A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections, including with SARS-CoV-2. Here, we identified a gene program, defined by correlation with EN-RAGE (S100A12) gene expression, which was up-regulated in airway and blood myeloid cells from COVID-19 patients. The EN-RAGE program was expressed in 7 cohorts and observed in patients with both COVID-19 and acute respiratory distress syndrome (ARDS) from other causes. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGE+ myeloid cells express features consistent with suppressor cell functionality, with low HLA-DR and high PD-L1 surface expression and higher expression of T cell-suppressive genes. Sustained EN-RAGE signature expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell exhaustion markers, such as PD-1. IL-6 treatment of monocytes in vitro upregulated many of the severity-associated genes in the EN-RAGE gene program, along with potential mediators of T cell suppression, such as IL-10. Blockade of IL-6 signaling by tocilizumab in a placebo-controlled clinical trial led to a rapid normalization of ENRAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.

Tocilizumab treatment leads to early resolution of myeloid dysfunction and lymphopenia in patients hospitalized with COVID-19

Tocilizumab, an anti-interleukin-6 receptor inhibitor, is recommended in global treatment guidelines for patients hospitalized with severe COVID-19. Using proteomic and transcriptomic analysis, we characterized the immune profile and identified cellular and molecular pathways directly modified by tocilizumab in peripheral blood samples collected from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial, to assess the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19 pneumonia. We identified factors predicting disease severity and clinical outcomes, including markers of inflammation, lymphopenia, myeloid dysfunction, and organ injury. Proteomic analysis confirmed a pharmacodynamic effect for tocilizumab. Transcriptomic analysis revealed that tocilizumab treatment leads to faster resolution of lymphopenia and myeloid dysfunction associated with severe COVID-19, thus defining an anti-inflammatory mechanism of action for the beneficial effects of tocilizumab in patients hospitalized with COVID-19. One sentence summaryInterleukin-6 receptor blockade with tocilizumab accelerated resolution of myeloid dysfunction and lymphopenia in patients hospitalized with COVID-19

Follow-up and prognosis analysis of rheumatic disease complicated with pulmonary arterial hypertension in children / 中华实用儿科临床杂志

Objective:To explore the clinical features, follow-up characteristics and prognosis of rheumatic disease complicated with pulmonary arterial hypertension (PAH) in children, and to provide support for its clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the data of rheumatic 24 patients complicated with PAH hospitalized in the Department of Rheumatology and Immunology, Children′s Hospital Affiliated to the Capital Institute of Pediatrics, Department of Rheumatology and Immunology, Jiangxi Children′s Hospital, Department of Pediatrics Ⅰ, the First Affiliated Hospital of Zhengzhou University and Department of Pediatrics, the Affiliated Hospital of Inner Mongolia Medical University from January 2013 to June 2022.The rheumatic patients complicated with PAH were followed up by telephone on June 30, 2022, and their clinical symptoms, treatment, follow-up, and prognosis data were collected.According to different treatment methods, the patients were divided into different clinical subgroups. The change of PAH was analyzed. The t-test was used for comparison between groups. P<0.05 was statistically significant. Results:A total of 24 cases were enrolled, with 7 males and 17 females.The average onset age of PAH was (10.97±3.79) years old.The median duration of PAH was 6.00 (32.20) months.The average pulmonary artery pressure was (51.71±17.66) mmHg(1 mmHg=0.133 kPa). There were 9 cases of systemic lupus erythematosus, 5 cases of Takayasu′s arteritis, 3 cases of juvenile dermatomyositis, 3 cases of undifferentiated connective tissue disease, 2 cases of systemic juvenile idiopathic arthritis, 1 case of Behcet′s disease, and 1 case of Kawasaki disease.Among 24 cases, the common symptoms were fever (14 cases), fatigue (10 cases) and dyspnea (7 cases). Of the 24 cases, 10 cases were complicated with hydropericardium, 9 cases with valve regurgitation, and 5 cases with decreased systolic and/or diastolic function.Lung changes were observed in 17 cases.Eleven cases were tested for B-type natriuretic peptide (BNP), and the BNP levels were all elevated in them (11 cases), with a median BNP of 3 073 (10 645) ng/L.After the first occurrence of PAH, 12 cases were treated with Methylprednisolone therapy, 10 cases received Cyclophosphamide therapy, and 2 cases who were both systemic lupus erythematosus, underwent blood purification.In the treatment of PAH, 11 cases were treated with pulmonary artery pressure reduction, and 7 of the 11 cases took PAH-targeted drugs.The mean decrease of the average pulmonary artery pressure in children receiving the targeted therapy[(44.80±24.08) mmHg] was significant higher than that in children not receiving the targeted therapy [(16.15±17.25) mmHg] ( t=2.661, P=0.016). Twenty children were reexamined and/or followed up, and the average course of PAH at the telephone follow-up was (36.29±26.67) months.The pulmonary arterial hypertension in 6 cases completely recovered, with median recovery time of 8.00 (13.47) months, but 2 of them died after the complete recovery.The pulmonary arterial hypertension improved in 11 children, 1 of whom died and the remaining children were in stable condition.The pulmonary arterial hypertension worsened in 2 children, 1 of them improved previously but aggravated recently, and the other child did not monitor pulmonary artery pressure and died during telephone follow-up. Conclusions:Rheumatic diseases complicated with PAH are rare and most often diagnosed in severe rheumatic children.It can lead to death, and is commonly accompanied by notably elevated BNP levels.The patients who have early PAH detection, intensive treatment of the primary disease, symptomatic and targeted pulmonary artery pressure reduction show a better prognosis.

