Description: Objective Published research has not considered acute diseases and injuries in assessing the impact of varying disease counts on health-related quality of life (HRQoL). We used Chinese value sets of EQ-5D-3L to examine the relationship between the number of diseases individuals had (including chronic diseases, acute diseases and injuries) and their HRQoL. Methods A total of 19 387 individuals aged 18 years and older were included in the study. Using data from the First Provincial Health Services Survey of Hunan, China, HRQoL was assessed with the EQ-5D-3L scale, a standardized instrument developed by the EuroQoL group. The EQ-5D-3L utility score was calculated using the Chinese EQ-5D-3L value set. This survey coded disease using the list of 133 conditions that was defined by the First Provincial Health Services Survey of Hunan, China, based on the 10th International Classification of Diseases. 126 conditions were disease-related and were therefore included in data analysis. Results Of 15 245 respondents, urban residents and male constituted 53.0% and 48.2%, respectively. 19.3% of respondents had one disease and 5.0% had at least two diseases. Of the five dimensions of the EQ-5D-3L, the pain/discomfort dimension had the highest proportion of moderate or serious problems among the respondents (14.4%, 95% CI 10.5% to 18.2%). The average Visual Analogue Scale (VAS) score and utility score were 78.0 (95% CI 76.9 to 79.1) and 0.958 (95% CI 0.946 to 0.970), respectively. Residents with 1 and ≥2 diseases had higher proportions of moderate or serious problems in five dimensions of the EQ-5D-3L scale during the previous 2 weeks than those without disease after controlling for location (urban/rural), sex, age, education level and household income, respectively (adjusted ORs: 3.1–3.7 and 4.4–6.6, respectively). The mean of the EQ VAS score was 8.4 and 13.6 points lower in respondents with 1 and ≥2 diseases than in respondents without disease; the corresponding mean score difference was 0.048 and 0.086 in EQ-5D-3L utility score. Disease-specific analyses were not conducted due to the inadequacy of sample size. Conclusions The HRQoL of residents aged 18 years and older declines distinctly as the number of diseases increases. Actions should be taken to improve the HRQoL of residents with multiple diseases in China (including acute diseases, chronic diseases and injuries).

Description: The myelodysplastic syndromes (MDSs) include a spectrum of stem cell malignancies characterized by an increased risk of developing acute myeloid leukemia. Heterozygous loss of chromosome 5q (del[5q]) is the most common cytogenetic abnormality in MDS. DIAPH1 is localized to 5q31 and encodes one of the formin proteins, mDia1, which is involved in linear actin polymerization. Mice with mDia1 deficiency develop hematologic features with age mimicking human myeloid neoplasm, but its role in the pathogenesis of MDS is unclear. Here we report that mDia1 heterozygous and knockout mice develop MDS phenotypes with age. In these mice, CD14 was aberrantly overexpressed on granulocytes in a cell-autonomous manner, leading to a hypersensitive innate immune response to lipopolysaccharide (LPS) stimuli through CD14/Toll-like receptor 4 signaling. Chronic stimulation with LPS accelerated the development of MDS in mDia1 heterozygous and knockout mice that can be rescued by lenalidomide. Similar findings of CD14 overexpression were observed on the bone marrow granulocytes of del(5q) MDS patients. Mechanistically, mDia1 deficiency led to a downregulation of membrane-associated genes and a specific upregulation of CD14 messenger RNA in granulocytes, but not in other lineages. These results underscore the significance of mDia1 heterozygosity in deregulated innate immune responses in del(5q) MDS.

Description: Small-conductance Ca 2+ -activated K + (SK Ca ) channels are crucial in regulating vascular tone and blood pressure. The present study tested the hypothesis that SK Ca channels play an important role in uterine vascular adaptation in pregnancy, which is inhibited by chronic hypoxia during gestation. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. Immunohistochemistry revealed the presence of SK Ca channels type 2 (SK2) and type 3 (SK3) in both smooth muscles and endothelium of uterine arteries. The expression of SK2 and SK3 channels was significantly increased during pregnancy, which was inhibited by chronic hypoxia. In normoxic animals, both SK Ca channel opener NS309 and a large-conductance (BK Ca ) channel opener NS1619 relaxed norepinephrine-contracted uterine arteries in pregnant but not nonpregnant sheep. These relaxations were inhibited by selective SK Ca and BK Ca channel blockers, respectively. NS309-induced relaxation was largely endothelium-independent. In high-altitude hypoxic animals, neither NS1691 nor NS309 produced significant relaxation of uterine arteries in either nonpregnant or pregnant sheep. Similarly, the role of SK Ca channels in regulating the myogenic reactivity of uterine arteries in pregnant animals was abrogated by chronic hypoxia. Accordingly, the enhanced SK Ca channel activity in uterine arterial myocytes of pregnant animals was ablated by chronic hypoxia. The findings suggest a novel mechanism of SK Ca channels in regulating myogenic adaptation of uterine arteries in pregnancy and in the maladaptation of uteroplacental circulation caused by chronic hypoxia during gestation.

