Sharp needle reconstructs peripheral outflow for patients with malfunctional arteriovenous fistula.

OBJECTIVE: To investigate the feasibility and efficacy of combining ultrasound-guided sharp needle technique with percutaneous transluminal angioplasty (PTA) for treating outflow stenosis or dysfunction in arteriovenous fistula (AVF) among hemodialysis patients. METHODS: From October 2021 to March 2023, patients with occluded or malfunctional fistula veins not amenable to regularly angioplasty were retrospectively enrolled in the study. They underwent ultrasound-guided sharp needle intervention followed by PTA. Data on the location and length between the two veins, technical success, clinical outcomes, and complications were collected. Patency rates post-angioplasty were calculated through Kaplan-Meier analysis. RESULTS: A total of 23 patients were included. The mean length of the reconstructed extraluminal segment was 3.18 cm. The sharp needle opening was performed on the basilic vein (60.9%), brachial vein (26.1%), or upper arm cephalic vein (13%) to create outflow channels. Postoperatively, all cases presented with mild subcutaneous hematomas around the tunneling site and minor diffuse bleeding. The immediate patency rate for the internal fistulas was 100%, with 3-month, 6-month, and 12-month patency rates at 91.3%, 78.3%, and 43.5%, respectively. CONCLUSION: Sharp needle technology merged with PTA presents an effective and secure minimally invasive method for reconstructing the outflow tract, offering a new solution for recanalizing high-pressure or occluded fistulas.

Semaphorins in tumor microenvironment: Biological mechanisms and therapeutic progress.

Hallmark features of the tumor microenvironment include immune cells, stromal cells, blood vessels, and extracellular matrix (ECM), providing a conducive environment for the growth and survival of tumors. Recent advances in the understanding of cancer biology have highlighted the functional role of semaphorins (SEMAs). SEMAs are a large and diverse family of widely expressed secreted and membrane-binding proteins, which were initially implicated in axon guidance and neural development. However, it is now clear that they are widely expressed beyond the nervous system and participate in regulating immune responses and cancer progression. In fact, accumulating evidence disclosed that different SEMAs can either stimulate or restrict tumor progression, some of which act as important regulators of tumor angiogenesis. Conversely, limited information is known about the functional relevance of SEMA signals in TME. In this setting, we systematically elaborate the role SEMAs and their major receptors played in characterized components of TME. Furthermore, we provide a convergent view of current SEMAs pharmacological progress in clinical treatment and also put forward their potential application value and clinical prospects in the future.

Echocardiographic assessment of pediatric heart transplantation: A single-center experience in China.

BACKGROUND: Pediatric heart transplant (HT) has become the standard of care for end-stage heart failure in children worldwide. Serial echocardiographic evaluations of graft anatomy and function during follow-up are crucial for post-HT management. However, evolution of cardiac structure and function after pediatric HT has not been well described, especially during first year post-HT. This study aimed to characterize the evolution of cardiac structure and function after pediatric HT and investigate the correlation between biventricular function with adverse clinical outcomes. METHODS: A single-center retrospective study of echocardiographic data obtained among 99 pediatric HT patients was conducted. Comprehensive echocardiographic examination was performed in all patients at 1-, 3-, 6-, 9- and 12-months post-HT. We obtained structural, functional and hemodynamic parameters from both left- and right-side heart, such as left ventricular stroke volume (LVSV), left ventricular ejection fraction (LVEF), right ventricular fractional area change (RVFAC), etc. The cardiac evolution of pediatric HT patients during first post-HT year was described and compared between different time points. We also explored the correlation between cardiac function and major adverse transplant events (MATEs). RESULTS: 1) Evolution of left heart parameters: left atrial length, mitral E velocity, E/A ratio, LVSV and LVEF significantly increased while mitral A velocity significantly decreased over the first year after HT (P < .05). Compared with 1 month after HT, interventricular septum (IVS) and left ventricular posterior wall (LVPW) decreased at 3 months but increased afterwards. (2) Evolution of right heart parameters: right ventricular base diameter and mid-diameter; right ventricular length diameter, tricuspid E velocity, E/A ratio, tricuspid annular velocity e' at free wall, and RVFAC increased, while tricuspid A velocity decreased over the first year after HT (P < .05). (3) Univariate logistic regression model suggests that biventricular function parameters at 1-year post-HT (LVEF, RVFAC, tricuspid annular plane systolic excursion and tricuspid lateral annular systolic velocity) were associated with MATEs. CONCLUSION: Gradual improvement of LV and RV function was seen in pediatric HT patients within the first year. Biventricular function parameters associated with MATEs. The results of this study pave way for designing larger and longer follow-up of this population, potentially aiming at using multiparameter echocardiographic prediction of adverse events.

