Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

[The effects and mechanisms of Gefitinib on airway inflammation and airway remodeling in C57BL/6 mice with asthma].

Objective: To investigate the effects of the epidermal growth factor receptor(EGFR) inhibitor Gefitinib on airway inflammation and airway remodelling in asthmatic C57BL/6 mice, and to analyze its possible mechanisms. Methods: Male C57BL/6 mice, aged 6-8 weeks, were randomly assigned into five groups: Group A (control group), Group B (asthma group), Group C (asthma+20 mg/kg gefitinib group), Group D (asthma+40 mg/kg gefitinib group), and Group E (40 mg/kg gefitinib group), with seven mice per group. Mice were sensitized by intraperitoneal injection of a mixture of 0.2 ml solution containing OVA and Al(OH)3 [20 µg OVA+2 mg Al(OH)3 dissolved in 0.2 ml of physiological saline] at Day 0 and 14. Starting from Day 25 to 31, Group B, C, and D were challenged with nebulization of 1% OVA solution (8 ml) to induce asthma, once a day for approximately 40 minutes, with continuous aerosolization for 7 days. Group C and D were given 0.2 ml of Gefitinib dissolved in 0.5% carboxymethylcellulose sodium (CMCNa) by gavage half an hour before challenging, and Group E was simultaneously given with 0.2 ml of Gefitinib dissolved in 0.5% CMCNa only. Group A and B were given an equivalent volume of 0.5% CMCNa by gavage. After 24 h of final challenge, the bronchoalveolar lavage fluid (BALF) was prepared for the determination of total cell count and eosinophil count. The levels of total immune globulin E (IgE) in serum and interleukin (IL)-4, IL-5 and IL-13 in BALF and lung tissue homogenates were measured by ELISA. The mRNA expression levels of IL-4, IL-5, IL-13 in lung were measured. Immunohistochemistry and Western blot experiments were used to detect the expression levels of EGFR in lung tissues. Results: In Group B, the level of total IgE in serum, total cell count, eosinophil count, the levels of IL-4, IL-5, IL-13 in BALF and the phosphorylation of EGFR and its downstream activation in lung were higher than those in Group A (all P<0.05). The levels of total IgE in serum [(261.32±44.38) ng/ml, (194.09±52.39) ng/ml vs (1 023.70±105.51) ng/ml], total cell count [(23.70±4.08)×105/ml, (14.92±4.06)×105/ml vs (35.36±6.30)×105/ml], eosinophil count [(108.00±13.69)×104/ml, (67.00±17.28)×104/ml vs (147.86±20.06)×104/ml], IL-4 [(36.42±4.48) pg/ml, (30.45±8.12) pg/ml vs (58.72±7.17) pg/ml], IL-5 [(16.20±4.62) pg/ml, (13.38±5.14) pg/ml vs (23.46±5.38) pg/ml], IL-13 [(18.45±7.28) pg/ml, (14.33±7.70) pg/ml vs (104.12±24.66) pg/ml] in BALF of Group C and D were lower than those in Group B (all P<0.05). The levels of IL-4, IL-5, and IL-13 as well as their mRNA levels in the lung tissue of Group C and D were lower than those in Group B (all P<0.05). In Group C and D, the positive expression rate of phosphorylated epidermal growth factor receptor (p-EGFR) in lung tissue [(40.53±6.80)%, (23.60±4.42)% vs (70.78±5.36)%], p-EGFR/EGFR (61.68±7.48, 51.13±5.19 vs 105.90±11.66), phosphorylated extracellular regulated protein kinase (p-Erk)/extracellular regulated protein kinase (Erk) (75.28±7.11, 47.54±4.83 vs 98.76±4.71), and phosphorylated protein kinase B (p-Akt)/protein kinase B (Akt) (96.24±5.40, 68.52±2.73 vs 103.30±4.52) was lower than those of Group B (all P<0.05). There was no statistically significant difference in the relevant indicators between Group A and E (all P>0.05). Conclusion: Gefitinib may alleviate airway inflammation and airway remodeling in asthmatic mice by inhibiting EGFR phosphorylation and affecting the activation of downstream Erk and Akt.

[Analysis on occupational dust or harmful gas exposure and protection in people aged 40 and above in China, 2019-2020].

