Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

Objective To establish a method for determination of the azide ions in blood by gas chromatography-mass spectrometry （GC-MS） following pentafluorobenzyl derivatization. Methods A blood sample of 0.2 mL was placed into a 10 mL glass test tube, and the internal standard sodium cyanide, derivatization reagent pentafluorobenzyl bromide and catalyst tetradecyl benzyl dimethyl ammonium chloride were added in turn. After vortex mixing, the mixture was heated with low-power microwave for 3 min. After centrifugation, the organic phase was taken for GC-MS analysis. Results The azide ions in blood had a good linear relationship in the mass concentration range of 0.5 to 20 μg/mL. The lowest detection limit was 0.25 μg/mL and the relative recovery was 91.36%-94.58%. The method was successfully applied to a case of death from sodium azide poisoning. The mass concentration of azide ions in the blood of the dead was 11.11 μg/mL. Conclusion The method developed in this paper has strong specificity and is easy to operate, which is suitable for the rapid detection of azide ions in blood.
Azides ; Gas Chromatography-Mass Spectrometry ; Humans ; Ions

To analyze the TCM health culture level and influence factors of Chinese citizens in 2017. PPS sampling combined with random sampling was used to select the residents aged between 15-69 years old in 30 provinces as the respondents,and a questionnaire study was conducted to investigate their TCM health culture level. In 2017,there were 87 287 valid questionnaires for Chinese citizens' TCM health culture level,including 48. 25% male and 51. 75% female,with a sex ratio of 1 ∶ 1. 073. In 2017,the overall TCM health culture level was 13. 39%,specifically 18. 77% for the urban areas and 10. 51% for the rural areas. Compared with people who were illiterate or less literate,people with an educational background of elementary school,junior high school,high school/vocational/technical school and junior college/university had a higher TCM health culture level,and the OR values were 1. 584( 95% CI[1. 166,2. 152]),2. 827( 95%CI[1. 839,4. 345]),5. 651( 95%CI[3. 637,8. 781]),9. 785( 95%CI[6. 187,15. 477]) in order. With civil servants as the reference,medical workers had a higher TCM health culture level( OR = 1. 829,95%CI[1. 279,2. 616]),while farmers had the lowest TCM health culture level( OR = 0. 493,95% CI[0. 349,0. 697]). Compared with people with the annual household income per capita of 20 000 yuan and below,people with the annual household income per capita between 20 000-50 000,50 000-80 000,80 000 yuan or above had a higher TCM health culture level,and the OR values were 1. 176( 95% CI[0. 963,1. 437]),1. 458( 95%CI[1. 168,1. 820]) and 1. 930( 95%CI[1. 509,2. 469]). Based on the differences between urban and rural areas,the influence factors of citizens' TCM health culture level include education,occupation and income.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; China ; Female ; Health Literacy ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Surveys and Questionnaires ; Young Adult

OBJECTIVE: To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms. METHODS: Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1β(MIP-1β), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip. RESULTS: Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1β, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1β and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1β (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1β TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated. CONCLUSION There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.
Cytokines ; Humans ; Leukocytes, Mononuclear ; Scleroderma, Systemic ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A

