Deep learning using contrast-enhanced ultrasound images to predict the nuclear grade of clear cell renal cell carcinoma.

PURPOSE: To assess the effectiveness of a deep learning model using contrastenhanced ultrasound (CEUS) images in distinguishing between low-grade (grade I and II) and high-grade (grade III and IV) clear cell renal cell carcinoma (ccRCC). METHODS: A retrospective study was conducted using CEUS images of 177 Fuhrmangraded ccRCCs (93 low-grade and 84 high-grade) from May 2017 to December 2020. A total of 6412 CEUS images were captured from the videos and normalized for subsequent analysis. A deep learning model using the RepVGG architecture was proposed to differentiate between low-grade and high-grade ccRCC. The model's performance was evaluated based on sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC). Class activation mapping (CAM) was used to visualize the specific areas that contribute to the model's predictions. RESULTS: For discriminating high-grade ccRCC from low-grade, the deep learning model achieved a sensitivity of 74.8%, specificity of 79.1%, accuracy of 77.0%, and an AUC of 0.852 in the test set. CONCLUSION: The deep learning model based on CEUS images can accurately differentiate between low-grade and high-grade ccRCC in a non-invasive manner.

Uncoupling of the center-to-periphery arterial stiffness gradient and pulse pressure amplification in viral pneumonia infection.

OBJECTIVES: Arterial stiffness is a common manifestation of viral pneumonia infections, including COVID-19. Nevertheless, the relationship between the center-to-periphery arterial stiffness gradient and pulse pressure amplification (PPA) in infectious diseases remains unclear. This study aimed to investigate this relationship utilizing arterial pressure volume index (API) and arterial velocity pulse index (AVI) ratio. METHODS: API/AVI and PPA were measured in 219 participants with COVID-19 and 374 normal participants. Multiple linear regression was used to assess the association of API/AVI and PPA, and restricted cubic spline was used to investigate the non-linear relationship between API/AVI and PPA. Receiver operating characteristic curve (ROC) analysis was used to evaluate the effects of API/AVI in identifying COVID-19 infection and severe stage. RESULTS: There was a significant J-shaped relationship between API/AVI and PPA in COVID-19 group, while a M-shaped relationship was observed in normal group. API/AVI decreased rapidly as PPA decreased until API/AVI decreased slowly at PPA of 1.07, and then API/AVI decreased slowly again at PPA of 0.78. ROC results showed that API/AVI demonstrated excellent accuracy in identifying COVID-19 infection (AUC = 0.781) and a high specificity (84.88%) in identifying severe stage. CONCLUSIONS: There was a J-shaped association between the API/AVI and PPA in viral infected patients, while a M-shaped relationship in the normal participants. API/AVI is better for identifying infected and uninfected patients, with a high specificity in identifying those in severe stages of the disease. The attenuation or reversal of API/AVI may be associated with the loss of PPA coupling.

Increased arterial pressure volume index and cardiovascular risk score in China.

BACKGROUND AND OBJECTIVE: The new non-invasive arterial stiffness indices, arterial pressure volume index (API) is explored as a novel marker of residual stress in the wall of the peripheral muscular arteries at zero-stress state in clinical settings. The present study aimed to study the association of API with cardiovascular disease (CVD) risk in China (China-PAR). METHODS: According to China-PAR score, participants were divided into three groups: low risk (< 5%), medium risk (5-9.9%), and high risk (≥ 10.0%). API ≥ 31 was defined as high API, and the incidences of high API were compared. Logistic regression models were used to analyze the risk factors of high API and high risk China-PAR categories. The association between China-PAR and API was analyzed by restrictive cubic spline. RESULTS: The study included 4311 participants. After adjustments for confounding factors, high API was independent factor associated with high risk China-PAR categories, and the probability of high API was 1.366 times higher than that in normal API subjects. While, the independent factors associated with high API were BMI, blood pressure and heart rate. Furthermore, API had a significant U-shaped association with China-PAR. CVD risk was lowest with API of 19 units, the fastest increase at 26 units and the flattest starting point at 59 units. CONCLUSION: API, an indicator of arterial stiffness and residual stress, had a U-shaped association with China-PAR score and might play an important role in predicting CVD risk in Chinese natural populations.

