AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Metabolic profiles of Fufang Xiling Jiedu capsule in rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Fufang Xiling Jiedu capsule (FXJC), a traditional Chinese medicine that evolved from "Yinqiao Powder", is widely used for the treatment of cold and influenza. However, due to a lack of in vivo metabolism research, the chemical components responsible for the therapeutic effects still remain unclear. Hence, this study aimed to describe the metabolic profiles of the FXJC in rat plasma, urine, and feces. A combined data mining strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was employed and 201 xenobiotics, including 117 prototype components and 84 metabolites were detected. Phenolic acids, flavonoids, triterpenes, and lignans were prominent ingredients absorbed in vivo, and the major metabolic pathways of the detected metabolites were glucuronidation, sulfation, methylation, and oxidation. This is the first systematic study on the metabolism of the FXJC in vivo, providing valuable information for future studies on the efficacy, toxicity, and mechanism of the FXJC.

The evolution of hot Jupiters revealed by the age distribution of their host stars.

The unexpected discovery of hot Jupiters challenged the classical theory of planet formation inspired by our solar system. Until now, the origin and evolution of hot Jupiters are still uncertain. Determining their age distribution and temporal evolution can provide more clues into the mechanism of their formation and subsequent evolution. Using a sample of 383 giant planets around Sun-like stars collected from the kinematic catalogs of the Planets Across Space and Time project, we find that hot Jupiters are preferentially hosted by relatively younger stars in the Galactic thin disk. We subsequently find that the frequency of hot Jupiters declines with age as [Formula: see text]. In contrast, the frequency of warm/cold Jupiters shows no significant dependence on age. Such a trend is expected from the tidal evolution of hot Jupiters' orbits, and our result offers supporting evidence using a large sample. We also perform a joint analysis on the planet frequencies in the stellar age-metallicity plane. The result suggests that the frequencies of hot Jupiters and warm/cold Jupiters, after removing the age dependence are both correlated with stellar metallicities as [Formula: see text] and [Formula: see text], respectively. Moreover, we show that the above correlations can explain the bulk of the discrepancy in hot Jupiter frequencies inferred from the transit and radial velocity (RV) surveys, given that RV targets tend to be more metal-rich and younger than transits.

A study on inhibition of the Aß1-42-induced inflammatory response by the Huatuo Zaizao pill through the NF-κB signaling pathway.

Introduction: The pathology of Alzheimer's disease (AD) includes ß-amyloid (Aß) (plaques) and neurofibrillary tangles (NFTs). This study aimed to explore the efficacy of Huatuo Zaizao pill (HTZP) in an AD mouse model induced by injecting Aß1-42, and the neuroprotective mechanism of HTZP in AD. Material and methods: C57BL/6 (B6) mice were randomly divided into 4 groups (n = 10, per group): control group, AD model group, and 2 different doses of HTZP treated groups. The Morris water maze test was carried out on AD mice to assess the learning ability after treatment with HTZP for 15 day. The levels of inflammatory factors and the nuclear factor-κB (NF-κB) pathway were examined by western blot and real-time polymerase chain reaction (PCR). The content of microglia was investigated by immunofluorescence. Results: This study revealed that a cognitive disorder could be mitigated when the AD mice were treated with HTZP, which might be associated with the decreased level of pro-inflammatory factors, and the inhibitory activities of microglia. Additionally, phosphorylation of IκB and NF-κB p65 could be reduced by prohibiting the neuroinflammation of NF-κB activation in the hippocampus of AD mice. Conclusions: These results showed that HTZP could mitigate a cognitive disorder, diminish the activation of microglia, and inhibit the content of inflammatory factors through the NF-κB pathway in Aß1-42-induced AD mice. HTZP may be an appropriate agent for AD treatment in the future.

Evaluating the ecological vulnerability of Chongqing using deep learning.