Aim To observe the effect of capsaicin on the experimental autoimmune neuritis (EAN) in rats and explore the mechanism.Methods To induce EAN,male Lewis rats were immunized with peripheralnerve myelin sheath antigen (P257481) peptide and complete Freund's adjuvant (CFA) mixed liquor.Rapamycin (RAPA,2.5 mg · kg-1) was administered by intraperitoneal injection 0.5 h after immunization and capsaicin (1 mg · kg-1 · d-1) was administered by intragastric administration 1.0 h after immunization for 15 days.The incidence and clinical characteristics of EAN were observed.The clinical scores of neurological signs were completed and body weight was measured.Pathological morphology of sciatic nerve was observed by HE staining and Lauck fast blue staining.Ultrastructure of sciatic nerve was observed by transmission electron microscope.Levels of serum tumor necrosis factor alpha (TNF-α),interferon gamma (IFN-γ),interleukin 1β (IL-1β) and intedeukin-6 (IL-6) were tested by enzyme linked immunosorbent assay (ELISA).Expressions of autophagy related protein were measured by Western blot.Results Compared with EAN group,the clinical scores of neurological signs significantly decreased from day 7 to day 16 of post-immunization (P ＜ 0.05),body weight significantly increased from day 3 to day 16 of post-immunization (P ＜ 0.05),demyelination obviously decreased,inflammatory cell infiltration number obviously decreased (P ＜ 0.05),the levels of TNF-α,IFN-γ,IL-1β and IL-6 significantly decreased (P ＜ 0.05),the number of autophagosome in axon of sciatic nerve significantly decreased (P ＜ 0.05),and expressions of Beclin-1 and LC3-Ⅱ and the ratio of LC3-Ⅱ and LC3-Ⅰ were significantly down-regulated,and the expression of p62 was significantly up-regulated (P ＜ 0.05) in EAN + capsaicin group.Rapamycin partially reversed the action of capsaicin.Conclusions Capsaicin inhibits EAN in rats,and the mechanism may be related with the inhibition of autophagy activity.

Objective:Tacrolimus prolonged-release(PR) formulation is a new once-daily formulation of the calcineurin inhibitor tacrolimus,which is currently used in adult liver or kidney transplant patients,and is also gradually widely used in children with nephrotic syndrome.The present study was undertaken to preliminarily investigate the pharmacokinetic characteristics of tacrolimus PR in pediatric nephrotic syndrome recipients.Methods:This single-center open-label prospective study was performed in pediatric nephrotic syndrome recipients.Pharmacokinetic samples were collected from eight pediatric subjects with nephrotic syndrome from Department of Pediatric Nephrology in Peking University First Hospital between June and August 2011.They followed administration of single oral doses of tacrolimus PR formulation at 0.02 mg/kg (n =2),0.05 mg/kg (n =2) and 0.10 mg/kg (n =4).Blood samples were taken before the dose and 1,2,4,6,8,10,12 and 24 h after drug intake.No other medicines or interacting food or drinks were taken during the study period.Blood concentrations were measured using an enzyme multiplied immunoassay technique.Pharmacokinetic analysis was performed using WinNolin Phoenix software Version 6.0 (Pharsight,Cary,NC,USA).Results:The pharmacokinetic data were best described by a non-compartment model.Pharmacokinetic parameters of tacrolimus PR formulation in the 3 ascending doses groups (0.02 mg/kg,0.05 mg/kg and 0.10 mg/kg) were as follows:the maxi mum drug concentrations (Cm=/D) were (1.7 ± 1.0) μg/L,(3.1 ± 1.9) μg/L,(8.0 ± 3.5) μg/L,respectively;Areas under the drug concentration-time curve (AUCo-∞/D) were (47.2 ± 47.1) h · μg/ L,(84.0 ± 13.1) h · μg/L,(175.6 ± 107.1) h · μg/L,respectively;Oral clearance rates were (0.8±0.9) L/(h·kg),(0.4±0.1) L/(h · kg),(1.9 ±1.3) L/(h · kg),respectively;Body weight normalized distribution volumes were (7.0 ± 3.4) L/kg,(12.4 ± 8.4) L/kg and (73.6 ± 68.6) L/kg,respectively.Both mean Cmax normalized level for the administered dose (Cmax/D) and mean AUC0-∞ normalized level for the administered dose (AUC0-∞/D) were higher in the 0.05 mg/kg dosage group than in the 0.02 and 0.10 mg/kg dosage group.There were two peaks in the drug concentrations in every dose group;a primary peak appeared at the end of about 2 h followed by a small secondary peak at h 12,which was more noticeable in the 0.10 mg/kg dose group than in the two lower dosages.Conclusion:The pharmacokinetic characteristics of tacrolimus PR formulation were initially explored in pediatric patients with nephritic syndrome.The data presented form a basis for subsequent larger scale studies on pharmacokinetics of tacrolimus PR formulation in nephritic syndrome children.