Post-COVID-19 Epidemic: Allostatic Load among Medical and Nonmedical Workers in China.

BACKGROUND: As the fight against the COVID-19 epidemic continues, medical workers may have allostatic load. OBJECTIVE: During the reopening of society, medical and nonmedical workers were compared in terms of allostatic load. METHODS: An online study was performed; 3,590 Chinese subjects were analyzed. Socio-demographic variables, allostatic load, stress, abnormal illness behavior, global well-being, mental status, and social support were assessed. RESULTS: There was no difference in allostatic load in medical workers compared to nonmedical workers (15.8 vs. 17.8%; p = 0.22). Multivariate conditional logistic regression revealed that anxiety (OR = 1.24; 95% CI 1.18-1.31; p < 0.01), depression (OR = 1.23; 95% CI 1.17-1.29; p < 0.01), somatization (OR = 1.20; 95% CI 1.14-1.25; p < 0.01), hostility (OR = 1.24; 95% CI 1.18-1.30; p < 0.01), and abnormal illness behavior (OR = 1.49; 95% CI 1.34-1.66; p < 0.01) were positively associated with allostatic load, while objective support (OR = 0.84; 95% CI 0.78-0.89; p < 0.01), subjective support (OR = 0.84; 95% CI 0.80-0.88; p < 0.01), utilization of support (OR = 0.80; 95% CI 0.72-0.88; p < 0.01), social support (OR = 0.90; 95% CI 0.87-0.93; p < 0.01), and global well-being (OR = 0.30; 95% CI 0.22-0.41; p < 0.01) were negatively associated. CONCLUSIONS: In the post-COVID-19 epidemic time, medical and nonmedical workers had similar allostatic load. Psychological distress and abnormal illness behavior were risk factors for it, while social support could relieve it.

Research progress on susceptibility to diabetic retinopathy and related gene polymorphism / 国际眼科杂志(Guoji Yanke Zazhi)

@#Diabetic retinopathy(DR)is a kind of multi-factor mediated diseases, currently accepted DR environment that is caused by chronic high blood glucose metabolic abnormalities caused by, but it is regulated by the genetic factors, is considered to be a classic case of complex diseases, can be attributed to genetic factors, environmental factors and the interaction of the results. Genetic studies on the occurrence and development of DR have achieved some results, but the specific pathogenic genes and their pathogenesis are still not clear. In this study, potential DR susceptibility genes and their polymorphisms have been identified so far, so as to provide reference for further study of DR pathogenic genes and their pathogenesis.