This study used deep learning to evaluate the ecological vulnerability of Chongqing, China, discuss the deep learning evaluations of ecological vulnerability, and generate vulnerability maps that support local ecological environment protection and governance decisions and provide reference for future studies. The information gain ratio was used to screen the influencing factors, selecting 16 factors that influence ecological vulnerability. Deep neural network (DNN) and convolutional neural network (CNN) methods were used for modeling, and two ecological vulnerability maps of the study area were generated. The results showed that the mean absolute error and root mean square error of the DNN and CNN models were relatively small, and the fitting accuracy was high. The area under the receiver operating characteristic curve of the CNN model was 0.926, which was better than that of the DNN model (0.888). Random forest was applied to calculate the importance of the influencing factors in the two models. Because the main factor was geological features, the relative ecological vulnerability was mainly affected by karst topography. Through the analysis of the ecological vulnerability map, the areas with higher vulnerability are the karst mountains of Dabashan, Wushan, and Qiyaoshan in the northeast and southeast, as well as the valley between mountains and cities in the center and west of the study area. According to the investigation of these areas, the primary ecological problems are low forest quality, structural irregularities caused by self-geological factors, severe desertification, and soil erosion. Human activity is also an important factor that causes ecological vulnerability in the study area. In conclusion, deep learning, particularly CNN models, can be used for ecological vulnerability assessments. The ecological vulnerability maps conformed to the basic cognition of field surveys and can provide references for other deep learning vulnerability studies. While the overall vulnerability of the study area is not high, ecological problems that lead to its vulnerability should be addressed by future ecological protection and management measures.

Smoking Bans and Circulatory System Disease Mortality Reduction in Macao (China): Using GRA Models.

This study evaluates the association between smoking rates and mortality from circulatory system diseases (CSD) after implementing a series of smoking bans in Macao (China). (1) Background: Macao phased in strict total smoking bans since 2012. During the past decade, smoking rates among Macao women have dropped by half. CSD mortalities in Macao also show a declining trend. (2) Method: Grey relational analysis (GRA) models were adopted to rank the importance of some key factors, such as income per capita, physician density, and smoking rates. Additionally, regressions were performed with the bootstrapping method. (3) Results: Overall, smoking rate was ranked as the most important factor affecting CSD mortality among the Macao population. It consistently remains the primary factor among Macao's female population. Each year, on average 5 CSD-caused deaths were avoided among every 100,000 women, equivalent to about 11.45% of the mean annual CSD mortality. (4) Conclusions: After the implementation of smoking bans in Macao, the decrease in smoking rate among women plays a primary role in the reduction in CSD mortality. To avoid excess CSD mortality due to smoking, Macao needs to continue to promote smoking cessation among the male population.

Analysis of the split insemination (IVF+ICSI) treatment in patients with borderline semen in first cycle.

PURPOSE: The aim of this study was to verify the effectiveness of the split insemination (IVF+ICSI) in patients with borderline semen for the first cycle, we furthermore compared the treatment outcome of the conventional IVF and ICSI on sibling oocytes with the rate of blastocyst formation in different days (day 5 or day 6) as primary outcome and pregnancy as secondary outcome to provide theoretical support for embryo selection. METHODS: Between January 2017 and November 2021,190 couples undergoing the split insemination (IVF+ICSI) cycle were enrolled in the study with at least eight oocytes and the borderline semen in first cycle to analyze the basic characteristics and clinical outcome. The remaining 157 patients were analyzed in this study to compare the IVF and ICSI after excluding those who were completely unfertilized by IVF (n=33) including a patient who was completely unfertilized by IVF and ICSI. RESULTS: Present study showed that about 32(32/190,16.8%) patients with borderline semen in first cycle were completely unfertilized performing the conventional IVF and only 1(1/190,0.53%) patient was completely unfertilized using the IVF and ICSI in the split insemination (IVF+ICSI), the rate of total fertilization failure (TFF) was significantly decrease by the ICSI treatment (16.8%&0.53%,P<0.0001). By the split oocytes, the fertilization rate was significantly superior in ICSI(729/982,74.2%) compared to IVF (486/940, 51.7%, P<0.0001), the usable blastocyst and high-quality blastocyst rate on the fifth day were statistically superior in IVF compared to ICSI(31.3% &22.8%,P=0.009) (27.3%&20.6%,P=0.03), The pregnancy rate, implantation rate and live birth rate in the IVF first cycle were higher than the ICSI(75.9%&64%, respectively) (52.3%&41.8%, respectively)(64.8%&54.7%, respectively),although there was no statistical difference,it is also about ten percentage points difference. CONCLUSIONS: The treatment of sibling oocyte with both IVF and ICSI could be an appropriate choice to prevent TFF and preserve the embryo development potential for the patients with the borderline semen in present study. Furthermore, the embryo development potential from conventional IVF was better than the embryo from the ICSI technology, the ICSI technology may have a negative effect on the embryo development.

