BACKGROUND: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA. METHODS: A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease. RESULTS: The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production. CONCLUSION Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

Population bioequivalence (PBE) is a statistical approach recommended by FDA to evaluate the consistency of particle size distribution of numerous nanoparticle products.However, when particle size distribution (PSD) profile exhibits multiple peaks or other complex distributions, the traditional descriptors D50 and SPAN are no longer suitable to describe PSD.Earth mover''s distance (EMD) is a new statistical metric for assessing the difference between distributions.In this study, we used EMD to measure the discrepancy between PSD and then PBE was applied to perform statistical test to establish equivalence.Our results showed that the proposed method can effectively reject an unequivalent product and pass an equivalent product, thus indicating its helpfulness in guiding the optimization of formulation and preparation process.

This article researches how to allocate medical protective consumables in hospital and ensure the safety of emergency marketing procurement under the condition that people are easily susceptible to COVID-19. To inform medical staffs about the standard instruction, we establish the corresponding hierarchical control management system and standards of medical protective consumables. To reduce the stress of clinical medical staff and prevent excessive protection, we enhance the training mechanisms and promote the superior normative guidance. The aim is to fully play the effectiveness of the key departments of medical protective consumables, reduce the risk of infection of clinical medical staff and ensure the safety of medical staffs.
Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2

Objective To explore the application of double-parameter three-dimension arterial spin labeling (3D-ASL) in evaluating collateral circulation in patients with unilateral chronic middle cerebral artery (MCA) occlusion.Methods From May 2015 to November 2017,24 patients with unilateral chronic MCA occlusion were scanned in Yantaishan Hospital by conventional MRI,DWI,3D-TOF-MRA and 3D-ASL (post-labeling delays:1.5 s and 2.5 s respectively) using a 3.0 T MR scanner.The cerebral blood flow (CBF) values were measured in region of interest in the occlusive cortical area and in the contralateral normal cerebral area.The differences in CBF value measured by 3D-ASL (PLD=1.5 s and PLD=2.5 s) were analyzed by statistical methods.Results All the patients (n=24) on 3D-ASL (PLD=1.5 s) presented with apparent hypoperfusion in the MCA occlusion territory;but 3D-ASL (PLD=2.5 s) demonstrated the basically same perfusion in bilateral MCA territories,without apparent hypoperfusion in one cerebral hemisphere.The subtraction images of 3D-ASL (PLD 2.5 s-PLD 1.5 s)presented laminated high signal areas in the cortical region of MCA occlusion.There was no statistically significant difference in CBF value of the contralateral normal cerebral area between measurements by 3D-ASL (PLD=1.5 s) and by 3D-ASL (PLD=2.5 s) (6.39±5.01 mL/100 g·min versus 55.87±6.89 mL/100 g· min) (P＞0.05).The CBF value of region of interest in the occluded cortical area (23.34±4.53 mL/100 g· min) was significantly lower than that in the contralateral normal cerebral area (55.87±6.89 mL/100 g·min) by 3D-ASL (PLD=1.5 s) (P＜0.05).The CBF value of region of interest in the occluded cortical area (53.93±8.59 mL/100 g·min) by 3D-ASL (PLD=2.5 s) was significantly higher than that by 3D-ASL (PLD=1.5 s) (23.34±4.53 mL/100 g·min) (P＜0.05).There was no statistically significant difference between the CBF value of region of interest in the occluded cortical area and that in the contralateral normal cerebral area by 3D-ASL (PLD=2.5 s) (P＞0.05).Conclusions 3D-ASL (PLD=1.5 s and PLD=2.5 s) can noninvasively and intuitively demonstrate the collateral circulation compensation in patients with chronic MCA occlusion.3D-ASL (PLD=1.5 s) can reflect the first-order collateral circulation compensation while 3D-ASL (PLD=2.5 s) can reflect accurately the secondary collateral circulation compensation.

BACKGROUNDScreening on multidrug-resistant tuberculosis (MDR-TB) has been limited to the serious TB subpopulations excluding the new TB patients. This study aimed to examine MDR-TB burden among the new TB patients.

METHODSWe conducted a study in Zhejiang Province during 2009-2013 to screen for MDR-TB patients among the low MDR-TB risk patients and five subpopulations of high MDR-TB risk patients. The number, prevalence, and trend of MDR-TB were compared while the logistic regression model was used to examine risk factors related to MDR-TB.

