Exome-wide screening identifies novel rare risk variants for bone mineral density.

Bone mineral density (BMD) is an independent risk factor of osteoporosis-related fractures. We performed gene-based burden tests to assess the association between rare variants and BMD, and identified several BMD candidate genes. PURPOSE: BMD is highly heritable and a major predictor of osteoporotic fractures, but its genetic basis remains unclear. We aimed to identify rare risk variants contributing to BMD. METHODS: Utilizing the newly released UK Biobank 200,643 exome dataset, we conducted a gene-based exome-wide association study in males and females, respectively. First, 100,639 males and 117,338 females with BMD values were included in the polygenic risk scores (PRS) analysis. Among individuals with lower 30% PRS, cases were individuals with top 10% BMD, and individuals with bottom 10% BMD were the controls. Considering the effects of vitamin D (VD), individuals with the highest 30% VD concentration were selected for VD-BMD analysis. After quality control, 741 males and 697 females were included in the BMD analysis, and 717 males and 708 females were included in the VD-BMD analysis. The variants were annotated by ANNOVAR software, then BMD and VD-BMD qualified variants were imported into the SKAT R-package to perform gene-based burden tests, respectively. RESULTS: The gene-based burden test of the exonic variants identified genome-wide candidate associations in ANKRD18A (P = 1.60 × 10-5, PBonferroni adjust = 2.11 × 10-3), C22orf31 (P = 3.49 × 10-4, PBonferroni adjust = 3.17 × 10-2), and SPATC1L (P = 1.09 × 10-5, PBonferroni adjust = 8.80 × 10-3). For VD-BMD analysis, three genes were associated with BMD, such as NIPAL1 (P = 1.06 × 10-3, PBonferroni adjust = 3.91 × 10-2). CONCLUSIONS: Our study suggested that rare variants contribute to BMD, providing new sights for broadening the genetic structure of BMD.

[Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy].

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

[Comparative study of laparoscopic Keyhole and Sugarbaker technique in the treatment of terminal paracolostomy hernia].

Objective: To compare laparoscopic Keyhole repair with Sugarbaker repair in consecutive patients with parastomal hernia. Methods: From January 2015 to December 2021, 117 patients with parastomal hernia were treated with Keyhole or Sugarbaker laparoscopy repairs in the Department of Hernia and Bariatrci Surgery, the First Affiliated Hospital of University of Science and Technology of China, and the clinical data were retrospectively analyzed. There were 45 males and 72 females, aged (68.6±8.6) years (range: 44 to 84 years). Laparoscopic Sugarbaker repair was performed in 89 cases, and Keyhole repair was performed in 28 cases. The t-test, Mann-Whitney U test, χ2 test and Fisher exact test were used to compare the observation indicators between the two groups, such as operation time, incidence of operation-related complications, and postoperative recurrence rate. Results: The follow-up period was (M(IQR)) 33 (36) months (range: 12 to 84 months). Compared to the Sugarbaker group, the hernia ring area of the Keyhole group was bigger (35 (26) cm2 vs. 25 (16) cm2, Z=1.974, P=0.048), length of stay was longer ((22.0±8.0) d vs. (14.1±6.2) d, t=5.485, P<0.01), and the postoperative rate of recurrence was higher (28.6% (8/28) vs. 6.7% (6/89), χ2=7.675, P=0.006). There was no difference in operation time and postoperative complications between the two groups. Conclusions: Laparoscopic Sugarbaker repair is superior to Keyhole repair in the recurrence rate of parastomal hernia treated with compsite mesh (not funnel-shaped mesh). There are no differences in operation time and postoperative complications between the two groups.

[Optic atrophy in a patient with axonal Charcot-Marie-Tooth disease 2A2A due to MFN2 gene mutations].

A 27-year-old male patient had progressive vision loss in both eyes, which was mainly manifested by impaired ganglion cells in the macular area, accompanied by systemic muscle atrophy in limbs. A complete mitochondrial exon gene detection was performed. The final diagnosis was bilateral optic atrophy and axonal Charcot-Marie-Tooth disease 2A2A caused by mutations of the MFN2 gene. There has been no effective treatment. Applications of nutrients to restore the mitochondrial function may alleviate the clinical symptoms.