Socioeconomic inequality in public satisfaction with the healthcare system in China: a quantile regression analysis.

BACKGROUND: As China pursues better social equality and improvement in public services (healthcare), public satisfaction has been considered as a key performance indicator. There is a great need to better understand the disparities and inequalities in the public satisfaction with its healthcare system. METHODS: Based on Chinese General Social Survey (CGSS) 2015 ( a set of nationally representative survey data, the most recent wave containing information about public satisfaction with the healthcare system), this study utilizes the quantile regression method to analyze how the public satisfaction at high or low quantile of the score distribution varies according to the socio-economic status and healthcare system performance indicators, especially in rural areas. RESULTS: This study found that, at the highest percentile, better Self-Reported-Health (SRH) is associated significantly with a lower satisfaction score (coefficient -4.10, P < 0.01). High socioeconomic status (especially "above average" group) has higher satisfaction scores at both mean (coefficient 3.74, P<0.01) and median (coefficient 3.83, P<0.01). This effect is also significant across the lower quantiles of the satisfaction levels. West and Middle region (the less developed regions) tended to be more satisfied, whereas those in Northeast reported a large negative effect (coefficient -7.07, P < 0.01) at the median. While rural residents generally reported higher levels of satisfaction, rural residents' preference regarding hospital beds and primary care access seems generally to be opposite to that of urban residents. CONCLUSION: Our findings suggest that the ongoing healthcare reform needs to integrate more preventive care to meet the healthy residents' expectation and demands. More attention should be guided to the vulnerable healthcare system in the Northeast region, which has a stagnant local economy. Outcome-based quality care is especially preferred in rural healthcare, in addition to improvement of utilization and access. In addition, the "pro-rich" inequality is an ongoing concern about the system.

The proteomics analysis of the effects of Zhishi Rhubarb soup on ischaemic stroke.

BACKGROUND: Stroke has always been a major threat worldwide but is most severe in China, with 2.5 million new stroke cases each year and 7.5 million stroke survivors, placing a heavy burden on the social and national health care systems. Zhishi Rhubarb Soup (ZRS) is a traditional Chinese medicine (TCM) that has been used clinically for many years in China. To explore the potential mechanism of ZRS in the treatment of stroke, liquid chromatography with mass spectrometry (LC-MS) was performed. METHODS: In this study, a quantitative proteomic method with LC-MS was used to analyse the proteomic differences between MACO samples treated with ZRS and those without ZRS treatment. RESULTS: Liquid chromatography with mass spectrometry (LC-MS) analysis led to the identification of 35,006 peptides, with 5160.0 proteins identified and 4094.0 quantified. Significantly differentially expressed proteins were identified through data analysis, and the difference was found to be more than 1.2 times (P < 0.05). The Gene Ontology (GO) analysis provided a summary of the dysregulated protein expression in the biological process (BP), cell component (CC), and molecular function (MF) categories. Proteins related to brain repair, including BDNF, IL-10, IL-6, and TGF-ß, were found to change significantly, partially demonstrating the effectiveness of ZRS to attenuate tissue injury. CONCLUSION: In this study, LC-MS/MS was performed to assess the effects of ZRS on differentially expressed proteins in rats with cerebral infarction. These promising results could help to improve the understanding of the effects of drugs on stroke.