Objective: To understand the current status of occupational exposure to dust or harmful gases and occupational protection in people aged ≥40 years in China, and provide data support for the prevention and control of occupational dust or harmful gas exposure. Methods: The data were obtained from the surveillance for chronic obstructive pulmonary disease (COPD) in adults aged ≥40 years selected by multi-stage stratified cluster sampling from 125 surveillance points in 31 provinces (autonomous regions and municipalities) during 2014-2015 and 2019-2020, and relevant information about occupational dust or harmful gas exposure and protection measures were collected through face-to-face interviews. Occupational dust or harmful gas exposure rate and occupational protection rate were estimated by using weighting complex sampling methods, and then the results were compared. Results: From 2014 to 2015 and from 2019 to 2020, a total of 71 061 and 71 023 individuals aged ≥40 years were surveyed, respectively. The rate of occupational exposure to dust or hazardous gas was 33.8% (95%CI: 29.9%-37.7%) during 2019-2020. The occupational exposure rate was higher in men than in women and in rural residents than in urban residents. With the increase of education level, the rate of occupational exposure to dust or harmful gas showed a downward trend. The protection rate against occupational dust or hazardous gas exposure was 47.9% (95%CI: 43.2%-52.6%) during 2019-2020. Compared with 2014-2015, the rate of occupational exposure to dust or hazardous gas decreased by 10.7 percentage points in different gender, area and occupational groups and the occupational protection rate increased by 21.9 percentage points during 2019-2020. The decrease in occupational exposure rate was higher in western China than in eastern and central China, and the increase in occupational protection rate was higher in western China than in eastern and central China. Conclusions: The rate of occupational exposure to dust or harmful gas decreased and the rate of occupational protection against dust or harmful gas exposure increased in China during 2019-2020. However, about one-third of the population still suffer from the occupational exposure, and less than half of them take protection measures. It is necessary to pay more attention to the key populations, such as workers with lower cultural level and rural migrant workers, in occupational health practice.

[Analysis on passive smoking exposure in adults aged 40 years and above in China, 2019-2020].

Objective: To understand the passive smoking exposure status in adults aged ≥40 years in China. Methods: Local residents aged ≥40 years were enrolled as study subjects from 125 areas of chronic obstructive pulmonary disease (COPD) surveillance during 2014-2015 and 2019-2020 in 31 provinces of China. A total of 74 559 adults aged ≥40 years were selected through multi-stage stratified cluster sampling for a face to face questionnaire survey and the data from 64 142 study subjects were used for the analysis. The passive smoking exposure rate, the proportions of the adults reporting passive smoking exposure at four types of places and the proportion of the adults living with daily smokers were described by using complicated sampling weighting method, the related factors were analyzed and the results were compared with the data of COPD surveillance during 2014-2015. Results: The passive smoking exposure rate in the adults aged ≥40 years was 46.4% (95%CI: 44.1%-48.8%) in China during 2019-2020, and the rate was higher in women (47.2%, 95%CI:44.8%-49.7%) than in men (44.8%, 95%CI:42.0%-47.6%) and lower in the older people. The office workers had the highest passive smoking exposure rate. The proportions of those reporting passive smoking exposure at homes, workplaces, restaurants, and public transports were 24.3% (95%CI:22.2%-26.4%)、23.3% (95%CI:21.1%-25.5%)、6.6% (95%CI:5.3%-7.9%) and 2.2% (95%CI:1.6%-2.7%). The higher education level the adults had, the less passive smoking exposure at home they reported. The proportions of those living with daily smokers before 14 years old and since 14 years old were 56.4% and 59.2%. Compared with the data during 2014-2015, the overall passive smoking exposure rate in the adults aged ≥40 years during 2019-2020 showed an increase, and the difference was not significant (P=0.356); The passive smoking exposure rate at homes declined, but the exposure rate at workplaces increased, with the biggest increase found in those being engaged in farming, forestry, husbandry, fishery and water conservancy. Multivariate analysis indicated that the factors influencing the passive smoking exposure and the exposure proportions at different places included gender, age, occupation, and education level. Conclusions: The passive smoking exposure rate in China is still high, especially in those being engaged in farming, forestry, husbandry, fishery and water conservancy. It is necessary to strengthen supervision of the enforcement of current smoking bans in public places and promote the legislation of ban smoking in public places. More attention should be paid to smoking ban and protection against passive smoking exposure in women, people with lower education level and people being engaged in in farming, forestry, husbandry, fishery and water conservancy.

