Bone metastases in oral squamous cell carcinoma: A real-world retrospective study based on the SEER database.

BACKGROUND: Bone metastases are rare in oral squamous cell carcinoma (OSCC). It has not been defined on the risk and prognosis of OSCC patients with bone metastases. The purpose of this study was to assess the factors associated with the development and prognosis of bone metastases among OSCC patients. METHODS: Demographic and clinicopathological characteristics of OSCC patients diagnosed between 2010 and 2019 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. To explore risk factors for developing bone metastases and prognosis, the univariate and multivariate logistic and Cox regression analysis were performed, further the predictive nomogram models were constructed. RESULTS: The incidence rate of bone metastases in newly diagnosed OSCC patients was 0.91 % (95 %CI 0.81% -1.02 %). Ultimately, 137 OSCC patients with bone metastases and 19,469 OSCC patients without bone metastases were included in the present study. Pathological grade, primary site, T/N stage and distant organ metastases (liver/lung/brain) were independently associated with the risk of developing bone metastases among OSCC patients. The C-index of a constructed risk-predicting nomogram was 0.86 (95 %CI 0.83-0.89). Multivariate Cox regression analysis indicated that lung metastases, the use of surgery as well as chemotherapy were three independent prognostic factors. The C-indexes of constructed risk-predicting nomograms were 0.70 (95 %CI 0.65-0.75), 0.68 (95 %CI 0.63-0.73) for OS and CSS, respectively. Calibration plots demonstrated an agreementbetween the established nomogram's predicted survival and actual survival. In addition, decision curve analysis (DCA) indicated these established nomograms had considerable net benefits and clinical utilities. CONCLUSION: This study defined the risk and prognostic factors for bone metastases among OSCC patients and the established nomograms were well calibrated for discrimination to predict bone metastasis development and prognosis.

TRIM31 promotes the progression of oral squamous cell carcinoma through upregulating AKT phosphorylation and subsequent cellular glycolysis.

The regulation of protein kinase B (AKT) phosphorylation by Tripartite motif-containing protein 31 (TRIM31) is implicated as an essential mechanism in the progression of many malignant tumors. Nevertheless, the function of the TRIM31/AKT pathway in oral squamous cell carcinoma (OSCC) remains elusive. Here, immunohistochemistry analysis of human OSCC tissue microarrays indicated significantly higher levels of TRIM31 and phosphorylated AKT (p-AKT) in OSCC tumors than in adjacent tissue samples. Also, we detected a positive association between TRIM31 expression and clinical OSCC development. In in vitro studies, TRIM31 knockdown severely impaired OSCC cell growth, invasion, and migration. By contrast, TRIM31 overexpression improved these cell behaviors, while subsequent AKT inhibition abrogated the effect. In vivo tumorigenesis experiments using nude mice also validated the effects of TRIM31/AKT signaling in tumor growth. Furthermore, TRIM31 upregulation facilitated glucose uptake, as well as lactate and adenosine triphosphate production of OSCC cells, while such positive effects on glycolysis and malignant cell phenotypes were reversed by treatment with AKT or glycolysis inhibitors. In conclusion, TRIM31 may improve OSCC progression by enhancing AKT phosphorylation and subsequent glycolysis. Hence, TRIM31 has the potential as a treatment target in OSCC.

Assessment of immediate clotting after flapless extraction using piezosurgery or turbine handpiece in patients receiving dual antiplatelet therapy.

