[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.

[Determination of triclocarban and triclosan in urine by QuEChERS extraction and ultra-performance liquid chromatography-tandem mass spectrometry].

Objective: To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS. Methods: In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI(-)) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results: The linear ranges of TCC and TCS were 0.5-100.0 µg/L and 1.0-100.0 µg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 µg/L, and 0.5 and 1.0 µg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 µg/L. Conclusion: QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.

Comparative transcriptomic analysis reveals candidate genes for seasonal breeding in the male Lion-Head goose.

1. Due to seasonal breeding, geese breeds from Southern China have low egg yield. The genetic makeup underlying performance of local breeds is largely unknown, and few studies have investigated this problem. This study integrated 21 newly generated and 50 publicly existing RNA-seq libraries, representing the hypothalamus, pituitary and testis, to identify candidate genes and importantly related pathways associated with seasonal breeding in male Lion-Head geese.2. In total, 19, 119 and 302 differentially expressed genes (DEGs) were detected in the hypothalamus, pituitary and testis, respectively, of male Lion-Head geese between non-breeding and breeding periods. These genes were significantly involved in the neuropeptide signalling pathway, gland development, neuroactive ligand-receptor interaction, JAK-STAT signalling pathway, cAMP signalling pathway, PI3K-Akt signalling pathway and Foxo signalling pathway.3. By integrating another 50 RNA-seq samples 4, 18 and 40 promising DEGs were confirmed in hypothalamus, pituitary and testis, respectively.4. HOX genes were identified as having important roles in the development of testis between non-breeding and breeding periods of male Lion-Head geese.

[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.

[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.

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.

Global disease burden of COPD from 1990 to 2019 and prediction of future disease burden trend in China.

OBJECTIVES: This study aimed to assess and predict the disease burden attributable to chronic obstructive pulmonary disease (COPD) in a timely, comprehensive, and reliable manner, thereby mitigating the health hazards of COPD. STUDY DESIGN AND METHODS: Data on the disease burden owing to COPD from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study 2019. Linear regression analysis was used to calculate the estimated annual percentage change (EAPC) in the age-standardized rates. Non-parametric tests were used for subgroup analysis. The Bayesian age-period-cohot (BAPC) model integrated nested Laplace approximations to predict the disease burden over the next 25 years. Sensitivity analysis was performed using the Norpred APC model. RESULTS: Globally, the COPD-related age-standardized incidence rate decreased from 216.48/100,000 in 1990 to 200.49/100,000 in 2019, with an EAPC of -0.33. But the number of new cases increased from 8,722,966 in 1990 to 16, 214, 828 in 2019. Trends in prevalence, deaths, and disability-adjusted life years (DALYs) were the same as incidence. There were significant differences in disease burden between the genders and all age groups (P < 0.05) in China. The projections suggested that the COPD-related number of new cases and deaths in China would increase by approximately 1.5 times over the next 25 years. CONCLUSIONS: The number of incidence, prevalence, deaths, and DALYs had all increased in China in the past and would continue to grow over the next 25 years. Therefore, measures should be taken to target risk factors and high-risk groups.

[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.

[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.

[Clinical features of young inpatients with angle-closure glaucoma].

