Transition status and influencing factors of newly graduated nurses: A descriptive survey design.

AIMS: To assess the transition status of newly graduated nurses in China and identify its influencing factors. BACKGROUND: Newly graduated nurses are the indispensable part of nursing human resource. The successful transition of into clinical work is crucial for their future career development. However, the transition status of new nurses in China remains inadequately explored. DESIGN: A descriptive survey design was employed in this study. METHODS: From October 2022 to January 2023, 1261 newly graduated nurses were surveyed online with the Transition Status Scale for Newly Graduated Nurses. Description statistical analysis was adopted to evaluate the transition status of new nurses. Independent-samples t-test, Analysis of Variance and Multiple Regression Analysis was used to explore the influencing factors of the transition status. RESULTS: The total mean score of Transition Status Scale for Newly Graduated Nurses was 4.00 (SD=0.61). Competence for nursing work (Mean=4.20; SD=0.57) was rated the highest among the five dimensions of the scale, while the dimension of balance between work and life (Mean=3.65; SD=0.89) was rated the lowest. Mentored by senior nurses, night shift, attribute of working hospital, educational background, interned in the same department, tertiary general hospital, reasons for choosing nursing and working time can affect the transition status of new nurses, accounting for 17.9% of the variance in transition status (R²= 0.179, P＜0.001). CONCLUSION: The transition status of newly graduated nurses in China is at a relatively high level, especially in the dimension of competence for nursing work. However, newly graduated nurses are in a relatively poor status of work-life balance. Nurse educators and managers need to pay more attention to the transitional training of highly educated nursing talents and the optimization of clinical transition training programs to prevent talent loss. Experienced tutors should be allocated to provide guidance for newly graduated nurses.

Armed with IL-2 based fusion protein improves CAR-T cell fitness and efficacy against solid tumors.

Chimeric antigen receptor T (CAR-T) cell therapy is regarded as a potent immunotherapy and has made significant success in hematologic malignancies by eliciting antigen-specific immune responses. However, response rates of CAR-T cell therapy against solid tumors with immunosuppressive microenvironments remain limited. Co-engineering strategies are advancing methods to overcome immunosuppressive barriers and enhance antitumor responses. Here, we engineered an IL-2 mutein co-engineered CAR-T for the improvement of CAR-T cells against solid tumors and the efficient inhibition of solid tumors. We equipped the CAR-T cells with co-expressing both tumor antigen-targeted CAR and a mutated human interleukin-2 (IL-2m), conferring enhanced CAR-T cells fitness in vitro, reshaped immune-excluded TME, enhanced CAR-T infiltration in solid tumors, and improved tumor control without significant systemic toxicity. Overall, this subject demonstrates the universal CAR-T cells armed strategy for the development and optimization of CAR-T cells against solid tumors.

Perspectives of Chinese New Nurses Regarding Successful Transition: A Qualitative Study.

BACKGROUND: Transition issues have been discussed for many decades, yet little is known about successful transition expectations in the context of Chinese culture. PURPOSE: This article was designed to describe the expectations of newly graduated nurses in China regarding successful transition. METHODS: A qualitative, descriptive study design was employed, and a purposive sampling method was used to recruit interviewees. All of the one-to-one conversations were held in a quiet room to ensure privacy. All of the interviews were transcribed and then analyzed using thematic analysis. RESULTS: Nineteen new nurses were recruited from seven tertiary hospitals and participated in the in-depth interview process. Transition success, that is, "professional metamorphosis," was revealed through the four themes of "being competent in nursing work," "establishing a professional identity," "establishing comfortable interpersonal relationships," and "achieving balance between work and life." CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Chinese new nurses expect their successful transition to achieve a professional metamorphosis in many aspects. A successful transition is not only a journey of professionalization but also a process of socialization. New nurses expect to achieve both maturity in their work and wisdom in life. The results of this study provide a greater understanding of transition issues in the context of Chinese culture. Thus, support and strategies cannot be limited to interventions designed to improve working competence but should be individualized to help new nurses achieve a smooth transition.