PURPOSE: This study aimed to investigate the efficacy of piezosurgery (PI) in promoting immediate clotting after flapless extraction in patients undergoing dual antiplatelet therapy (DAPT). METHODS: In this randomized controlled trial, 80 DAPT patients were equally divided into the PI and turbine handpiece (TH) groups. Accordingly, flapless extraction of a single tooth using PI or TH was performed on each patient, and the immediate clotting status was evaluated. The results of the preoperative hematological examinations, surgery-related variables and postoperative complications were recorded for analysis. RESULTS: Both groups presented with low platelet aggregation and similar coagulation functions. The PI group exhibited a higher proportion of patients with normal intra-alveolar clotting (≤30 min) (70% vs. 40%, P = 0.007) and fewer intraoperative complications (25% vs. 47.5%, P = 0.036) than that in the TH group. Logistic regression analysis indicated that the applied instrument was an independent risk factor for prolonged immediate bleeding (odds ratio = 3.10, 95% confidence interval: 1.20-8.00, P = 0.019). Intergroup differences were insignificant in terms of the other surgery-related variables and postoperative complications, except for the longer surgical duration in the PI group. CONCLUSION: The application of PI may contribute to better immediate clotting in DAPT patients after flapless extraction compared with the use of TH.

Malignant Myoepithelioma of the Head and Neck: Demographics, Clinicopathological Characteristics, Treatment, and Prognosis.

Malignant myoepithelioma of the head and neck (HNMM) is a rare malignancy, and its characteristics and survival rates have not been well-defined. This study aimed to define the epidemiology of HNMM and identify the prognostic factors associated with the disease. Data on all patients diagnosed with HNMM between 1991 and 2016 were gathered from the Surveillance Epidemiology and End Results (SEER) database. The demographics, clinicopathological characteristics, treatment, and prognoses of the patients were described. Cox regression analysis was used to identify the prognostic factors, and the prognostic nomograms for overall survival (OS) and disease-specific survival (DSS) were constructed. A total of 333 cases of HNMM were identified. The average age at diagnosis was 60.6 years, and 50.1% of the patients were men. After diagnosis, 46.2% of patients underwent surgery alone, 43.5% of patients underwent surgery and radiotherapy, and 3.6% of patients received only radiotherapy. Survival analysis showed that the 5-year OS and DSS for all HNMM patients were 69.7 and 82.1%, respectively. In the multivariate analysis model, the undifferentiated pathological grade (P <0.05) and M1 in the M category (P <0.01) were independent prognostic factors for poor OS and DSS, whereas the use of surgical resection was an independent favorable prognostic factor for both OS and DSS (P <0.05). The prognostic nomograms for OS and DSS prediction were constructed; the C-index values for OS and DSS prediction were 0.78 (95% CI 0.70-0.86) and 0.79 (95% CI 0.67-0.90), respectively. In conclusion, this SEER data-based study demonstrated that HNMM patients often had a favorable prognosis, and distant metastasis, pathological grade, and the use of surgery contributed to their survival. Furthermore, we developed a prognostic nomogram to predict OS and DSS for HNMM patients to aid physicians in the clinical management of this rare disease.

Genome-Wide Investigation of the PtrCHLP Family Reveals That PtrCHLP3 Actively Mediates Poplar Growth and Development by Regulating Photosynthesis.

Chlorophyll (Chl) plays a crucial role in plant photosynthesis. The geranylgeraniol reductase gene (CHLP) participates in the terminal hydrogenation of chlorophyll biosynthesis. Although there are many studies related to the genome-wide analysis of Populus trichocarpa, little research has been conducted on CHLP family genes, especially those concerning growth and photosynthesis. In this study, three CHLP genes were identified in Populus. The evolutionary tree indicated that the CHLP family genes were divided into six groups. Moreover, one pair of genes was derived from segmental duplications in Populus. Many elements related to growth were detected by cis-acting element analysis of the promoters of diverse PtrCHLPs. Furthermore, PtrCHLPs exhibit different tissue expression patterns. In addition, PtrCHLP3 is preferentially expressed in the leaves and plays an important role in regulating chlorophyll biosynthesis. Silencing of PtrCHLP3 in poplar resulted in a decrease in chlorophyll synthesis in plants, thus blocking electron transport during photosynthesis. Furthermore, inhibition of PtrCHLP3 expression in poplar can inhibit plant growth through the downregulation of photosynthesis. Ultimately, PtrCHLP3 formed a co-expression network with photosynthesis and chlorophyll biosynthesis-related genes, which synergistically affected the growth and photosynthesis of poplars. Thus, this study provides genetic resources for the improved breeding of fast-growing tree traits.