[Impact of VA-ECMO combined with IABP and timing on outcome of patients with acute myocardial infarction complicated with cardiogenic shock].

Objective: To investigate the impact of combined use and timing of arterial-venous extracorporeal membrane oxygenation (VA-ECMO) with intra-aortic balloon pump (IABP) on the prognosis of patients with acute myocardial infarction complicated with cardiogenic shock (AMICS). Methods: This was a prospective cohort study, patients with acute myocardial infarction and cardiogenic shock who received VA-ECMO support from the Heart Center of Lanzhou University First Hospital from March 2019 to March 2022 in the registration database of the Chinese Society for Extracorporeal Life Support were enrolled. According to combination with IABP and time point, patients were divided into VA-ECMO alone group, VA-ECMO+IABP concurrent group and VA-ECMO+IABP non-concurrent group. Data from 3 groups of patients were collected, including the demographic characteristics, risk factors, ECG and echocardiographic examination results, critical illness characteristics, coronary intervention results, VA-ECMO related parameters and complications were compared among the three groups. The primary clinical endpoint was all-cause death, and the safety indicators of mechanical circulatory support included a decrease in hemoglobin greater than 50 g/L, gastrointestinal bleeding, bacteremia, lower extremity ischemia, lower extremity thrombosis, acute kidney injury, pulmonary edema and stroke. Kaplan-Meier survival curves were used to analyze the survival outcomes of patients within 30 days of follow-up. Using VA-ECMO+IABP concurrent group as reference, multivariate Cox regression model was used to evaluate the effect of the combination of VA-ECMO+IABP at different time points on the prognosis of AMICS patients within 30 days. Results: The study included 68 AMICS patients who were supported by VA-ECMO, average age was (59.8±10.8) years, there were 12 female patients (17.6%), 19 cases were in VA-ECMO alone group, 34 cases in VA-ECMO+IABP concurrent group and 15 cases in VA-ECMO+IABP non-concurrent group. The success rate of ECMO weaning in the VA-ECMO+IABP concurrent group was significantly higher than that in the VA-ECMO alone group and the VA-ECMO+IABP non-concurrent group (all P<0.05). Compared with the ECMO+IABP non-concurrent group, the other two groups had shorter ECMO support time, lower rates of acute kidney injury complications (all P<0.05), and lower rates of pulmonary edema complications in the ECMO alone group (P<0.05). In-hospital survival rate was significantly higher in the VA-ECMO+IABP concurrent group (28 patients (82.4%)) than in the VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (7 patients) (all P<0.05). The survival rate up to 30 days of follow-up was also significantly higher surviving patients within were in the ECMO+IABP concurrent group (26 cases) than in VA-ECMO alone group (9 patients) and VA-ECMO+IABP non-concurrent group (4 patients) (all P<0.05). Multivariate Cox regression analysis showed that compared with the concurrent use of VA-ECMO+IABP, the use of VA-ECMO alone and non-concurrent use of VA-ECMO+IABP were associated with increased 30-day mortality in AMICS patients (HR=2.801, P=0.036; HR=2.985, P=0.033, respectively). Conclusions: When VA-ECMO is indicated for AMICS patients, combined use with IABP at the same time can improve the ECMO weaning rate, in-hospital survival and survival at 30 days post discharge, and which does not increase additional complications.

Antibacterial activity and mechanism of chloroform fraction from aqueous extract of mugwort leaves (Artemisia argyi L.) against Staphylococcus aureus.