Evaluation of whole axillary status with lymphatic contrast-enhanced ultrasound in patients with breast cancer.

OBJECTIVES: This study aims to evaluate the whole axillary status of patients with breast cancer by lymphatic contrast-enhanced ultrasound (LCEUS). METHODS: LCEUS was applied for 169 patients with suspected breast cancer. Abnormal patterns in lymphatic channels, sentinel lymph nodes (SLNs), and non-enhanced but abnormal lymph nodes were investigated. The signs of distorted, attenuated, netted, or interrupted lymphatic channels, defective-filling or no-filling SLNs, and the appearance of non-enhanced but abnormal lymph nodes were designated as features of axillary metastasis. A positive outcome was given when any of the abnormal patterns was found in the LCEUS. The diagnostic efficiencies were calculated to differentiate the axillary lymphatic status using LCEUS for the whole axilla, compared with conventional ultrasound (US) and LCEUS for SLNs. RESULTS: The LCEUS procedure was successfully performed for 157 breast cancer patients with axillary dissection. Compared to normal axillae, abnormal patterns had a significantly higher frequency in metastatic axillae (p = 0.000). Using conventional US to evaluate the whole axillae, the diagnostic sensitivity, specificity, and accuracy were 69.1%, 71.9%, and 70.7%, respectively. When LCEUS was used for SLN evaluation to predict the whole axilla, the diagnostic sensitivity, specificity, and accuracy were 66.2%, 89.9%, and 79.6%, respectively. When LCEUS was used as the whole axillary evaluation method, the diagnostic sensitivity, specificity, and accuracy were 76.5%, 86.5%, and 82.2%, respectively. CONCLUSION: LCEUS can be an accurate method to observe the whole axillae in breast cancer patients. Lymphatic channels, SLNs, and non-enhanced but abnormal lymph nodes constitute the LCEUS for whole axillary evaluation. KEY POINTS: • LCEUS can be an accurate method to observe the whole axillae in breast cancer patients. • Three aspects in the LCEUS for whole axillary evaluation are the lymphatic channels, sentinel lymph nodes (SLNs), and non-enhanced but abnormal lymph nodes. • Signs of distorted, attenuated, netted, or interrupted lymphatic channels, defective-filling or no-filling SLNs, and the appearance of non-enhanced but abnormal lymph nodes were considered as features of axillary metastasis.

Role of Platelet-Derived Growth Factor on the Fibrosis Process in Thyroid Carcinoma: Evaluation by Shear Wave Elastography.

OBJECTIVES: We aimed to determine the correlation between fibrosis and elastic values in papillary thyroid carcinoma (PTC) by shear wave elastography and to evaluate the effect of platelet-derived growth factor (PDGF) on the fibrosis process. METHODS: Small interfering RNA (siRNA)-PDGF and normal BCPAP cell lines were injected subcutaneously into the backs of nude mice. The elastic values of all tumors were measured by shear wave elastography. The content of collagen fibers and the expression of PDGF and type IV collagen (COL4) were evaluated by Masson staining and western blotting. RESULTS: There were 32 tumors in the control group and 30 tumors in the siRNA-PDGF group. The tumors were divided into 4 subgroups based on maximum diameters of the tumors. The mean elastic values ± SD (Emean , 29.79 ± 11.04 kPa; Emin , 16.98 ± 7.51 kPa, Emax , 39.99 ± 15.30 kPa; and SD, 5.92 ± 2.00 kPa) in the siRNA-PDGF group were lower than in the control group (Emean , 35.73 ± 18.49 kPa; Emin , 23.65 ± 14.92 kPa, Emax , 45.73 ± 22.88 kPa; and SD, 6.02 ± 3.38 kPa). The content of collagen fibers and the expression of platelet-derived growth factor B (PDGFB) and COL4 proteins in the siRNA-PDGF group were lower than in the control group (11.43% ± 6.99% and 19.80% ± 11.70%; P = .010; 0.14 ± 0.06 and 0.27 ± 0.10; P = .002; and 0.11 ± 0.06 and 0.15 ± 0.07; P = .101). The elastic values, collagen fiber content, and PDGFB and COL4 in the 4 subgroups gradually increased with the maximum diameter of tumors. CONCLUSIONS: There was a positive correlation among PDGF, tumor stiffness, and fibrosis in the growth of PTC. Thus, PDGF might play an important role in the development of PTC.

