Multi-modality deep learning model reaches high prediction accuracy in the diagnosis of ovarian cancer.

We evaluated the diagnostic performance of a multimodal deep-learning (DL) model for ovarian mass differential diagnosis. This single-center retrospective study included 1,054 ultrasound (US)-detected ovarian tumors (699 benign and 355 malignant). Patients were randomly divided into training (n = 675), validation (n = 169), and testing (n = 210) sets. The model was developed using ResNet-50. Three DL-based models were proposed for benign-malignant classification of these lesions: single-modality model that only utilized US images; dual-modality model that used US images and menopausal status as inputs; and multi-modality model that integrated US images, menopausal status, and serum indicators. After 5-fold cross-validation, 210 lesions were tested. We evaluated the three models using the area under the curve (AUC), accuracy, sensitivity, and specificity. The multimodal model outperformed the single- and dual-modality models with 93.80% accuracy and 0.983 AUC. The Multimodal ResNet-50 DL model outperformed the single- and dual-modality models in identifying benign and malignant ovarian tumors.

Stormwater runoff pollution control performance of permeable concrete pavement and constructed wetland combined system: toward on-site reuse.

Urban waterlogging and the deterioration of receiving water quality caused by stormwater runoff have become increasingly significant problems. Based on the concept of combining grey and green infrastructure, a combined permeable concrete pavement (PCP) and constructed wetland (CW) system has been developed to treat stormwater runoff and enable on-site reuse. The results showed that the removal rate of suspended solids (SS) by PCP ranged from 96.61 to 99.20%; however, the chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) concentrations in the effluent did not meet the standards required for rainwater reuse. For the combined PCP-CW system, the removal rates of COD, TN and TP by the CW were 48.45-75.12%, 47.26-53.05%, and 59.04-75.28%, respectively, under different hydraulic loading (HL) rates; thus, the effluent TN concentrations did not consistently meet the reuse standards. Further optimization of aeration in different parts of the CW revealed that aeration in the middle and front sections of the wetland had the most significant effect on pollutant removal, under which the TN concentrations in the effluent met the standard required for reuse. The effluent from the combined PCP-CW system was able to fully meet the stormwater reuse standards under these optimized conditions, and the reuse of urban stormwater runoff can therefore be realized.

Relationship among subjective exercise experience, exercise behavior, and trait anxiety in adolescents.

OBJECTIVE: To investigate the influence of subjective exercise experience on adolescent trait anxiety and to reveal the mediating effect of exercise behavior. METHODS: Using the Subjective Exercise Experience Scale (SEES), Physical Exercise Rating Scale (PARS-3), and Trait Anxiety Inventory (T-AI), a questionnaire survey was conducted among 500 adolescents in Southwest China, and the SPSS21.0 and AMOS21.0 statistical analysis software was used to statistics and analysis on the questionnaires. RESULTS: 1) Among adolescents, the exercise behavior of boys was significantly higher than that of girls (p < 0.05), and the subjective exercise experience of students aged 9 to 12 was significantly higher than that of students aged 12 to 15 (p < 0.05). 2) The subjective exercise experience could directly and positively predict exercise behavior (ß = 0.45, p < 0.001) and negatively predict trait anxiety (ß = -0.26, p < 0.05), and exercise behavior could directly and negatively predict trait anxiety (ß = -0.32, p < 0.01). 3) The exercise behavior played a partial mediating effect between subjective exercise experience and trait anxiety (the mediation effect was -0.14). Among them, compared with low- and high-exercise amounts, the exercise behavior of moderate exercise amounts had the strongest mediating effect between subjective exercise experience and trait anxiety. CONCLUSION: The good subjective exercise experience not only has direct benefits for improving trait anxiety in adolescents but also helps to improve their exercise behavior, enrich daily physical exercise activities, and indirectly promote the reduction of trait anxiety.

Feasibility and reproducibility of semi-automated longitudinal strain analysis: a comparative study with conventional manual strain analysis.