Changing trend of abdominal regional oxygen saturation in very/extremely low birth weight infants in the early postnatal stage: a prospective study. / 极/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿ç”ŸåŽæ—©æœŸè ¹éƒ¨å±€éƒ¨ç»„ç»‡æ°§é¥±å’Œåº¦å˜åŒ–è¶‹åŠ¿çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the changing trend of abdominal regional oxygen saturation (A-rSO2) in very/extremely low birth weight (VLBW/ELBW) infants after birth. METHODS: The VLBW/ELBW infants who were admitted to the neonatal intensive care unit from September 2019 to May 2021 were enrolled as subjects. Near-infrared spectroscopy was used to monitor A-rSO2 since day 1 after birth for 4 weeks. According to gestational age, the infants were divided into a low gestational age (<29 weeks) group and a high gestational age (≥29 weeks) group. The two groups were compared in terms of A-rSO2 within 4 weeks after birth. RESULTS: A total of 63 VLBW/ELBW infants were enrolled, with 30 infants in the <29 weeks group and 33 in the ≥29 weeks group. A-rSO2 fluctuated within the first 2 weeks after birth in the 63 infants and had the lowest level of 47.9% on day 1 after birth and then gradually increased, reaching the peak level of 67.4% on day 4; it gradually decreased on days 5-9, then gradually increased, and became relatively stable 2 weeks after birth. The ≥29 weeks group had significantly higher A-rSO2 than the <29 weeks group at weeks 1 and 2 after birth (P<0.05), while there was no significant difference in A-rSO2 between the two groups at weeks 3 and 4 after birth (P>0.05). CONCLUSIONS: In infants with VLBW/ELBW, A-rSO2 fluctuates within the first 2 weeks after birth and then gradually becomes stable. A-rSO2 is associated with gestational age within 2 weeks after birth.

Effects of the lncRNA ENST00000623984 on colon cancer and the biological characteristics of colon cancer cells.

The aim of this study was to explore the effects of the lncRNA ENST00000623984 on colorectal cancer. In this study, the expression levels of ENST000000623984 were first examined in tumor tissue and adjacent normal tissue from 40 patients with colorectal cancer and LoVo cells using quantitative real-time PCR. By siRNA transfection, ENST00000623984 expression was knocked down. Using flow cytometry, cell cycle progression and cell viability were examined in basal and knockdown LoVo cells. The CCK-8 assay was used to assess the cell proliferation rate, and the Transwell assay was used to determine the migration and invasion abilities. The ENST000000623984 expression level was increased in colorectal cancer. Knockdown of ENST000000623984 reduced cell viability, proliferation rate, cell migration and invasion. These results suggested that lncRNA ENST000000623984 may be involved in colorectal cancer development.

Effects of Berberine on Diabetes and Cognitive Impairment in an Animal Model: The Mechanisms of Action.

Diabetes is a group of metabolic disorders with an increased risk of developing cognitive impairment and dementia. The hippocampus in the forebrain contains an abundance of insulin receptors related to cognitive function and plays an important role in the pathophysiology of neurodegenerative disorders. Berberine from traditional Chinese medicine has been used to treat diabetes and diabetic cognitive impairment, although its related mechanisms are largely unknown. In this study, a STZ diabetes rat model feeding with a high-fat diet was used to test the effects of berberine compared with metformin. Oral glucose tolerance and hyperinsulinemic-euglycemic clamp were used for glucose metabolism and insulin resistance. The Morris water maze was used to observe the compound effects on cognitive impairment. Serum and hippocampal [Formula: see text]-amyloid peptide (A[Formula: see text], Tau and phosphorylated Tau protein deposition in the hippocampi were measured. The TUNEL assay was used to detect the neuronal apoptosis, supported by histomorphological changes and transmissional electron microscopy (TEM) image. Our data showed that the diabetic rats had a significantly cognitive impairment. In addition to improving glucose metabolism and reducing insulin resistance, berberine significantly improved the cognitive function in the rat. Berberine also effectively decreased the expression of hippocampal tau protein, phosphorylated Tau, and increased insulin receptor antibodies. Moreover, berberine downregulated the abnormal phosphorylation of A[Formula: see text] and Tau protein and improved hippocampal insulin signaling. The TUNEL assay confirmed that berberine reduced hippocampal neuronal apoptosis supported by TEM. Thus, berberine significantly improved the cognitive function in diabetic rats by changing the peripheral and central insulin resistance. The reduction of neuronal injury, A[Formula: see text] deposition, abnormal phosphorylation of Tau protein, and neuronal apoptosis in the hippocampus were observed as the related mechanisms of action.