Genome-wide analysis and expression profiling of Cation/H+ exchanger (CAX) family genes reveal likely functions in cadmium stress responses in poplar.

Cadmium, a toxic heavy metal, seriously affects human health and ecological security. The cation/H+ exchanger (CAX) family is a unique metal transporter that plays a crucial role in Cd acquisition, transfer, and remission in plants. Although there are many studies related to the genome-wide analysis of Populus trichocarpa, little research has been done on the CAX family genes, especially concerning Cd stress. In this study, genome-wide analysis of the Populus CAX family identified seven stress-related CAX genes. The evolutionary tree indicated that the CaCA family genes were grouped into four clusters. Moreover, seven pairs of genes were derived by segmental duplication in poplars. Cis-acting element analysis identified numerous stress-related elements in the promoters of diverse PtrCAXs. Furthermore, some PtrCAXs were up-regulated by drought, beetle, and mechanical damage, indicating their possible function in regulating stress response. Under cadmium stress, all CAX genes in the roots were up-regulated. Our findings suggest that plants may regulate their response to Cd stress through the TF-CAXs module. Comprehensively investigating the CAX family provides a scientific basis for the phytoremediation of heavy metal pollution by Populus.

Patients With cT1N0M0 Oral Squamous Cell Carcinoma Benefit From Elective Neck Dissection: A SEER-Based Study.

BACKGROUND: The incidence of oral squamous cell carcinoma (OSCC) is increasing, with an estimated 369,000 new patients each year worldwide. Surgery is the primary treatment modality for early-stage OSCC, but there is scant evidence to prove the value of elective neck dissection (END) for relatively small early-stage OSCC. This study aimed to identify factors predicting survival for patients with clinical stage T1N0M0 (cT1N0M0) OSCC and whether up-front END improved survival. PATIENTS AND METHODS: Patients with cT1N0M0 OSCC who underwent tumor resection with or without END were identified and extracted from the SEER database. Kaplan-Meier survival analysis was used to assess overall survival and disease-specific survival. Prognostic factors were determined using Cox regression analysis. RESULTS: A total of 5,752 patients with cT1N0M0 OSCC were extracted, of whom 2,194 (38.1%) underwent tumor resection surgery with concurrent END and 3,558 (61.9%) underwent only tumor resection. In a multivariate Cox analysis, a relatively advanced age (>62 years) and relatively high pathologic grade were the significant negative predictors, but married status (hazard ratio, 0.709; P=.006) and undergoing END (hazard ratio, 0.708; P<.001) were identified as significant independent positive factors. CONCLUSIONS: Patients with cT1N0M0 OSCC gain significant overall and disease-specific survival benefit from END.

Clinicopathological characteristics, treatment and prognosis of head & neck small cell carcinoma: a SEER population-based study.

BACKGROUND: To investigate the clinicopathological characteristics of head and neck small cell carcinoma (H&NSmCC) and identify prognostic factors on the basis of the Surveillance, Epidemiology and End Results (SEER) database. METHODS: Total of 789 primary cases from 1973 to 2016 were included. Univariate and multivariate analyses were performed to identify independent prognostic indicators. An H&NSmCC-specific nomogram was constructed and compared with the AJCC staging system by calculating the time-dependent area under the curve (AUC) of the receiver operating characteristic (ROC) curves. RESULTS: The incidence of H&NSmCC peaked during the period of 50 to 70 years old, and the most frequent location was the salivary gland. The 5-year disease specific survival (DSS) was 27%. In the multivariate survival analysis, AJCC III + IV stage [HR = 2.5, P = 0.03, I + II stage as Ref], positive N stage [HR = 1.67, P = 0.05, negative N stage as Ref], positive M stage [HR = 4.12, P = 0.000, negative M stage as Ref] and without chemotherapy [HR = 0.56, P = 0.023, received chemotherapy as Ref] were independently associated with DSS. The H&NSmCC-specific nomogram was built based on the independent prognostic indicators. The nomogram demonstrated better predictive capacity than the AJCC staging system for 5-year DSS [(AUC: 0.75 vs 0.634; Harrell's C-index (95% CI): 0.7(0.66-0.74) vs 0.59(0.55-0.62), P < 0.05]. CONCLUSION: N stage, M stage, AJCC stage and chemotherapy were independent prognostic indicators included in the prognostic nomogram model, which can better predict the survival of H&NSmCC than the AJCC staging system.