Quantifying Levator Ani Muscle Elasticity Under Normal and Prolapse Conditions by Shear Wave Elastography: A Preliminary Study.

OBJECTIVES: The primary purpose of this study was to determine whether elasticity quantification of the levator ani muscle (LAM) using shear wave elastography (SWE) is different between women with and without pelvic organ prolapse (POP) and to determine whether LAM elasticity is associated with the prolapse stage or the dimensions of the levator hiatus. The secondary aim was to evaluate the intraobserver and interobserver reliability of LAM elasticity measurements using SWE. METHODS: The study participants included 20 women with normal pelvic support and 38 women with prolapse (stages I-III). The levator hiatus was imaged by transperineal 3-dimensional ultrasound, and LAM elasticity and the elastic modulus were measured by SWE at rest and while performing the Valsalva maneuver. RESULTS: The elastic modulus increased significantly from rest to during to maximal Valsalva maneuver (29.2 versus 54.1 kPa; P < .05) in all women. Levator ani muscle elasticity was significantly higher under prolapse conditions than under normal conditions at rest (27.9 versus 31 kPa; P < .001) but was lower during the maximal Valsalva maneuver than under normal conditions (57.3 versus 53.1 kPa; P < .05). Levator ani muscle elasticity at rest was associated with the hiatus area during the Valsalva maneuver (Spearman r = 0.608; P < .001) and distensibility of the levator hiatus (r = 0.594; P < .001), and the hiatus area decreased as the LAM elastic modulus increased during the maximal Valsalva maneuver (r = -0.414; P < .05). Moreover, LAM elasticity was associated with the severity of prolapse (P < .001). CONCLUSIONS: As a noninvasive quantitative method, SWE, may be used to assess the biomechanical properties of the pelvic floor muscle, providing some research basis for a thorough understanding of POP and its treatment and prevention.

Role of Ultrasound in the Detection of Rotator-Cuff Syndrome: An Observational Study.

BACKGROUND Physical tests are usually preferred to assess rotator-cuff syndrome but are insufficient to predict the morphology and size of the rotator-cuff. The objective of the study was to rate the ultrasound findings for patients with sudden shoulder pain and to determine potential predictors of the same. MATERIAL AND METHODS A total of 112 patients with sudden shoulder pain with rotator-cuff syndrome, suspected by orthopedic doctors, were subjected to ultrasonography. Real-time ultrasonography was done for the acromioclavicular joint, biceps, infraspinatus, posterior labrum, subscapularis, supraspinatus, teres minor tendon, and the sub-acromial-subdeltoid bursa. Each tendon was assessed via scanning planes in orientation as per longer and shorter axis, and from their myotendinous junction shoulder to bony insertions. Linear and logistic regression analysis were performed to predict the associations of medical history with rotator-cuff injury. RESULTS Ultrasonography identified that 82% of the enrolled patients had at least one particular cause of the rotator-cuff disorder. Among the rotator-cuff disorders, calcific tendonitis (54%) was observed more frequently followed by tendinopathy (32%), subacromial-subdeltoid bursitis (22%), and partial thickness tear (21%). Also, 46 patients (41%) had multiple findings. Older age (older than 40 years) was a strong predicting factor of rotator-cuff disorder (r²=0.36, P=0.0004). CONCLUSIONS Ultrasonography is a vital diagnostic procedure used by orthopedic surgeons for diagnosis of the rotator-cuff disorder(s) in patients with sudden shoulder pain.

Ultrasound assessment of tensile stress in carotid arteries of healthy human subjects with varying age.