Clinical efficacy of transconjunctival lower eyelid blepharoplasty on correction of the eyelid orbital sulcus deformity / 中华医学美学美容杂志

Objective:To investigate the clinical experience about the transconjunctival lower eyelid blepharoplasty with correction of the eyelid orbital sulcus deformity.Methods:This group received 67 cases from June 2016 to July 2018, including 3 males and 64 females. The average age was 22 years. All the cases were diagnosed as lower eyelid bag with different degrees of fat herniation after orbital septum, with no or slight lower eyelid skin relaxation. Orbital sulcus of different degree appeared with outline of bony orbital margin, or accompanied by underdevelopment of the suborbital region. Through a transconjunctival incision or with short external canthal incision, the adipose mass was fully exposed behind the anterior wall of lower eyelid, the arcuate edge was released, and the pedicled orbital fat was transferred to the gap between the orbital eyelid sulcus and fixed in the lower orbital margin. If there was insufficient fat behind the orbital septum, a retroauricular fascia graft was used to make up.Results:No postoperative complications occured in all cases. After followed up for more than 3-month, 3 of 67 cases showed mild fat bulging pouch deformity in bilateral eyelids and 1 case was in unilateral eyelid. In other cases, deformity of the pouch and the eyelid orbital sulcus were improved significantly, and dynamic expression (orbicularis muscle contraction) showed no local uplift in lower eyelid morphology.Conclusion:The transconjunctival lower eyelid blepharoplasty with correction of the eyelid orbital sulcus deformity can obtain good clinical results in lower eyelid area.

Clinical features of sleep-disordered breathing in children with neuromuscular disease / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of sleep-disordered breathing (SDB) in children with neuromuscular disease (NMD).@*METHODS@#A retrospective analysis was performed on the medical data of 18 children who were diagnosed with NMD and underwent polysomnography (PSG) (NMD group). Eleven children without NMD who had abnormal sleeping habit and normal sleep structure on PSG were enrolled as the control group. The two groups were compared in terms of the daily and nocturnal symptoms of SDB, incidence rate of obstructive sleep apnea (OSA), pulmonary function, end-tidal partial pressure of carbon dioxide (PetCO@*RESULTS@#In the NMD group, 16 children (89%) had related daily and nocturnal symptoms of SDB, and the youngest age was 1 year at the onset of such symptoms. Compared with the control group, the NMD group had significant reductions in total sleep time and sleep efficiency (@*CONCLUSIONS@#There is a high proportion of children with SDB among the children with NMD, and SDB can be observed in the early stage of NMD, which results in the damage of sleep structure and the reduction in sleep efficiency. Respiratory events are mainly obstructive events, and oxygen reduction events are mainly observed during REM sleep.

Prognostic and predictive biomarkers in patients with COVID-19 treated with tocilizumab in a randomised controlled trial