In this work, the antibacterial activity and mechanism of chloroform fraction obtained from aqueous extract of mugwort leaves against Staphylococcus aureus were investigated. The extract showed obvious antibacterial activity against S. aureus which the minimum inhibitory concentration and minimum bactericidal concentration were determined to be 3·0 and 6·0 mg ml-1 respectively. The mechanism study suggested that the extract could destroy the integrity of the S. aureus cell walls and increase the permeability of cell membrane in a certain concentration, but it could not kill S. aureus in a short time. Instead, the extract could make bacteria in a state of apoptosis for a long time, interfere with the normal physiological metabolism of bacteria, and eventually make bacteria die, which was confirm by scanning electronic microscope.

[Respiratory drive in acute respiratory distress syndrome: evaluation and control].

Acute respiratory distress syndrome (ARDS) is a common critical disease, which often leads to poor prognosis in critically ill patients. The excessive respiratory drive in ARDS is related to lung injury. Control of excessive respiratory drive is helpful to reduce lung injury and mortality of ARDS. The mechanisms of abnormal increase in respiratory drive in ARDS include hypoxemia, hypercapnia, stretch reflex caused by alveolar collapse and inflammatory stimulation. Respiratory drive should be evaluated by clinical manifestations, physiological parameters and respiratory mechanics indexes. It is particularly important to make individual therapy strategies according to the evaluation of respiratory drive. Analgesia and sedation combined with muscle relaxation, high positive end-expiratory pressure (PEEP) and prone position can be used to control excess respiratory drive. This article reviews the evaluation and management of excess respiratory drive in ARDS patients.

[Effect of EIT-guided individualized PEEP setting on the incidence of hypoxemia in elderly patients undergoing robot-assisted radical prostatectomy].

Objective: To investigate the effect of individualized positive end expiratory pressure (PEEP) setting guided by chest electrical impedance tomography (EIT) on the incidence of hypoxemia in elderly patients undergoing robot-assisted radical prostatectomy in the post anesthesia care unit (PACU). Methods: From September 2020 to October 2021, sixty elderly patients, with the American Association of Anesthesiologists (ASA) of Grade Ⅰ to Ⅲ, who underwent selective robot-assisted radical prostatectomy under general anesthesia in the Cancer Hospital Affiliated to Fudan University were selected. The participants were divided into two groups by the minimum randomized grouping method: EIT-PEEP group (EP group, n=30) and fixed PEEP group (FP group, n=30). After completion of tracheal intubation and establishment of pneumoperitoneum flexion posture, the individualized PEEP setting was guided by EIT in EP group, and the PEEP setting in FP group was 5 cmH2O (1 cmH2O=0.098 kPa) to the end of operation. During the operation, the ventilation mode of pressure regulation volume control was adopted. The driving pressure, dynamic lung compliance (Cdyn), oxygenation index and hemodynamics were recorded at 5 min (T1), 30 min (T2), 60 min (T3) after PEEP setting and at the time of tracheal catheter removal (T4) in both groups. The primary end point was the incidence of hypoxemia in PACU after extubation. Results: The incidence of hypoxemia after extubation was 3.3% (1/30) in EP group and 26.7% (8/30) in FP group (P=0.030). The difference of driving pressure between the two groups at T2 [(13.1±2.4) cmH2O vs (14.9±2.9) cmH2O, P=0.012], T3 [(12.7±2.4) cmH2O vs (15.6±2.8) cmH2O, P<0.001] was statistically significant. In EP group, Cdyn was improved at T2 [(38.4±7.2) ml/cmH2O vs (31.9±5.2) ml/cmH2O, P=0.006] and T3 [(37.5±9.0) ml/cmH2O vs (30.4±5.9) ml/cmH2O, P=0.001]. In EP group, PaO2/FiO2 increased at T1 [(465.7±84.5) mmHg vs (383.5±58.0) mmHg, 1 mmHg=0.133 kPa, P<0.001], T2 [(504.7±105.8) mmHg vs (418.9±73.7) mmHg, P=0.001], T3 [(520.7±92.2) mmHg vs (423.2±90.7) mmHg, P<0.001], T4 [(368.7±42.0) mmHg vs (339.5±54.9) mmHg, P=0.024]. Conclusion: The individualized PEEP setting guided by EIT can reduce the incidence of hypoxemia in elderly patients undergoing robot assisted radical prostatectomy in PACU.