BACKGROUND: Conventional approach to myocardial strain analysis relies on a software designed for the left ventricle (LV) which is complex and time-consuming and is not specific for right ventricular (RV) and left atrial (LA) assessment. This study compared this conventional manual approach to strain evaluation with a novel semi-automatic analysis of myocardial strain, which is also chamber-specific. METHODS: Two experienced observers used the AutoStrain software and manual QLab analysis to measure the LV, RV and LA strains in 152 healthy volunteers. Fifty cases were randomly selected for timing evaluation. RESULTS: No significant differences in LV global longitudinal strain (LVGLS) were observed between the two methods (-21.0% ± 2.5% vs. -20.8% ± 2.4%, p = 0.230). Conversely, RV longitudinal free wall strain (RVFWS) and LA longitudinal strain during the reservoir phase (LASr) measured by the semi-automatic software differed from the manual analysis (RVFWS: -26.4% ± 4.8% vs. -31.3% ± 5.8%, p < 0.001; LAS: 48.0% ± 10.0% vs. 37.6% ± 9.9%, p < 0.001). Bland-Altman analysis showed a mean error of 0.1%, 4.9%, and 10.5% for LVGLS, RVFWS, and LASr, respectively, with limits of agreement of -2.9,2.6%, -8.1,17.9%, and -12.3,33.3%, respectively. The semi-automatic method had a significantly shorter strain analysis time compared with the manual method. CONCLUSIONS: The novel semi-automatic strain analysis has the potential to improve efficiency in measurement of longitudinal myocardial strain. It shows good agreement with manual analysis for LV strain measurement.

Evaluation of left ventricular myocardial work in patients with hyperthyroidism with different heart rates with noninvasive pressure-strain loop based on two-dimensional speck tracking imaging.

Background: We investigated the application value of no-invasive myocardial work in evaluating left ventricular (LV) function in patients with hyperthyroidism. Methods: Sixty-five patients with an initial hyperthyroidism diagnosis were sorted into tachycardia (group TH1, n=31) and without tachycardia (group TH2, n=34) groups. Thirty healthy participants served as the control group (group CON). LV strain parameters and LV myocardial work parameters were evaluated at rest. Each parameter's value in identifying myocardial damage was analyzed using receiver operating characteristic curves. The correlation of myocardial work parameters with global longitudinal strain (GLS), longitudinal peak strain dispersion (normalized by heart rate, PSDN), and systolic blood pressure (SBP) was analyzed. Results: There was no difference in classic echocardiographic parameters between the groups. Compared with that in group CON, GLS decreased in groups TH1 and TH2 (TH1 17.99%±2.21% and TH2: 19.00%±2.85% vs. 20.27%±1.49%; both P<0.05); there was no significant difference between groups TH1 and TH2. PSDN increased in groups TH1 and TH2 (TH1 73.13±19.51 ms and TH2 55.06±17.03 vs. 44.13±8.65 ms; both P<0.05); it was higher in group TH1 than in group TH2 (P<0.05). Myocardial global work efficiency (GWE) decreased in groups TH1 and TH2 {TH1 95% [interquartile range (IQR), 94-95%] and TH2 96% (IQR, 95-97%) vs. 97% (IQR, 96-97%); both P<0.05}; it was lower in group TH1 than in group TH2 (P<0.05). Global constructive work (GCW) decreased in group TH1 (1,865.29±284.13 vs. 2,030.33±252.52 mmHg%; P<0.05), but was not different from that in group TH2; there was no difference between groups TH2 and CON. Global wasted work (GWW) increased in groups TH1 and TH2 [TH1 83.00 (IQR, 74.00-97.00) mmHg% and TH2 69.50 (IQR, 51.25-84.25) vs. 50.50 (IQR, 40.75-65.25) mmHg%; both P<0.05]; it was higher in group TH1 than in group TH2 (P<0.05). The area under the GWE curve was the largest (area under the curve =0.835), and the optimal cutoff point was 96.5%, with a sensitivity of 0.83 and a specificity of 0.70. GWE and GCW were positively correlated with GLS and negatively correlated with PSDN. GWW was negatively correlated with GLS and positively correlated with PSDN. In group CON, GCW and GWW were positively correlated with SBP; GWE was not correlated with SBP. In groups TH1 and TH2, GCW was positively correlated with SBP, but not with GWW or GWE. Conclusions: Hyperthyroidism can significantly decrease the GWE and increase GWW of the left ventricle. This change is more pronounced in patients with tachycardia. Myocardial work could be a novel method for the evaluation of LV myocardial function in patients with hyperthyroidism.