Behavioral Intention of Receiving Monkeypox Vaccination and Undergoing Monkeypox Testing and the Associated Factors Among Young Men Who Have Sex With Men in China: Large Cross-Sectional Study.

BACKGROUND: The worldwide human monkeypox (mpox) outbreak in 2022 mainly affected men who have sex with men (MSM). In China, young men who have sex with men (YMSM) were at a potential high risk of mpox infection due to their sexual activeness and the eased COVID-19 restrictions at the end of 2022. OBJECTIVE: This study aimed to investigate the behavioral intention of receiving mpox vaccination and undergoing mpox testing in 4 different scenarios and explore their associations with background and behavioral theory-related factors among Chinese YMSM. METHODS: An online cross-sectional survey was conducted among YMSM aged 18-29 years from 6 representative provinces of China in September 2022. Participants recruited (recruitment rate=2918/4342, 67.2%) were asked to self-administer an anonymous questionnaire designed based on prior knowledge about mpox and classic health behavior theories. Data on the participants' background, mpox knowledge and cognition, mpox vaccination and testing cognition, and the behavioral intention of receiving mpox vaccination and undergoing mpox testing were collected. Descriptive analysis and univariate and multivariate linear regressions were performed. Geodetector was used to measure the stratified heterogeneity of behavioral intention. RESULTS: A total of 2493 YMSM with a mean age of 24.6 (SD 2.9) years were included. The prevalence of having a behavioral intention of receiving mpox vaccination ranged from 66.2% to 88.4% by scenario, varying in epidemic status and cost. The prevalence of having an mpox testing intention was above 90% in all scenarios regardless of the presence of symptoms and the cost. The positive factors related to vaccination intention included mpox knowledge (ba=0.060, 95% CI 0.016-0.103), perceived susceptibility of mpox (ba=0.091, 95% CI 0.035-0.146), perceived severity of mpox (ba=0.230, 95% CI 0.164-0.296), emotional distress caused by mpox (ba=0.270, 95% CI 0.160-0.380), perceived benefits of mpox vaccination (ba=0.455, 95% CI 0.411-0.498), self-efficacy of mpox vaccination (ba=0.586, 95% CI 0.504-0.668), and having 1 male sex partner (ba=0.452, 95% CI 0.098-0.806), while the negative factor was perceived barriers to vaccination (ba=-0.056, 95% CI -0.090 to -0.022). The positive factors related to testing intention were perceived severity of mpox (ba=0.283, 95% CI 0.241-0.325), perceived benefits of mpox testing (ba=0.679, 95% CI 0.636-0.721), self-efficacy of mpox testing (ba=0.195, 95% CI 0.146-0.245), having 1 male sex partner (ba=0.290, 95% CI 0.070-0.510), and having in-person gatherings with MSM (ba=0.219, 95% CI 0.072-0.366), while the negative factor was emotional distress caused by mpox (ba=-0.069, 95% CI -0.137 to -0.001). CONCLUSIONS: Among Chinese YMSM, the intention of undergoing mpox testing is optimal, while the mpox vaccination intention has room for improvement. A future national response should raise YMSM's mpox knowledge, disseminate updated information about mpox and preventive measures, improve preventive service accessibility and privacy, and provide advice on positively coping with the associated emotional distress.

The effects of clinical learning environment and career adaptability on resilience: A mediating analysis based on a survey of nursing interns.