RESULTSA total of 200 and 791 MDR-TB cases were, respectively, identified from the 9830 new TB cases and 2372 high-risk suspects who took MDR-TB screening from 2009 to 2013. The MDR-TB rates went down in both of the new TB patients and five MDR-TB high-risk groups over the study time, but the percentage of MDR-TB patients identified from the new TB patients in all diagnosed MDR-TB cases kept stable from 28.3% in 2011 to 27.0% in 2012 to 26.0% in 2013.

CONCLUSIONSThe study indicated that MDR-TB burden among new TB patients was high, thus screening for MDR-TB among the new TB patients should be recommended in China as well as in the similar situation worldwide.

Objective To compare the clinical efficacy of nasal intermittent positive pressure ventilation (NIPPV) and heated humidified high flow nasal cannula (HHHFNC) in the treatment of respiratory distress syndrome (RDS) among low-birth-weight premature infants.Method From May to December 2015,low-birth-weight premature infants with RDS who were born and treated in our hospital were randomly assigned into NIPPV group and HHHFNC group according to their initial ventilation mode.The incidence of initial treatment failure,the usage of pulmonary surfactant (PS),the parameters of respiratory support treatment and the incidence of complications were analyzed.Result A total of 70 cases with grade Ⅰ ～ llⅢ of RDS were included,including 33 males and 37 females.The birth weight ranged from 1 020 to 2 450 g,with a average of (1 845 ± 475) g.NIPPV and HHHFNC group each had 35 cases.No significant differences existed between the two group in the following items:the rate of mechanical intubation within 72 h (5.7％ vs.11.4％),use of PS (0％ vs.8.6％),incidence of severe apnea (11.4％ vs.14.3％),pneumonia (11.4％ vs.14.3％),the duration of invasive mechanical ventilation [76.3 (30.8,150.4) h vs.97.6 (56.2,142.6) h],non-invasive ventilation [65.0 (43.0,119.0) h vs.96.0 (65.0,134.0) h] and the duration of oxygen therapy [154.0 (47.0,340.0) h vs.148.0 (72.0,327.0) h,it was no (P ＞ 0.05).Also,no significant differences in the incidence of bronchopulmonary dysplasia,necrotizing enterocolitis,retinopathy of prematurity,patent ductus arteriosus,intra-ventricular hemorrhage,nose injury,pneumothorax between the two groups.Conclusion As an initial respiratory support for the treatment of low-birth-weight RDS preterm infants,HHHFNC has similar efficacy and safety with NIPPV,and further clinical research is needed.

Objective To investigate mechanisms underlying the prevention of experimental autoimmune encephalomyelitis (EAE) in mice by intraperitoneal infusion of myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) (MOG i.p.).Methods C57BL/6 mice were immunized with MOG35-55 to establish the model of EAE and then were intraperitoneally injected daily with MOG35-55 or ovalbumin (OVA, served as control) from day 6 to day 16.EAE was evaluated daily using a general clinical scoring system and histological analysis.Numbers of lymphocytes in peripheral blood and central nervous system (CNS) were detected at different time points.Effects of MOG i.p.on the migration of MOG-T cells in vivo were analyzed by an adoptive transfer experiment.Maturation of splenic antigen-presenting cells (APCs) and migration of MOG-T cells in vitro were examined by fluorescence activated cell sorting (FACS) and a Transwell system, respectively.Results MOG i.p.protected the mice from development of EAE by blocking the lymphocyte recruitment to CNS.More effector T cells were trapped in the periphery of EAE and naive mice in adoptive transfer experiment after MOG i.p.treatment.MOG i.p.induced the maturation of splenic APCs and enhanced the expression of CD80, CD86 and major histocompatibility complex class Ⅱ (MHCⅡ) molecules.Mature APCs blocked the recruitment of effector T cells to CNS.Conclusion MOG i.p.protects mice from EAE by inducing the maturation of splenic APCs.