[Prevalence of exposure to household cooking oil fumes in women aged 40 years and older in China, 2019].

Objective: To understand the prevalence of exposure to household cooking oil fumes in women ≥40 years old. Methods: The data were from Chronic Obstructive Pulmonary Disease (COPD) Surveillance in China during 2019-2020, which selected permanent residents ≥40 years old from 125 counties (districts) in 31 provinces (autonomous regions and municipalities) across the country by multi-stage stratified cluster random sampling method. The relevant demographic information and cooking oil fumes were collected by face-to-face interview. Our study served 37 164 women with complete cooking practice information as the subject. After complex sample weighting, we analyzed the prevalence of cooking oil fumes exposure in women from cooking time, kitchen characteristics, and Self-reported cooking oil fumes exposure. Results: In 2019, 83.9% (95%CI: 82.1%-85.7%) and 4.5% (95%CI: 3.8%-5.2%) of Chinese women ≥40 years old cooked daily and often, respectively. The average daily cooking duration is 1.8 hours/day, 31.1% of women who cooked daily more than 2.0 hours, and the average cumulative cooking years of cooking women were 32.8 years. 79.3% of cooking women used ventilation devices, and 3.2% cooked in the living room. 8.9% and 7.2% of cooking women in south China and northwest China cooked in the living room, significantly higher than in other regions (P=0.036). The self-reported exposure rate to cooking oil fumes was 81.0% (95%CI: 79.3%-82.7%). Rural, older, lower education level and women engaged in agriculture had a higher proportion of cooking daily, average daily cooking duration, cumulative cooking years, the proportion of cooking in the living room, and rate of self-reported cooking oil fumes exposure, but a lower proportion of using ventilation devices during cooking (P<0.001). Conclusions: The exposure to household cooking oil fumes was serious in Chinese women, and some women still did not take any ventilation measures when cooking. More attention should be paid to the exposure to home cooking oil fumes and its health hazards in women, especially those with lower socioeconomic status.

[Analysis of disease composition and primary surgical procedures in pediatric secondary glaucoma inpatients: a single-center study].

Objective: To analyze the disease composition and primary surgical procedures in pediatric inpatients with secondary glaucoma. Methods: A retrospective case series study was conducted. Clinical data of children aged≤16 years with secondary glaucoma who were admitted to the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 1, 2017, and December 31, 2021, were included. The patients were classified according to the Childhood Glaucoma Research Network (CGRN) classification system, and their diagnoses, underlying factors, gender, age of onset, affected eye(s), age and type of initial surgery, and ophthalmic examination data were analyzed. Statistical analysis was performed using Kruskal-Wallis rank sum test and χ2 test. Results: A total of 540 patients (744 eyes) were included in this study, comprising 319 males (59.1%) and 221 females (40.9%). Unilateral disease was observed in 336 cases (62.2%), while bilateral involvement was present in 204 cases (37.8%). The age of onset was 4.0 (0.0, 9.0) years, and the median age of the first anti-glaucoma surgery was 5.0 (0.7, 10.0) years. Among them, there were 195 cases (36.1%) of secondary glaucoma associated with non-acquired ocular anomalies (SCG-O), with a median age of onset of 0.0 (0.0, 4.0) years, and 97 of these cases (49.7%) were male. secondary glaucoma associated with non-acquired systemic disease or syndrome (SCG-S) were observed in 68 cases (12.6%), with a median age of glaucoma onset of 0.1 (0.0, 4.0) years, and 47 of these cases (69.1%) were male. Secondary glaucoma associated with acquired conditions (SCG-A) accounted for 192 cases (35.6%), with a median age of onset of 9.0 (5.0, 13.0) years, and 125 of these cases (65.1%) were male. There were 85 cases (15.7%) of secondary glaucoma following cataract surgery (SCG-C), with a median age of onset of 3.0 (0.8, 7.0) years, and 50 of these cases (58.8%) were male. Male patients were predominant in SCG-S and SCG-A, with 47 cases (69.1%) and 125 cases (65.1%), respectively (χ2=9.94, 17.52; P=0.002,<0.001). Except for SCG-O, all other types of pediatric secondary glaucoma predominantly affected only one eye: SCG-S in 52 cases (76.5%), SCG-A in 128 cases (66.7%), and SCG-C in 54 cases (63.5%) (χ2=19.06, 21.33, 6.22; all P<0.05). The highest proportion of SCG-O was attributed to congenital ectropion uveae (46 cases, 23.6%). Sturge-Weber syndrome was the most common SCG-S (45 cases, 66.3%), while SCG-A mostly resulted from trauma (59 cases, 30.8%) and corticosteroid use (56 cases, 29.2%). Trabeculectomy (211 eyes, 30.8%) and glaucoma drainage device implantation (197 eyes, 28.7%) were the most frequently performed primary surgical procedures. Conclusions: SCG-O and SCG-A were found to be common types of pediatric secondary glaucoma. The age of onset and the choice of primary anti-glaucoma surgical procedures varied among different types of pediatric secondary glaucoma. However, overall, trabeculectomy and glaucoma drainage device implantation were the primary surgical procedures predominantly employed.

[Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience].

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.

The tumor suppressor role and ceRNA network of miR-1294 in cancer.

miRNAs are endogenous small RNAs that are important regulators of gene expression. miR-1294 was found to be significantly down-regulated in 15 cancers and regulated by 21 upstream regulators. miR-1294 affects the proliferation, migration, invasion, and apoptosis of cancer cells. The target genes of miR-1294 are involved in the PI3K/AKT/mTOR, RAS, and JAK/STAT signaling pathways. Six target genes of miR-1294 are the targets of a variety of drugs. Low expression of miR-1294 is associated with resistance to cisplatin and TMZ and a poorer prognosis in patients with ESCC, GC, EOC, PDAC, or NSCLC. Therefore, this work outlines the molecular mechanisms and provides a basis for the clinical significance of the tumor suppressor miR-1294 in cancer.

Pseudoangiomatous stromal hyperplasia of the breast, imaging and clinical perspective: A review.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast pathology, which most commonly presents incidentally along with other breast pathologies. The etiology and pathogenesis of PASH are still unknown; however, there is some evidence suggesting PASH is hormone dependent. The clinical history, presentation, and imaging appearance of PASH are variable. Clinically, PASH has a wide spectrum of presentations, from being silent to gigantomastia. On imaging, PASH demonstrates various benign to suspicious features. Here we summarize PASH's clinical presentation, histopathology, imaging features, and management.

[Prevalence of smoking in adults aged 40 years and above in China, 2019-2020].

Objective: To understand the prevalence of smoking and its change in adults aged ≥40 years in China and provide evidence for the development of chronic obstructive pulmonary disease (COPD) prevention and control strategies. Methods: The data of this study were obtained from COPD surveillance in China during 2014-2015 and during 2019-2020. The surveillance covered 31 provinces (autonomous regions and municipalities). A multi-stage stratified cluster random sampling were used to select residents aged ≥40 years, and face-to-face interviews were conducted to collect the information about their tobacco use. After complex sampling weighting of the samples, the current smoking rate, average age to start smoking and average daily cigarette consumption of people with different characteristics during 2019-2020 were estimated, and the changes in the current smoking rate and average daily cigarette consumption were analyzed from 2014-2015 to 2019-2020. Results: During 2019-2020, the current smoking rate in adults aged ≥40 years was 27.2%, and the rate was much higher in men (52.1%) than in women (2.5%).The average age of the smokers to start smoking was 20.0 years old, and men usually started smoking at younger age (19.6 years) compared with women (27.9 years). The average daily cigarette consumption of daily smokers was 18.0 sticks, and the consumption of men (18.3 cigarettes) was higher than that of women (11.1 cigarettes). Compared with the surveillance results during 2014-2015, the current smoking rate had decreased by 2.8 percentage points in the general population, 4.1 percentage points in males, 1.6 percentage points in females, and the urban and rural areas fell by 3.1 percentage points and 2.5 percentage points, respectively. The average daily cigarette consumption decreased by 0.6 sticks. Conclusions: In recent years, the current smoking rate and average daily cigarette consumption in adults aged ≥40 years decreased in China, but smoking is still common in more than quarter of this population and more than half of men aged ≥40 years. It is necessary to take targeted tobacco control measures based on population and regional characteristics to further reduce the smoking level of the population.

[Clinical characteristics of Danon disease].

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

[Clinical features, risk factors and prognosis of idiopathic dilated cardiomyopathy complicated by ischemic stroke].

