overexpression of UCA1 promoted the proliferation of EC cells, while silence of UCA1 inhibited EC cells growth. Furthermore, we found that Sox4 was a direct target gene of UCA1. UCA1 regulated Sox4 expression through functioning as a competing endogenous RNA (ceRNA). UCA1 directly interacted with miR-204 and decreased the binding of miR-204 to Sox4 3'UTR, which suppressed the degradation of Sox4 mRNA by miR-204. This study provides the first evidence that UCA1 promotes cell proliferation through Sox4 in EC, suggesting that UCA1 and Sox4 may be potential therapeutic targets for EC.

Upregulated miR-193a-3p as an oncogene in esophageal squamous cell carcinoma regulating cellular proliferation, migration and apoptosis.

MicroRNAs (miRs) are small endogenous non-coding RNAs that play a vital role in carcinogenesis. miR-193a-3p has been described in multiple cancers. However, the function of miR-193a-3p in esophageal squamous cell carcinoma (ESCC) is still unclear. To explore the role of miR-193a-3p in ESCC, reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression of miR-193a-3p in 48 paired ESCC and adjacent normal tissues. In addition, the impact of miR-193a-3p on cell proliferation, migration and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound scratch assay and flow cytometry, respectively. The results revealed that miR-193a-3p was upregulated in ESCC, compared with adjacent normal tissues. Downregulation of miR-193a-3p expression using a synthesized inhibitor suppressed cell proliferation and migration, and induced cell apoptosis, indicating that miR-193a-3p could be characterized as an oncogene in ESCC. In summary, the present study demonstrated that miR-193a-3p was upregulated in ESCC, where it plays a significant role by affecting cellular proliferation, migration and apoptosis.

Single-step assembly of polymer-lipid hybrid nanoparticles for mitomycin C delivery.

Mitomycin C is one of the most effective chemotherapeutic agents for a wide spectrum of cancers, but its clinical use is still hindered by the mitomycin C (MMC) delivery systems. In this study, the MMC-loaded polymer-lipid hybrid nanoparticles (NPs) were prepared by a single-step assembly (ACS Nano 2012, 6:4955 to 4965) of MMC-soybean phosphatidyhlcholine (SPC) complex (Mol. Pharmaceutics 2013, 10:90 to 101) and biodegradable polylactic acid (PLA) polymers for intravenous MMC delivery. The advantage of the MMC-SPC complex on the polymer-lipid hybrid NPs was that MMC-SPC was used as a structural element to offer the integrity of the hybrid NPs, served as a drug preparation to increase the effectiveness and safety and control the release of MMC, and acted as an emulsifier to facilitate and stabilize the formation. Compared to the PLA NPs/MMC, the PLA NPs/MMC-SPC showed a significant accumulation of MMC in the nuclei as the action site of MMC. The PLA NPs/MMC-SPC also exhibited a significantly higher anticancer effect compared to the PLA NPs/MMC or free MMC injection in vitro and in vivo. These results suggested that the MMC-loaded polymer-lipid hybrid NPs might be useful and efficient drug delivery systems for widening the therapeutic window of MMC and bringing the clinical use of MMC one step closer to reality.

Ethylenediaminetetraacetic acid as capping ligands for highly water-dispersible iron oxide particles.

Monodispersed magnetite (Fe3O4) particles were synthesized using a high-temperature hydrolysis reaction with the assistance of ethylenediaminetetraacetic acid (EDTA) as capping ligands. These particles were composed of small primary nanocrystals and their sizes could be tuned from about 400 to about 800 nm by simply changing the EDTA or precursor concentration. Surface-tethered EDTA made the particles highly water-dispersible. The as-prepared magnetite particles also showed superparamagnetic behavior at room temperature, and their magnetic properties were size dependent. In addition, the particles had a strong response to external magnetic field due to their high magnetization saturation values. These properties were very important for some potential biomedical applications, such as magnetic separation and magnetic-targeted substrate delivery.

Both FA- and mPEG-conjugated chitosan nanoparticles for targeted cellular uptake and enhanced tumor tissue distribution.

Both folic acid (FA)- and methoxypoly(ethylene glycol) (mPEG)-conjugated chitosan nanoparticles (NPs) had been designed for targeted and prolong anticancer drug delivery system. The chitosan NPs were prepared with combination of ionic gelation and chemical cross-linking method, followed by conjugation with both FA and mPEG, respectively. FA-mPEG-NPs were compared with either NPs or mPEG-/FA-NPs in terms of their size, targeting cellular efficiency and tumor tissue distribution. The specificity of the mPEG-FA-NPs targeting cancerous cells was demonstrated by comparative intracellular uptake of NPs and mPEG-/FA-NPs by human adenocarcinoma HeLa cells. Mitomycin C (MMC), as a model drug, was loaded to the mPEG-FA-NPs. Results show that the chitosan NPs presented a narrow-size distribution with an average diameter about 200 nm regardless of the type of functional group. In addition, MMC was easily loaded to the mPEG-FA-NPs with drug-loading content of 9.1%, and the drug releases were biphasic with an initial burst release, followed by a subsequent slower release. Laser confocal scanning imaging proved that both mPEG-FA-NPs and FA-NPs could greatly enhance uptake by HeLa cells. In vivo animal experiments, using a nude mice xenograft model, demonstrated that an increased amount of mPEG-FA-NPs or FA-NPs were accumulated in the tumor tissue relative to the mPEG-NPs or NPs alone. These results suggest that both FA- and mPEG-conjugated chitosan NPs are potentially prolonged drug delivery system for tumor cell-selective targeting treatments.