Malignant tumours of temporomandibular joint.

BACKGROUND: Malignant tumours of the temporomandibular joint (MTTMJ) are extremely rare. Studies describing its unique epidemiology, clinicopathological features, treatment and prognosis comprehensively are limited. To address these issues, current investigation was performed. METHODS: A retrospective research was carried out by using population-based data from the Surveillance, Epidemiology, and End Results database (1973-2016). RESULTS: Data for a total of 734 patients, including 376 men and 358 women, was found. The median age was 47 years. The 5-year and 10-year disease specific survival (DSS) rates were 69.2 and 63.6%, respectively. Significant differences in DSS were found according to age, race, tumour type, AJCC/TNM stage, surgery, radiotherapy, chemotherapy and different treatment modalities (P < 0.05). In the multivariate survival analysis, age > 44 years and AJCC stage III and IV were associated with poor DSS. CONCLUSION: MTTMJ was mostly found in white people with a median age of 47 years without any sex predominance. Patient's age and AJCC stage was independent predictor of DSS.

Head & neck acinar cell carcinoma: a population-based study using the seer registry.

BACKGROUND: To explore the clinicopathologic characteristics, treatment and prognostic factors of head and neck acinar cell carcinoma (HNACC) comprehensively. METHODS: A population-based study was conducted using data from the Surveillance, Epidemiology, and End Results database (1975-2016). Overall survival (OS) and HNACC-specific survival of patients with different clinicopathologic variables were compared using the Kaplan-Meier method and Cox multivariate regression. RESULTS: A total of 2624 primary HNACC cases (1052 males, 1572 females) were identified. There was a significant difference in gender distribution. Among the total cohort, 2416 cases originated from salivary glands, including 2325 parotid gland ACC cases. Regardless of confounding factors, the 10-year and 20-year disease-specific survival (DSS) was 93.6 and 90%, respectively. Surgery was favourably associated with better DSS and OS [HR = 0.13, P = 0.0092 and HR = 0.23, P = 0.0203]. Gender was the only demographic independent prognostic factor for both DSS and OS [Male vs female, HR = 3.3, P = 0.0028 for DSS; HR = 2.44, P = 0.0376 for OS]. Higher pathological grade was adversely associated with DSS and OS [Grade II, HR = 4.03, P = 0.0444; Grade III + IV, HR = 35.64, P = 0.0000 for DSS; Grade III + IV, HR = 4.49, P = 0.0000 for OS, Grade I as reference]. In addition, TNM/AJCC stage was commonly associated with prognosis. CONCLUSION: Surgery was the only favourable prognostic indicator for both DSS and OS. Gender, age, pathological differentiation and TNM/AJCC stage were independent prognostic factors for survival.

[Interventional effects of metformin on senescence induced by D-galactose in middle-aged male mice].