Prediction of Surgical Approach in Mitral Valve Disease by XGBoost Algorithm Based on Echocardiographic Features.

In this study, we aimed to develop a prediction model to assist surgeons in choosing an appropriate surgical approach for mitral valve disease patients. We retrospectively analyzed a total of 143 patients who underwent surgery for mitral valve disease. The XGBoost algorithm was used to establish a predictive model to decide a surgical approach (mitral valve repair or replacement) based on the echocardiographic features of the mitral valve apparatus, such as leaflets, the annulus, and sub-valvular structures. The results showed that the accuracy of the predictive model was 81.09% in predicting the appropriate surgical approach based on the patient's preoperative echocardiography. The result of the predictive model was superior to the traditional complexity score (81.09% vs. 75%). Additionally, the predictive model showed that the three main factors affecting the choice of surgical approach were leaflet restriction, calcification of the leaflet, and perforation or cleft of the leaflet. We developed a novel predictive model using the XGBoost algorithm based on echocardiographic features to assist surgeons in choosing an appropriate surgical approach for patients with mitral valve disease.

[Development law of soil cracks in karst peak-cluster depressions under dry and wet alternations]. / 干湿交替条件下喀斯特峰丛洼地土壤裂隙发育规律.

In an experiment with alternating dry and wet conditions of soil in cultivated land, orchards and forest lands with limestone and dolomite in karst peak depression, combined with digital image processing technology, we investigated the development law of soil surface cracks under alternating dry and wet condition. The results showed that with the alternation of wet and dry, the average width of cracks decreased at a fast-slow-slower rate, with an order of limestone > dolomite under the same land use, and orchard > cultivated land > forest soil under the same soil-forming parent rock. In the first four dry and wet alternations, the degrees of soil fragmentation and connectivity were higher in dolomite development than in limestone, with significant differences in fracture development rose diagrams. In the subsequent cycles, soil fragmentation of most samples increased, the difference dominated by parent rock gradually decreased, the crack development rose diagram converged, and the connectivity showed the pattern of forest land > orchard > cultivated land. After the fourth cycle, the alternations of dry and wet seriously damaged soil structure. The physical and chemical properties of capillary porosity and non-capillary tube porosity were dominant in the development of cracks before that, but it was more dependent on the organic matter content and the sand composition after that.

Development of PI3Kα inhibitors for tumor therapy.

The PI3K/AKT/mTOR signaling pathway is well known to be involved in cell growth, proliferation, metabolism and other cellular physiological processes. Abnormal activation of this pathway is closely related to tumorigenesis and metastasis. As the starting node of the pathway, PI3K is known to contain 4 isoforms, including PI3Kα, a heterodimer composed of the catalytic subunit p110α and the regulatory subunit p85. PIK3CA, which encodes p110α, is frequently mutated in cancer, especially breast cancer. Abnormal activation of PI3Kα promotes cancer cell proliferation, migration, invasion, and angiogenesis; therefore, PI3Kα has become a key target for the development of anticancer drugs. The hinge region and the region of the mutation site in the PI3Kα protein are important for designing PI3Kα-specific inhibitors. As the group shared by the most PI3Kα-specific inhibitors reported thus far, carboxamide can produce hydrogen bonds with Gln859 and Ser854. Gln859 is specific to the p110α protein in producing hydrogen bond interactions with PI3Kα-specific inhibitors and this is a key point for designing PI3Kα inhibitors. To date, alpelisib is the only PI3Kα inhibitor approved for the treatment of breast cancer. Several other PI3Kα inhibitors are under evaluation in clinical trials. In this review, we briefly describe PI3Kα and its role in tumorigenesis, summarize the clinical trial results of some PI3Kα inhibitors as well as the synthetic routes of alpelisib, and finally give our proposal for the development of novel PI3Kα inhibitors for tumor therapy. HighlightsWe summarize the progress of PI3Kα and PI3Kα inhibitors in cancer from the second half of the 20th century to the present.We describe the clinical trial results of PI3Kα inhibitors as well as the synthetic routes of the only approved PI3Kα inhibitor alpelisib.Crystal structure of alpelisib bound to the PI3Kα receptor binding domain.This review gives proposal for the development of novel PI3Kα inhibitors and will serve as a complementary summary to other reviews in the research field of PI3K inhibitors.Communicated by Ramaswamy H. Sarma.