BACKGROUNDThe key components of metabolic syndrome (MS) are waist circumference, blood pressure, fast blood glucose, high density lipoprotein cholesterol (HDL-c) and triglycerides (TG). These components have, separately and jointly, been associated with an increased risk of cardiovascular diseases. In this study, we aimed to explore the association between MS components and cancer risk in a population-based cohort in China.

METHODSWe established a population-based cohort with 17 779 individuals aged 35 and above at baseline in 2004 and 2005 in Changzhou, Jiangsu Province, China. All participants were face-to-face interviewed to complete a questionnaire and were accepted physical examinations including blood tests for glucose and lipids and physical measurements for obesity and blood pressure. In 2009, a total of 16 284 subjects (6886 men and 9398 women, 91.6%) attended the flow-up interviews and the participants or their family members reported all the hospitalizations and diseases including cancer occurred during the follow-up period. Multivariate Cox regression was used to estimate the hazard ratios (HRs) of metabolic syndrome components and cancer incidence.

RESULTSThere was a dose-response association between cancer risk and the number of MS components presented at baseline (P for trend = 0.012) and the HR (95% confidence interval (CI)) was 2.63 (1.27 - 5.45) for subjects carrying 3 or more metabolic syndrome components after adjustment for possible confounding factors. Specifically, the multivariate-adjusted HRs (95%CIs) for cancer risk in subjects with central obesity, high fasting glucose, low HDL-c were 1.94 (1.01 - 3.74), 2.04 (1.10 - 3.77) and 2.05 (1.09 - 3.88), respectively.

CONCLUSIONSIn this population-based, prospective cohort study in China, we found MS components, e.g., central obesity, high fasting glucose, low HDL-c were risk factors for cancer development. Early intervention of MS components may be also beneficial to reduce cancer burden.

Adult ; Asian Continental Ancestry Group ; Blood Glucose ; physiology ; China ; Female ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; Middle Aged ; Multivariate Analysis ; Neoplasms ; epidemiology ; Prospective Studies ; Triglycerides ; blood ; Waist Circumference ; physiology

OBJECTIVEThe objective of this study is to investigate the influence of mechanical properties and sintering performance by adding 5% weight percentage aids to nano-compound zirconia toughened alumina (ZTA) ceramics.

METHODSMicrometer Al2O3 and nanometer ZrO2 (quality ratio 4:1) were used to get 55% volume percentage slurry. Magnesium oxide and titanium oxide were taken as aids which were 5% weight percentage of the Al2O3 and ZrO2 powder. Five groups (number 0, 1, 2, 3, 4 group) were divided according to different proportion of aids. After gel-casting, the porcelain pieces were sintered at 1150, 1200, 1300, 1400, 1450, 1500, 1600 degrees C for 2 hours. Static three-point flexure strength, line shrinkage, relative density were measured and scanning electron microscopy (SEM) was used to observe section.

RESULTSNumber 1 (MgO 1%, TiO2 4%) group had the highest bending strength. It was (401.78+/-19.50) MPa after sintering at 1600 degrees C for 2 hours and was higher than 0 group (380.64+/-44.50) MPa. Bending strength became lower than 0 group when MgO was more than 2% or more than that weight percentage of ZTA powder. When MgO content was higher than 2% or more than that weight percentage, there was no difference in relative density raising rate between each sintering assistants groups. When the sintering temperature was higher than 1200 degrees C, all groups showed obvious line-shrinkage and the groups which contained sintering assistants were all was higher than 0 group.

CONCLUSIONAdding MgO and TiO2 aids from 1% to 4% weight percentage of ZTA will promote fritting and increase ZTA nano-compound ceramics mechanical properties. Adding 2% MgO aids or more than that weight percent will has no obvious help to increase the relative density raising rate of ZTA nano-compound ceramics and will degrade the mechanical properties of ZTA nano-compound ceramics.

Aluminum Oxide ; Dental Porcelain ; Microscopy, Electron, Scanning ; Temperature ; Titanium ; Zirconium