BACKGROUND:Oligodendrocytes are mostly differentiated from oligodendrocyte precursor cel s. A suitable medium and cel seeding density have a significant impact on the process of the isolation of oligodendrocyte precursor cel s to obtain oligodendrocytes. OBJECTIVE:To explore the optimization of oligodendrocyte culture conditions. METHODS:Oligodendrocyte precursor cel s isolated from the newborn rats 48 hours after birth were cultured in DMEM/high glucose medium or DMEM/F12 medium using seeding densities of 2×104 cel s/cm2, 4×104 cel s/cm2, 8×104 cel s/cm2, 16×104 cel s/cm2, 32×104 cel s/cm2, and 64×104 cel s/cm2, respectively. Oligodendrocyte precursor cel s were induced to differentiate into oligodendrocytes at 72 hours after cel adhesion. Morphology of differentiated oligodendrocyte precursor cel s were observed under a light microscope, and the differentiation results were identified by immunofluorescence staining after 7-day induced differentiation. RESULTS AND CONCLUSION:Morphology of oligodendrocyte precursor cel s were recognized when cultured in DMEM/high glucose medium or DMEM/F12 medium using seeding densities of 2×104 cel s/cm2, 4×104 cel s/cm2, and 8×104 cel s/cm2, respectively. Immunofluorescence staining showed that myelin basic protein-positive cel s were found after 7-day induced differentiation, and the positive cel number were 16.40±3.30, 49.95±2.33, and 76.95±4.86 in DMEM/F12 medium, and 12.65±2.53, 32.10±1.17, and 54.05±1.56 in DMEM/high glucose medium (P<0.05). These findings indicate that DMEM/F12 medium is more suitable for culturing oligodendrocyte precursor cel s compared with DMEM/high glucose medium to some extent. The number of differentiated oligodendrocytes was gradual y increased with the enhanced seeding density of oligodendrocyte precursor cel s, and the seeding densities from 4×104 to 8×104 cel s/cm2 were appropriate for the observation of cel morphology.

Objective To investigate the effectiveness and safety of peritoneal dialysis(PD) in premature infants with acute renal failure(ARF).Methods In the neonatal intensive care unit (NICU) of Guangdong Province Maternal and Children Hospital, 12 premature infants underwent continuous PD due to ARF from March 2012 to March 2015, without using any antibiotics in the dialysis fluid.Before and after dialysis, the changes of serum urea nitrogen, creatinine, potassium and pH were compared.The complications (blockage, leakage, infection and necrotizing enterocolitis) and gastrointestinal nutrition situation were observed.Wilcoxon signed rank sum test was used for statistical analysis.Results Among the 12 premature infants, the underlying causes of ARF were sepsis (n=9), perinatal asphyxia (n=2), twin twin transfusion syndrome (n=l).The average gestational age was (30.9±3.2) weeks, the average body weight (before PD) was (1 461 ±525) g, the duration of PD was (3.8±2.6) d.Complications associated with PD included leakage (n=3) and peritonitis (n=2) in which Candids albicans and Klebsiella pneumonia were identified in ascites.Gastrointestinal nutrition was built up in six cases within one to four days after dialysis, among which one developing necrotizing enterocolitis on the 7th d after feeding.Finally, eight babies died (six died after initiative discontinued treatment and two died because of critically illness) and four patients were cured and discharged.Lower serum urea nitrogen and potassium levels and higher pH value were shown after dialysis than before [(9.16 ± 3.15) vs (12.71 ±6.98) mmol/L;(4.36±0.82) vs (6.24± 1.72) mmol/L;7.32±0.17 vs 7.21 ±0.17;Z=-2.118,-2.197 and-2.981, all P ＜ 0.05).Conclusion PD is an alternative safe and effective treatment for premature infants with ARF due to its simplicity both in manipulation and equipment requirement.

Assessing dry weight accurately is crucial in providing effective and safe haemodialysis. Biases towards dry weight assessment may bring a series of dialysis complications. This study introduces an online detection technique of relative blood volume (RBV) based on ultrasound, which analyzes the correlation between changes in blood density and sound speed. By measuring the attenuation in sound velocity, this method was employed to calculate RBV, and then to evaluate the dry weight of patients on dialysis. TDC-GP2 time measurement chip and MSP430 Single-chip Microcontroller (SCM) were used in the system to measure the ultrasonic travel time. In the clinical trials, RBV values range between 71.3% and 108.1%, showing consistent result with Fresenius 4008S blood volume monitor (BVM). This detection method possesses several advantages, such as real time, convenient, reproducible, non-invasive, and etc.
Blood Volume ; Body Weight ; Humans ; Monitoring, Physiologic ; Renal Dialysis ; Ultrasonics