BACKGROUND: The resilience education of intern nursing students has significant implications for the development and improvement of the nursing workforce. The clinical internship period is a critical time for enhancing resilience. AIMS: To evaluate the resilience level of Chinese nursing interns and explore the effects of factors affecting resilience early in their careers, focusing on the mediating roles of career adaptability between clinical learning environment and resilience. METHODS: The cross-sectional study design was adopted. From March 2022 to May 2023, 512 nursing interns in tertiary care hospitals were surveyed online with the Connor-Davidson Resilience Scale, the Clinical Learning Environment Scale for Nurse and the Career Adapt-Abilities Scale. Structural equation modelling was used to clarify the relationships among these factors. Indirect effects were tested using bootstrapped confidence intervals. RESULTS: The nursing interns showed a moderately high level of resilience [M (SD) = 70.15 (19.90)]. Gender, scholastic attainment, scholarship, career adaptability and clinical learning environment were influencing factors of nursing interns' resilience. Male interns with good academic performance showed higher levels of resilience. Career adaptability and clinical learning environment positively and directly affected their resilience level (ß = 0.62, 0.18, respectively, p < .01). Career adaptability was also positively affected by the clinical learning environment (ß = 0.36, p < .01), and mediated the effect of clinical learning environment on resilience (ß = 0.22, p < .01). CONCLUSION: Clinical learning environment can positively affect the resilience level of nursing interns. Career adaptability can affect resilience directly and also play a mediating role between clinical learning environment and resilience. Thus, promotion of career adaptability and clinical teaching environment should be the potential strategies for nursing interns to improve their resilience, especially for female nursing interns with low academic performance.

All-Photolithography Fabrication of Ion-Gated Flexible Organic Transistor Array for Multimode Neuromorphic Computing.

Organic ion-gated transistors (OIGTs) demonstrate commendable performance for versatile neuromorphic systems. However, due to the fragility of organic materials to organic solvents, efficient and reliable all-photolithography methods for scalable manufacturing of high-density OIGT arrays with multimode neuromorphic functions are still missing, especially when all active layers are patterned in high-density. Here, a flexible high-density (9662 devices per cm2 ) OIGT array with high yield and minimal device-to-device variation is fabricated by a modified all-photolithography method. The unencapsulated flexible array can withstand 1000 times' bending at a radius of 1 mm, and 3 months' storage test in air, without obvious performance degradation. More interesting, the OIGTs can be configured between volatile and nonvolatile modes, suitable for constructing reservoir computing systems to achieve high accuracy in classifying handwritten digits with low training costs. This work proposes a promising design of organic and flexible electronics for affordable neuromorphic systems, encompassing both array and algorithm aspects.

Comparisons of fentanyl and sufentanil on recovery time after inguinal hernia repair in children: a randomized clinical trial.

BACKGROUND: Inguinal hernia repair is a common pediatric procedure. We studied postoperative recovery times in children undergoing laparoscopic inguinal hernia repair with anesthesia induced by fentanyl versus sufentanil. METHODS: We performed a pilot randomized clinical trial between February and December 2022. Eligible children were assigned into two age groups, 2-6 and 6-12 years old groups. Then, children in each age group were randomly assigned into either the fentanyl (2 µg/kg) or sufentanil (0.2 µg/kg) group for anesthesia induction. Baseline characteristics were collected. The primary outcome was the postoperative recovery time, which was recorded as the time period from extubation to a Steward recovery score reaching 6. Secondary outcomes included surgical duration, anesthetic duration, intubation duration, and intraoperative hemorrhage. RESULTS: There were 300 children, with 75 children in each group. In the 2-6 years old group, children who received fentanyl had statistically significantly shorter postoperative recovery times than children who received sufentanil (0.9 ± 0.4 versus 1.5 ± 0.3 h, P < 0.001). However, in the 6-12 years old group, children who received fentanyl had statistically significantly longer postoperative recovery times than children who received sufentanil (1.2 ± 0.4 versus 0.8 ± 0.4 h, P < 0.001). Baseline characteristics and secondary outcomes were comparable between two groups. CONCLUSIONS: Anesthesia induction with fentanyl or sufentanil resulted in different postoperative recovery times after laparoscopic inguinal hernia repair in children in different age groups. More studies are required to determine the appropriate induction anesthetic in children of different ages. TRIAL REGISTRATION: The study protocol was retrospectively registered online at the Chinese Clinical Trial Registry (registration number ChiCTR2300072177, retrospectively registered on 06/06/2023).

Behavioral intentions of self-isolation and informing close contacts after developing mpox-related symptoms among young men who have sex with men in China.

