Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

OBJECTIVE: The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody in hospital patients, evaluate the epidemic trend of hepatitis C and formulate screening strategies. METHODS: Patient information and HCV antibody testing results were collected from January 2017 to December 2019 in 77 HCV sentinel hospitals in China. Univariate and multivariate logistic regression was used to determine the characteristics and associations. RESULTS: HCV antibody prevalence rates were distinct among patients in different departments, with a range of 0.33%-6.93%. Patients who were admitted to the liver disease-related departments (a OR = 10.76; 95% CI, 10.27-11.28), Internal Medicine (a OR = 2.87; 95% CI, 2.75-3.00), and Department of Surgery (a OR = 1.95; 95% CI, 1.87-2.04), were more likely to be tested for HCV antibody positive. HCV antibody prevalence was associated with patients aged 45 years and older (a OR = 2.74; 95% CI, 2.69-2.80), testing in infetious disease hospitals (a OR = 2.33; 95% CI, 2.26-2.40) and secondary hospitals (a OR = 1.72; 95% CI, 1.69-1.75). Patients in sentinel hospitals of the Northeast (a OR = 12.75; 95% CI, 12.40-13.11), the Central (a OR = 1.65; 95% CI, 1.61-1.70), and the West (a OR = 1.78; 95% CI, 1.73-1.83) China had higher HCV prevalence than those who were in the Eastern coastal area. CONCLUSION Those who were over 45 years old and saw doctors for liver diseases, and invasive diagnosis and treatment should be referred to HCV antibody testing.
Humans ; Middle Aged ; Prevalence ; Hepatitis C/complications* ; Hepacivirus ; Hospitals ; Hepatitis C Antibodies ; China/epidemiology* ; Risk Factors

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Objective:To estimate the incidence and risk factors of acute kidney injury (AKI) in preterm infants, and provide basis for better evaluation and treatment of renal function in preterm infants.Methods:All the hospitalized premature infants who were admitted to three research centers (Department of Neonatology at Beijing Children′s Hospital; Department of Neonatology at Beijing Obstetrics and Gynecology Hospital; Department of Neonatology at Shunyi Maternal and Children′s Hospital of Beijing Children′s Hospital)from January 1, 2017 to June 30, 2019 and had more than two serum creatinine values or urine output were included.The incidence of AKI in preterm infants was calculated and the difference among different gestational weeks was compared.Preterm infants were divided into AKI and non-AKI groups according to AKI diagnostic criteria, and the clinical characteristics between two groups were compared, and the risk factors of AKI in preterm infants were analyzed.Results:A total of 763 premature infants were included in the analysis.Twenty two cases were diagnosed with AKI.The incidence of AKI in premature infants was 2.9%.The incidence of AKI was 33.3% (3/9), 3.7% (5/134), and 2.3% (14/620) in the 24-27 + 6 weeks, 28-31 + 6 weeks, and 32-36 + 6 weeks gestational age, respectively, and the difference was statistically significant ( χ2=31.010, P<0.001). Preterm infants in AKI group had a higher proportion of males(77.3% vs. 53.3%), lower gestational weeks[29(27, 33) weeks vs.31(29, 33)weeks], higher proportions of infants with diabetic mothers(40.9% vs.19.4%), lower Apgar scores at 1 and 5 minutes[8(7, 10) vs.9(8, 10), 9(9, 10) vs.10(9, 10), respectively], higher proportions of invasive and noninvasive respiratory support(45.5% vs.11.3%, 63.6% vs.19.2%, respectively), longer duration of invasive respiratory support[260(136, 742)h vs.72(18, 160)h], longer hospital stays[66(19, 88)d vs.42(26, 58)d], and higher rates of sepsis (27.3% vs. 6.5%), respiratory distress syndrome(40.9% vs. 11.6%), and patent ductus arteriosus that requiring ibuprofen or surgical closure(13.6% vs. 3.0%), diuretic(27.3% vs. 3.9%), and vasoactive drug use (22.7% vs. 3.6%) than those in non-AKI group, and the differences were statistically significant(all P<0.05). Multivariate regression analysis showed that sepsis was an independent risk factor for AKI in preterm infants ( P=0.039, OR=3.498, 95% CI 1.065-11.490) after adjustment of gestational age and birth weight. Conclusion:The incidence of AKI is relatively high in preterm infants with gestational age<28 weeks.Compared with preterm infants without AKI, preterm infants with AKI have smaller gestational weeks and longer hospital stay.Sepsis is an independent risk factor for AKI in preterm infants.