Objective: To analyze the clinical features, risk factors and prognosis of idiopathic dilated cardiomyopathy (DCM) complicated with ischemic stroke (IS) (DCM-IS). Methods: The clinical data of patients with idiopathic DCM (n=613) in Beijing Anzhen Hospital, Liangxiang Hospital and Fuxing Hospital from January 2016 to December 2020 were retrospectively collected, and among them, 123 cases were DCM-IS. Clinical features of patients with DCM-IS were summarized and multivariate logistic regression model was utilized to analyze the independent risk factors of DCM-IS. Furthermore, 1-year follow-up was conducted and Kaplan-Meier curve was adopted to analyze the prognosis of DCM, using all-cause death and heart transplantation as adverse outcomes. Results: Among the 70 patients with DCM-IS, 6 patients (8.6%, 6/70) were in accordance with the subtype of large artery atherosclerosis, and 47 patients (67.1%, 47/70) were in line with the subtype of cardiogenic embolism, and small artery occlusion subtype (ie, lacunar infarction) were detected in 17 cases (24.3%, 17/70). Hypertension [odds ratio (OR)=1.617, 95% confidence interval (CI): 1.049-2.491, P=0.029], hyperlipidemia (OR=1.918, 95%CI: 1.198-3.073, P=0.007), atrial fibrillation (AF) (OR=1.617, 95%CI: 1.016-2.572, P=0.043), lower estimated glomerular filtration rate (eGFR) (OR=0.986, 95%CI: 0.977-0.996, P=0.005) and a higher incidence of intracardiac thrombus (OR=6.127, 95%CI: 3.174-11.827, P<0.001) were risk factors for DCM-IS. The overall 1-year survival rate was lower in DCM-IS patients (70.7%) than DCM patients without stroke (83.6%, P=0.004), and the main causes of death included obstinate heart failure (3 cases of DCM-IS, and 5 cases of non-DCM-IS) and malignant arrhythmia (DCM-IS) (22 cases of DCM-IS, and 18 cases of non-DCM-IS). Conclusions: Among IS patients with idiopathic DCM, cardioembolism is the most common, followed by lacunar infarction, and the large-artery atherosclerotic subtype is the least common.Hypertension, hyperlipidemia, AF, lower eGFR value and higher incidence of intracardiac thrombus are risk factors for DCM-IS. DCM patients complicated with IS have poor short-term prognosis, and obstinate heart failure and malignant arrhythmia are their main causes of death.

[Identification and functional analysis of combined oxidative phosphorylation deficiency 28 gene mutation].

Objective: To report a case of combined oxidative phosphorylation deficiency 28 (COXPD28) in China, identified the pathogenic mutation and explored the pathogenic mechanism preliminarily. Methods: The clinical characteristics of a patient with COXPD28 were retrospectively analyzed and the pathogenic mutations were identified by mitochondrial gene sequencing and whole exome sequencing. The wild-type and mutant plasmids of pathogenic genes were constructed, and effect of mutation on protein expression by quantitative real-time PCR (qPCR) and Western blot were evaluated. Statistical methods mainly used one-way ANOVA and LSD test. Results: A 21 year old female patient presented with lactic acid poisoning due to repeated chest distress and wheezing since childhood. The sequencing of the whole exon group gene found that solute carrier family 25 member 26 (SLC25A26) gene had a compound heterozygous mutation (c.34G>C, p.A12P; c.197C>A, p.A66E), which was the first report in China. In vitro function test showed that the expression levels of SLC25A26 mRNA and S-adenosylmethionine carrier (SAMC) protein in cells transfected with SLC25A26 mutant plasmid were significantly lower than those transfected with wild type plasmid. The p.A66E mutant plasmid reduced the expression level of SLC25A26 mRNA and SAMC protein to 6% and 26% of wild type plasmids respectively (both P<0.001), while p.A12P mutant plasmid decreased to 62% and 82% of wild type plasmids respectively (P<0.001, P=0.044). When the double mutant (p.A66E+p.A12P) plasmids were co-transfected, the expression levels of SLC25A26 mRNA and SAMC protein decreased to 47% and 57% of the wild type plasmids, respectively (P<0.001, P=0.001). Conclusion: The pathogenic mutation gene of this patient with COXPD28 is SLC25A26 gene mutation (p.A66E, p.A12P), which causes the decrease of SLC25A26 expression level, mitochondrial oxidative phosphorylation dysfunction, and induces COXPD28.

Implementing nitrous oxide cracking technology in the labour ward to reduce occupational exposure and environmental emissions: a quality improvement study.