Berberine and Ginsenoside Rb1 Ameliorate Depression-Like Behavior in Diabetic Rats.

Rhizoma coptidis (Huang-lian) and Asian ginseng have been widely used in the treatment of diabetes and other concurrent diseases with apparent effects. This study investigated the effects of the active ingredients of R. coptidis and ginseng, berberine and ginsenoside Rb1, on depression-like behavior in a rat diabetes model. The animal model was established via a high-fat diet and intraperitoneal injection of streptozotocin, while the animal's depression-like behavior was induced via chronic unpredictable mild stress. These experimental rats were divided into four groups: control, depression-like behavior (DLB), metformin plus fluoxetine hydrochloride (M+FH), and berberine plus ginsenoside Rb1 (B+GRb1) groups. Glucose metabolism and insulin resistance were evaluated by oral glucose test and glucose clamp study. Depression-like behavior was evaluated via behavioral analyses, including forced swim, sucrose preference, elevated plus maze, and open-field tests. HE and Nissl staining, plasma cortisol expression of adrenocorticotropic hormone, and brain-derived neurotrophic factor (BDNF) levels were assayed to explore the mechanisms of action. Compared with the control, rats in the DLB group had a significant increase in the levels of blood glucose and depression-like behavior. The B+GRb1 group significantly improved glucose metabolism and insulin resistance, reduced depression-like behavior, downregulated levels of plasma cortisol and adrenocorticotropic hormone under stress, and upregulated BDNF protein expression compared to the DLB rats. HE and Nissl staining data revealed that B+GRb1 protected neurons from pathological and morphological changes. Thus, berberine and ginsenoside Rb1 not only improved glucose metabolism in diabetic rats but also ameliorated their depression-like behavior under chronic unpredictable stress. Mechanistically, studied data with plasma hormonal levels and brain neuronal pathological/morphological changes supported the observed effects. The combination of berberine and ginsenoside Rb1 may have a clinical value in the management of diabetic patients with depression.

Ryanodine receptor and immune-related molecules in diabetic cardiomyopathy.

Hyperglycaemia is a major aetiological factor in the development of diabetic cardiomyopathy. Excessive hyperglycaemia increases the levels of reactive carbonyl species (RCS), reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the heart and causes derangements in calcium homeostasis, inflammation and immune-system disorders. Ryanodine receptor 2 (RyR2) plays a key role in excitation-contraction coupling during heart contractions, including rhythmic contraction and relaxation of the heart. Cardiac inflammation has been indicated in part though interleukin 1 (IL-1) signals, supporting a role for B and T lymphocytes in diabetic cardiomyopathy. Some of the post-translational modifications of the ryanodine receptor (RyR) by RCS, ROS and RNS stress are known to affect its gating and Ca2+ sensitivity, which contributes to RyR dysregulation in diabetic cardiomyopathy. RyRs and immune-related molecules are important signalling species in many physiological and pathophysiological processes in various heart and cardiovascular diseases. However, little is known regarding the mechanistic relationship between RyRs and immune-related molecules in diabetes, as well as the mechanisms mediating complex communication among cardiomyocytes, fibroblasts and immune cells. This review highlights new findings on the complex cellular communications in the pathogenesis and progression of diabetic cardiomyopathy. We discuss potential therapeutic applications targeting RyRs and immune-related molecules in diabetic complications.

Ranking the Healthcare Resource Factors for Public Satisfaction with Health System in China-Based on the Grey Relational Analysis Models.

