Search

Abstract Background Extracellular vesicles (EVs) are mediators between cancer cells and other types of cells, such as tumor-associated macrophages (TAMs), in the tumor microenvironment. EVs can remodel the tumor microenvironment and regulate tumor progression. However, the underlying molecular mechanism of these interactions remains unclear. Methods First, we explored the effect of TAMs on the survival prognosis of patients with ovarian cancer. Next, we isolated EVs derived from ovarian cancer cells (OV-EVs) through ultracentrifugation and analyzed the capacity of OV-EVs to regulate macrophage polarization in ovarian tumors and in whole peripheral blood. Moreover, we explored the roles of OV-EVs-induced macrophages in tumor progression through in vitro and in vivo assays. Results OV-EVs were encapsulated by macrophages and induced the polarization of macrophages toward the M2 phenotype. Moreover, OV-EVs-induced M2 macrophages promoted angiogenesis and cancer progression both in vitro and in vivo. In addition, OV-EVs-induced macrophages increased the expression level of VEGF and increased the expression level of VEGFR in tumors, which resulted in angiogenesis in ovarian cancer. Conclusions The present study demonstrated that OV-EVs induce M2 polarization in macrophages and promote the progression of ovarian cancer. This study provides novel insight into the mechanism of ovarian cancer progression.

Abstract Background Central nervous system leukemia (CNSL) is one of the major causes of the poor prognosis of childhood leukemia. We aimed to compare the sensitivity of cytomorphology (CM) and flow cytometry (FCM) in diagnosing CNSL, emphasizing the importance of FCM in the diagnosis process. Methods One-hundred-sixty-five children with newly diagnosed B-cell Acute Lymphoblastic Leukemia (B-cell ALL) were included in this study. Cerebrospinal fluid (CSF) samples were taken for routine CSF analysis, CM analysis, and FCM examination. Computed tomography scans and/or magnetic resonance imaging were performed at diagnosis. Patients with CNS2, CNS3, and traumatic lumbar puncture (TLP) at diagnosis received two additional courses of triple intrathecal injections during induction treatment. We compared the sensitivity of FCM and CM in the diagnosis of children with CNSL. Results One hundred and twenty-eight (77.58%) CSF samples were negative by either CM or FCM (CM−/FCM−), four (2.42%) were positive by both CM and FCM (CM+/FCM+), and thirty-three (20%) displayed a single positive finding by FCM (CM−/FCM+) (p = 0.044). By adding two intrathecal injections in the induction treatment, ten children with TLP+ had no CNS relapse, like those with TLP−. However, compared to CNS1 and TLP, the event-free survival (EFS) did not significantly improve in patients with CNS2 and CNS3. Moreover, CNSL status was associated with worse 3-year EFS (p

Abstract Background In 2018, an innovative case-based payment scheme called Diagnosis-Intervention Packet (DIP) was piloted in a large developed city in southern China. This study aimed to investigate the impact of the new payment method on total medical expenditure per case, length of stay (LOS), and in-hospital mortality rate across different hospitals. Methods We used the de-identified patient-level discharge data of hospitalized patients from 2016 to 2019 in our study city. The interrupted time series model was used to examine the impact of the DIP payment reform on inflation-adjusted total expenditure per case, LOS, and in-hospital mortality rate across different hospitals, which were stratified into different hospital ownerships (public and private) and hospital levels (tertiary, secondary, and primary). Results We included 2.08 million and 2.98 million discharge cases of insured patients before and after the DIP payment reform, respectively. The DIP payment reform resulted in a significant increase of the monthly trend of adjusted total expenditure per case in public (1.1%, P = 0.000), tertiary (0.6%, P = 0.000), secondary (0.4%, P = 0.047) and primary hospitals (0.9%, P = 0.039). The monthly trend of LOS increased significantly in public (0.022 days, P = 0.041) and primary (0.235 days, P = 0.032) hospitals. The monthly trend of in-hospital mortality rate decreased significantly in private (0.083 percentage points, P = 0.002) and secondary (0.037 percentage points, P = 0.002) hospitals. Conclusions We conclude that implementing the DIP payment reform yields inconsistent consequences across different hospitals. DIP reform encouraged public hospitals and high-level hospitals to treat patients with higher illness severities and requiring high treatment intensity, resulting in a significant increase in total expenditure per case. The inconsistencies between public and private hospitals may be attributed to their different baseline levels prior to the reform and their different responses to the incentives created by the reform.