Nitrous oxide, a potent greenhouse gas, is a common labour analgesic. One method which may reduce its carbon footprint is to 'crack' the exhaled gas into nitrogen and oxygen using catalytic destruction. In this quality improvement project, based on environmental monitoring and staff feedback, we assessed the impact of nitrous oxide cracking technology in the maternity setting. Mean ambient nitrous oxide levels were recorded during the final 30 minutes of uncomplicated labour in 36 cases and plotted on a run chart. Interventions were implemented in four stages, comprising: stage 1, baseline (12 cases); stage 2, cracking with nitrous oxide delivered and scavenged via a mouthpiece (eight cases); stage 3, cracking with nitrous oxide via a facemask with an air-filled cushion (eight cases); stage 4, cracking with nitrous oxide via a low-profile facemask, and enhanced coaching on the use of the technology (eight cases). The median ambient nitrous oxide levels were 71% lower than baseline in stage 2 and 81% lower in stage 4. Staff feedback was generally positive, though some found the technology to be cumbersome; successful implementation relies on effective staff engagement. Our results indicate that cracking technology can reduce ambient nitrous oxide levels in the obstetric setting, with potential for reductions in environmental impacts and occupational exposure.

[Hypoxia promotes differentiation of human induced pluripotent stem cells into embryoid bodies in vitro].

OBJECTIVE: To investigate effects of physiological hypoxic conditions on suspension and adherence of embryoid bodies (EBs) during differentiation of human induced pluripotent stem cells (hiPSCs) and explore the underlying mechanisms. METHODS: EBs in suspension culture were divided into normoxic (21% O2) and hypoxic (5% O2) groups, and those in adherent culture were divided into normoxic, hypoxic and hypoxia + HIF-1α inhibitor (echinomycin) groups. After characterization of the pluripotency with immunofluorescence assay, the hiPSCs were digested and suspended under normoxic and hypoxic conditions for 5 days, and the formation and morphological changes of the EBs were observed microscopically; the expressions of the markers genes of the 3 germ layers in the EBs were detected. The EBs were then inoculated into petri dishes for further culture in normoxic and hypoxic conditions for another 2 days, after which the adhesion and peripheral expansion rate of the adherent EBs were observed; the changes in the expressions of HIF-1α, ß-catenin and VEGFA were detected in response to hypoxic culture and echinomycin treatment. RESULTS: The EBs cultured in normoxic and hypoxic conditions were all capable of differentiation into the 3 germ layers. The EBs cultured in hypoxic conditions showed reduced apoptotic debris around them with earlier appearance of cystic EBs and more uniform sizes as compared with those in normoxic culture. Hypoxic culture induced more adherent EBs than normoxic culture (P < 0.05) with also a greater outgrowth rate of the adherent EBs (P < 0.05). The EBs in hypoxic culture showed significantly up-regulated mRNA expressions of ß-catenin and VEGFA (P < 0.05) and protein expressions of HIF-1 α, ß-catenin and VEGFA (P < 0.05), and their protein expresisons levels were significantly lowered after treatment with echinomycin (P < 0.05). CONCLUSION: Hypoxia can promote the formation and maturation of suspended EBs and enhance their adherence and post-adherent proliferation without affecting their pluripotency for differentiation into all the 3 germ layers. Our results provide preliminary evidence that activation of HIF-1α/ß-catenin/VEGFA signaling pathway can enhance the differentiation potential of hiPSCs.

[Prevalence of chronic respiratory symptoms and dyspnea and related factors in residents in China].