OBJECTIVE: To investigate the effects of metformin (Met) on middle-aged male mice aging induced by D-galactose. METHODS: Fifty nine-month-old male ICR mice were fed in SPF experimental environment and fed freely with water. Subsequently, the mice were randomly divided into 5 groups(n=10): control group, model group, metformin low, medium and high dose groups(Met 50 mg/kg, Met 100 mg/kg, Met 200 mg/kg). The mice in different doses of Met group and model group were subcutaneously injected with D-galactose 100 mg/kg at the back of neck to induce senescence every day. At the same time, the mice were respectively treated with Met (50, 100, 200 mg/kg) or NS of equal volume by gavage. The control group was injected and gavage with equal volume NS. All treatments lasted for 8 weeks. During the study, the general condition, body weight, blood glucose,the activities of superoxide dismutase (SOD) and malonic dialdehyde (MDA) in serum and liver tissue of each mouse were tested, learning and memory ability were measured by Mirris water maze test, HE staining was used to observe the pathology of hippocampus in the mice. RESULTS: Met 200 mg/kg per day could reduce body weight (P＜0.05). Met intervention had no effect on normal fasting blood glucose in model rats. Compared with model group, the daily dose of Met 50, 100, 200 mg/kg could significantly increase SOD activity in serum and liver tissues of model mice (P＜0.05) and decrease MDA content in serum of model mice (P＜0.05), and improve most of the indicators of learning and memory ability of Morris water maze test (P＜0.05). HE staining showed that the neurons with nuclear condensation and deep staining were obviously decreased in the dentate gyrus of hippocampus. Met intervention has dose-dependent effects on most indicators. CONCLUSION: Long-term treatment of Met can delay the aging process of middle-aged male mice induced by D-galactose, which may be related to reducing the weight of mice and enhancing the body's antioxidant level.

Redox/pH dual-controlled release of chlorhexidine and silver ions from biodegradable mesoporous silica nanoparticles against oral biofilms.

BACKGROUND: Oral plaque biofilms pose a threat to periodontal health and are challenging to eradicate. There is a growing belief that a combination of silver nanoparticles and chlorhexidine (CHX) is a promising strategy against oral biofilms. PURPOSE: To overcome the side effects of this strategy and to exert maximum efficiency, we fabricated biodegradable disulfide-bridged mesoporous silica nanoparticles (MSNs) to co-deliver silver nanoparticles and CHX for biofilm inhibition. MATERIALS AND METHODS: CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) were fabricated after CHX loading, and the pH- and glutathione-responsive release profiles of CHX and silver ions along with their mechanism of degradation were systematically investigated. Then, the efficacy of Ag-MSNs@CHX against Streptococcus mutans and its biofilm was comprehensively assessed by determining the minimum inhibitory concentration, minimum bactericidal concentration, minimal biofilm inhibitory concentration, and the inhibitory effect on S. mutans biofilm formation. In addition, the biosafety of nanocarriers was evaluated by oral epithelial cells and a mouse model. RESULTS: The obtained Ag-MSNs@CHX possessed redox/pH-responsive release properties of CHX and silver ions, which may be attributed to the redox-triggered matrix degradation mechanism of exposure to biofilm-mimetic microenvironments. Ag-MSNs@CHX displayed dose-dependent antibacterial activity against planktonic and clone formation of S. mutans. Importantly, Ag-MSNs@CHX had an increased and long-term ability to restrict the growth of S. mutans biofilms compared to free CHX. Moreover, Ag-MSNs@CHX showed less cytotoxicity to oral epithelial cells, whereas orally administered Ag-MSNs exhibited no obvious toxic effects in mice. CONCLUSION: Our findings constitute a highly effective and safe strategy against biofilms that has a good potential as an oral biofilm therapy.

Antibacterial and biodegradable tissue nano-adhesives for rapid wound closure.