[Clinical study on the relationship between the exosomes in bronchoalveolar lavage fluid and plasma and the severity of lung injury and outcome in early acute respiratory distress syndrome patients].

Objective: To investigate the relationship between the levels of exosomes in bronchoalveolar lavage fluid (BALF) and plasma and the severity of lung injury and its outcome in patients with acute respiratory distress syndrome (ARDS). Methods: Patients who were admitted to the Department of Critical Care Medicine, Zhongda Hospital Affiliated to Southeast University and received invasive mechanical ventilation were selected from August 2020 to April 2021, and they were divided into ARDS group and non-ARDS group. Finally, 33 ARDS patients were included, including 18 males and 15 females, aged (65.5±15.5) years; 10 non-ARDS patients, 8 males and 2 females, aged (57.2±15.3) years. The BALF and plasma of the two groups of patients were collected within 24 hours after enrollment, and the total exosomes of the samples were collected by ultracentrifugation. Nanoparticle tracking analysis (NTA) was used to detect and compare the differences in exosome content between the two groups. Correlation of content with the severity and prognosis of lung injury in ARDS patients. Results: There was no significant difference in gender and age between ARDS group and non-ARDS group (both P>0.05). The exosome in plasma of ARDS group was significantly higher than that of non-ARDS group [(25.3±1.2)/ml vs (24.2±1.6)/ml, P=0.031], while the exosomes in BALF of ARDS group was also higher than that of non-ARDS group [(26.5±1.6)/ml vs (24.6±1.1)/ml, P=0.001]. The exosomes in BALF of patients with ARDS caused by intrapulmonary causes was higher than that in ARDS group caused by extrapulmonary causes [(26.9±1.5)/ml vs (25.2±0.9)/ml, P=0.01], and the infection caused by bacterial shows that the highest exosome level in BALF. The exosomes in the BALF of the mild ARDS group was significantly lower than that of the severe ARDS group [(25.7±1.3)/ml vs (27.2±1.5)/ml, P=0.038]; the exosomes in BALF of ARDS patients was negatively correlated with P/F ratio (r=-0.38, P=0.03); and it was positively correlated with Murray lung injury score (r=0.47, P=0.01). However, the static compliance levels, length of hospital stay, duration of mechanical ventilation, and 28-day outcome were not associated with the exosomes in BALF. Conclusion: Compared with non-ARDS patients, ARDS patients have significantly higher levels of exosomes in BALF and plasma, there is a certain correlation between exosomes derived from BALF and the severity of lung injury in ARDS.

[Analysis of clinical features and the outcome of in-hospital mortality of myocardial infarction with non-obstructive coronary arteries].