Role of the tumor microenvironment in the lymphatic metastasis of cervical cancer (Review).

Lymphatic metastasis is the primary type of cervical cancer metastasis and is associated with an extremely poor prognosis in patients. The tumor microenvironment primarily includes cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, immune and inflammatory cells, and blood and lymphatic vascular networks, which can promote the establishment of lymphatic metastatic sites within immunosuppressive microenvironments or promote lymphatic metastasis by stimulating lymphangiogenesis and epithelial-mesenchymal transformation. As the most important feature of the tumor microenvironment, hypoxia plays an essential role in lymph node metastasis. In this review, the known mechanisms of hypoxia, and the involvement of stromal components and immune inflammatory cells in the tumor microenvironment of lymphatic metastasis of cervical cancer are discussed. Additionally, a summary of the clinical trials targeting the tumor microenvironment for the treatment of cervical cancer is provided, emphasizing the potential and challenges of immunotherapy.

Amplification of Plasma MicroRNAs for Non-invasive Early Detection of Acute Rejection after Heart Transplantation With Ultrasound-Targeted Microbubble Destruction.

OBJECTIVE: Acute rejection (AR) screening has always been the focus of patient management in the first several years after heart transplantation (HT). As potential biomarkers for the non-invasive diagnosis of AR, microRNAs (miRNAs) are limited by their low abundance and complex origin. Ultrasound-targeted microbubble destruction (UTMD) technique could temporarily alter vascular permeability through cavitation. We hypothesized that increasing the permeability of myocardial vessels might enhance the abundance of circulating AR-related miRNAs, thus enabling the non-invasive monitoring of AR. METHODS: The Evans blue assay was applied to determine efficient UTMD parameters. Blood biochemistry and echocardiographic indicators were used to ensure the safety of the UTMD. AR of the HT model was constructed using Brown-Norway and Lewis rats. Grafted hearts were sonicated with UTMD on postoperative day (POD) 3. The polymerase chain reaction was used to identify upregulated miRNA biomarkers in graft tissues and their relative amounts in the blood. RESULTS: Amounts of six kinds of plasma miRNA, including miR-142-3p, miR-181a-5p, miR-326-3p, miR-182, miR-155-5p and miR-223-3p, were 10.89 ± 1.36, 13.54 ± 2.15, 9.84 ± 0.70, 8.55 ± 2.00, 12.50 ± 3.96 and 11.02 ± 3.47 times higher in the UTMD group than those in the control group on POD 3. Plasma miRNA abundance in the allograft group without UTMD did not differ from that in the isograft group on POD 3. After FK506 treatment, no miRNAs increased in the plasma after UTMD. CONCLUSION: UTMD can promote the transfer of AR-related miRNAs from grafted heart tissue to the blood, allowing non-invasive early detection of AR.

Ultrasonic Microbubble Cavitation Deliver Gal-3 shRNA to Inhibit Myocardial Fibrosis after Myocardial Infarction.

Galectin-3 (Gal-3) participates in myocardial fibrosis (MF) in a variety of ways. Inhibiting the expression of Gal-3 can effectively interfere with MF. This study aimed to explore the value of Gal-3 short hairpin RNA (shRNA) transfection mediated by ultrasound-targeted microbubble destruction (UTMD) in anti-myocardial fibrosis and its mechanism. A rat model of myocardial infarction (MI) was established and randomly divided into control and Gal-3 shRNA/cationic microbubbles + ultrasound (Gal-3 shRNA/CMBs + US) groups. Echocardiography measured the left ventricular ejection fraction (LVEF) weekly, and the heart was harvested to analyze fibrosis, Gal-3, and collagen expression. LVEF in the Gal-3 shRNA/CMB + US group was improved compared with the control group. On day 21, the myocardial Gal-3 expression decreased in the Gal-3 shRNA/CMBs + US group. Furthermore, the proportion of the myocardial fibrosis area in the Gal-3 shRNA/CMBs + US group was 6.9 ± 0.41% lower than in the control group. After inhibition of Gal-3, there was a downregulation in collagen production (collagen I and III), and the ratio of Col I/Col III decreased. In conclusion, UTMD-mediated Gal-3 shRNA transfection can effectively silence the expression of Gal-3 in myocardial tissue, reduce myocardial fibrosis, and protect the cardiac ejection function.