BACKGROUND: Although various organic tissue adhesives designed to facilitate would healing are gaining popularity in diverse clinical applications, they present significant inherent limitations, such as rejection, infections, toxicity and/or excessive swelling. It is highly desirable to develop efficient, biocompatible and anti-bacterial tissue adhesives for skin wound healing. PURPOSE: Inspired by the fact that inorganic nanoparticles can directly glue tissues through the "nanobridging effect", herein disulfide bond-bridged nanosilver-decorated mesoporous silica nanoparticles (Ag-MSNs) was constructed as an effective and safe tissue adhesive with antibacterial and degradable properties for wound closure and healing. MATERIALS AND METHODS: Ag-MSNs was fabricated by controlled reduce of ultrasmall nanosilvers onto the both surface and large pore of biodegradable MSNs. The obtained MSNs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and measurement of size distribution, zeta potential, and mesopore properties. Furthermore, adhesion strength test, anti-bacterial assessment, mouse skin wound model, and MTT assays were used to investigate the tissue adhesive property, antibacterial effect, biodegradability and biocompatibility of the Ag-MSNs. RESULTS: Ag-MSNs exhibited not only strong adhesive properties but also excellent antibacterial activities than that of MSNs. Importantly, this antibacterial nano-adhesive achieved rapid and efficient closure and healing of wounds in comparison to sutures or MSNs in a mouse skin wound model. Furthermore, Ag-MSNs with fast degradable behavior caused little cellular toxicity and even less systemic toxicity during wound healing. CONCLUSION: Our findings suggest that biodegradable Ag-MSNs can be employed as the next generation of nano-adhesives for rapid wound closure and aesthetic wound healing.

A comparison of mesoporous silica nanoparticles and mesoporous organosilica nanoparticles as drug vehicles for cancer therapy.

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for use in cancer treatment owing to their excellent biocompatibility and drug-loading capacity. However, MSN's incomplete drug release and toxic bioaccumulation phenomena limit their clinical application. Recently, researchers have presented redox responsive mesoporous organosilica nanoparticles containing disulfide (S-S) bridges (ss-MONs). These nanoparticles retained their ability to undergo structural degradation and increased their local release activity when exposed to reducing agents. Disulfide-based mesoporous organosilica nanoparticles offer researchers a better option for loading chemotherapeutic drugs due to their effective biodegradability through the reduction of glutathione. Although the potential of ss-MONs in cancer theranostics has been studied, few researchers have systematically compared ss-MONs with MSNs with regard to endocytosis, drug release, cytotoxicity, and therapeutic effect. In this work, ss-MONs and MSNs with equal morphology and size were designed and used to payload doxorubicin hydrochloride (DOX) for liver cancer chemotherapy. The ss-MONs showed considerable degradability in the presence of glutathione and performed comparably to MSNs on biocompatibility measures, including cytotoxicity and endocytosis, as well as in drug-loading capacity. Notably, DOX-loaded ss-MONs exhibited higher intracellular drug release in cancer cells and better anticancer effects in comparison with DOX-loaded MSNs. Hence, the ss-MONs may be more desirable carriers for a highly efficient and safe treatment of cancer.

Janus silver mesoporous silica nanobullets with synergistic antibacterial functions.

In this study, we exploited a one-pot method to fabricate cetyltrimethylammonium bromide (CTAB)-loaded Janus silver mesoporous silica nanoparticles (Janus Ag-MSNs@CTAB). These bullet-like nanoparticles had a silver head (80nm in diameter) attached to a mesoporous silica stick (200-300nm in length). The CTAB-loaded nanobullets exhibited a marked affinity for the bacterial cell surface and the simultaneously sustained release behavior of CTAB and silver ions. The minimum inhibitory concentrations (MIC) of Janus Ag-MSNs@CTAB were determined to be 10µg/mL and 20µg/mL for E. coli and S. Aureus, respectively. Importantly, Janus Ag-MSNs@CTAB provided a single-particle nanoplatform with a synergistic effect against both Gram-positive and Gram-negative bacteria. A thorough investigation indicated that CTAB induces a dramatic loss of bacterial membrane integrity, which facilitated the internalization of silver. This report described an efficient and convenient method of synthesizing Janus silver mesoporous silica nanoparticles, and these nanobullets show promising potential in biomedical applications.

Synergistic bactericidal activity of chlorhexidine-loaded, silver-decorated mesoporous silica nanoparticles.