(1) Background: Public satisfaction with the health system is a very important comprehensive indicator. Given the limited healthcare resources in a society, it is always important for policymakers to have full information about the priority and the ranking order of the factors of healthcare resources for improving public satisfaction. (2) Methods: Grey Relational Analysis (GRA) is advantageous for satisfaction analysis because satisfaction is a "grey concept" of "having a clear boundary but vague connotation". The data were from the CGSS and the China Health Statistics Yearbook (2013 and 2015), with a total of 15,969 samples (average satisfaction score = 68.5, age = 51.9, female = 49.4%). (3) Results: The government's percentage of total expenditure on healthcare was ranked as the most important factor for public satisfaction with the health system in China in both 2013 and 2015. The second most important factor changed from "Out-of-pocket percentage of individuals" in 2013 to "Hospital beds per thousand populations" in 2015. Meanwhile, "Healthcare workforce per thousand populations" increased from the least important factor in 2013 to the 3rd in 2015. Disparities in the ranking orders of the factors among regions of China were identified too. (4) Conclusions: The analysis results suggest that during recent years the priority of Chinese residents' healthcare satisfaction for healthcare resources has shifted on the national level from economic affordability to more intensive "people-centered" services, while the regional disparities and gaps need to receive more attention and be further improved in the healthcare reform of next round.

Dentists' entrepreneurial intention and associated factors in public hospitals in major cities in Guangdong (South China): a cross-sectional study.

BACKGROUND: A rapid growth in private dentistry in China has been observed during recent years. Promoting the entrepreneurship of dentists has increasingly received attention in both dentistry and dental education worldwide. However, understanding about the unique features of entrepreneurial behaviors of dentists remains inadequate. METHODS: This study examines dentist's entrepreneurial intention (EI), which was represented by his/her intention of leaving the public hospital system to be engaged in the private sector. Through a snowball sampling method, a total of 336 questionnaires from public hospitals in five major cities in Guangdong Province (China) were collected. The association between the dentists' EI and their individual characteristics were analyzed using a logistic regression model. RESULTS: In the sample studied, 35.7% of the respondents reported to have EI. Female dentists are less likely to report EI (OR = 0.365, p = 0.001). Dentists in the age group of 36 to 45 years (OR = 14.205, p = 0.012) and those aged over 45 years (OR = 8.45, p = 0.066) reported respectively a much stronger EI than those in their 20s. Compared with intern dentists, attending dentists (OR = 7.812, p = 0.016) and associate/chief dentists (OR = 9.857, p = 0.021) were significantly more likely to report EI. Those with master level (OR = 0.221, p = 0.021) or doctorate degrees (OR = 0.118, p = 0.005) are much less likely to report EI. Meanwhile, those in mid-large hospitals (with 101-200 employees) (OR = 3.554, p = 0.036) and small hospitals (with < 50 employees) (OR = 2.398, p = 0.044) reported a stronger EI than those in large hospitals. Additionally, dentists' entrepreneurial behaviors, risk aversion attitudes and their family background all have significant associations. CONCLUSIONS: Since dentistry is a knowledge-intensive industry, dentists' entrepreneurial behaviors have their own features. The findings by this study suggest that, accumulation of practical skills in a dental career, as implied by age, professional qualifications and leadership skills, help to promote EI, whereas an academic oriented education degree per se does not. Dentists in mid-large and small hospitals, rather than in top large hospitals in China, have higher EI. Additionally, female dentists may need more social supports to develop a higher EI. These findings have practical implications for the promotion of EI among dentists.

Multi-center investigation of the clinical and pathological characteristics of inflammatory breast cancer based on Chinese Society of Breast Surgery (CSBrs-007).