BackgroundRetrospective observational studies suggest that interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, lymphocytes, monocytes, neutrophils, D-dimer, and platelets are associated with disease progression, treatment outcomes, or both, in patients with COVID-19 pneumonia. We explored these candidate prognostic and predictive biomarkers with efficacy outcomes after treatment with tocilizumab, an anti-IL-6 receptor antibody using data from the COVACTA trial for patients hospitalised with severe COVID-19 pneumonia. MethodsCandidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomisation) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. FindingsModelling in the placebo arm showed all candidate biomarkers except LDH and D-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modelling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction p=0.03), mechanical ventilation (predictive interaction p=0.01), and clinical status (predictive interaction p=0.02) compared with placebo. InterpretationMultiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28. RESEARCH IN CONTEXT Evidence before this studyThe efficacy and safety of the anti-interleukin-6 receptor antibody tocilizumab in the treatment of patients hospitalised with COVID-19 pneumonia was investigated in COVACTA, a double-blind, randomised, placebo-controlled trial. The primary endpoint of improved clinical status on a seven-category ordinal scale (1, discharged/ready for discharge; 7, death) at day 28 was not met in this trial. Among the secondary endpoints, no difference in mortality at day 28 was observed, but time to hospital discharge was shorter in the tocilizumab group. Subgroup analysis suggested there might be a treatment benefit in patients grouped according to their ordinal scale category at baseline. We searched PubMed on September 14, 2020, using the terms "tocilizumab AND (COVID-19 OR coronavirus) AND biomarker" with no language or date restrictions. The search retrieved 18 articles, four of which identified laboratory measures as potential biomarkers in patients who received tocilizumab for the treatment of COVID-19 pneumonia. The biomarkers reported in these studies include interleukin-6, C-reactive protein, ferritin, fibrinogen, liver transaminases, lymphocytes, platelets, and D-dimer. However, these previous studies were single-centre, retrospective, observational studies. Larger, prospective, controlled trials are needed to investigate potential prognostic and predictive biomarkers to assess the outcomes and response to treatments for COVID-19. Added value of this studyThis exploratory analysis of data from COVACTA demonstrated interleukin-6, C-reactive protein, ferritin, neutrophils (percentage and absolute count), neutrophil-to-lymphocyte ratio, lymphocytes (percentage and absolute count), monocytes (percentage), and platelets as strong prognostic biomarkers in patients hospitalised with severe COVID-19 pneumonia. More important, ferritin showed predictive value for tocilizumab treatment effects on day 28 clinical outcomes of mortality, mechanical ventilation (among the subgroup of patients not receiving mechanical ventilation at randomisation), and clinical status compared with placebo. Implications of all the available evidenceIn patients with elevated levels of ferritin at baseline, tocilizumab decreased the probability of death, mechanical ventilation, and worsening clinical status at day 28 compared with placebo, suggesting that ferritin might be useful as a predictive biomarker of efficacy outcomes for tocilizumab in patients with severe COVID-19 pneumonia.

Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia

BACKGROUNDCOVID-19 is associated with immune dysregulation and hyperinflammation. Tocilizumab is an anti-interleukin-6 receptor antibody. METHODSPatients hospitalized with severe COVID-19 pneumonia receiving standard care were randomized (2:1) to double-blinded intravenous tocilizumab 8 mg/kg or placebo. The primary outcome measure was clinical status on a 7-category ordinal scale at day 28 (1, discharged/ready for discharge; 7, death). RESULTSOverall, 452 patients were randomized; the modified-intention-to-treat population included 294 tocilizumab-treated and 144 placebo-treated patients. Clinical status at day 28 was not statistically significantly improved for tocilizumab versus placebo (P=0.36). Median (95% CI) ordinal scale values at day 28: 1.0 (1.0 to 1.0) for tocilizumab and 2.0 (1.0 to 4.0) for placebo (odds ratio, 1.19 [0.81 to 1.76]). There was no difference in mortality at day 28 between tocilizumab (19.7%) and placebo (19.4%) (difference, 0.3% [95% CI, -7.6 to 8.2]; nominal P=0.94). Median time to hospital discharge was 8 days shorter with tocilizumab than placebo (20.0 and 28.0, respectively; nominal P=0.037; hazard ratio 1.35 [95% CI 1.02 to 1.79]). Median duration of ICU stay was 5.8 days shorter with tocilizumab than placebo (9.8 and 15.5, respectively; nominal P=0.045). In the safety population, serious adverse events occurred in 34.9% of 295 patients in the tocilizumab arm and 38.5% of 143 in the placebo arm. CONCLUSIONSIn this randomized placebo-controlled trial in hospitalized COVID-19 pneumonia patients, tocilizumab did not improve clinical status or mortality. Potential benefits in time to hospital discharge and duration of ICU stay are being investigated in ongoing clinical trials. Trial registrationClinicalTrials.gov NCT04320615

Mental Health and Psychosocial Problems of Medical Health Workers during the COVID-19 Epidemic in China.