The 2022 multi-country mpox outbreak raised public concern globally. Self-isolation and informing close contacts after developing mpox-related symptoms are critical measures in controlling the outbreak. This study investigated behavioral intentions of self-isolation and informing close contacts after developing mpox-related symptoms and associated factors among young men who have sex with men (YMSM) aged 18-29 years in China. The cross-sectional study was conducted among 2493 YMSM in six provincial regions in China from September 10th to 30th, 2022. Descriptive and logistic analyses were applied, using the intentions of self-isolation and informing close contacts after developing mpox-related symptoms as binary outcomes. The mean age of the participants was 24.6 (SD = 2.9) years. The prevalence of having intentions of self-isolation and informing close contacts after developing mpox-related symptoms was 88.6% (95% CI: 87.3%-89.9%) and 84.9% (95% CI: 83.5%-86.3%). Participants who were employed (adjusted odds ratio (AOR) = 1.474, 95% CI: 1.035-2.097; AOR = 1.371, 95% CI:1.002, 1.876), had higher mpox knowledge scores (AOR = 1.474, 95% CI: 1.035-2.097; AOR = 1.371, 95% CI: 1.002-1.876), and had higher perceived threats of mpox (AOR = 1.079, 95% CI: 1.030-1.130; AOR = 1.045, 95% CI: 1.002-1.090) were more likely to intend to self-isolate and inform close contacts. Participants who had MSM in-person gatherings in the past 6 months were more likely to intend to self-isolate (AOR = 1.392, 95% CI: 1.066-1.208). Participants with higher depression scores (AOR = 0.968, 95% CI: 0.948-0.989) and self-stigma (AOR = 0.975, 95% CI: 0.954-0.997) were less likely to intend to self-isolate and inform close contacts, respectively. Self-isolation and informing close contacts when developing disease-related symptoms are acceptable measures in response to mpox in China. Strengthening targeted risk communication and self-efficacy, raising disease knowledge, providing mental support, and reducing stigma toward the affected community are warranted.

Humidity/Oxygen-Insensitive Organic Synaptic Transistors Based on Optical Radical Effect.

For most organic synaptic transistors based on the charge trapping effect, different atmosphere conditions lead to significantly different device performance. Some devices even lose the synaptic responses under vacuum or inert atmosphere. The stable device performance of these organic synaptic transistors under varied working environments with different humidity and oxygen levels can be a challenge. Herein, a moisture- and oxygen-insensitive organic synaptic device based on the organic semiconductor and photoinitiator molecules is reported. Unlike the widely reported charge trapping effect, the photoinduced free radical is utilized to realize the photosynaptic performance. The resulting synaptic transistor displays typical excitatory postsynaptic current, paired-pulse facilitation, learning, and forgetting behaviors. Furthermore, the device exhibits decent and stable photosynaptic performances under high humidity and vacuum conditions. This type of organic synaptic device also demonstrates high potential in ultraviolet B perception based on its environmental stability and broad ultraviolet detection capability. Finally, the contrast-enhanced capability of the device is successfully validated by the single-layer-perceptron/double-layer network based Modified National Institute of Standards and Technology pattern recognition. This work could have important implications for the development of next-generation environment-stable organic synaptic devices and systems.

SIRT6 Improves Hippocampal Neurogenesis Following Prolonged Sleep Deprivation Through Modulating Energy Metabolism in Developing rats.