Objective: To analyze the composition of diagnosis in young inpatients with angle-closure glaucoma and to compare the clinical characteristics between primary angle-closure glaucoma (PACG) and secondary angle-closure glaucoma (SACG). Methods: This was a retrospective case series study. Angle-closure glaucoma patients aged 40 years or younger and hospitalized in Zhongshan Ophthalmic Center from January 2012 to December 2019 were included. The clinical diagnosis, gender, onset age, and results of general ophthalmic examination, A-scan ultrasonography measurements, ultrasound biomicroscopy, optical coherence tomography and visual field were recorded. The proportions and composition of PACG and SACG, as well as the misdiagnosis ratio, were analyzed. The onset age, visual acuity, visual field, and ocular parameters were compared between patients with PACG and SACG. Non-normally distributed data were represented by M (Q1, Q3). The difference between groups were compared by Mann-Whitney U test, Chi square test, and independent sample t test. Results: A total of 243 patients (243 eyes) were included in this study. The mean onset age was (28±9) years, and the male-to-female ratio was 1∶1.79. There were 93 patients (38.3%) in PACG group and 150 (61.7%) in SACG group. The age of PACG [34(28, 38)] was older than that of SACG [28(19, 34)], and the proportion of males in the SACG group (44.0%, 66/150) was significantly higher than that in the PACG group (22.6%, 21/93) (Z=-5.34, χ2=11.46; both P<0.01). Nanophthalmos (22.7%, 34 cases), autosomal recessive bestrophinopathy (ARB) (19.3%, 29 cases), uveitis (18.7%, 28 cases) and retinitis pigmentosa (14.0%, 21 cases) were the most common causes of SACG. The best corrected visual acuity (logarithm of the minimum angle of resolution) was 0.10 (0.00, 0.48) and 0.40 (0.06, 1.00), mean deviation of visual field was -8.07 (-27.49, -2.09) and -15.04 (-28.75, -5.97) dB, and subfoveal choroidal thickness was (452.3±130.7) and (396.3±120.9) µm in the PACG and SACG groups, respectively. The differences were statistically significant (Z=-4.86, -2.14; t=2.37; all P<0.05). There was no statistical difference in intraocular pressure, cup-to-disc ratio, extent of peripheral anterior synechia, central anterior chamber depth, lens thickness, mean retinal nerve fiber layer thickness between these two groups (all P>0.05). The misdiagnosis ratio was 10.7% (26/243) in all patients, while the misdiagnosis ratio of the SACG group (16.7%, 25/150) was higher than that of the PACG group (1.1%, 1/93) (χ²=14.61, P<0.001). Conclusions: PACG, nanophthalmos and ARB are the most common etiologies in young inpatients with angle-closure glaucoma. Compared to PACG, patients with SACG are younger, with worse visual acuity and more severe visual field defects, and easier to be misdiagnosed.

[Occupational stress of air traffic controllers and its influencing factors].

Objective: To investigate the occupational stress status of air traffic controllers (ATC) and analyze its influencing factors. Methods: By using cluster sampling method, 457 ATCs in an air traffic management bureau were selected as the investigation objects. The job content questionnaire (JCQ) and the effort reward imbalance questionnaire (ERI) were used to measure work requirements independent imbalance type and ERI type occupational stress separately and analyze the influencing factors. Results: Of the 457 ATCs, 81.84% (374/457) ATGs had work requirements independent imbalance type of occupational stress and 84.46% (386/457) ATGs had ERI type occupational stress. Univariate analysis showed that the factors of marital status, degree of education, age, length of service, title, job post, family monthly income, views on regular training, occurrence of emergency or unsafe events in last month and monthly night shift frequency had various degrees of influence on the different factor scores of JCQ and ERI (P<0.01) . Logistic regression analysis showed that the level of JCQ type occupational stress of ATCs with junior titles and probationers was higher than those of intermediate/senior titles (P=0.000, 0.000) ; The ERI type occupational stress of probationers and junior titles ATCs was lower than those with intermediate/senior titles (P=0.000) . The ERI and JCQ type occupational stress level of tower post ATCs was higher than that of other two job post ATCs (P=0.001, 0.000, 0.000, 0.000) . The ATCs considering regular training had more disadvantages than advantages showed lower ERI type occupational stress level than those considering more advantages than disadvantages (P=0.000) . The ERI type occupational stress level of ATCs who experienced emergency or unsafe events in last month was higher than those who didn't (P=0.007) . Conclusion: A large proportion of ATCs had occupational stress. Management should adjust its policies and pay were attention to occupational stress of ATLs.

NF-κB and FosB mediate inflammation and oxidative stress in the blast lung injury of rats exposed to shock waves.

Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats' lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.

[Comparative study ofmethylene blue tracer and double tracer containing nuclide in sentinel lymph node biopsy of breast cancer].

Objective: To compare the application effect of blue dye single tracer and blue dye combined with nuclide double tracer in sentinel lymph node biopsy (SLNB) of breast cancer surgery. Methods: A total of 92 breast cancer patients in Shandong Cancer Hospital and Institute from November 2017 to October 2019 underwent methyleneblue dye combined with (99)Tc(m) sulfur colloid nuclide double tracer in SLNB, while other 92 cases in Jining First People Hospital underwent blue dye single tracer. The number of SLN detection, detection rate, accuracy rate, sensitivity, and false negative rate of the two groups were compared. The impacts of age, menstruation, tumor location, tumor size, clinical stage, pathological type, and estrogen receptor (ER), progesterone receptor (PR), human epidermal receptor 2 (HER-2), molecular typing, dynamic enhanced magnetic resonance imaging (DCE-MRI)on the detection rate of SLN were analyzed. Results: The number of detection, detection rate, accuracy, sensitivity, and false negative rate of the blue dye single tracer group were 3.20±1.10, 90.22%, 93.48%, 95.24% and 4.76%, respectively; the double tracer group were 3.37±1.02, 92.39%, 95.65%, 95.65% and 4.35%, respectively, without significant difference (all P>0.05). In different age, menstrual condition, tumor location, clinical stage, pathological type, ER, PR, HER-2 expression and molecular typing, the detection rate of single tracer group and double tracer group had no significant difference (all P>0.05). However, in the tumor size of 2-5 cm and without DCE-MRI examination, the detection rate of single tracer group was significantly lower than that of double tracer group. Conclusion: The effect of blue dye single tracer in detecting SLN of breast cancer is equivalent to that of double tracer method, which is worthy of promotion and application in primary hospitals.