Discovery of Novel PI3Kδ Inhibitors Based on the p110δ Crystal Structure.

PI3Kδ is a key mediator of B-cell receptor signaling and plays an important role in the pathogenesis of certain hematological malignancies, such as chronic lymphocytic leukemia. Idelalisib, which targets PI3Kδ specifically, is the first approved PI3K inhibitor for cancer therapy. Recently, we carried out virtual screening, cell-based assays, adapta kinase assays, and molecular dynamic analysis to discover novel PI3Kδ inhibitors and identified NSC348884 as a lead PI3Kδ inhibitor. NSC348884 had an excellent docking score, potent PI3Kδ-inhibitory activity, antitumor effects on various cancer cell lines, and a favorable binding mode with the active site of PI3Kδ. Moreover, through the structural modification of NSC348884, we further discovered comp#1, which forms H-bonds with both Val828 and Lys779 in the ATP binding pocket of PI3Kδ, with a more favorable conformation binding to PI3Kδ. In addition, we found that N1, N1, N2-trimethyl-N2-((6-methyl-1H-benzo[d]imidazol-2-yl) methyl) ethane-1,2-diamine might be a potential scaffold structure. Thus, the result of this study provides a far more efficient approach for discovering novel inhibitors targeting PI3Kδ.

Effect of Lemon Essential Oil Microemulsion on the Cariogenic Virulence Factor of Streptococcus mutans via the Glycolytic Pathway.

PURPOSE: To investigate the effects and mechanisms of lemon essential oil products on dental caries prevention. MATERIALS AND METHODS: Lemon essential oil microemulsions (LEOM) with concentrations of 1/8 minimum inhibitory concentration (MIC), 1/4 MIC, and 1/2 MIC were applied to S. mutans at concentrations of 0.2%, 1%, and 5% glucose, respectively. Changes in acid production capacity of S. mutans were measured based on changes in pH. The effect of the reductive coenzyme I oxidation method on LDH activity was examined. The effect of lemon essential oil microemulsion on the expression of the lactate dehydrogenase gene (ldh) was detected by a quantitative real-time polymerase chain reaction. RESULTS: Lemon essential oil microemulsion at 1/2 MIC concentration reduced the environmental pH value at different glucose concentrations, compared to those observed in the control group (p < 0.05). LDH activity of S. mutans was decreased at three subinhibitory concentrations of lemon essential oil microemulsions (p < 0.05). The effect of lemon essential oil microemulsions on S. mutans LDH activity and bacterial acid production were positively correlated (r = 0.825, p < 0.05). Lemon essential oil microemulsion at 1/2 MIC concentration downregulated the expression of the ldh gene of S. mutans at different glucose concentrations (p < 0.05). In different glucose environments, lemon essential oil microemulsions at subminimum inhibitory concentrations can inhibit the acid production of S. mutans by reducing ldh expression and LDH activity in the glycolytic pathway, proving its anti-caries potential. CONCLUSIONS: LEOM can effectively prevent dental caries and maintain the microecological balance of the oral environment.

Growth Inhibitory and Pro-Apoptotic Effects of Hirsuteine in Chronic Myeloid Leukemia Cells through Targeting Sphingosine Kinase 1.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

Early detect left ventricular subclinical myocardial dysfunction in patients with systemic lupus erythematosus by a left ventricular pressure-strain loop.