OBJECTIVE: Prolonged sleep deprivation is known to have detrimental effects on the hippocampus during development or in adulthood. Furthermore, it is well-established that sleep deprivation disrupts energy metabolism broadly. SIRT6 is a critical regulator of energy metabolism in both central and peripheral tissues. This study aims to investigate the role of SIRT6 in modulating hippocampal neurogenesis following sleep deprivation during development, and elucidate the underlying mechanism. METHODS: Male Sprague-Dawley rats, aged three weeks, were subjected to 2 weeks of sleep deprivation using the modified multiple platform method. Metabolomic profiling was carried out using the liquid chromatography-electrospray ionization-tandem mass spectrometry (LC‒ESI‒MS/MS). To investigate the role of SIRT6 in energy metabolism, the rats were administered with either the SIRT6-specific inhibitor, OSS128167, or SIRT6-overexpressing adeno-associated virus (AAV). Hippocampal neurogenesis was assessed by immunostaining with markers for neural stem cells (SOX2), immature neurons [doublecortin (DCX)] and newborn cells (BrdU). Sparse labeling of adult neurons was used to determine the density of dendritic spines in the dentate gyrus (DG). The Y-maze and novel object recognition (NOR) tests were performed to evaluate the spatial and recognition memory. SIRT6 expression was examined using immunofluorescence and western blotting (WB). The inhibition of SIRT6 was confirmed by assessing the acetylation of histone 3 lysine 9 (aceH3K9), a well-known substrate of SIRT6, through WB. RESULTS: Sleep deprivation for a period of two weeks leads to inhibited hippocampal neurogenesis, reduced density of dendritic spines in the DG, and impaired memory, accompanied by decreased SIRT6 expression and disrupted energy metabolism. Similar to sleep deprivation, administration of OSS128167 significantly decreased energy metabolism, leading to reduced neurogenesis and memory dysfunction. Notably, the abnormal hippocampal energy metabolism, neurogenetic pathological changes and memory dysfunction caused by sleep deprivation were alleviated by SIRT6 overexpression in the DG. CONCLUSION: Our results suggest that SIRT6 plays a critical role in maintaining energy metabolism homeostasis in the hippocampus after sleep deprivation, promoting hippocampal neurogenesis and enhancing memory during development.

Organic High-Temperature Synaptic Phototransistors for Energy-Efficient Neuromorphic Computing.

Organic optoelectronic synaptic devices that can reliably operate in high-temperature environments (i.e., beyond 121°C) or remain stable after high-temperature treatments have significant potential in biomedical electronics and bionic robotic engineering. However, it is challenging to acquire this type of organic devices considering the thermal instability of conventional organic materials and the degradation of photoresponse mechanisms at high temperatures. Here, high-temperature synaptic phototransistors (HTSPs) based on thermally stable semiconductor polymer blends as the photosensitive layer are developed, successfully simulating fundamental optical-modulated synaptic characteristics at a wide operating temperature range from room temperature to 220°C. Robust optoelectronic performance can be observed in HTSPs even after experiencing 750 h of the double 85 testing due to the enhanced operational reliability. Using HTSPs, Morse-code optical decoding scheme and the visual object recognition capability are also verified at elevated temperatures. Furthermore, flexible HTSPs are fabricated, demonstrating an ultralow power consumption of 12.3 aJ per synaptic event at a low operating voltage of -0.05 mV. Overall, the conundrum of achieving reliable optical-modulated neuromorphic applications while balancing low power consumption can be effectively addressed. This research opens up a simple but effective avenue for the development of high-temperature and energy-efficient wearable optoelectronic devices in neuromorphic computing applications.

Stretchable and neuromorphic transistors for pain perception and sensitization emulation.

Pain perception nociceptors (PPN), an important type of sensory neuron, are capable of sending out alarm signals when the human body is exposed to destructive stimuli. Simulating the human ability to perceive the external environment and spontaneously avoid injury is a critical function of neural sensing of artificial intelligence devices. The demand for developing artificial PPN has subsequently increased. However, due to the application scenarios of bionic electronic devices such as human skin, electronic prostheses, and robot bodies, where a certain degree of surface deformation constantly occurs, the ideal artificial PPN should have the stretchability to adapt to real scenarios. Here, an organic semiconductor nanofiber artificial pain perception nociceptor (NAPPN) based on a pre-stretching strategy is demonstrated to achieve key pain aspects such as threshold, sensitization, and desensitization. Remarkably, while stretching up to 50%, the synaptic behaviors and injury warning ability of NAPPN can be retained. To verify the wearability of the device, NAPPN was attached to a curved human finger joint, on which PPN behaviors were successfully mimicked. This provides a promising strategy for realizing neural sensing function on either deformed or mobile electronic devices.

Mpox risk perception and associated factors among Chinese young men who have sex with men: Results from a large cross-sectional survey.