Clinical data of 289 patients aged 60 years old and above with acute intestinal obstruction operated in Drum Tower Hospital during June 2010 to December 2020 were analyzed retrospectively. Among 289 cases, 97 cases(33.6%)had tumor, 66(22.8%)had external hernias, 44(15.2%)had adhesions, 36(12.5%)had volvulus, 20(6.9%)had internal hernias, 8(2.8%)had intussusception and 18(6.2%)had other causes. Of 156 strangulated intestinal obstruction cases, 51 cases(32.7%)had external hernias,36(23.1%)had volvulus, 26(16.7%)had adhesions, 18(11.5%)had internal hernias, 14(9.0%)had tumor, 8(5.1%)had intussusception, and 3(1.9%)had other causes. There was a history of abdominal surgery in 88.6%(39/44)cases of adhesion, 85.0% (17/20) cases of internal hernia and 61.1%(22/36)cases of volvulus. For patients with acute intestinal obstruction caused by intestinal tumor, the cases of small bowel obstruction, strangulated intestinal obstruction and the strangulated large bowel were significantly less than those of large bowel obstruction, the non-strangulated intestinal obstruction and the non-strangulated large bowel obstruction (5 vs. 92, 14 vs. 80, 12 vs. 83, respectively; all P<0.05). For patients with strangulated intestinal obstruction caused by external hernias, volvulus, internal hernias and intussusception were significantly more than those with non-strangulated intestinal obstruction groups(51 vs.15, 36 vs. 0, 18 vs. 2, 8 vs. 0, respectively; P<0.05). The patients with strangulated large bowel obstruction caused by external hernias( n=4) and volvulus( n=9)were significantly more than those with non-strangulated large bowel obstruction( n=1 and 0, respectively; P<0.05). The patients with strangulated small bowel obstruction caused by adhesions( n=26)and volvulus( n=27)were significantly more than those with non-strangulated small bowel obstruction( n=18 and 0,respectively; P<0.05).The study showed that the principal causes of emergency operation for acute intestinal obstruction and strangulated intestinal obstruction are intestinal tumor and external hernias in elderly patients.

Antibodies, Viral ; blood ; Betacoronavirus ; Coronavirus ; immunology ; Coronavirus Infections ; immunology ; Humans ; Immunoglobulin G ; blood ; Pandemics ; Pneumonia, Viral ; immunology

【Objective】To investigate the effect of dexmedetomidine on the phagocytosis of macrophages.【Methods】 RAW264.7 cells were divided into control group，DEX group，and BRL44408 + DEX group. Expression of α2A adrenergic receptor，p-Akt and Akt were detected by Western Blotting；Phagocytosis Assay Kit（IgG PE）was used to measure the phagocytosis of macrophages. 【Results】 α2A adrenergic receptor was detected in RAW264.7 cells；Dexmedetomidine could enhance the phagocytosis of macrophages（P < 0.001），and BRL44408 reversed the enhancement of phagocytic ability of macrophages（P < 0.001）；Dexmedetomidine upregulated the expression of Akt in RAW264.7 cells，while the use of BRL44408 inhibited the activation of the Akt pathway（P < 0.01）.【Conclusion】Dexmedetomidine could enhance phagocytosis of RAW264.7 by activating the Akt pathway through the α2A adrenergic receptor.

BackgroundRecent advances in extracorporeal membrane oxygenation (ECMO) have led to increasing interest in its use during cardiopulmonary resuscitation (CPR). However, decisions regarding extracorporeal CPR (ECPR) in children are difficult as a result of limited studies, especially in Asia Pacific. The objective of this study was to investigate trends in survival and demographic details for children with ECPR in Asia Pacific recorded in the Extracorporeal Life Support Organization (ELSO) registry from 1999 to 2016 and identify the risk factors associated with in-hospital mortality.

MethodsThe data of children younger than 18 years of age who received ECPR over the past 18 years in Asia Pacific were retrospectively analyzed. The data were extracted from the ELSO registry and divided into two 9-year groups (Group 1: 1999-2007 and Group 2: 2008-2016) to assess temporal changes using univariate analysis. Then, univariate and multiple logistic regression analyses were performed between survivors and nonsurvivors to identify factors independently associated with in-hospital mortality.