Abstract Context A patient classification-based payment system called diagnosis-intervention packet (DIP) was piloted in a large city in southeast China in 2018. Objective This study evaluates the impact of DIP payment reform on total costs, out-of-pocket (OOP) payments, length of stay (LOS), and quality of care in hospitalised patients of different age. Methods An interrupted time series model was employed to examine the monthly trend changes of outcome variables before and after the DIP reform in adult patients, who were stratified into a younger (18–64 years) and an older group (≥ 65 years), further stratified into young-old (65–79 years) and oldest-old (≥ 80 years) groups. Results The adjusted monthly trend of costs per case significantly increased in the older adults (0.5%, P = 0.002) and oldest-old group (0.6%, P = 0.015). The adjusted monthly trend of average LOS decreased in the younger and young-old groups (monthly slope change: -0.058 days, P = 0.035; -0.025 days, P = 0.024, respectively), and increased in the oldest-old group (monthly slope change: 0.107 days, P = 0.030) significantly. The changes of adjusted monthly trends of in-hospital mortality rate were not significant in all age groups. Conclusion Implementation of the DIP payment reform associated with increase in total costs per case in the older and oldest-old groups, and reduction in LOS in the younger and young-old groups without deteriorating quality of care.

Abstract Objectives To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs. Methods Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. Results In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. Conclusions Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.

Abstract Background Rural residents with chronic conditions have a stronger need for health services, which should make using family doctor contract services a priority. This study aimed to evaluate the rate of willingness among rural residents with chronic conditions to contract with family doctors and examine its determinants. Methods A cross-sectional study was conducted from May, 2018 to June, 2018 in Shandong Province in China. A total of 769 rural unsigned residents with chronic conditions were included in the analysis. Using the Andersen model as the theoretical framework, logistic regression models were chosen to analyse the factors associated with willingness to contract with family doctors. Results This study found that the rate of willingness to contract with family doctors among chronic patients in rural Shandong was 46.7%. A higher willingness was observed in those living a further distance from the village clinic (more than 600 m: OR = 1.85, 95%CI =1.17–2.93), having received publicity for family doctor contract services (OR = 1.71, 95% CI = 1.06–2.76), reporting need for utilizing a chronic disease management program (OR = 3.36, 95% CI = 2.20–5.23), and reporting need for higher medical insurance reimbursement (OR = 1.91, 95% CI = 1.28–2.83). Conclusions The prevalence of contract willingness was relatively low among unsigned rural residents with chronic conditions in rural Shandong, China. The need factors were powerful factors affecting their willingness to contract with family doctors. The government should therefore strengthen targeted publicity and education to rural residents with chronic conditions and provide targeted healthcare services, such as chronic disease management programs and medical services with higher reimbursement rates, to promote their willingness to contract with family doctors.

Abstract Background Married female caregivers face a higher risk of an informal care burden than other caregivers. No study has explored the effect of socioeconomic status (SES) on the intensity of informal care provided by married female caregivers in China. The purpose of this study is to empirically examine how the SES of married female caregivers affects the intensity of the informal care they provide for their parents/parents-in-law in China. Methods The data for this study were drawn from 8 waves of the China Health and Nutrition Survey (CHNS). The respondents were married women whose parents/parents-in-law needed care and lived in the same city as them. SES was defined based on four indicators: education, economic status, employment status, and hukou (China’s household registration system). Informal caregivers were divided into three categories: non-caregivers (0 h/week), low-intensity caregivers (less than 10 h/week), and high-intensity caregivers (10 h/week and above). Multinomial logistic regression analysis was used to examine the relation between SES and the likelihood of a low- and high-intensity caregiving among married female caregivers, adjusting for age, family characteristics and survey wave. Results Of the 2661 respondents, high-intensity and low-intensity caregivers accounted for 16.35 and 21.27%, respectively. The multinomial logistic regression results showed that the likelihood of being a high-intensity caregiver versus (vs. a non-caregiver) increased as the caregiver’s educational attainment increased (p