BACKGROUND: Arterial remodeling is thought to reflect the adaptation of the vessel wall to mechanical and hemodynamic stimuli and contributes to the progression of cardiovascular and cerebrovascular diseases. Tensile stress (TS) is one of the mechanical properties of the artery wall. The purpose of this study was to investigate the tensile stress change (TS) of carotid artery with varying viscoelasticity in healthy subjects within two groups of different ages. METHODS: Forty-five subjects were recruited and randomly assigned into the group at the age above 50 years and below 50 years. The carotid arteries were examined by ultrasonography, using the techniques of shear wave elastography (SWE), shear wave dispersion (SWD) and radiofrequency (RF) -based ultrasound. The following values, including elastic modulus (SWER) and viscous index (SWDR), as well as the peak and mean TS of the left and right carotid arteries (L-PTS, R-PTS, L-MTS and R-MTS) were measured. The correlations between SWER, SWDR and tensile stress were evaluated. RESULTS: The SWER and SWDR of carotid arteries are lower in the subjects ≥50 years old than the subjects younger than 50 years (SWER, 10.29 ± 9.57 kPa VS 17.24 ± 14.07 kPa; SWDR, 11.99 ± 3.51 (m/s)/kHz VS 13.97 ± 3.71 (m/s)/kHz, P < 0.05). The R-PTS was lower in the group with younger age (P < 0.05). Pearson correlation analysis showed that SWER of carotid artery was positively correlated with the parameters of tensile stress, R-PTS, R-MTS, L-PTS and L-MTS(r = 0.218, r = 0.359, r = 0.209 and r = 0.369, respectively, P < 0.05). However, SWDR of carotid arteries was not significantly associated with TS. CONCLUSION: Ultrasonic shear wave imaging could be used to quantitatively assess carotid viscoelasticity. The carotid TS was related to its elasticity while little related to its viscosity, suggesting that mechanical properties of the arterial wall might be better revealed. TRIAL REGISTRATION: Date of our trial registration: 2018-06-11. Registered with the official website of China Clinical Trial Registration Center (ChiCTR1800016590).

Relation between carotid vulnerable plaques and peripheral leukocyte: a case-control study of comparison utilizing multi-parametric contrast-enhanced ultrasound.

BACKGROUND: This study evaluates carotid vulnerable plaques using contrast-enhanced ultrasound (CEUS) and explores the relationship between vulnerable plaques and leukocytes. METHODS: Sixty-two symptomatic and 54 asymptomatic patients underwent CEUS. The images were analyzed using time-intensity and fitting curves, and peak (PTIC), mean (MTIC), peak (PFC), sharpness (SFC), and area under the curve (AUCFC) were obtained. The relations between CEUS parameters and leukocytes were analyzed. RESULTS: In the symptomatic group, total leukocytes and neutrophils were higher, while lymphocyte was decreased; PTIC, MTIC, PFC, SFC, and AUCFC were significantly higher; MTIC and AUCFC were negatively correlated with lymphocytes, and MTIC was positively correlated with neutrophils. Classification and regression tree analysis showed that MTIC at a cutoff of 20.8 and AUCFC at a cutoff of 8.8 resulted in a predictive of acute cerebral infarction, accuracy of 84.3%, sensitivity of 87.1%, and specificity of 81.5%. CONCLUSIONS: The variation in the perivascular leucocyte is significantly related to intraplaque inflammatory activities, CEUS is a feasible monitor of intraplaque neovascularization, so CEUS combined with perivascular leucocyte could be helpful as a warning for vulnerable plaques.

Value of Contrast-Enhanced Ultrasound in the Diagnosis of Renal Cancer and in Comparison With Contrast-Enhanced Computed Tomography: A Meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in renal cancer and to compare it with contrast-enhanced computed tomography (CECT). METHODS: A systematic search was performed to recruit eligible original studies published until December 2017. Two reviewers independently extracted data. A meta-analysis was performed, and the pooled sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, diagnostic odds ratio, summary receiver operating characteristic curve, and area under the curve were calculated. The extent and potential sources of heterogeneity were further explored. Moreover, a head-to-head comparison was also performed to compare the diagnostic value between CEUS and CECT in renal cancer. RESULTS: Twenty-two studies were included in this meta-analysis. The summary sensitivity and specificity of CEUS for detecting renal cancer were 0.96 (95% confidence interval [CI], 0.94-0.97) and 0.82 (95% CI, 0.74-0.88), respectively. The summary diagnostic odds ratio was 102.04 (95% CI, 49.55-210.13). The area under the summary receiver operating characteristic curve was 0.97 (95% CI, 0.95-0.98). In the head-to-head comparison, CEUS showed higher diagnostic sensitivity than CECT (0.94 versus 0.85) for renal cancer, whereas the specificities were comparable between CEUS and CECT (0.77 versus 0.75). CONCLUSIONS: Contrast-enhanced US has high sensitivity and moderate specificity in the differential diagnosis of renal cancer. The diagnostic sensitivity of CEUS in renal cancer was higher than that of CECT, suggesting that CEUS could be used as a preferred diagnostic tool for renal cancer.