Targeted microRNA delivery by lipid nanoparticles and gas vesicle-assisted ultrasound cavitation to treat heart transplant rejection.

Despite exquisite immune response modulation, the extensive application of microRNA therapy in treating heart transplant rejection is still impeded by poor stability and low target efficiency. Here we have developed a low-intensity pulsed ultrasound (LIPUS) cavitation-assisted genetic therapy after executing the heart transplantation (LIGHT) strategy, facilitating microRNA delivery to target tissues through the LIPUS cavitation of gas vesicles (GVs), a class of air-filled protein nanostructures. We prepared antagomir-155 encapsulated liposome nanoparticles to enhance the stability. Then the murine heterotopic transplantation model was established, and antagomir-155 was delivered to murine allografted hearts via the cavitation of GVs agitated by LIPUS, which reinforced the target efficiency while guaranteeing safety owing to the specific acoustic property of GVs. This LIGHT strategy significantly depleted miR-155, upregulating the suppressors of cytokine signaling 1 (SOCS1), leading to reparative polarization of macrophages, decrease of T lymphocytes and reduction of inflammatory factors. Thereby, rejection was attenuated and the allografted heart survival was markedly prolonged. The LIGHT strategy achieves targeted delivery of microRNA with minimal invasiveness and great efficiency, paving the way towards novel ultrasound cavitation-assisted strategies of targeted genetic therapy for heart transplantation rejection.

Alphaherpesvirus upregulates NDRG1 expression to facilitate the nuclear import of viral UL31 and UL34 proteins.

Proteins UL31 and UL34 encoded by alphaherpesvirus are critical for viral primary envelopment and nuclear egress. We report here that pseudorabies virus (PRV), a useful model for research on herpesvirus pathogenesis, uses N-myc downstream regulated 1 (NDRG1) to assist the nuclear import of UL31 and UL34. PRV promoted NDRG1 expression through DNA damage-induced P53 activation, which was beneficial to viral proliferation. PRV induced the nuclear translocation of NDRG1, and its deficiency resulted in the cytosolic retention of UL31 and UL34. Therefore, NDRG1 assisted the nuclear import of UL31 and UL34. Furthermore, in the absence of the nuclear localization signal (NLS), UL31 could still translocate to the nucleus, and NDRG1 lacked an NLS, thus suggesting the existence of other mediators for the nuclear import of UL31 and UL34. We demonstrated that heat shock cognate protein 70 (HSC70) was the key factor in this process. UL31 and UL34 interacted with the N-terminal domain of NDRG1 and the C-terminal domain of NDRG1 bound to HSC70. Replenishment of HSC70ΔNLS in HSC70-knockdown cells, or interference in importin α expression, abolished the nuclear translocation of UL31, UL34, and NDRG1. These results indicated that NDRG1 employs HSC70 to facilitate viral proliferation in the nuclear import of PRV UL31 and UL34.

Orally Administrable Aggregation-Induced Emission-Based Bionic Probe for Imaging and Ameliorating Dextran Sulfate Sodium-Induced Inflammatory Bowel Diseases.