Abstract Background Social integration has been demonstrated to be associated with the health care use among migrants, but few studies have focused on migrant pregnant women. This study aims to explore the association between social integration and childbirth at woman’s hometown (childbirth return) of internal migrant pregnant women in China. Method Using the data of “Monitoring Data of Chinese Migrants” in 2014, a total of 3412 internal migrant pregnant women were included in this study. Social integration was measured by economic integration, acculturation, and identification. The childbirth locations of internal migrant pregnant women were divided into current residency and the woman’s hometown. Univariate logistic regression and two multivariable logistic regression models were employed to assess the association between social integration and childbirth return among internal migrant pregnant women. Result Our study finds that 24.56% of migrant pregnant women choose to have a childbirth return. As for social integration, those who have their own house (OR = 0.351 95% CI 0.207–0.595) in current residence, who have been staying in current residence for at least 5 years (OR = 0.449; 95% CI 0.322–0.626), and who are willing to stay in the current residence for a long time (OR = 0.731; 95% CI 0.537–0.995) are less likely to have a childbirth return. Apart from social integration, our results also show that those migrant pregnant women who are older, who have higher education level, who have at least two family members in current residence, with a migration reason of work and business, who have established health record in the current residency, and who were not covered by medical insurances, are less likely to have a childbirth return. Conclusion Social integration is negatively associated with childbirth return among internal migrant pregnant women in China. To improve the utilization of maternal care services for migrant pregnant women in current residence, targeted policies should be made to improve social integration status for migrant pregnant women.

Abstract Background Providing equal treatment for those who have the same need for healthcare, regardless of their socioeconomic and cultural background, has become a shared goal among policymakers who strive to improve healthcare. This study aims to identify the socioeconomic status (SES) inequities in inpatient service utilization based on need among migrants by using a nationally representative study in China. Methods The data used in this study was derived from the 2014 National Internal Migrant Population Dynamic Monitoring Survey collected by the National Health Commission of China. The sampling frame for this study was taken using the stratified multistage random sampling method. All provincial urban belt and key cities were stratified, and 119 strata were finally determined. We used logistic regression method and Blinder-Oaxaca decomposition and calculated the concentration index to measure inequities of SES in inpatient service utilization based on need. Sample weights provided in the survey were applied in all the analysis and all standard errors in this study were clustered at the strata level. Results Of the total internal migrants, 18.75% unmet the inpatient service need. Results showed that inpatient service utilization concentrated among high-SES migrants (Concentration Index: 0.036, p

Abstract Background Reasonable use of antenatal care (ANC) services by pregnant women played a crucial role in ensuring maternal and child safety and reducing the risk of complications, disability, and death in mothers and their infants. This study aimed to investigate the ANC use, and to explore the factors associated with ANC use among migrant women during the first delivery in China. Methods This study used the data of National Health and Family Planning Commission of People Republic of China in 2014. A total of 1505 migrant primiparous women were included in our current analysis. Frequencies and proportions were used to describe the data. Chi-square tests and multivariate binary logistic regression models were performed to explore the determinants that affect the number of times migrant women used ANC during their first delivery. Results Of the 1505 participants, 279 (18.54%) women received the ANC less than 5 times, and 1226 (81.46%) women used the ANC at least 5 times during the first delivery. The multivariate logistic regression model showed that migrant primiparous women with college and above education(P