OBJECTIVE: Noninvasive myocardial work (MW) is a new technology which is based on strain after considering the load influence on myocardial deformation. We aimed to investigate the feasibility of quantitatively assessing left ventricular myocardial work (LVMW) in patients with systemic lupus erythematosus (SLE) using a left ventricular pressure-strain loop (LVPSL). METHODS: 76 patients with SLE were included in the study (A), further divided into two subgroups according to the presence of lupus nephritis (LN). Global longitudinal strain (GLS), peak strain dispersion (PSD), global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained. RESULTS: 1: Patients with SLE demonstrated a significantly reduced GWE and GLS compared with control group, GWW and PSD were increased, above changes were more pronounced in patients with LN. There was no significant difference in GWI and GCW. 2: Receiver operating characteristic (ROC) analysis demonstrated that GWE was the most powerful tool for detecting myocardial insufficiency early in SLE patients, and the area under the curve (AUC) was 0.804, and was superior to GLS (AUC = 0.707). GWE remains the best indicator of subclinical myocardial injury in patients with LN. The AUC was 0.910, and the best cutoff point was 96.5% (sensitivity 83.3%, specificity 73.3%). CONCLUSIONS: LVPSL can be used to noninvasively assess changes in MW in patients with SLE. Noninvasive GWE is a more sensitive index than GLS to detect subclinical myocardial injury early in SLE patients. This is a potential valuable clinical tool to assist in the early-find myocardial damage.

[Effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum GH and PG in chronic atrophic gastritis rats].

OBJECTIVE: To observe the effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum growth hormone (GH) and pepsinogen (PG) in chronic atrophic gastritis (CAG) rats, and to explore the potential mechanism of heat-sensitive moxibustion for CAG. METHODS: A total of 66 male SD rats were randomized into a blank group (12 rats) and a model establishment group (54 rats). No intervention was given in the blank group. Rats in the model establishment group were intervented with compound pathogeny method for 12 weeks to establish CAG model, which were further divided into a model group (11 rats), a vitacoenzyme group (11 rats) and a moxibustion group (22 rats). In the moxibustion group, suspending moxibustion was applied at "Zhongwan" (CV 12) for 40 min. After the intervention of moxibustion, 0.9% sodium chloride solution was given by gavage (2 mL·kg-1·d-1). According to the changes of tail temperature, rats in the moxibustion group were divided into a heat-sensitive moxibustion group (11 rats) and a non-heat-sensitive moxibustion group (8 rats). The vitacoenzyme group was given vitacoenzyme as the same dose by gavage. The intervention was adopted once a day for 28 days. Changes of body weight were observed among the groups. Expressions of serum GH, PGⅠand PGⅡwere detected by ELISA, and the ratio of PGⅠand PGⅡ (PGR) was calculated. The morphological changes of gastric mucosa were observed by macroscopy and light microscope. RESULTS: ①After modeling, the body weight of rats in the model establishment group was lower than the blank group (P<0.01). Compared with the model group, the body weight of rats in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group was increased after intervention (P<0.05), and there were no significant differences among the intervention groups (P>0.05). ②Under macroscopy and light microscope, gastric tissue of rats after modeling showed dark red and pale gastric mucosa, lower plica and mucosal congestion. The glands of lamina propria were atrophied or disappeared with sparse and disordered arrangement, in which, lymphoid follicles and inflammatory cells could be observed. After intervention, morphology of gastric mucosa was improved in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group. ③Compared with the blank group, the serum levels of GH, PGⅠ, PGⅡ and PGR were decreased in the model group (P<0.05, P<0.01). Compared with the model group, the serum levels of GH, PGⅠand PGⅡwere increased in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group (P<0.05, P<0.01), the levels of PGR were increased without statistical difference (P>0.05). Compared with the vitacoenzyme group and the non-heat-sensitive moxibustion group, the serum levels of GH and PGⅠwere increased in the heat-sensitive moxibustion group (P<0.05). CONCLUSION: Heat-sensitive moxibustion at "Zhongwan" (CV 12) can improve the morphology of gastric mucosa in chronic atrophic gastritis rats, its mechanism may be related to the up-regulation of serum GH and PGⅠ.