[Clinical characteristics of 21 infertile women with non-classic 21-hydroxylase deficiency].

Objective: To investigate the clinical features of infertile women with non-classic 21-hydroxylase deficiency (21-OHD). Methods: The study enrolled 21 infertile women with non-classic 21-OHD in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2009 to December 2018. The clinical presentation, endocrine hormone, glucolipid metabolism and treatment outcome were retrospectively analyzed. The diagnosis of non-classic 21-OHD was comprehensively based on clinical and hormonal characteristics. Results: Among 21 cases, the age was (29.9±2.9) years, the mean age at menarche was (13.6±2.0) years, body mass index was (22.1±2.9) kg/m2, and 38% (8/21) had oligomenorrhea. Hirsutism was diagnosed in 3 cases (14%, 3/21). Clitoromegaly was seen in 14% (3/21) and polycystic ovarian morphology was found in 33% (7/21) of the patients. The mean serum level of basal progesterone was (11.3±21.0) nmol/L, with 48% (10/21) having high basal progesterone level; after therapy by glucocorticoid, the level of progesterone was (1.9±2.0) nmol/L. Serum 17-hydroxyprogesterone concentration was (66.4±123.6) nmol/L; after therapy by glucocorticoid, it was (2.4±1.8) nmol/L. In the study increased testosterone, androstenedione and dehydroepiandrosterone sulfate were present in 62% (13/21), 52% (11/21) and 43% (9/21), respectively; and 52% (11/21) of patients manifested androgen excess and basal progesterone elevation; androgen levels decreased after therapy by glucocorticoid. The pregnancy rate was 76% (16/21). Out of 19 pregnancies, 6/19 ended in spontaneous miscarriages. Conclusions: Infertile women with non-classic 21-OHD are characterized by hyperandrogenism and basal progesterone elevation, whereas gonad axis disorder is not apparent. After no response to conventional therapy, adult infertile women with non-classic 21-OHD could achieve a desirable pregnancy outcome with proper treatment of glucocorticoid.

[Evaluation on effectiveness of community-based comprehensive intervention and internet-based intervention for vaccination among patients with chronic diseases].

To evaluate the effectiveness of community-based comprehensive intervention and internet-based intervention on influenza and pneumococcal vaccination in patients with diabetes or chronic obstructive pulmonary disease (COPD) in communities. Before the onset of influenza in 2015 and 2016, five demonstration areas for comprehensive prevention and control of chronic diseases were selected in the study. Patients aged 35 years old and above with diabetes and COPD were selected from selected demonstration areas as study participants. Two communities were selected from each demonstration area and randomly divided into Group A with the community-based comprehensive intervention and Group B with the combination of community-based comprehensive intervention and internet-based intervention within 6 months. The differences of vaccination knowledge, vaccination intention and vaccination proportion in study participants between the two groups before and after interventions were analyzed and compared. A total of 15 226 patients were included in the study. After the intervention the increase in the vaccine knowledge score, vaccination intention and vaccination proportion of patients in the two groups were all higher than those before the intervention. After intervention, the increase of the median score of vaccine knowledge in group B (50.00 points) was higher than that in Group A (42.86 points). The increase of influenza vaccination intention in Group B (6.91%) was higher than that in Group A (4.16%). The increase of proportion of influenza vaccination in Group B (7.35%) was lower than that in Group A (16.61%). The increase of pneumococcal vaccination intention in Group B (7.90%) was lower than that in Group A (9.08%). The proportion of pneumococcal vaccination in Group B (3.37%) was lower than that in Group A (4.06%). Community-based comprehensive intervention could improve the level of vaccine knowledge, vaccination intention and vaccination proportion of patients in this study. Combined with community-based intervention, internet-based intervention could have a better effect on improving vaccine knowledge and influenza vaccination intention, but its impact on vaccination proportion needs to be further explored.