As macrophage infiltration is significantly related to the progression of inflammatory bowel disease (IBD), monitoring the macrophages is a valuable strategy for IBD diagnosis. However, owing to the harsh physiological environment of the gastrointestinal tract and enzymatic degradation, the development of orally administrable imaging probes for tracking macrophages remains a considerable challenge. Accordingly, herein, an orally administrable aggregation-induced emission biomimetic probe (HBTTPIP/ß-glucan particles [GPs]) is developed for tracing macrophages; HBTTPIP/GPs can diagnose and alleviate dextran sulfate sodium (DSS)-induced colonic inflammation and self-report the treatment efficiency. The fluorophore HBTTPIP can effectively aggregate in GPs, restricting intramolecular rotation and activating the fluorescence of HBTTPIP. After being orally administrated, HBTTPIP/GPs are phagocytosed by intestinal macrophages, which then migrate to colonic lesions, enabling non-invasive monitoring of the severity of IBD via in vivo fluorescence imaging. Notably, oral HBTTPIP/GPs ameliorate DSS-induced IBD by inhibiting the expressions of pro-inflammatory factors and improving colonic mucosal barrier function. Furthermore, these HBTTPIP/GPs realize self-feedback of the therapeutic effects of GPs on DSS-induced colitis. The oral biomimetic probe HBTTPIP/GPs reported herein provide a novel theranostic platform for IBD, integrating non-invasive diagnosis of IBD in situ and the corresponding treatment.

Fetal and Neonatal Middle Cerebral Artery Hemodynamic Changes and Significance under Ultrasound Detection in Hypertensive Disorder Complicating Pregnancy Patients with Different Severities.

Colour Doppler ultrasound was applied for monitoring the hemodynamic parameters of fetal uterine artery (UtA), umbilical artery (UA), and middle cerebral artery (MCA) during pregnancy. In hypertension disease complicating pregnancy, these hemodynamic measures and their therapeutic applicability value were reviewed (HDCP). 120 singleton pregnant women were chosen, with 40 cases of mild preeclampsia (mild group), 40 cases of severe preeclampsia (severe group), and 40 normal control pregnant women (control group). The hemodynamic parameters of UtA, MCA, and UA were monitored in the three groups, including pulsatility index (PI), resistance index (RI), and the systolic/diastolic velocity (S/D). The parameters PI, RI, S/D, and venous catheter shunt rate (Qdv/Quv) of UtA and UA in the severe group were higher than those in the normal group and the mild group, showing the differences statistically significant (P < 0.05). The PI, RI, and S/D of MCA in the severe group were lower than those in the normal group and the mild group (P < 0.05). The changing trends of PI, RI, and S/D in the severe group were all first increased and then decreased in the early, middle, and later pregnancy (P < 0.05). The area under the curve (AUC) was 0.98 in the receiver operating characteristic (ROC) curve created using a combination of hemodynamic measures and pregnancy outcomes, and the sensitivity and specificity for predicting bad outcomes were 94.7 percent and 96.4 percent, respectively. Colour Doppler ultrasound may accurately detect changes in the PI, RI, and S/D of UtA, MCA, and UA in pregnant women and serve as a reference for determining the intrauterine state of the fetuses and predicting bad pregnancy outcomes. In particular, the parameters in later pregnancy were higher worthy of diagnostic value for adverse pregnancy outcomes. The combination of various parameters could make an improvement of the diagnostic accuracy and provide a basis for guiding treatment as well as determining the optimal timing of delivery.

Systematic review and meta-analysis on the influence of thyroid dysfunction in early pregnancy on pregnancy outcomes under ultrasound guidance.

BACKGROUND: Thyroid dysfunction during pregnancy has a certain impact on pregnancy outcomes and neonatal growth, but there is no systematic evaluation of the influence of thyroid dysfunction during early pregnancy under ultrasound guidance on pregnancy outcomes. METHODS: PubMed, Web of Science, Springer, and Science Direct databases were used to screen clinical studies on the effect of thyroid dysfunction during pregnancy on pregnancy outcomes from January 2010 to June 2021. Meta-analysis of data was conducted using RevMan 5.3 software. Differences of indicators were compared between the normal and abnormal thyroid function groups, including the ratio of primiparas, anemia, intrauterine growth restriction, perinatal fetal death, preterm delivery, fetal distress syndrome, cesarean section, preeclampsia, placental abruption, postpartum hemorrhage, and neonatal complications. Heterogeneity of results was assessed by chi-square test and I2 test in RevMan5.3. RESULTS: A total of 788,867 pregnant women were included in 13 studies. Cochrane scores were grade B or above, and Jadad scale scores were higher than 3. Anemia [odds ratio (OR) =0.82, 95% confidence interval (CI): 0.70-0.96, Z=2.48, P=0.01], premature birth (OR =0.56, 95% CI: 0.36-0.86, Z=2.66, P=0.008), fetal distress syndrome (OR =0.76, 95% CI: 0.68-0.85, Z=4.74, P<0.00001), Apgar score <7 (OR =0.52, 95% CI: 0.34-0.80, Z=2.97, P=0.003), preeclampsia (OR =0.65, 95% CI: 0.48-0.87, Z=2.91, P=0.004), placental abruption (OR =0.27, 95% CI: 0.19-0.38, Z=7.31, P<0.00001), and the rate of postpartum hemorrhage (OR =0.62, 95% CI: 0.42-0.92, Z=2.38, P=0.02) were dramatically higher in the abnormal thyroid function group compared with the normal group. DISCUSSION: Few studies were included on the effect of thyroid dysfunction on abortion, and further validation is needed. Thyroid dysfunction was proven to be associated with a variety of adverse pregnancy outcomes.