Abstract Background γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and reported to maintain the redox homeostasis and insulin secretion function of pancreatic β cells. This study tested the hypothesis that GABA maintains cellular redox status, and modulates glycogen synthase kinase (GSK)-3β and antioxidant-related nuclear factor erythroid 2-related factor 2 (NRF2) nuclear mass ratio in the H2O2-injured RINm5F cells. Methods RINm5F cells were treated with/without GABA (50, 100 and 200 μmol/L) for 48 h and then exposed to 100 μmol/L H2O2 for 30 min. Viable cells were harvested, and dichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to detect reactive oxygen species (ROS) level; cellular redox status and insulin secretion were measured; cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; mitochondrial membrane potential (MMP) was detected by flow cytometry; relative genes levels were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR); western blotting was used to determine protein expression of GSK-3β and p-GSK-3β (Ser9), and nuclear and cytoplasmic NRF2. Results H2O2 increased ROS production, and induced adverse affects in relation to antioxidant defense systems and insulin secretion. These changes were restored by treatment with 100 and 200 μmol/L GABA. In addition, 100 or 200 μmol/L GABA induced membrane depolarization and increased cell viability. These effects were mediated by Caspase-3, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) expression. Western blotting indicated that GABA inhibited GSK-3β by increasing p-GSK-3β (Ser9) level, and directed the transcription factor NRF2 to the nucleus. Conclusion In rat insulin-producing RINm5F cells, GABA exerts its protective effect by regulating GSK-3β and NRF2, which governs redox homeostasis by inhibiting apoptosis and abnormal insulin secretion by exposure to H2O2.

Abstract Background Wounded personnel who work at sea often encounter a plethora of difficulties. The most important of these difficulties is seawater immersion. Common medical dressings have little effect when the affected area is immersed in seawater, and only rarely dressings have been reported for the treatment of seawater-immersed wounds. The objective of this study is to develop a new dressing which should be suitable to prevent the wound from seawater immersion and to promote the wound healing. Methods Shark skin collagen (SSC) was purified via ethanol de-sugaring and de-pigmentation and adjusted for pH. A shark skin collagen sponge (SSCS) was prepared by freeze-drying. SSCS was attached to an anti-seawater immersion polyurethane (PU) film (SSCS + PU) to compose a new dressing. The biochemical properties of SSC and physicochemical properties of SSCS were assessed by standard methods. The effects of SSCS and SSCS + PU on the healing of seawater-immersed wounds were studied using a seawater immersion rat model. For the detection of SSCS effects on seawater-immersed wounds, 12 SD rats, with four wounds created in each rat, were divided into four groups: the 3rd day group, 5th day group, 7th day group and 12th day group. In each group, six wounds were treated with SSCS, three wounds treated with chitosan served as the positive control, and three wounds treated with gauze served as the negative control. For the detection of the SSCS + PU effects on seawater-immersed wounds, 36 SD rats were divided into three groups: the gauze (GZ) + PU group, chitosan (CS) + PU group and SSCS + PU group, with 12 rats in each group, and two wounds in each rat. The wound sizes were measured to calculate the healing rate, and histomorphology and the immunohistochemistry of the CD31 and TGF-β expression levels in the wounded tissues were measured by standard methods. Results The results of Ultraviolet-visible (UV-vis) spectrum, Fourier-transform infrared (FTIR) spectrum, circular dichroism (CD) spectra, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and amino acid composition analyses of SSC demonstrated that SSC is type I collagen. SSCS had a homogeneous porous structure of approximately 200 μm, porosity rate of 83.57% ± 2.64%, water vapor transmission ratio (WVTR) of 4500 g/m2, tensile strength of 1.79 ± 0.41 N/mm, and elongation at break of 4.52% ± 0.01%. SSCS had significant beneficial effects on seawater-immersed wound healing. On the 3rd day, the healing rates in the GZ negative control, CS positive control and SSCS rats were 13.94% ± 5.50%, 29.40% ± 1.10% and 47.24% ± 8.40%, respectively. SSCS also enhanced TGF-β and CD31 expression in the initial stage of the healing period. The SSCS + PU dressing effectively protected wounds from seawater immersion for at least 4 h, and accelerated re-epithelialization, vascularization and granulation formation of seawater-immersed wounds in the earlier stages of wound healing, and as well as significantly promoted wound healing. The SSCS + PU dressing also enhanced expression of TGF-β and CD31. The effects of SSCS and SSCS + PU were superior to those of both the chitosan and gauze dressings. Conclusions SSCS has significant positive effects on the promotion of seawater-immersed wound healing, and a SSCS + PU dressing effectively prevents seawater immersion, and significantly promotes seawater-immersed wound healing.