Objective: To compare the clinical features and the outcome of in-hospital mortality between patients with myocardial infarction with non-obstructive coronary arteries(MINOCA)and myocardial infarction with obstructive coronary artery disease (MI-CAD). Methods: This is a retrospective study. The clinical data of acute myocardial infarction (AMI) patients admitted to Qilu Hospital of Shandong University from January 2017 to May 2021, who underwent coronary angiography, were collected. Patients were divided into MINOCA group and MI-CAD group according to the degree of coronary stenosis (<50% or ≥50%). Baseline clinical characteristics, electrocardiograph during hospitalization, myocardial bridge, length of stay in hospital, discharge medication and the outcome of in-hospital mortality were collected and compared between the two groups. Univariate and multivariate logistic regression analysis was used to screen the related factors of MINOCA and the factors predicting the nosocomial death outcome of patients with AMI. Results: A total of 3 048 AMI patients were enrolled, age was 62 (54, 69) years, 741 (24.3%) patients were women including 165 patients (5.4%) in the MINOCA group and 2 883 patients (94.6%) in the MI-CAD group. Compared with MI-CAD patients, MINOCA patients were younger, had a higher proportion of females and a higher incidence of NSTEMI, and had a lower history of smoking, diabetes, coronary heart disease and myocardial infarction. Baseline inflammatory markers such as neutrophil count, monocyte count, neutrophil count/lymphocyte count (NLR), and monocyte count/high-density lipoprotein count (MHR) were lower, creatinine, N-terminal pro-brain B-type Natriuretic peptides (NT-proBNP), creatine kinase-MB, hypersensitive troponin I, fibrinogen, baseline blood glucose levels were lower, high-density lipoprotein cholesterol was higher, and the incidence of myocardial bridge, arrhythmia, tachycardia and atrial fibrillation was higher (P<0.05). The application rates of calcium antagonists and non-vitamin K antagonists oral anticoagulants were higher in MINOCA group (P<0.05), and there was no statistical difference in hospitalization days and in-hospital death between the two groups (P>0.05). Multiple logistic regression analysis showed that young age, female, non-smoker, no history of coronary heart disease and low MHR were risk factors of MINOCA (P<0.05). MINCOA was not associated with higher in-hospital death (P>0.05). Patients with AMI and a history of coronary heart disease, chronic renal failure, higher baseline blood glucose, higher NLR, and higher D-dimer were risk factors of in-hospital death (P<0.05). Conclusions: Compared with MI-CAD patients, MINOCA patients are younger, more likely to be female and non-smokers and on history of coronary heart disease, and have lower baseline MHR. MINOCA is often associated with myocardial bridge and atrial fibrillation. The incidence of in-hospital death in MINCOA patients is similar as in MI-CAD patients.

Correlations of the expression of γδ T cells and their co-stimulatory molecules TIGIT, PD-1, ICOS and BTLA with PR and PIBF in the peripheral blood and decidual tissues of women with unexplained recurrent spontaneous abortion.

Semi-allogeneic embryos are not rejected by the maternal immune system due to maternal-fetal immune tolerance. Progesterone (P) receptor (PR)-expressing γδ T cells are present in healthy pregnant women. In the presence of P, these cells secrete an immunomodulatory protein called progesterone-induced blocking factor (PIBF), which can facilitate immune escape and is important in preventing embryonic rejection. This work investigated the correlations of the expression of γδ T cells and their co-stimulatory molecules T cell immunoglobulin and ITIM domain (TIGIT), programmed cell death 1 (PD-1), inducible co-stimulator (ICOS) and B and T lymphocyte attenuator (BTLA) with progesterone receptor (PR) and progesterone-induced blocking factor (PIBF) in peripheral blood and decidual tissue in women with unexplained recurrent spontaneous abortion (URSA) and normal pregnant (NP) women. We confirmed that γδ T cell proportions and PIBF expression in the peripheral blood and decidua of URSA women decreased significantly, while PR expression in decidua decreased. However, TIGIT, PD-1, ICOS and BTLA expression in γδ T cells in peripheral blood did not change, while TIGIT and PD-1 expression in γδ T cells in decidua increased significantly. Under the action of PHA-P (10 µg/ml), co-blocking of TIGIT (15 µg/ml) and PD-1 (10 µg/ml) antibodies further induced γδ T cell proliferation, but PIBF levels in the culture medium supernatant did not change. At 10-10 M P, γδ T cells proliferated significantly, and PIBF concentrations in the culture medium supernatant increased. γδ T cells co-cultured with P, TIGIT and PD-1 blocking antibodies showed the most significant proliferation, and PIBF concentrations in the culture medium supernatant were the highest. These results confirm that P is necessary for PIBF production. The TIGIT and PD-1 pathways participate in γδ T cell proliferation and activation and PIBF expression and play important roles in maintaining pregnancy.

A test-retest multisite reproducibility study of cardiovascular four-dimensional flow MRI without respiratory gating.