Pseudorabies Virus Inhibits Expression of Liver X Receptors to Assist Viral Infection.

Pseudorabies virus (PRV) is a contagious herpesvirus that causes Aujeszky's disease and economic losses worldwide. Liver X receptors (LXRs) belong to the nuclear receptor superfamily and are critical for the control of lipid homeostasis. However, the role of LXR in PRV infection has not been fully established. In this study, we found that PRV infection downregulated the mRNA and protein levels of LXRα and LXRß in vitro and in vivo. Furthermore, we discovered that LXR activation suppressed PRV proliferation, while LXR inhibition promoted PRV proliferation. We demonstrated that LXR activation-mediated reduction of cellular cholesterol was critical for the dynamics of PRV entry-dependent clathrin-coated pits. Replenishment of cholesterol restored the dynamics of clathrin-coated pits and PRV entry under LXR activation conditions. Interestingly, T0901317, an LXR agonist, prevented PRV infection in mice. Our results support a model that PRV modulates LXR-regulated cholesterol metabolism to facilitate viral proliferation.

Systematic review and meta-analysis of evaluation of selective cesarean section in postpartum pelvic floor function recovery under perineal ultrasound.

BACKGROUND: Different delivery modes can affect the early pelvic floor function of puerpera, but there are no reports on the systematic evaluation of the effects of selective cesarean section delivery (CSD) and vaginal delivery (VD) on the pelvic floor function of puerpera. METHODS: We searched for clinical controlled studies on the evaluation of pelvic floor function and performance after CSD and VD, published between 1 January 2010 and 1 August 2021, in the databases of PubMed, Embase, The Cochrane Library, and Web of Science. Literature was screened according to the inclusion and exclusion criteria. The quality of trials included in the studies was evaluated using the Cochrane Working Manual (5.3). Meta-analysis of the extracted data from the eligible articles was performed using Review Manager 5.3 software. The heterogeneity was assessed by chi-square, and P<0.05 was considered statistically significant among groups. RESULTS: A total of 3,704 parturient women were included in 10 articles, including 1,072 cases in the CSD group and 2,632 cases in the VD group. Meta-analysis showed that pelvic floor muscle strength {mean difference (MD) [95% confidence interval (CI)]: -12.51 (-17.10 to -7.91); Z=5.34; P<0.00001} and bladder neck strength decreases in the CSD group [standardized mean difference (SMD) (95% CI): 1.01 (0.73 to 1.29); Z=7.08; P<0.00001] were higher than those in the VD group. In addition, the maximum urine flow [MD (95% CI): -6.86 (-9.32 to -4.39); Z=5.46; P<0.00001], bladder angle [MD (95% CI): -3.82 (-4.54 to -3.11); Z=10.46; P<0.00001], stress urinary incontinence (SUI) rate [relative risk (RR) (95% CI): 0.56 (0.35 to 0.88); Z=2.52; P=0.01], and pelvic floor organ prolapse rate [odds ratio (OR) (95% CI): 0.29 (0.09 to 0.89); Z=2.17; P=0.03] were lower than VD group, and the differences were significant (P<0.05). CONCLUSIONS: Selective CSD can reduce the injury of pelvic floor muscle during delivery to a certain extent, and reduce the incidence of SUI and pelvic floor organ prolapse in early puerpera; however, such impacts cannot be completely avoided.

Biogenic Gas Vesicles for Ultrasound Imaging and Targeted Therapeutics.