[Prevalence of urogenital tract infections with Ureaplasma urealyticum or HPV among men of reproductive age and the associated factors].

OBJECTIVE: To investigate the prevalence of urogenital tract infections with Ureaplasma urealyticum (UU) and human papilloma virus (HPV) in males of reproductive age and the associated factors. METHODS: Using the multi-stage cluster sampling method and a structured questionnaire, we conducted an investigation among 18－50 years old males in Songjiang District, Shanghai, from August 2016 to July 2018. We collected secretory specimens from the urogenital tract of the subjects and detected the infections of UU and HPV by laboratory examination. RESULTS: Among the 621 males included in this study, 279 (44.93%) were found infected with UU, 18 (2.90%) with HPV, and 15 (2.42%) with both UU and HPV. Univariate analysis showed that smokers had a higher rate of UU infection (50.54% ［140/277］) than non-smokers (40.41 ［139/344］), and those with senior high school or secondary technical school education had a higher rate of HPV infection (4.84% ［12/248］) than others (1.61% ［6/373］). Binary stepwise logistic regression analysis revealed a higher risk of UU infection in the subjects with junior high school or lower education than in others (OR = 0.61, 95% CI: 0.39－0.96) as well as in smokers than in non-smokers (OR = 1.46, 95% CI: 1.01－2.01). CONCLUSIONS: The prevalence of UU infection is high, while that of HPV is low among men of reproductive age in Songjiang, Shanghai. The screening of UU infection should be enhanced among men of reproductive age, especially among smokers and those with lower education.

A Microfluidic Chip Integrated with Hyaluronic Acid-Functionalized Electrospun Chitosan Nanofibers for Specific Capture and Nondestructive Release of CD44-Overexpressing Circulating Tumor Cells.

Detection of circulating tumor cells (CTCs) in peripheral blood is of paramount significance for early-stage cancer diagnosis, estimation of cancer development, and individualized cancer therapy. Herein, we report the development of hyaluronic acid (HA)-functionalized electrospun chitosan nanofiber (CNF)-integrated microfludic platform for highly specific capture and nondestructive release of CTCs. First, electrospun CNFs were formed and modified with zwitterion of carboxyl betaine acrylamide (CBAA) via Michael addition reaction and then targeting ligand HA through a disulfide bond. We show that the formed nanofibers still maintain the smooth fibrous morphology after sequential surface modifications, have a good hemocompatibility, and exhibit an excellent antifouling property due to the CBAA modification. After being embedded within a microfluidic chip, the fibrous mat can capture cancer cells (A549, a human lung cancer cell line) with an efficiency of 91% at a flow rate of 1.0 mL/h. Additionally, intact release of cancer cells is able to be achieved after treatment with glutathione for 40 min to have a release efficiency of 90%. Clinical applications show that 9 of 10 nonsmall-cell lung cancer patients and 5 of 5 breast cancer patients are diagnosed to have CTCs (1 to 18 CTCs per mL of blood). Our results suggest that the developed microfluidic system integrated with functionalized CNF mats may be employed for effective CTCs capture for clinical diagnosis of cancer.

Use of atropine in four-dimensional hysterosalpingo-contrast sonography: Does it suppress pain during infertility examination?