OBJECTIVE: We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak. METHODS: An online survey was run from February 19 to March 6, 2020; a total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2). RESULTS: Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05). CONCLUSIONS: During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.

Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial.

BACKGROUND: Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD. METHODS: This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0-52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study. DISCUSSION: The tACS applied in this trial may have treatment effects on MDD with minimal side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.

Effect of Transcranial Alternating Current Stimulation for the Treatment of Chronic Insomnia: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Clinical Trial.

BACKGROUND: Not all adults with chronic insomnia respond to the recommended therapeutic options of cognitive behavioral therapy and approved hypnotic drugs. Transcranial alternating current stimulation (tACS) may offer a novel potential treatment modality for insomnia. OBJECTIVES: This study aimed to examine the efficacy and safety of tACS for treating adult patients with chronic insomnia. METHODS: Sixty-two participants with chronic primary insomnia received 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas in the laboratory on weekdays for 4 consecutive weeks, followed by a 4-week follow-up period. The primary outcome was response rate measured by the Pittsburgh Sleep Quality Index (PSQI) at week 8. Secondary outcomes were remission rate, insomnia severity, sleep onset latency (SOL), total sleep time (TST), sleep efficiency, sleep quality, daily disturbances, and adverse events at the end of the 4-week intervention and at the 4-week follow-up. RESULTS: Of 62 randomized patients, 60 completed the trial. During the 4-week intervention, 1 subject per group withdrew due to loss of interest and time restriction, respectively. Based on PSQI, at 4-week follow-up, the active group had a higher response rate compared to the sham group (53.4% [16/30] vs. 16.7% [5/30], p = 0.009), but remission rates were not different between groups. At the end of the 4-week intervention, the active group had higher response and remission rates than the sham group (p < 0.001 and p = 0.026, respectively). During the trial, compared with the sham group, the active group showed a statistically significant decrease in PSQI total score, a shortened SOL, an increased TST, improved sleep efficiency, and improved sleep quality (p < 0.05 or p < 0.001). Post hoc analysis revealed that, in comparison with the sham group, the active group had improved symptoms, except for daily disturbances, at the end of the 4-week intervention, and significant improvements in all symptoms at the 4-week follow-up. No adverse events or serious adverse responses occurred during the study. CONCLUSION: The findings show that the tACS applied in the present study has potential as an effective and safe intervention for chronic insomnia within 8 weeks.

Clinical study on intradermal needle therapy in treating urinary retention after cervical cancer surgery / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of intradermal needle therapy for urinary retention after cervical cancer surgery. Methods: A total of 100 patients with urinary retention after cervical cancer surgery were randomized into a control group and an observation group, with 50 cases in each group. The control group was treated with basic nursing only, and the observation group was treated with additional intradermal needle therapy. Both groups were treated for 2 courses of treatment. The main symptom scores and residual urine volume of the two groups were observed before and after treatment, and the inpatient time, catheter indwelling time and the clinical efficacy were compared between the two groups. Results: The total effective rate was 96.0％ in the observation group and 88.0％ in the control group, and the difference between the two groups was statistically significant (P<0.05). After treatment, the main symptom scores and residual urine volume in both groups decreased significantly (all P<0.05), and the scores and residual urine volume in the observation group were significantly lower than those in the control group (all P<0.05). The inpatient time and catheter indwelling time in the observation group were significantly shorter than those in the control group (both P<0.05). Conclusion: Intradermal needle therapy has an obvious effect in improving symptoms of urinary retention after cervical cancer surgery, and the effect is significantly more persistent than that of simple basic nursing.