Objective: To understand the prevalence of chronic cough, chronic expectoration and dyspnea and related factors in residents aged ≥40 years in China, and provide basic data for the prevention and control of chronic respiratory diseases. Methods: Data were from 2014-2015 chronic obstructive pulmonary disease surveillance in China. The information about chronic respiratory symptoms were collected by face-to-face interview. The prevalence rates of chronic cough, chronic expectoration, dyspnea and chronic respiratory symptoms and their 95%CI were estimated with complex sampling weights. Results: A total of 75 082 subjects were included in the analysis. The prevalence rates of chronic cough, chronic expectoration, dyspnea and chronic respiratory symptoms in the Chinese aged ≥40 years were 3.75% (95%CI: 3.38%-4.11%), 5.83% (95%CI: 5.40%-6.26%), 2.45% (95%CI: 2.02%-2.87%) and 8.93% (95%CI: 8.25%-9.62%), respectively. The prevalence rates of chronic cough, chronic expectoration, dyspnea and chronic respiratory symptoms in patients with chronic respiratory diseases were relatively higher, which were 10.27%, 13.85%, 6.43%, 20.72% respectively. Multivariate logistic regression analysis showed that age, region, education level, occupation, BMI, family history of respiratory diseases, history of severe respiratory infections in childhood, exposure to dust or chemicals in workplace and smoking status affected the prevalence of chronic cough, chronic expectoration and dyspnea. The prevalence of the three types of chronic respiratory symptoms increased significantly with age, which were higher in western region, smokers and underweight/obese subjects. The three prevalence rates mentioned above were higher in those with a history of severe respiratory infection in childhood, those exposed to biomass fuel in household, and those exposed to dust or chemicals in workplace. Conclusions: The prevalence rate of chronic respiratory symptoms was high in residents aged ≥40 years in China. Many factors affected the prevalence of chronic respiratory symptoms. Comprehensive prevention and control measures targeting risk factors should be taken to reduce the burden of chronic respiratory diseases.

Clinical characteristics and microbiology of nosocomial enterococcal bloodstream infections in a tertiary-level hospital: a retrospective study, 2007-2019.

BACKGROUND: Enterococci are important pathogens causing nosocomial bloodstream infections (BSIs) and cannot be treated with appropriate timely empirical antibiotics due to their natural resistance to many kinds of antibiotics. AIM: To analyse the clinical characteristics and microbiological features of nosocomial bloodstream infections caused by enterococci. METHODS: The clinical characteristics and microbiological features of nosocomial enterococcal BSI patients in Xiamen University Zhongshan Hospital were examined in a case-controlled retrospective study. All patient information was collected through an electronic surveillance system. FINDINGS: A total of 199 cases were identified as nosocomial enterococcal BSIs over a period of 13 years. The incidence of BSIs fluctuated from 0.21% to 0.81%. In the distribution of wards, enterococcal BSIs in hepatobiliary surgery ranked first. Intra-abdominal diseases (odds ratio: 3.36; 95% confidence interval: 2.15-5.27; P < 0.001), chemotherapy history (4.37; 2.06-9.25; P < 0.001), and urinary catheterization (2.34; 1.52-3.61; P < 0.001) were risk factors for nosocomial enterococcal BSI acquisition. Vancomycin-resistant enterococci and linezolid-insensitive enterococci strains were not found. CONCLUSION: Patients with a history of intra-abdominal disease, chemotherapy and urinary catheterization are at higher risk of nosocomial enterococcal bloodstream infections. The enterococcus strains were still sensitive to commonly used antibiotics.

[Tobacco dependence status and influencing factors among smokers aged 40 or older in China].

Objective: To understanding tobacco dependence and its influencing factors among smokers aged 40 or older in China and provide scientific data for the implementation of smoking cessation intervention. Methods: The data of this study were collected from 125 surveillance sites in 31 provinces (autonomous regions and municipalities) of chronic obstructive pulmonary disease (COPD) surveillance in China (2014 and 2015). The relevant variables of smoking status and tobacco dependence among people aged 40 or older were collected by face-to-face interview. The weighted proportion of tobacco dependence and its 95%CI and influencing factors among current smokers and daily smokers aged 40 or older in China were estimated with complex sampling weights. Results: A total of 22 380 current smokers and 19 999 daily smokers were included in the analysis. The proportion of high tobacco dependence of current smokers aged 40 or older was 31.1% (29.3%-32.9%). The proportion of high tobacco dependence was higher in men than in women, and higher in rural smokers than urban smokers. The proportion was 33.3% (31.3%-35.2%) in 40 to 59 years old smokers, which was higher than older age group. The proportion of high tobacco dependence among daily smokers aged 40 or older was 35.0% (33.0%-37.0%), and was 35.8% (33.8%-37.8%) in men and 22.0% (16.8%-27.2%) in women. Among current smokers and daily smokers, with the decrease of education level, the proportion of high tobacco dependence increased. The proportion of high tobacco dependence of smokers who started smoking before 18 years old was significantly higher than those who started smoking after 18 years old. The ratio of high tobacco dependence of smokers with chronic respiratory symptoms was higher than that of asymptomatic smokers. There was no significant difference in the tobacco dependence between patients with chronic diseases or chronic respiratory diseases and non patients (P>0.05). Smokers with diabetes, cardiovascular and cerebrovascular diseases and hypertension had a slightly lower proportion of high tobacco dependence than smokers without above diseases (P<0.05). Multivariate logistic regression analysis showed that men, central and eastern regions, 40-59 age group, engaged in agriculture, forestry, animal husbandry, fishery industry, water conservancy, manufacture, transportation and commercial services occupation, low education level and smoking onset age less than 18 years old had a high risk of high tobacco dependence. Conclusions: The proportion of high tobacco dependence among current smokers aged 40 or older is high in China, so there is a huge demand for smoking cessation interventions. Effective measures should be taken to promote smoking cessation intervention in China.