The mpox outbreak since 2022 had attacked the community of men who have sex with men (MSM) heavily. This large cross-sectional study investigated the levels and associated factors of mpox risk perception among young MSM (YMSM) aged 18-29 years in six provincial regions of China in September 2022. The participants were recruited via facility-based sampling. Mpox risk perception was measured by perceived susceptibility and perceived severity of mpox. Geodetector was used to measure stratified heterogeneity of mpox risk perception. Univariate and multivariable linear regressions were used to examine the factors associated with mpox risk perception. A total of 2493 participants were included with a mean age of 24.6 years. The proportion of perceiving a susceptibility of mpox under different scenarios ranged 3.7%-17.0% and that of perceiving a severity of mpox ranged 81.6%-83.2%. Stratified heterogeneity of perceived susceptibility, perceived severity, and overall perceived risk of mpox were observed in several characteristics such as study sites, monthly income, risk behaviors, and psychosocial factors. Multivariable regression showed the level of mpox risk perception was positively associated with having in-person gathering activities (ba = 0.457, 95% CI: 0.208, 0.705), history of HIV infection (ba = 0.431, 95% CI: 0.028, 0.834), depressive symptoms (ba = 0.069, 95% CI: 0.049, 0.090), and self-stigma to MSM identity (ba = 0.047, 95% CI: 0.024, 0.071). The Chinese YMSM showed a high level of perceived severity of mpox but a low level of perceived susceptibility. It is warranted to strengthen targeted risk communication of mpox, develop comprehensive and unstigmatized health messages, and provide mental health support for YMSM.

Emerging Iontronic Neural Devices for Neuromorphic Sensory Computing.

Living organisms have a very mysterious and powerful sensory computing system based on ion activity. Interestingly, studies on iontronic devices in the past few years have proposed a promising platform for simulating the sensing and computing functions of living organisms, because: 1) iontronic devices can generate, store, and transmit a variety of signals by adjusting the concentration and spatiotemporal distribution of ions, which analogs to how the brain performs intelligent functions by alternating ion flux and polarization; 2) through ionic-electronic coupling, iontronic devices can bridge the biosystem with electronics and offer profound implications for soft electronics; 3) with the diversity of ions, iontronic devices can be designed to recognize specific ions or molecules by customizing the charge selectivity, and the ionic conductivity and capacitance can be adjusted to respond to external stimuli for a variety of sensing schemes, which can be more difficult for electron-based devices. This review provides a comprehensive overview of emerging neuromorphic sensory computing by iontronic devices, highlighting representative concepts of both low-level and high-level sensory computing and introducing important material and device breakthroughs. Moreover, iontronic devices as a means of neuromorphic sensing and computing are discussed regarding the pending challenges and future directions.

[Comparison of Disease Burden Factors of Thyroid Cancer Between China and the World From 1990 to 2019].

Objective To compare the prevalence and disease burden of thyroid cancer and their trends between China and the globe from 1990 to 2019.Methods With the global disease burden data in 2019,Joinpoint was used to predict the trends of the disease burden of thyroid cancer in China and the globe from 1990 to 2019,and logarithmic linear model was used to test the predicted trends.The R language was used for predictive analysis and graphic plotting of the disease burden from 2020 to 2035.Results From 1990 to 2019,the standardized incidence rate and the standardized mortality rate of thyroid cancer in China were lower than those in the globe.The standardized incidence rate in China and the globe showed an increasing trend(with the increases of 102.65% and 40.65%,respectively),while the standardized mortality rate showed a decreasing trend(with the decreases of 7.63% and 4.91%,respectively).Compared with those of the female population,the standardized incidence and mortality rates of the Chinese male population increased significantly from 1990 to 2019(the rates of change in the male population were 48.65% and 214.60%,respectively;and the rates of change in the female population were -39.01% and 60.44%,respectively).China's overall standardized years of life lost(YLL),years lived with disability(YLD),and disability-adjusted life years(DALY)rates during the 30-year period were lower than the global average.The Chinese and global populations showed the standardized YLL rate decreasing by 16.61% and 6.88% and the standardized DALY rate decreasing by 10.77% and 3.65%,respectively,while the rates of standardized YLD increased by 128.91% and 46.89%,respectively.The magnitude of DALY in China and the world was mainly influenced by YLL.The standardized incidence,mortality,and DALY rates of the Chinese male population were gradually approaching the global levels.From 1990 and 2019,thyroid cancer showed a higher mortality rate in the population with the age ≥ 75 years and a higher incidence rate in the population with the age <75 years.It is projected that from 2020 to 2035,the standardized incidence rates in China and the world will increase by 36.66% and 21.15%,respectively;the standardized mortality rates will decrease by 20.19% and 3.46%,respectively;and the standardized DALY rate is expected to decrease by 7.08% in China and increase by 4.35% in the world.Conclusions From 1990 to 2019,China's standardized incidence rate of thyroid cancer increased and had a higher increase than the global level,and the standardized mortality rate decreased,with a slightly higher decrease than the global level.However,the increases in the standardized incidence rate and mortality rate of this disease in China's ≥75 years male population were severe.Although China's disease burden of thyroid cancer showed a decreasing trend in line with the global trend as a whole,the disease burden in the Chinese males was higher than that in the females.Specifically,the disease burden due to premature death was predominant,and the burden in specific populations requires policy attention.