Prospective Study About the Relationship Between CEUS of Carotid Intraplaque Neovascularization and Ischemic Stroke in TIA Patients.

Objective: To evaluate the relationship between contrast-enhanced ultrasonography (CEUS) of carotid intraplaque neovascularization and ischemic stroke in transient ischemic attack (TIA) patients. Methods: A total of 112 TIA patients were selected for the study. Routine carotid ultrasonic examination was performed for all the patients. CEUS was carried out for consecutive patients with plaque thicker than 2.5 mm in carotid bifurcation and follow-up for at least 24 months. The number of patients with incurrence of ischemic stroke or recurrence of TIA was obtained during the follow-up period. To detect the risk factors for incurrence of ischemic stroke or recurrence of TIA in 24 months, multivariate logistic regression analyses were performed for all the risk factors in all the selected patients. Results: Ninety-one patients underwent CEUS and were followed up at least 24 months. There were statistical differences between recurrent and non-recurrent groups about hypertension, diabetes, hyperlipemia, smoking history, family history of stroke, medication compliance, two-dimensional ultrasound, and CEUS (P < 0.05). The higher CEUS intensity in the carotid plaque was, the higher was the possibility of ischemic stroke or recurrent TIA. Multivariate logistic regression analysis showed that the CEUS characteristics of carotid plaque such as linear enhancement or diffuse enhancement were independent risk factors for ischemic stroke or recurrent TIA in TIA patients (P < 0.05). Conclusion: For carotid plaques, CEUS could evaluate the infusion mode, which could reflect the neovascularization in plaques. CEUS could predict the incurrence of ischemic stroke or recurrence of TIA in TIA patients, which is useful information when making a clinical decision.

In vitro and in vivo evaluation of chitosan scaffolds combined with simvastatin-loaded nanoparticles for guided bone regeneration.

The objective of this study was to fabricate and characterize chitosan combined with different amounts of simvastatin-loaded nanoparticles and to investigate their potential for guided bone regeneration in vitro and in vivo. Different SIM-CSN formulations were combined into a chitosan scaffold (SIM-CSNs-S), and the morphology, simvastatin release profile, and effect on cell proliferation and differentiation were investigated. For in vivo experiments, ectopic osteogenesis and the critical-size cranial defect model in SD rats were chosen to evaluate bone regeneration potential. All three SIM-CSNs-S formulations had a porous structure and exhibited sustained simvastatin release. CSNs-S showed excellent degradation and biocompatibility characteristics. The 4 mg SIM-CSNs-S formulation stimulated higher BMSC ALP activity levels, demonstrated significantly earlier collagen enhancement, and led to faster bone regeneration than the other formulations. SIM-CSNs-S should have a significant effect on bone regeneration.

Mutant monocyte chemoattractant protein-1 protein (7ND) inhibits osteoclast differentiation and reduces oral squamous carcinoma cell bone invasion.

The seven-amino acid truncated (7ND) protein is an N-terminal deletion mutant of monocyte chemoattractant protein-1 (MCP-1) and it functions as a dominant-negative inhibitor. 7ND and wild-type MCP-1 form a heterodimer, which binds to MCP-1 receptors and inhibits monocyte chemotaxis. In the present study, the 7ND protein was cloned, expressed and purified. An MTT assay revealed that the proliferation of oral squamous cell carcinoma (OSCC) SCC25 cells was not affected following 3 days of treatment with synthetic 7ND protein. Serial dilutions of the 7ND protein were tested for monocyte migration and osteoclast differentiation, and tartrate-resistant acid phosphatase staining demonstrated that significantly fewer osteoclasts were differentiated from cluster of differentiation 14+ (CD14+) monocytes using magnetic activated cell sorting. Immunofluorescence confirmed these results and significantly less F-actin staining was observed in 7ND-treated osteoclasts. Furthermore, bone invasion was examined by subcutaneously injecting SCC25 cells into the area overlaying the calvariae of nude mice. The results demonstrated that the average tumor volume of SCC25 cells with 7ND protein was similar to the average volume of tumors formed by untreated SCC25 cells. Flow cytometric analysis suggested that the CD14+ subpopulation in the bone marrow of 7ND-treated mice was reduced compared with that of untreated mice. Micro-computed tomography imaging revealed significantly less bone resorption in the calvariae injected with SCC25 cells plus the 7ND protein. Taken together, the results of the present study demonstrated the potential therapeutic value of the 7ND protein. The 7ND MCP-1 variant not only functions in vitro to inhibit osteoclast differentiation, but also reduces the progression of bone invasion by OSCC cells in vivo.