Combination of chlorhexidine (CHX) and silver ions could engender synergistic bactericidal effect and improve the bactericidal efficacy. It is highly desired to develop an efficient carrier for the antiseptics codelivery targeting infection foci with acidic microenvironment. In this work, monodisperse mesoporous silica nanoparticle (MSN) nanospheres were successfully developed as an ideal carrier for CHX and nanosilver codelivery through a facile and environmentally friendly method. The CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) exhibited a pH-responsive release manner of CHX and silver ions simultaneously, leading to synergistically antibacterial effect against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. Moreover, the effective antibacterial concentration of Ag-MSNs@CHX showed less cytotoxicity on normal cells. Given their synergistically bactericidal ability and good biocompatibility, these nanoantiseptics might have effective and broad clinical applications for bacterial infections.

The shape effect of magnetic mesoporous silica nanoparticles on endocytosis, biocompatibility and biodistribution.

Although the aspect ratio (AR) play a crucial role in determining biological effects of homogeneous nanomaterials, studies available concerning how the shape contributes to biological effect of heterogeneous nanomaterials is limited. To systematically clarify the shape influence on the endocytosis, biocompatibility and biodistribution of magnetic mesoporous silica nanoparticles (M-MSNPs), three FITC-labeled M-MSNPs with different aspect ratio (AR=1, 2, and 4) were specifically designed and constructed through altering the ratios of CTAB/TEOS in a modified so-gel method. We have demonstrated that long-rod M-MSNP2 possessed higher intracellular internalization amount than the short-rod M-MSNP1 and the sphere-like M-MSNP0 in both cancer cells and normal cells due to the difference in the endocytosis pathways. However, there are no significant shape effects on biocompatibility including cytotoxicity and hemolytic rate. Moreover, biodistribution in HepG2 tumor-bearing mice showed that M-MSNPs administrated intravenously were mainly presented in reticuloendothelial system (RES) organs including liver, spleen and kidney. In particular, sphere-like M-MSNP0 were easily trapped in the liver, while long-rod M-MSP2 exhibited more retention in the spleen. It is worth noting that rod-like M-MSNPs are preferentially accumulated in tumor sites than sphere-like M-MSNPs, indicating an improved drug delivery efficacy in cancer therapy. Our findings may provide useful data for deeply understanding the interaction between the different shapes and biological behavior of M-MSNPs, which is expected to give rise to a new generation of heterogeneous M-MSNPs with significantly enhanced efficacy and safety for the cancer theranostics. STATEMENT OF SIGNIFICANCE: In this work, we systematically clarified the shape influence on the endocytosis, biocompatibility and biodistribution of homogeneous nanomaterials. We have demonstrated that rod-like magnetic mesoporous silica nanoparticles (M-MSNPs) were capable of higher intracellular internalization and tumor accumulation than sphere-like M-MSNPs, which was expected to give rise to a new generation of heterogeneous M-MSNPs with significantly enhanced efficacy and safety for the cancer theranostics.

Berberine-loaded Janus nanocarriers for magnetic field-enhanced therapy against hepatocellular carcinoma.

Berberine, an bioactive isoquinolin alkaloid from traditional Chinese herbs, is considered to be a promising agent based on its remarkable activity against hepatocellular carcinoma. However, the clinical application of this nature compound had been hampered owing to its properties such as poor aqueous solubility, low gastrointestinal absorption, and reduced bioavailability. Therefore, we developed Janus magnetic mesoporous silica nanoparticles (Fe3 O4 -mSiO2 NPs) consisting of a Fe3 O4 head for magnetic targeting and a mesoporous SiO2 body for berberine delivery. A pH-sensitive group was introduced on the surface of mesoporous silica for berberine loading to develop a tumor microenvironment-responsive nanocarrier, which exhibited uniform morphology, good superparamagnetic properties, high drug-loading amounts, superior endocytic ability, and low cytotoxicity. Berberine-loaded Fe3 O4 -mSiO2 NPs exerted extraordinarily high specificity for hepatocellular carcinoma cells, which was due to the pH-responsive berberine release, as well as higher endocytosis capacity in hepatocellular carcinoma cells rather than normal liver cells. More importantly, an external magnetic field could significantly improve antitumor activity of Ber-loaded Fe3 O4 -mSiO2 NPs through enhancing berberine internalization. Taken together, our results suggest that Janus nanocarriers driven by the magnetic field may provide an effective and safe way to facilitate clinical use of berberine against hepatocellular carcinoma.