AIM: To systematically investigate the multisite reproducibility, test-retest reliability, and observer variability of non-respiratory-gated four-dimensional (4D) flow magnetic resonance imaging (MRI) in the thoracic great vessels for the assessment of blood flow and peak velocity. MATERIALS AND METHODS: Electrocardiogram (ECG)-gated 4D flow MRI data were acquired without respiratory gating in 10 healthy volunteers. To analyse multisite reproducibility, 4D flow was scanned at three different sites using a 3 T GE MRI machine with identical protocols for the group of participants. In addition, to evaluate test-retest reliability, the same volunteers were scanned in each centre during a second visit. Data analysis included calculation of peak systolic velocity and time-resolved and total flow of both the ascending aorta and pulmonary artery. Two observers conducted the above measurements to assess the interobserver variability. RESULTS: Multisite, test-retest, interobserver agreement were good for the calculation of total flow and peak systolic velocity (mean differences <10% of the average flow parameter). CONCLUSION: Non-respiratory-gated 4D MRI-based assessment of aortic and pulmonary blood flow can be performed with good reproducibility. It may facilitate the potential clinical application of this technique.

SEAIC Specialty Forum: Analysis of the Current Situation of Allergology in Spain and Outlook for the Future.

BACKGROUND AND OBJECTIVES: Allergology has been a recognized medical specialty in Spain, with fully defined aims and competencies for more than 4 decades. However, in recent years, its visibility seems to have decreased somewhat. Objectives: To identify which specific factors have contributed to the waning of the importance of the specialty and find tangible solutions to consolidate its place as a front-line medical specialty. MATERIAL AND METHODS: An online population survey comprising 60 items of interest was prepared. The degree of agreement and the level of satisfaction with each item were assessed, and implementable initiatives in the short, medium, and long terms were defined in order to provide solutions to the issues identified. RESULTS: The survey was completed by a total of 167 specialists with an average of 18 years' experience. Most were from public reference hospitals, and 29.3% were heads of department. The line of action for which a good degree of agreement was achieved was to promote the inclusion of an allergist in multidisciplinary teams. The priority lines of action were to improve undergraduate and graduate training in allergology and specialized nursing, to identify curricula in Spain, and to develop robust teaching projects. CONCLUSIONS: The results revealed a high degree of homogeneity between professionals. The basic pillars highlighted were as follows: quality training, knowledge, and research in immunotherapy; an innovative portfolio of services endorsed by clinical practice guidelines; and presence in multidisciplinary teams and relevant hospital committees.

Joint trajectories of disability and related factors among older adults in China.

OBJECTIVES: This study aimed to identify disability trajectories and discover early disablement process factors associated with disability trajectories among older adults in China. STUDY DESIGN: This is a prospective cohort study. METHODS: Data were obtained from five waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS, 2005 to 2018). The multitrajectory modelling approach was used to estimate the joint trajectories of activity of daily living (ADL) disability and instrumental activity of daily living (IADL) disability. A multinomial regression model was used to investigate how baseline disablement process factors among individuals aged 65-95 years are related to joint disability trajectory groups. RESULTS: We identified three typical joint ADL and IADL disability trajectories. Demographic characters, social participation, community services, disease, impairment and functional limitations can all impact the disability trajectories among older adults. CONCLUSIONS: The joint ADL and IADL disability trajectories of older adults are increasing, and the Chinese government should pay more attention to disability process elements to improve disability interventions among older adults.

[The effects of positive end-expiratory pressure on central venous pressure in patients with different chest wall elastic resistance].