This study aimed to ascertain if atropine is useful for suppressing the pain suffered during four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) when assessing infertility in women. A total of 252 patients were divided into 2 groups to receive or not receive atropine (0.5 mg) injection 30 minutes before 4D-HyCoSy. Pain was evaluated using a numerical rating scale (NRS): during 4D-HyCoSy; upon 2-dimensional transvaginal sonography; before catheter insertion; upon insertion and fixation of the catheter into the uterine cavity; 30 minutes after 4D-HyCoSy. According to the degree of patency of Fallopian tubes, the 6 patterns observed were integrated further into 3 patient groups: all-negative (both Fallopian tubes were negative), positive-and-negative (one Fallopian tube showed patency and the other showed stenosis or non-patency), and all-positive (both Fallopian tubes showed stenosis or non-patency). We compared the NRS scores and prevalence of side-effects other than pain between the atropine-injection and non-atropine-injection groups within the three groups mentioned above. The NRS score showed no significant differences among the groups at any time point (all P > .05). The different prevalence of side-effects other than pain was significant between the atropine-injection and atropine-non-injection groups (P = .012). These data suggest that atropine does not reduce pain in patients during 4D-HyCoSy. However, atropine may reduce the prevalence of other side-effects during 4D-HyCoSy, which needs a further, large, prospective, multi-cohort study to verify.

An improvement of carotid intima-media thickness and pulse wave velocity in renal transplant recipients.

BACKGROUND: Renal transplantation can significantly improve the quality of life of patients with end stage renal disease (ESRD) who would otherwise require dialysis. Renal transplant (RT) recipients have higher risks of cardiovascular disease compared with general population. The carotid intima-media thickness (CIMT) and pulse wave velocity (PWV) have been used as the important predicting factor of vascular arteriosclerosis. Therefore, this study was to investigate the improvement of carotid intima-media thickness and pulse wave velocity in renal transplant recipients. METHODS: Thirty-one patients with chronic kidney disease being treated with hemodialysis, 31 renal transplant recipients and 84 healthy control subjects were included to have the clinical evaluations and ultrasonography of bilateral carotid arteries. CIMT and PWV were independently measured by two ultrasonographers using the technique of ultrasonic radiofrequency tracking and correlated with arteriosclerosis risk factors. The progression of CIMT and PWV with age were analyzed by linear regression models, and the slopes of curves were compared using Z test. RESULTS: Compared with the patients on hemodialysis, the CIMT was significantly lower in renal transplant recipients and healthy control. The PWV were higher in hemodialysis patients and renal transplant recipients than that of the subjects in control group. The progression is CIMT positively corelated with age and cumulative duration in renal transplant recipients and hemodialysis patients. In both hemodialysis patients and renal transplant recipients, age and cumulative time on dialysis were all positively correlated with the increase of PWV as well. CONCLUSIONS: Carotid intima-media thickness and pulse wave velocity is the predicting factors of developing arteriosclerosis, which were improved in renal transplant recipients.

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a promising drug delivery system to enhance the therapeutic effects of these chemotherapeutics at the cellular level.

Periostin promotes the chemotherapy resistance to gemcitabine in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths. The nucleoside analog gemcitabine has been the cornerstone of adjuvant chemotherapy in PDAC for decades. However, gemcitabine resistance develops within weeks of chemotherapy initiation, which might be intrinsic to cancer cells and influenced by tumor microenvironment. Recently, pancreatic stellate cells (PSCs) have greatly increased our attention on tumor microenvironment-mediated drug resistance. Periostin is exclusively overexpressed in PSCs and the stroma of PDAC creating a tumor-supportive microenvironment in the pancreas. However, whether periostin contributed to chemoresistance in PDAC remains unknown. Therefore, we focused on the role of periostin in PDAC by observing the effects of silencing this gene on gemcitabine resistance in vitro and in vivo aiming to explore the possible molecular mechanism. In this study, the pancreatic cancer cell (PCC) proliferation and apoptosis were assayed to investigate the sensitivity to gemcitabine after silencing periostin. We provide the evidence that periostin not only drives the carcinogenic process itself but also significantly associated with gemcitabine-induced apoptosis. These findings collectively indicated that periostin increases the chemoresistance to gemcitabine. Thus, targeting periostin might offer a new opportunity to overcome the gemcitabine resistance of PDAC.