[Correlation between platelet aggregation rates of aspirin users and intra-socket clotting after extraction of a maxillary tooth with periodontitis].

PURPOSE: To explore the optimal platelet aggregation rates (PAgTs) of aspirin users, which can ensure normal intra-socket clotting after extraction of a maxillary tooth with serious periodontitis, and to determine the reasonable time of pre-extraction aspirin suspension. METHODS: Ninety aspirin users (100mg/d) requiring extraction of a maxillary tooth with serious periodontitis were enrolled and divided into anterior tooth group (group A), premolar group (group B) and molar group (group C). Each group contained 10 cases with aspirin continuation, 10 cases with aspirin withdrawal 3 days pre-extraction and 10 cases with 5-day of aspirin withdrawal. After preoperative light transmission aggregometry (LTA) using arachidonic acid (AA) as the inducer to each case, the extractions were preformed. According to the intra-socket clotting classification table (class I indicated normal clotting, class II-III indicated successively increasing bleeding amount), the evaluation for each case was implemented and the analysis of the impacts caused by pre-extraction aspirin continuation and suspension on intra-socket clotting was conducted. The research on the best cut-off value of AA-induced PAgT to predict normal post-extraction clotting was also carried out by using receiver operating characteristic curve (ROC curve, SPSS11.6). RESULTS: (1)There were 4 cases of Class II in group A (3 without aspirin cessation and 1 with 3-day suspension), 8 in group B (5 without aspirin cessation, 2 with 3-day suspension and 1 with 5-day suspension) and 11 in group C (6 without aspirin cessation, 4 with 3-day suspension and 1 with 5-day suspension). The other cases in 3 groups were Class I. (2) The best cut-off value of AA induced PAgT was 10.15%, 13.25%, 16.5% for group A, B, C, respectively. CONCLUSIONS: For aspirin users (100mg/d) who will accept extraction of a maxillary tooth with serious periodontitis, a detection of pre-extraction LTA-AA is profitable, AA induced PAgT≥10.15% for an anterior tooth extraction, PAgT≥13.25% for a premolar extraction and PAgT≥16.5% for a molar extraction indicate normal postoperative intra-socket clotting, so aspirin continuation is feasible under such conditions. Otherwise, post-extraction bleeding amount can increase and preoperative aspirin cessation should be considered. The reasonable time of aspirin suspension is 3 days for an anterior tooth extraction and 5 days for a premolar or molar extraction. Additionally, hemostatic measures on the surgical site should be strengthened.

[A dye densitometry analysis method for noninvasive measurement of cardiac output based on NIRS].

Currently, there exist technology problems in cardiac output (CO) parameter detection clinically, such as invasive and complex operation, as well as possibility of infection and death for patients. In order to solve these problems, a noninvasive and continuous method based on NIRS for CO detection was presented. In this way, the concentration changing of indocyanine green (ICG) dye in the patient's arterial blood was dynamically measured and analyzed, so that the CO could be noninvasively and continuously measured according to the characteristic parameters of dye densitometry curve. While the ICG dye was injected into the patient's body by the median cubital vein, block of photoelectric pulse dye densitometry measurement system as the lower machine acquired pulse wave data and uploaded the data to upper computer. In the scheme, two specialized light sources of LED at 940 and 805 nm were used to capture the signals of sufferer's fingertip pulse wave synchronously and successively. The CO value could then be successfully calculated through drawing complete ICG concentration variation of dye dilution and excretion process and computing mean transmission time (MTT) by upper computer. Compared with the "gold standard" method of thermodilution, the maximum relative error of this method was below 9. 76%, and the mean relative error was below 4. 39%. The result indicates that the method can be used as a kind of convenient operation, noninvasive and continuous solution for clinical CO measurement.