Objective: To investigate the role of chest wall elastic resistance in determining the effects of positive end-expiratory pressure (PEEP) on central venous pressure (CVP) in patients with mechanical ventilation (MV). Methods: In this prospective study, according to the median of ratio of chest wall elastic resistance to respiratory system elastic resistance (Ers), patients were divided into high chest wall elastic resistance group (Ecw/Ers≥0.24) and low chest wall elastic resistance group [elastance of chest wall (Ecw)/Ers<0.24]. PEEP was set at 5, 10, 15 cmH2O (1 cmH2O=0.098 kPa) respectively. Clinical data including CVP, heart rate (HR), blood pressure (BP) and respiratory mechanics were recorded. Results: Seventy patients receiving MV were included from November 2017 to December 2018. Clinical characteristics including age, BP, HR, baseline PEEP, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) and comorbidities were comparable in two groups. However, patients with high Ecw/Ers ratio presented higher body mass index (BMI) than those with low Ecw/Ers ratio[ (25.4±3.2) kg/m2 vs. (23.4±3.2) kg/m2, P=0.011]. As PEEP increased from 5 cmH2O to 10 cmH2O, CVP in high Ecw/Ers group increased significantly compared with that in low Ecw/Ers group [1.75(1.00, 2.13) mmHg (1 mmHg=0.133kPa) vs. 1.50(0.50, 2.00)mmHg,P=0.038], which was the same as PEEP increased from 10 cmH2O to 15 cmH2O [2.00(1.50, 3.00)mmHg vs. 1.50(1.00, 2.00)mmHg,P=0.041] or PEEP increased from 5 cmH2O to 15 cmH2O [ 3.75(3.00,4.63)mmHg vs. 3.00(1.63, 4.00)mmHg, P=0.012]. When PEEP increased from 5 cmH2O to 10 cmH2O, 10 cmH2O to 15 cmH2O and 10 cmH2O to 15 cmH2O, there were significant correlations between Ecw/Ers and CVP elevation (r=0.29, P=0.016; r=0.31, P=0.011; r=0.31, P=0.01 respectively). Conclusions: In patients receiving mechanical ventilation, elevation of PEEP leads to a synchronous change of CVP, which is corelated with patients' chest wall elastic resistances.

[Epidemiology and the risk factors of myopia among children and youths in Yunnan province].

Objective: The purpose of the study was to describe the prevalence of myopia and to explore the associated factors of myopia among Han and Yi students aged 5-16 years in Yunnan province, China. Methods: A total of 5 971 Han and Yi students were included in the data analysis from the Yunnan eye study which was conducted from March to August, 2014. Information regarding demographic factors, socioeconomic status and lifestyle-related exposures were collected by per-designed questionnaires. The ophthalmic examinations including distance visual acuity, anterior segment examination, cycloplegic auto-refraction, and ocular motility examination were conducted. Logistic regression models were fitted to estimate the risk factors for myopia. Results: The age of 5 971 subjects was (10.68±2.24)years old, and the total prevalence of myopia and high myopia was 48.05% and 0.59%. Myopia prevalence was found to be higher in Han students compared with Yi ethnicity (50.20% vs. 47.10%,P=0.029). In multivariate analysis, the occurrence of myopia was associated with age (OR=1.28, 95%CI: 1.25-1.31), girls (OR=1.32, 95%CI: 1.18-1.48), increasing reading and writing time per day (OR=1.13, 95%CI: 1.07-1.20), having self-reported myopia among friend(s) (OR=1.15, 95%CI: 1.02-1.29), having myopic father (OR=1.38, 95%CI: 1.06-1.79), having myopic mother (OR=1.43, 95%CI: 1.12-1.83) and higher educated mother (OR=1.24, 95%CI: 1.03-1.51). Conclusions: We observed a high prevalence of myopia among Mangshi students. The presence of myopia was associated with increasing age, girls, increasing reading and writing time per day, having self-reported myopia among friend(s), having myopic father, having myopic and high educated mother.

lncRNA CASC2 suppresses the growth of hemangioma cells by regulating miR-18a-5p/FBXL3 axis.

Dysregulation of lncRNA cancer susceptibility candidate 2 (CASC2) is involved in the pathogenesis of multiple malignancies. However, the underlying mechanisms by which lncRNA CASC2 regulates the proliferation of hemangiomas (HAs) remain undocumented. Herein, the expression levels of lncRNA CASC2 and VEGF in proliferating or involuting phase HAs were assessed by qRT-PCR analysis, and the effects of lncRNA CASC2 on HAs cell growth were evaluated by MTT, colony formation assays and Western blot analysis. lncRNA CASC2 specific binding with miR-18a-5p was confirmed by luciferase report assay. Consequently, we found that the expression of lncRNA CASC2 was reduced in proliferating phase HAs as compared with the involuting phase HAs or normal tissues, and possessed a negative correlation with VEGF expression in proliferating phase HAs. Restored expression of lncRNA CASC2 repressed cell viability and colony formation and downregulated VEGF expression, while silencing lncRNA CASC2 showed the opposite effects. Moreover, lncRNA CASC2 was confirmed to bind with miR-18a-5p, which could reverse lncRNA CASC2-induced anti-proliferative effects by targeting FBXL3 in HAs cells. Altogether, our findings demonstrated that lncRNA CASC2 suppressed the growth of HAs cells by regulating miR-18a-5p/FBXL3 axis.