The dosimetric benefit of in-advance respiratory training for deep inspiration breath holding is realized during daily treatment in left breast radiotherapy: A comparative retrospective study of serial surface motion tracking.

INTRODUCTION: A novel approach of in-advance preparatory respiratory training and practice for deep inspiration breath holding (DIBH) has been shown to further reduce cardiac dose in breast cancer radiotherapy patients, enabled by deeper (extended) DIBH. Here we investigated the consistency and stability of such training-induced extended DIBH after training completion and throughout the daily radiotherapy course. METHODS: Daily chestwall motion from real-time surface tracking transponder data was analysed in 67 left breast radiotherapy patients treated in DIBH. Twenty-seven received preparatory DIBH training/practice (prep Trn) 1-2 weeks prior to CT simulation, resulting in an extended DIBH (ext DIBH) and reduced cardiac dose at simulation. Forty had only conventional immediate pre-procedure DIBH instruction without prep Trn and without extended DIBH (non-Trn group). Day-to-day variability in chestwall excursion pattern during radiotherapy was compared among the groups. RESULTS: The average of daily maximum chestwall excursions was overall similar, 2.5 ± 0.6 mm for prep Trn/ext DIBH vs. 2.9 ± 0.8 mm for non-Trn patients (P = 0.24). Chestwall excursions beyond the 3-mm tolerance threshold were less common in the prep Trn/ext DIBH group (18.8% vs. 37.5% of all fractions within the respective groups, P = 0.038). Among patients with cardiopulmonary disease those with prep Trn/ext DIBH had fewer chestwall excursions beyond 3 mm (9.4% vs. 46.7%, P = 0.023) and smaller average maximum excursions than non-Trn patients (2.4 ± 0.3 vs. 3.0 ± 0.6 mm, P = 0.047, respectively). CONCLUSION: Similar stability of daily DIBH among patients with and without preparatory training/practice suggests that the training-induced extended DIBH and cardiac dose reductions were effectively sustained throughout the radiotherapy course. Training further reduced beyond-tolerance chestwall excursions, particularly in patients with cardiopulmonary disease.

[Clinical and imaging characteristics of patients with primary cardiac angiosarcoma].

Objective: To investigate the clinical, cardiac imaging characteristics and prognosis of patients with primary cardiac angiosarcoma. Methods: The clinical data of 14 patients hospitalized with primary cardiac angiosarcoma from January 2001 to December 2017 in Peking Union Medical College Hospital were collected and analyzed. Metastatic cardiac angiosarcoma was not included in this study. Patients were followed up post discharge per telephone call or clinical visit. Results: Of the 14 patients, 8 were males and 6 were females, average age was 48 years. The main clinical symptoms were shortness of breath (8/14), hemoptysis (6/14), fever (5/14), chest pain (4/14) and cough (3/14). Imaging examinations showed that the tumors of 8 patients were located in the right heart and 6 in the pericardial cavity. Tumors in the right heart often infiltrate the atrial wall and cause pericardial effusion (7/8). Tumors in the pericardium were characterized by recurrent bloody pericardial effusion (6/6), prone to progressive constrictive pericarditis (3/6), pericardial fluid cytology was often negative (6/6). MRI showed heterogeneous high signal intensity (cauliflower aspect) on T2-weighted image and heterogeneous enhancement with a"sunray" aspect at the perfusion study. At the time of diagnosis, 8 patients developed lung or adrenal metastasis (8/14). The median survival was only 305 days. Conclusions: Primary cardiac angiosarcoma is a rare disease with non-specific clinical manifestation and poor prognosis. Imaging examinations may help diagnosis. The high invasiveness and the easy-to-metastasis feature of the tumor contribute to the poor prognosis of cardiac angiosarcoma.