Ultrasound is not only the most widely used medical imaging mode for diagnostics owing to its real-time, non-radiation, portable and low-cost merits, but also a promising targeted drug/gene delivery technique by producing a series of powerful bioeffects. The development of micron-sized or nanometer-sized ultrasound agents or delivery carriers further makes ultrasound a distinctive modality in accurate diagnosis and effective treatment. In this review, we introduce one kind of unique biogenic gas-filled protein nanostructures called gas vesicles, which present some unique characteristics beyond the conventional microbubbles. Gas vesicles can not only serve as ultrasound contrast agent with innovative imaging methods such as cross-amplitude modulation harmonic imaging, but also can further be adjusted and optimized via genetic engineered techniques. Moreover, they could not only serve as acoustic gene reporters, acoustic biosensors to monitor the cell metabolism, but also serve as cavitation nuclei and drug carrier for therapeutic purpose. We focus on the latest development and applications in the area of ultrasound imaging and targeted therapeutics, and also give a brief introduction to the corresponding mechanisms. In summary, these biogenic gas vesicles show some advantages over conventional MBs that deserve making more efforts to promote their development.

Predicting pathologic response to neoadjuvant chemotherapy in patients with locally advanced breast cancer using multiparametric MRI.

BACKGROUND: This study aims to observe and analyze the effect of diffusion weighted magnetic resonance imaging (MRI) on the patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. METHODS: Fifty patients (mean age, 48.7 years) with stage II-III breast cancer who underwent neoadjuvant chemotherapy and preoperative MRI between 2016 and 2020 were retrospectively evaluated. The associations between preoperative breast MRI findings/clinicopathological features and outcomes of neoadjuvant chemotherapy were assessed. RESULTS: Clinical stage at baseline (OR: 0.104, 95% confidence interval (CI) 0.021-0.516, P = 0.006) and standard apparent diffusion coefficient (ADC) change (OR: 9.865, 95% CI 1.024-95.021, P = 0.048) were significant predictive factors of the effects of neoadjuvant chemotherapy. The percentage increase of standard ADC value in pathologic complete response (pCR) group was larger than that in non-pCR group at first time point (P < 0.05). A correlation was observed between the change in standard ADC values and tumor diameter at first follow-up (r: 0.438, P < 0.05). CONCLUSIONS: Our findings support that change in standard ADC values and clinical stage at baseline can predict the effects of neoadjuvant chemotherapy for patients with breast cancer in early stage.

Biventricular Longitudinal Strain Predict Mortality in COVID-19 Patients.

Background: Biventricular longitudinal strain has been recently demonstrated to be predictive of poor outcomes in various cardiovascular settings. Therefore, this study sought to investigate the prognostic implications of biventricular longitudinal strain in patients with coronavirus disease 2019 (COVID-19). Methods: We enrolled 132 consecutive patients with COVID-19. Left ventricular global longitudinal strain from the apical four-chamber views (LV GLS4CH) and right ventricular free wall longitudinal strain (RV FWLS) were obtained using two-dimensional speckle-tracking echocardiography. Results: Compared with patients without cardiac injury, those with cardiac injury had higher levels of coagulopathy and inflammatory biomarkers, higher incidence of complications, more mechanical ventilation therapy, and higher mortality. Patients with cardiac injury displayed decreased LV GLS4CH and RV FWLS, elevated pulmonary artery systolic pressure, and higher proportion of pericardial effusion. Higher biomarkers levels of inflammation and cardiac injury, and the presence of pericardial effusion were correlated with decreases in LV GLS4CH and RV FWLS. During hospitalization, 19 patients died. Compared with survivors, LV GLS4CH and RV FWLS were impaired in non-survivors. At a 3-month follow-up after discharge, significant improvements were observed in LV GLS4CH and RV FWLS. Multivariate Cox analysis revealed that LV GLS4CH [hazard ratio: 1.41; 95% confidence interval [CI]: 1.08 to 1.84; P = 0.011] and RV FWLS (HR: 1.29; 95% CI: 1.09-1.52; P = 0.003) were independent predictors of higher mortality in patients with COVID-19. Conclusions: LV GLS4CH and RV FWLS are independent and strong predictors of higher mortality in COVID-19 patients and can track improvement during the convalescent phase of their illness. Therefore, biventricular longitudinal strain may be crucial for risk stratification and serial follow-up in patients with COVID-19.