InDels within caprine IGF2BP1 intron 2 and the 3'-untranslated regions are associated with goat growth traits.

Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) is involved in the Hedgehog pathway and has been shown to regulate the RNA stability of several growth-related target genes. It is located in a quantitative trait locus showing a strong association with traits related to body size in ducks. Fibroblast growth factor receptor 1 (FGFR1) also participates in Hedgehog signaling pathways and has been reported to be associated with organic growth and development. FGFR1-knockout mice have been shown to have severe postnatal growth defects, including an approximately 50% reduction in body weight and bone mass. Meanwhile, nonsense-mediated mRNA decay factor (SMG6) can maintain genomic stability, which is associated with organic growth and development. Therefore, we hypothesized that IGF2BP1, FGFR1 and SMG6 genes may play important roles in the growth traits of goats. In this study, the existence of two insertion/deletion (InDel) variants within IGF2BP1, one InDel within FGFR1 and two InDels within SMG6 was verified and their correlation with growth traits was analyzed in 2429 female Shaanbei white cashmere goats. Results showed both the 15 bp InDel in intron 2 and the 5 bp InDel in the 3' regulatory region within IGF2BP1 were significantly associated with growth traits (P < 0.05) and goats with the combinatorial homozygous insertion genotypes of these two loci had the highest body weight (P = 0.046). The other InDels within FGFR1 and SMG6 were not obviously associated with growth traits (P > 0.05). Therefore, the two InDels in IGF2BP1 were vital mutations affecting goat growth traits.

Effects of Agrobacterium tumefaciens strain types on the Agrobacterium-mediated transformation efficiency of filamentous fungus Mortierella alpina.

Four Agrobacterium tumefaciens strains AGL-1, C58C1, EHA105 and LBA4404 were tested for the effects of strain types on the transformation efficiency in Mortierella alpina. Results showed that AGL-1, C58C1 and EHA105 transformed M. alpina successfully. Among them, A. tumefaciens EHA105 was first proven successful transformation of M. alpina. AGL-1 and EHA105 had the highest transformation efficiency among the four strains, while LBA4404 failed to transform M. alpina. The reason leading to the transformation efficiency difference among the four strains was explored by determining transcription levels of the virulence (vir) gene in the induction medium. Results showed that the expressions of virD1, virD2, virD4 and virE1 genes were obviously induced by acetosyringone in all the strains, and their transcriptional levels as well as virA's of AGL-1, C58C1 and EHA105 were higher than that of LBA4404, suggesting high transcriptional levels of vir genes were important for successful transformation. The study selected A. tumefaciens with high transformation efficiency of M. alpina, and would accelerate the genetic management of M. alpina. SIGNIFICANCE AND IMPACT OF THE STUDY: Oleaginous filamentous fungus Mortierella alpina is a commercial strain for the production of arachidonic acid. Genetic manipulation of M. alpina requires highly efficient transformation method. In this study, we explore the effect of Agrobacterium tumefaciens strain types on the transformation efficiency of M. alpina and select A. tumefaciens with the highest transformation efficiency, which accelerates the genetic manipulation of M. alpina. Besides, high transcriptional levels of virulence genes in A. tumefaciens were proven to play an important role for successful transformation.

[Establishment of clinical features and prognostic scoring model in early-stage hepatitis B-related acute-on-chronic liver failure].

Objective: To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients. Results: Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs(P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion: HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.