ResultsA total of 321 children were included in final analysis, with an overall survival rate of 50.8%. Although survival rates were similar between Group 1 and Group 2 (43.1% vs. 52.5%, χ = 1.67, P = 0.196), the median age (1.7 [0.3, 19.2] months for Group 1 vs. 5.6 [0.8, 64.9] months for Group 2, t = -2.93, P = 0.003) and weight (3.7 [3.0, 11.5] kg for Group 1 vs. 6.0 [3.4, 20.3] kg for Group 2, t = -3.14, P = 0.002) of children increased over time, while the proportion of congenital heart disease (75.9% for Group 1 vs. 57.8% for Group 2, χ = 6.52, P = 0.011) and cardiogenic shock (36.2% for Group 1 vs. 7.2% for Group 2, χ = 36.59, P < 0.001) decreased. Patient conditions before ECMO were worse, while ECMO complications decreased across time periods, especially renal complications. Multiple logistic regression analysis of ECMO complications showed that disseminated intravascular coagulation (DIC), myocardial stunning, and neurological complications were independently associated with increased odds of hospital mortality.

ConclusionsThe broader indications and decreased complication rates make EPCR to be applicated more and more extensive in children in Asia Pacific region. ECMO complications such as myocardial stunning are independently associated with decreased survival.

Asia ; Cardiopulmonary Resuscitation ; methods ; Child ; Child, Preschool ; Extracorporeal Membrane Oxygenation ; methods ; Female ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Registries ; Retrospective Studies ; Risk Factors ; Survival Rate ; Time Factors

BACKGROUNDHepatocyte transplantation has been proposed as an alternative to whole-organ transplantation to support many forms of hepatic insufficiency. Unfortunately, the lack of donor livers makes it difficult to obtain enough viable human hepatocytes for hepatocyte-based therapies. Therefore, it is urgent to find new ways to provide ample hepatocytes. Induced pluripotent stem (iPS) cells, a breakthrough in stem cell research, may terminate these hinders for cell transplantation. For the promise of iPS cells to be realized in liver diseases, it is necessary to determine if and how efficient they can be differentiated into functional hepatocytes.

METHODSIn this study, we directly compared the hepatic-differentiation capacity of mouse iPS cells and embryonic stem (ES) cells with three different induction approaches: conditions via embryonic body (EB) formation plus cytokines, conditions by combination of dimethyl sulfoxide and sodium butyrate and chemically defined, serum free monolayer conditions. Among these three induction conditions, more homogenous populations can be promoted under chemically defined, serum free conditions. The cells generated under these conditions exhibited hepatic functions in vitro, including glycogen storage, indocynine green (ICG) uptake and release as well as urea secretion. Although efficient hepatocytes differentiation from mouse iPS cells were observed, mouse iPS cells showed relatively lower hepatic induction efficiency compared with mouse ES cells.

RESULTSMouse iPS cells would be efficiently differentiated into functional hepatocytes in vitro, which may be helpful in facilitating the development of hepatocytes for transplantation and for research on drug discovery.

CONCLUSIONWe demonstrate that mouse iPS cells retain full potential for fetal liver development and describe procedures that facilitates the efficient generation of highly differentiated human hepatocyte-like cells from iPS cells in vitro.

Animals ; Butyrates ; pharmacology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Cytokines ; pharmacology ; Embryonic Stem Cells ; cytology ; drug effects ; Hepatocytes ; cytology ; drug effects ; metabolism ; Induced Pluripotent Stem Cells ; cytology ; drug effects ; Mice ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the role of microsatellite instability(MSI) in Chinese sporadic coloretal cancer.

METHODSA total of 146 patients with colorectal cancer were treated surgically from August 2004 to September 2006 in the Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Data were collected prospectively. Univariate and multivariable analyses were performed for parameters such as age, gender, tumor location, differentiation, MSI, tumor type, lymph node metastasis, TNM stage, and survival.

RESULTSFollow-up was available in 134 patients including telephone call and office visit. MSI(P=0.029), tumor type(P=0.000), TNM stage(P=0.000) were independently associated with survival on Cox regression model. There were 26 patients with MSI, and the 1-, 3-, and 5-year survival rates were 100%, 92.3%, and 92.3%, respectively. The remaining 108 patients had microsatellite stable tumor, and the 1-, 3-, and 5-year survival rates were 96.3%, 72.2%, and 63.5%, respectively. The difference was statistically significant(P=0.016).

CONCLUSIONMicrosatellite instability is an important factor associated with patient survival in Chinese sporadic colorectal cancer.

Aged ; China ; Colorectal Neoplasms ; diagnosis ; genetics ; Female ; Follow-Up Studies ; Humans ; Male ; Microsatellite Instability ; Middle Aged ; Prognosis ; Survival Rate