MicroRNA­4712­5p promotes proliferation of the vulvar squamous cell carcinoma cell line A431 by targeting PTEN through the AKT/cyclin D1 signaling pathways.

The aim of the present study was to screen differentially expressed miRNAs in vulvar squamous cell carcinoma (VSCC), observe the role of microRNA­4712­5p in VSCC and investigate its targets and regulatory mechanism. Differentially expressed miRNAs in human VSCC tissues were screened. microRNA­4712­5p was selected and its expression level was verified in clinical tissue samples and the VSCC cell line A431 by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) analysis. The overexpression vector of microRNA­4712­5p was prepared and transfected into A431 cells; subsequently, cell invasion and metastasis were examined by Cell Counting Kit­8 and Transwell migration assays. Furthermore, the target gene of miRNA­4712­5p was predicted by bioinformatics and verified by The Dual­Luciferase® Reporter (DLR™) Assay System. The expression of phosphatase and tensin homologue (PTEN) and its downstream proteins, such as protein kinase B (PKB; AKT), glycogen synthase kinase (GSK)3ß and cyclin D1, were detected by western blot assays. The expression level of microRNA­4712­5p in VSCC tissues and the A431 cell line was found to be significantly increased, promoting proliferation and invasion of VSCC. The DLR™ assay indicated that PTEN was a target of miR­4712­5p. RT­qPCR revealed that PTEN expression was markedly lower in VSCC tissues compared with that in adjacent tissues. After A431 cells were transfected with the miRNA­4712­5p overexpression vector, phospho­AKT (p­AKT) and cyclin D1 expression were notably increased, but miRNA­4712­5p­targeted PTEN and phospho­GSK3ß (p­GSK3ß) protein markedly decreased. Therefore, microRNA­4712­5p can reduce the expression of PTEN, further affecting its downstream p­AKT, p­GSK3ß and cyclin D1 signaling pathways, promoting the proliferation and invasion of VSCC.

Occurrences of the Typical Agricultural Non-ionic Surfactants Tristyrylphenol Ethoxylates in Cherries ( Cerasus pseudocerasus), Peaches ( Amygdalus persica), and Kiwifruit ( Actinidia chinensis) and the Implications of Human Exposure in China.

Tristyrylphenol ethoxylates (TSP nEOs) are widely used as non-ionic surfactants in pesticide formulations in China. However, limited information is available regarding the occurrences of TSP nEOs in fruits. In this study, 361 fruit samples were collected from the main growing areas in China from 2016 to 2017 and analyzed for TSP nEO contamination using gel permeation chromatography-high-performance liquid chromatography-tandem mass spectrometry. TSP nEOs were detected in all samples, with a total concentration range of 0.5-14786.0 µg/kg (median of 85.0 µg/kg). The total concentrations were significantly but weakly correlated with the residues of acetamiprid ( r = 0.119; p < 0.05) and carbendazim ( r = -0.170; p < 0.01), suggesting that the TSP nEO residues are probably associated with the use of these pesticides during fruit growth. A risk assessment showed that there were little or no risks to human health. However, the risks to health associated with exposure to TSP nEOs should not be ignored because of their ubiquitousness in fruit samples.

Phthalate esters in bottled drinking water and their human exposure in Beijing, China.

Phthalate esters (PAEs) have attracted much attention because of their ubiquity and toxicity. However, previous studies mainly focused on the occurrence of PAEs controlled by the Environmental Protection Agency and neglected most uncontrolled PAEs. In this study, the occurrence of 21 PAEs, including 6 controlled and 15 uncontrolled PAEs, was investigated in polyethylene terephthalate (PET)-bottled drinking water samples purchased from markets in Beijing. Seventeen PAEs were detected in all samples, with dibutyl phthalate, diisobutyl phthalate, and dimethyl phthalate as the predominant compounds. Correlation analysis suggested that PET bottles might be one of the potential sources of PAEs in PET-bottled drinking water. The human health risks assessments indicated little or no risks from four controlled PAEs in bottled water. In comparison, the risks of uncontrolled PAEs should be of greater concern for their ubiquities in bottled drinking water.