Ultrasound-targeted microbubble destruction-mediated Foxp3 knockdown may suppress the tumor growth of HCC mice by relieving immunosuppressive Tregs function.

The aim of the present study was to investigate the effect of Forkhead family transcription factor P3 (Foxp3) knockdown on the function of cluster of differentiation (CD)4+CD25+ regulatory T cell (Tregs) and the tumor growth of a hepatocellular carcinoma (HCC) mouse model. CD4+CD25+ Tregs and CD4+CD25- T cells were sorted from peripheral blood mononuclear cells (PBMCs) of patients with HCC. Then, ultrasound-targeted microbubble destruction (UTMD)-mediated Foxp3-microRNA (miRNA) was transfected into Tregs. Subsequently, CD4+CD25- T cells were co-cultured with PBMC and Tregs without Foxp3-miRNA (Foxp3+Tregs) or Tregs with Foxp3-miRNA (Foxp3-Tregs) and the proliferation-inhibition ratio of CD4+CD25- T cells was detected using a Cell Counting Kit-8. Additionally, HCC mice were treated with UTMD-mediated Foxp3-shRNA, the tumor volume was calculated and the content of CD4+ and CD25+ T cells in the blood were detected using flow cytometry. The content of interferon-γ (IFN-γ), interleukin (IL)-2, IL-10, transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor (VEGF) in cultural supernatant and serum were detected by ELISA analysis. Foxp3-Tregs significantly reduced the inhibition effect of Foxp3+Tregs on the proliferation of CD4+CD25- T cells (P<0.01). The content of IFN-γ and IL-2 significantly increased, while IL-10 and TGF-ß significantly decreased in the co-cultured system of Foxp3-Tregs compared with the co-cultured system of Foxp3+Tregs (P<0.01). Following treatment with Foxp3-shRNA, the average tumor volume, ratio of Tregs/CD4+ T cells and level of IL-10, TGF-ß and VEGF significantly decreased, however, the level of IFN-γ and IL-2 significantly increased compared with un-treated HCC mice (P<0.05). Foxp3 knockdown may suppress the tumor growth of HCC mice through relieving the immunosuppressive function of Tregs.

Hyperthermia with different temperatures inhibits proliferation and promotes apoptosis through the EGFR/STAT3 pathway in C6 rat glioma cells.

Malignant gliomas are a group of aggressive neoplasms among human cancers. The curative effects of current treatments are finite for improving the prognosis of patients. Hyperthermia (HT) is an effective treatment for cancers; however, the effects of HT with different temperatures in treatment of MG and relevant mechanisms remain unclear. MTT assay and Annexin V­fluorescein isothiocyanate/propidium iodide staining were used for investigating the proliferation and apoptosis of C6 cells, respectively. Western blotting was applied to detect the expression of proteins. Ultrasonography was employed to evaluate the tumor formation rate, growth rate, angiogenesis rate and degree of hardness of tumors in vivo. The authors certified that HT with 42­46˚C x 1 h, 1 t could inhibit proliferation, promote apoptosis, reduce tumor formation rate, growth rate, angiogenesis rate, degree of hardness of tumors, ischemic tolerance and anoxic tolerance, and have synergy with temozolomide in C6 cells. Long­term HT (43˚C x 1 h, 1 t/5 d, 90 d) did not cut down the sensitivity of C6 cells to HT, and sustainably inhibited the proliferation of C6 cells. Furthermore, the authors proved HT produced these effects primarily through inhibition of the EGFR/STAT3/HIF­1A/VEGF­A pathway.