Description: Objectives This study aimed to assess patients’ healthcare-seeking preferences in mild, chronic, and serious illness; identify influential factors; and examine the reasons underlying patients’ healthcare-seeking preference. Design A retrospective study. Setting The study was conducted in 14 tertiary hospitals in Shanghai, China. Participants Questionnaires were distributed to 1519 patients, and 1114 were completed and returned. All patients participated in the study voluntarily, provided written informed consent, and possessed the ability to complete the questionnaire. Main outcome measures We measured and compared preferences and choice of healthcare providers in patients if they had experienced mild, chronic, or serious illness. Results More than 50% of participants, including those who were 〉60 years of age, had consulted a doctor more than three times during the preceding year, were single, and were most likely to decide not to seek medical treatment. Community health facilities were the most frequently selected healthcare provider in mild illness. In addition, patients who had no personal preference, did not express a preference for a good environment or first-class medical technology, were concerned about close proximity and short waiting times, and pursued low medical costs were most likely to choose a community health facility. General hospitals were the most frequently selected healthcare provider in chronic and serious illness. In addition, patients who earned higher monthly incomes, did not pursue low medical costs, were not concerned about short waiting times or close proximity, and expressed a preference for first-class medical technology, were most likely to choose general hospitals. Conclusion Patients’ healthcare-seeking preference was influenced mainly by healthcare providers’ characteristics, illness severity, and sociodemographic characteristics. These findings indicate that patients’ current healthcare-seeking preference was not ideal and requires optimisation.

Description: Objectives Few studies of tornado injuries have considered differences related to damage levels and Enhanced-Fujita (EF) scale ratings. This study aimed to evaluate the pattern, spectrum and geographical distribution of injuries related to the Yancheng tornado and provide guidelines for effective emergency medical strategies. Setting The study was conducted at three hospitals which treated patients with injuries related to the tornado in Yancheng, China. Participants We obtained the records of 451 patients with tornado-related injuries. Of these, 401 valid trauma medical records were included; 50 other records were excluded for insufficient information. Informed consent was obtained from all patients by telephone. Main outcome measures We analysed patients’ injury sites and types and used the abbreviated injury scale (AIS) to standardise injury severity. Geographical information system and non-parametric tests were used to analyse the effects of geographical factors on casualties. Results Women, middle-aged/elderly individuals (age〉45 years) and children/adolescents (〈18 years) accounted for 51.62%, 77.30% and 12.47% of injured patients, respectively. This caused a dumbbell-shaped age distribution. Head (46.63%), body surface (39.90%) and lower-limb (29.43%) injuries were common, as were soft-tissue injuries (90.77%), fractures (38.90%) and organ damage (19.70%). Minor injuries (AIS=1) were common (60.85%), whereas critical/fatal injuries (AIS≥5) were very rare (2.50%). Although the densities of injury varied among damage levels and EF ratings for different areas, area-wise differences in injury severity (AIS scores) were not significant (p〉0.05). Conclusion We recommend the use of helmets to prevent head injuries caused by tornadoes and suggest prioritising the treatment of high-risk head and multiple-organ injuries. Additionally, medical rescuers should follow the ‘same quality and different quantity’ principle: the injured in all affected areas should receive equal attention, but numbers of medical personnel should be allocated based on the level of effects from the tornado.

Description: Our previous study demonstrated that increased Ca 2+ -activated K + (BK Ca ) channel activity played a key role in the normal adaptation of reduced myogenic tone of uterine arteries in pregnancy. The present study tested the hypothesis that chronic hypoxia during gestation inhibits pregnancy-induced upregulation of BK Ca channel function in uterine arteries. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. Hypoxia during gestation significantly inhibited pregnancy-induced upregulation of BK Ca channel activity and suppressed BK Ca channel current density in pregnant uterine arteries. This was mediated by a selective downregulation of BK Ca channel β1 subunit in the uterine arteries. In accordance, hypoxia abrogated the role of the BK Ca channel in regulating pressure-induced myogenic tone of uterine arteries that was significantly elevated in pregnant animals acclimatized to chronic hypoxia. In addition, hypoxia abolished the steroid hormone-mediated increase in the β1 subunit and BK Ca channel current density observed in nonpregnant uterine arteries. Although the activation of protein kinase C inhibited BK Ca channel current density in pregnant uterine arteries of normoxic sheep, this effect was ablated in the hypoxic animals. The results demonstrate that selectively targeting BK Ca channel β1 subunit plays a critical role in the maladaption of uteroplacental circulation caused by chronic hypoxia, which contributes to the increased incidence of preeclampsia and fetal intrauterine growth restriction associated with gestational hypoxia.

Description: Estrogen receptor-α (ERα) plays a key role in the adaptation of increased uterine blood flow in pregnancy. Chronic hypoxia is a common stress to maternal cardiovascular homeostasis and causes increased risk of preeclampsia. Studies in pregnant sheep demonstrated that hypoxia during gestation downregulated ERα gene expression in uterine arteries. The present study tested the hypothesis that hypoxia causes epigenetic repression of the ERα gene in uterine arteries via heightened promoter methylation. Ovine ERα promoter of 2035 bp spanning from –2000 to +35 of the transcription start site was cloned. No estrogen or hypoxia-inducible factor response elements were found at the promoter. Two transcription factor binding sites, USF –15 and Sp1 –520 , containing CpG dinucleotides were identified, which had significant effects on the promoter activity. The USF element binds transcription factors USF1 and USF2, and the Sp1 element binds Sp1, as well as ERα through Sp1. Deletion of the Sp1 site abrogated 17β-estradiol–induced increase in the promoter activity. In normoxic control sheep, CpG methylation at the Sp1 but not the USF site was significantly decreased in uterine arteries of pregnant as compared with nonpregnant animals. In pregnant sheep exposed to long-term high-altitude hypoxia, CpG methylation at both Sp1 and USF sites in uterine arteries was significantly increased. Methylation inhibited transcription factor binding and the promoter activity. The results provide evidence of hypoxia causing heightened promoter methylation and resultant ERα gene repression in uterine arteries and suggest new insights of molecular mechanisms linking gestational hypoxia to aberrant uteroplacental circulation and increased risk of preeclampsia.