[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.

MicroRNA-495 attenuates proliferation and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes through attenuating ß-catenin pathway.

Fibroblast-like synoviocytes (FLSs) exert a critical effect in the occurrence and progress of rheumatoid arthritis (RA). MicroRNA-495 (miR-495) can regulate many growth behaviors in various cell types. Nevertheless, the role of miR-495 is still unclear in RA-FLS. We aimed to explore the role and molecular mechanism of miR-495 in RA. The FLSs and synovial tissue from normal and RA cases were used in the study. RT-PCR analysis was used to examine the expression of miR-495. Western blot assay was conducted to determine the levels of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2) and ß-catenin. Cell counting kit-8 (CCK-8) assays were performed to determine the proliferation of RA-FLS in different treatment groups. The results showed that miR-495 is down-regulated in both RA-synovial tissue and RA-FLSs. Overexpression of miR-495 could inhibit RA-FLS proliferation and inflammatory factors of interleukin (IL)-6, IL-11 and tumor necrosis factor alpha (TNF-α), and decrease the protein expression of MMP-9 and MMP-2. In addition, miR-495 could negatively regulate the expression of ß-catenin in RA-FLSs. We also confirmed that the inhibitory role of miR-495 in RA-FLS is through the regulation of ß-catenin expression. Taken together, miR-495 is downregulated in RA-FLS and RA synovial tissue, and miR-495 inhibits proliferation and inflammatory response in RA-FLS, partially via regulating ß-catenin expression. The miR-495/ß-catenin pathway may serve as a new therapeutic target for RA.

Cardiac rehabilitation therapy for coronary slow flow phenomenon.

OBJECTIVE: To evaluate the effectiveness of cardiac rehabilitation on coronary slow flow phenomenon. METHOD: Included were 30 consecutive patients from June 2015 to June 2017. A thrombolysis in myocardial infarction (TIMI) frame evaluation was used to estimate coronary blood flow velocity. All coronary angiography diameters were normal, but blood flow levels did not reach the TIMI level 3. All patients were treated with aspirin and rosuvastatin. Patients were randomly assigned to an experimental group (cardiac rehabilitation treatment group, n = 15) or a control group (normal treatment without cardiac rehabilitation, n = 15). Plasma low density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-sensitivity C reactive protein (hs-CRP), homocysteine (Hcy) and arginine (Arg) expression levels were collected after admission. These indices were reviewed again after 20-30 weeks, improved subjective symptoms were evaluated by multiple outcome criteria (MOCs), and coronary angiography was used to evaluate the velocity of coronary artery blood flow. RESULT: The expression levels of LDL-C and TG in the experimental group were significantly lower than those of the control group (both P < 0.01). The plasma levels of hs-CRP, Hcy and Arg were lower than those in the control group (all P < 0.01). In the experimental group, subjective symptoms of chest pain were significantly improved and the coronary artery blood flow velocity was significantly increased compared with the control group (P < 0.01). CONCLUSION: Cardiac rehabilitation can reduce the plasma levels of LDL-C, TG, hs-CRP, Hcy and Arg, significantly improve the symptoms of coronary slow flow phenomenon and accelerate the speed of coronary artery blood flow.

[Practice guidelines for patients with rheumatoid arthritis].

In recent years, the clinical guidelines for the diagnosis and treatment of rheumatoid arthritis (RA) have been constantly updated. Among the general principles, it is particularly emphasized that, in order to improve the ratio of treat to target(T2T) of RA, doctors and patients should work together to negotiate the details of the guidelines. Therefore, it is important for patients to further understand the disease and clinical guidelines of RA, and to better cooperate with doctors. This study was based on the most concerned issues of RA patients and international standard procedure of guideline study, we organized the working group and introduce the following 16 recommendations constituting the RA patients' practice guidelines.

[Practice guideline for patients with ankylosing spondylitis/spondyloarthritis].

In recent years, the clinical experts consensuses or guidelines of ankylosing spondylitis (AS)/spondyloarthritis (SpA) have been constantly updated, but to better understand and practice, patient self-participation management is one of the key points to improve the level of diagnosis and treatment. Through questionnaire survey of these patients, we screened out the most concerned issues, and established the AS/SpA patient practice guideline working group with multidisciplinary physicians and patients. Fifteen opinions, as the AS/SpA patient practice guidelines, are proposed in accordance with the relevant principles of the "WHO guidelines development manual" , and with the international normative process.