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor prognosis and outcomes. This study aimed to investigate clinicopathological features, molecular characteristics, and treatments among Chinese patients diagnosed with IBC. METHODS: We collected data of 95 patients with IBC who were treated by members of the Chinese Society of Breast Surgery, from January 2017 to December 2018. The data, including demographic characteristics, pathological findings, surgical methods, systemic treatment plans, and follow-up, were obtained using a uniform electronic questionnaire. The clinicopathological features of different molecular types in patients without distant metastases were compared using the Kruskal-Wallis (H) test followed by post hoc analyses. RESULTS: Lymph node metastasis was noted in 75.8% of all patients, while distant metastasis was noted in 21.4%. Pathological findings indicated invasive ductal and lobular carcinomas in 86.8% and 5.3% of cases, respectively. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) (41.5%) and HR-/HER2+ (20.1%) were the most common biologic subtypes, followed by HR+/HER2+ (19.1%) and HR-/HER2- (19.1%). Stage III IBC was treated via pre-operative neoadjuvant chemotherapy in 87.7% of the cases, predominantly using anthracycline and taxanes. A total of 91.9% of patients underwent surgical treatment. Among them, 77.0% of the patients underwent modified radical mastectomy, 8.1% of whom also underwent immediate breast reconstruction. The Kruskal-Wallis test revealed that the efficacy of chemotherapy significantly differed among those with HR+/HER2- and HR-/HER2- tumors (adjusted P = 0.008), and Ki-67 expression significantly differed in HR-/HER2+ and HR+/HER2+ molecular subtypes (adjusted P = 0.008). CONCLUSION: Our study provides novel insight into clinicopathological characteristics and treatment status among patients with IBC in China, and might provide a direction and basis for further studies. TRIAL REGISTRATION: chictr.org.cn, No. ChiCTR1900027179; http://www.chictr.org.cn/showprojen.aspx?proj=45030.

WSTF acetylation by MOF promotes WSTF activities and oncogenic functions.

Williams syndrome transcription factor (WSTF) is a transcription factor and tyrosine kinase. WSTF overexpression promotes migration and proliferation of various cancers, and Ser158 (WSTFS158) phosphorylation plays an important role in this process. However, the role of the other posttranslational modifications of WSTF is unknown. Here, we report that lysine (K) 426 on WSTF is acetylated by MOF and deacetylated by SIRT1. Mechanistically, male-specific lethal (MSL) 1v1 interaction with WSTF facilitates its interaction with MOF for WSTF acetylation, which in turn promotes WSTFS158 phosphorylation. The kinase and transcriptional regulatory activity of WSTF were enhanced by acetylation. WSTFK426ac levels positively and significantly correlated with tumor size, histological grade, and age. Moreover, we demonstrated that acetylated WSTF promotes cancer cell proliferation, migration, invasion, and tumor formation. In conclusion, we identified the enzymes regulating WSTF K426 acetylation, and demonstrated an acetylation-dependent mechanism that modulates the activities of WSTF and contributes to tumorigenesis. Our findings provide new clues to study WSTF-mediated normal development and disease.

Public satisfaction with the healthcare system in China during 2013-2015: a cross-sectional survey of the associated factors.

OBJECTIVE: We explore how public satisfaction with the healthcare system in China varies with social and economic factors, especially regional variations and changes during 2013-2015. DESIGN: Population-based, cross-sectional survey performed between July 2013 and July 2015. SETTING: General population of China during 2013-2015. PARTICIPANTS: A total of 15 969 participants (women=49.4%, sample-weighted average age=51.9). PRIMARY OUTCOME MEASURE: Public satisfaction with the healthcare system, defined as 'being satisfied' if a respondent's satisfaction score is ≥70 points. RESULTS: The 2-year mean of the satisfaction score of the sample is 68.5 out of 100 points and the score in 2015 is higher than 2013 by 3.5 points. Senior respondents (OR=1.19, p<0.001), rural respondents (OR=1.23, p=0.009) and those with higher socioeconomic status are more likely to report being satisfied. Internal migrants (OR=0.75, p<0.001) and those with a higher level of education are less likely to report being satisfied. Total health expenditure as percentage of gross domestic product and density of hospital beds have a significantly positive association with satisfaction (OR=1.13, p<0.001). Meanwhile, the government's share in total healthcare expenditures has a moderately negative association with satisfaction (OR=0.97, p<0.001). In rural areas, the density of hospital beds has a positive association with satisfaction (OR=1.26, p=0.002). The Northeast region and Shanghai (OR=0.49, p<0.001; OR=0.71, p=0.034) are less likely to report being satisfied and this remained unchanged in 2015. CONCLUSION: There are considerable disparities in public satisfaction with the healthcare system in China, associated with demographic and socioeconomic characteristics, regional locations, urban-rural environment, and regional health resource abundance. Actions are recommended to improve satisfaction with the public healthcare system, especially in the Northeast region of China.