Role of pancreatic stellate cells and periostin in pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and one of the five most lethal malignancies characterized by prominent desmoplastic reaction. Accumulating evidences indicate that tumor desmoplasia plays a pivotal role in PDAC progression, and it has been largely ignored until recent times. It has now been unequivocally shown that pancreatic stellate cells (PSCs) are the principal effector cells responsible for stroma production. Periostin, also known as osteoblast-specific factor 2, is a secretory protein and originally identified as an osteoblast-specific factor that expressed in periosteum. Periostin is exclusively produced by activated PSCs, and periostin overexpression presents in various malignant tumors and closely relates with disease progression. In addition, periostin has been suggested to stimulate pancreatic cancer cells proliferation and enhance their resistance to serum starvation and hypoxia. Therefore, the interplay between cancer cells and stromal cells plays a vital role in PDAC development. However, the function of periostin in pancreatic cancer development is controversial. This review summarizes existing knowledge about the role of PSCs in cancer stroma production, the interaction between PSCs and pancreatic cancer cells, tumor angiogenesis, and hypoxic microenvironment, with particular focus on the expression and function as well as signaling pathways of periostin in PDAC cells and PSCs.

Gender Differences in Ventricular-vascular Coupling Following Exercise.

OBJECTIVE: To study the differences of cardiovascular system between men and women in response to exercise stress. METHODS: Forty healthy youth were tested according to Bruce protocol of exercise stress. They were detected by ultrasonography during the rest, peak exercise, and recovery stages, respectively. The left ventricular diastolic elastance (Ed), effective arterial elastance (Ea), left ventricular end-systolic elatance (Ees), ventricular-vascular coupling index (VVI), and total stiffness index (TSI) were measured and calculated according to the formulas. The results of all stages were compared according to genders. RESULTS: All stages, the Ed, TSI, and VVI of women were higher than those of men, but the Ees was lower than that of men (all P<0.05); there was no significant difference in Ea between men and women. The Ed, Ees, Ea, and TSI were closely related with left ventricular oxygen consumption and heart function, and women showed more closely. Before and after exercise, the changes were different in Ed, Ees, Ea, TSI, and VVI (all P<0.05), and VVI changed least. CONCLUSIONS: Before and after exercise, the ventricular stiffness matched well with arterial stiffness and maintained within a narrow range. For women, the tolerance of exercise was lower than that of men.

The dual effect of ultrasound-targeted microbubble destruction in mediating recombinant adeno-associated virus delivery in renal cell carcinoma: transfection enhancement and tumor inhibition.

BACKGROUND: Recombinant adeno-associated virus (rAAV) is recognized as a promising vector for cancer gene therapy, although its low transfer efficiency in less permissive cells limits extensive application. Our previous studies reported that ultrasound-targeted microbubble (MB) destruction (UTMD) enhanced rAAV transfer in its permissive retinal cells. In the present study, we investigated whether UTMD increased rAAV transfer in less permissive human renal cell carcinoma (hRCC) cells and tumors. METHODS: hRCC cells were treated with rAAV2 under different conditions of UTMD, and the viral transfer efficiency and cell viability were analyzed. Fifty-two male nude mice (BALB/c) implanted with hRCC cells were randomly assigned to four groups consisting of rAAV, rAAV + ultrasound and rAAV + UTMD (20 µl and 40 µl of MBs). UTMD was initiated immediately after intratumoral viral injection, and viral transfer efficiency and tumor volumes were analyzed at 12 weeks after infection. RESULTS: The efficiency of non-augmented transfer of rAAV2 into hRCC cells was low (17.28 ± 2.44%). The use of UTMD enhanced viral transfer efficiency by two- to three-fold, and enhanced viral genomic DNA by more than nine-fold, without decreasing cell viability. In vivo studies also showed that UTMD increased rAAV2 transfer in tumor. The enhancements were maintained for a period of 12 weeks. Tumor growth in mice was inhibited by UTMD treatment, and UTMD treatment augmented by MBs (40 µl) produced an even stronger effect. CONCLUSIONS: UTMD enhanced rAAV2 transfer into less permissive RCC cells and tumors, resulting in inhibition of tumor growth, which suggests that UTMD may be a useful delivery tool for cancer gene therapy.