Study on tricuspid annular plane systolic excusion(TAPSE) after congenital heart disease surgery / 中华胸心血管外科杂志

Objective:To explore the tricuspid annular plane systolic excusion(TAPSE) in children with left-to-right shunt after congenital heart disease surgery and to understand the early systolic function of right heart in thesepatient.Methods:From June 2018 to December 2018, a prospective study was conducted in 20 infants after repair of left-to-right shunt congenital heart disease, including 10 males(50%) and 10 females(50%) , aged from 1 to 12 months, with a median of 4.5(2.0, 6.8) months, a body mass of 3.0-9.0 kg with median of 6.0(3.7, 7.7) kg.On the first postoperative day, blood was taken from central venous for N-terminal pro-B-type natriuretic peptide(NT pro-BNP) test, TAPSE and left ventricular ejective fraction(LVEF) was measured by echocardiography.The effects of aortic occlusion time, cardiopulmonary bypass time, preoperative pneumonia and preoperative heart failure on TAPSE were compared. The relationship between TAPSE and heart rate, systolic pressure, central venous pressure, vasoactive drug score, endotracheal intubation time, detention time in intensive care unit, NT pro-BNP and LVEF after operation was analysed.Results:The aortic cross-clamping time was 15-87 minutes, with median 31(28, 50) minutes. The cardiopulmonary bypass time was 35-117 minutes, with an average of(68±22)minutes. The time of tracheal intubation was 4-117 hours, with an average of(50±35) hours. The stay time in CICU was 1-14 days, with a median of 5(2, 7) days.The LVEF was 0.18-0.66, with median 0.53(0.42, 0.57). The TAPSE was 2.0-10.0 mm, with an average of(5.2±2.0) mm. On the first day after operation, NT pro-BNP was 1 548-35 000 pg/ml, with an average of(9 446±8 130) pg/ml.TAPSE was negatively correlated with postoperative intubation time( r=-0.576, P= 0.007) and detention time in ICU( r=-0.765, P=0.000), and positively correlated with postoperative LVEF( r=0.461, P=0.041)( P<0.05). TAPSE was negatively correlated with heart rate( r=-0.303, P=0.193), central venous pressure( r=-0.425, P=0.062), vasoactive drug score( r=-0.418, P=0.067) and NT Pro BNP( r=-0.348, P=0.132), and positively correlated with systolic pressure( r=0.146, P=0.54), but there was no statistical significance in each item.Compared with patients with TAPSE≥5mm, the detention time and tracheal intubation time were longer than those TAPSE<5 mm, the central venous pressure and NT-pro BNP was higher than those TAPSE<5 mm( P<0.05), the difference was statistically significant, other indicators had no significant difference. Conclusion:It is simple and feasible to measure TAPSE by echocardiography in children after operation with left-to-right shunt congenital heart disease.TAPSE decreased postoperatively suggested that the function of right ventricle decreased at the early stage after surgery, and with left ventricle systolic function decreased, which eventually led to the increase of NT pro-BNP, the need for higher doses of vasoactive drug support, longer tracheal intubation time and the stay time in CICU.Attention should be paid to the right heart function of children after congenital heart surgery.

Pantothenate kinase-associated neurodegeneration with novel mutations: A case report

@#A 32-year-old male with pantothenate kinase-associated neurodegeneration (PKAN) disease who had two heterozygous mutations in the PANK2 gene presented with dystonic storm. The MRI T2WI showed the “eye of the tiger” sign, which combined the abnormal low signal in the globus pallidus due to accumulation of iron and the longitudinal strip of high signal due to gliosis. The patient underwent bilateral globus pallidus internus deep brain stimulation (GPi-DBS) implantation surgery under general anesthesia with marked improvement. Genetic test showed c.1550T>G and c.377G>C heterozygous mutations in the PANK2 gene. To our knowledge, this is the first report of a PKAN patient with the novel mutations in the PANK2 gene.