Critical Care Resources in Guangdong Province of China: Three Surveys from 2005 to 2015.

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.

[The effect of GDNF on matrix-degrading and cell-adhesion during perineural invasion of salivary adenoid cystic carcinoma].

PURPOSE: To investigate the possible contribution of GDNF in matrix-degrading, cell-adhesion during perineural invasion (PNI) of salivary adenoid cystic carcinoma (ACC). METHODS: Totally 42 ACCs and 5 normal salivary tissues were included in the present study．Immunohistochemical staining SP method was used to detect the expression of GDNF,MMP-9,NF-κB,integrin ß1 in ACC specimens and normal salivary tissues. Statistical analysis was performed using SPSS16.0 software package. RESULTS：GDNF was strongly expressed in ACC tumor cells and nerve fibers adjacent to ACC tumor cells. NF-κB, MMP-9, integrin ß1 were positively expressed in ACC cell cytoplasm, integrin ß1 was also found in ACC cell membrane, and NF-κB in nuclei occasionally. The positive expression rate was 69.05%（29/42）,66.67%（28/42）,61.90%（26/42）, respectively. The differences between the expression of NF-κB, MMP-9, integrinß1 in PNI group and non-PNI group were significant (P=0.005,P=0.011,P=0.001, respectively). Expression of NF-κB, MMP-9, integrin ß1 was correlated to that of GDNF(r=0.443, P=0.003; r=0.401, P=0.009; r=0.535, P=0.000, respectively). Expression of MMP-9 and integrin ß1 was positively correlated to that of NF-κB(r=0.501, P=0.001; r=0.429, P=0.005). Expression of MMP-9 was correlated positively to that of integrin ß1 (r=0.381, P=0.013). CONCLUSIONS：GDNF may increase the matrix-degrading and cell-adhesion of ACC in the process of PNI. NF-κB, MMP-9 and integrin ß1 involve in ACC cells invading nerves.

[Effect of nerve growth factor on adhesion and motional abilities of tumor cells and their correlation].

OBJECTIVE: To investigate the effect on adhesion and motion capbilities of adenoid cystic carcinoma (ACC), by detecting the expression of nerve growth factor (NGF), E-cadherin (E-cad) and S100A4 and the clinical significance in ACC tissues and analyzing the relationships between them with perineural invasion (PNI). METHODS: The expression of NGF, E-cad and S100A4 in ACC was detected with the way of immunohistochemistry SP, and then analyzing the expression level of them in different pathological types and histological regions in statistical ways on the basis of their relation with clinical and pathological parameters. RESULTS: The expression of NGF and S100A4 in PNI group [88% (23/26) and 77% (20/26)], was higher than that in NPNI group (8/16 and 7/16, P < 0.05), and a positive correlation between them was identified in PNI group (r = 0.316, P < 0.05). However the E-cad expression was lower in PNI group [31% (8/26), P < 0.05]. On the other hand it suggested a negative correlation with NGF (r = 0.385, P < 0.05) as well as that with S100A4 (r = -0.612, P = 0.000). The expression level of NGF in fasciculus [83% (25/30)] has significant deviation compared with it in distant tumor tissues [47% (14/30), P < 0.05]. CONCLUSIONS: In the PNI process of ACC, NGF plays important parts but not the only factor. It can increase the expression and activity of S100A4 but decrease E-cad expression through binding with its receptor. Thus, adhesion abilities of tumor cells was weakened and motional abilities was strengthen.