The prevalence and clinicopathological features of programmed death-ligand 1 (PD-L1) expression: a pooled analysis of literatures.

BACKGROUND & AIMS: Programmed death-ligand 1 (PD-L1) has been recognized as a critical and promising target in therapies that direct immune escape of cancers. However, its association with aggressive clinicopathological features in solid tumors remains unclear. We investigated this question by synthesizing published articles. METHODS: Electronic databases were searched for relevant studies. Outcomes of interest included age, gender, tumor size, tumor size, lymph node metastasis and tumor cell differentiation. RESULTS: A total of 61 studies involving 17 types of malignancies were included. The overall expression rate of PD-L1 was 44.5% (95% CI, 37.5% to 51.6 %). Patients with regional lymph node metastases (OR 1.38; P < 0.01), large size tumor (OR 1.89; P < 0.01) or poor differentiated tumors (OR 1.71; P < 0.01) were associated with higher PD-L1 expression rate. However, no significant association was observed between young and elder patients (OR 1.04; P = 0.58), or male and female patients (OR 1.13; P = 0.06). A numerically higher PD-L1 expression rate was detected in polyclonal antibodies (57.2%) than monoclonal antibodies (39.6%). In addition, the PD-L1 expression rate reported by studies from Asian areas (52.3%) was numerically higher than those from non-Asian areas, namely Caucasians (32.7%). CONCLUSIONS: This meta-analysis indicated that patients with larger tumors, regional lymph node metastases, or poor-differentiated tumors were associated with a higher PD-L1 expression rate; in addition the expression rate of PD-L1 in Asians might be higher than that of Caucasians. This information might be useful in screening candidates for relevant tests and treatments.

Combined effect of ultrasound/SonoVue microbubble on CD4(+)CD25(+) regulatory T cells viability and optimized parameters for its transfection.

The purpose of this study was to investigate the combined effect of ultrasound and SonoVue microbubble on CD4(+)CD25(+) regulatory T cells (Tregs) viability and to explore the appropriate parameters for Tregs transfection. Tregs were separated from peripheral venous blood of patients with hepatocellular carcinoma and seeded in 96-well plates. The optimal ultrasound exposure time and optimal SonoVue microbubble concentration for Tregs were measured by mechanical index (MI) of 1.2 or 1.4, exposure time of 0, 30, 60, 90, 120, 150, 180s, and 0, 10, 20, 30, 40, 50µL/100µL microbubble per well, respectively. In addition, the combined effect of ultrasound and microbubble on Tregs viability was evaluated according to the following parameters: MI 1.2/1.4+exposure time of 120, 150, 180s+0, 10, 20, 30, 40, 50µL/100µL microbubble per well. Tregs viability investigations were performed in order to explore the optimal transfection condition. The efficiency of plasmid transfer was determined by detection of luciferase activity on the microscopic examinations. The proliferation of Tregs could be promoted by ultrasound exposures, while being decreased with the increasing concentration of microbubbles. Under the current experimental conditions, the optimal ultrasound parameters were MI=1.4 and exposure time=150/180s. The optimal microbubble concentration was 10µL/100µL. Compared with treatment with ultrasound or microbubbles alone, the transfection efficiency of Tregs improved 50% by combining ultrasound and microbubble. The results indicate that both ultrasound and microbubble could affect the Tregs proliferation and the optimal Treg transfection rate was obtained by treating with 10% microbubbles and ultrasound exposure for 150/180s under ultrasound MI of 1.4.