Clinical features of influenza with plastic bronchitis in children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of influenza with plastic bronchitis (PB) in children, and to improve the awareness of the diagnosis and treatment of PB caused by influenza virus.@*METHODS@#A retrospective analysis was performed for the clinical data of 70 children with lower respiratory influenza virus infection from October 2018 to October 2019. According to the presence or absence of PB, they were divided into an influenza+PB group with 12 children and a non-PB influenza group with 58 children. Related clinical data were collected for the retrospective analysis, including general information, clinical manifestations, laboratory examination, imaging findings, treatment, and prognosis.@*RESULTS@#In the influenza+PB group, most children experienced disease onset at the age of 1-5 years, with the peak months of January, February, July, and September. Major clinical manifestations in the influenza+PB group included fever, cough, and shortness of breath. The influenza+PB group had significantly higher incidence rates of shortness of breath and allergic diseases such as asthma than the non-PB influenza group (P<0.05). Of the 12 children in the influenza+PB group, 7(58%) had influenza A virus infection and 5 (42%) had influenza B virus infection, among whom 1 had nephrotic syndrome. For the children in the influenza+PB group, major imaging findings included pulmonary consolidation with atelectasis, high-density infiltration, pleural effusion, and mediastinal emphysema. Compared with the non-PB influenza group, the influenza+PB group had a significantly higher proportion of children who were admitted to the pediatric intensive care unit (P<0.05). Bronchoscopic lavage was performed within 1 week after admission, and all children were improved and discharged after anti-infective therapy and symptomatic/supportive treatment.@*CONCLUSIONS@#Influenza with PB tends to have acute onset and rapid progression, and it is important to perform bronchoscopy as early as possible. The possibility of PB should be considered when the presence of shortness of breath, allergic diseases such as asthma or nephrotic syndrome in children with influenza.

Simultaneous determination of four sesquiterpene lactones in the whole herb of Elephantopus scaber Linn / 国际药学研究杂志

Objective: To establish an ultra-performance liquid chromatography(UPLC)method for the simul-taneous determination of four sesquiterpene lactones, deoxyelephantopin, isodeoxyelephantopin, isoscabertopin and sca- bertopin in Elephantopus scaber Linn.. Methods: The UPLC conditions were as follows: the separation was performed using an Acquity UPLC BEH C18(2.1 mm × 100 mm, 1.7 μm)column, the temperature of the column was maintained at 40℃, and the detection wavelength was 220 nm. The mobile phase was the water and acetonitrile solution in a binary gra- dient elution at the flow rate of 0.3 ml/min. Results: The four components, deoxyelephantopin, isodeoxyelephantopin, isoscabertopin and scabertopin were separated well under the UPLC conditions and showed a good linearity within the ranges of 0.383-76.500(R2=0.9999), 0.775-155.0(R2=0.9999), 0.507-101.5(R2=0.9999), and 0.850-(R2=0.9997), respectively. Their average recovery(n=6)was 102.31%, 103.87%, 102.66% and 105.68%, RSD was 1.20%, 2.00%, 1.24% and 1.73%, respectively. The four components were validated by the simultaneous termination in eleven batches of E. scaber samples from different areas in the present study. Conclusion: lished UPLC method could be used for the determination of four sesquiterpene lactones, deoxyelephantopin, elephantopin, isoscabertopin and scabertopin in E. scaber. The present results provide a reference for further velopment and quality evaluation of E. scaber.

Research progresses in microbial 1,3-1,4-β-glucanase: protein engineering and industrial applications / 生物工程学报

1,3-1,4-β-glucanase (E.C.3.2.1.73) is an important industrial enzyme which cleave β-glucans into oligosaccharides through strictly cutting the β-1,4 glycosidic bonds in 3-O-substituted glucopyranose units. Microbial 1,3-1,4-β-glucanase belongs to retaining glycosyl hydrolases of family 16 with a jellyroll β-sandwich fold structure. The present paper reviews the industrial application and protein engineering of microbial β-glucanases in the last decades and forecasts the research prospects of microbial β-glucanases.

Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds / 神经科学通报·英文版

Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases. A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.

Quantification of Tyrosine Hydroxylase and ErbB4 in the Locus Coeruleus of Mood Disorder Patients Using a Multispectral Method to Prevent Interference with Immunocytochemical Signals by Neuromelanin / 神经科学通报·英文版

The locus coeruleus (LC) has been studied in major depressive disorder (MDD) and bipolar disorder (BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown neuromelanin. We found significantly increased tyrosine hydroxylase (TH) in the LC of MDD patients-thus validating the method-but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.