Acute hemolytic transfusion reaction caused by anti-M antibodies: a case report and literature review.

OBJECTIVE: We report a rare case of acute hemolytic reactions caused by immunoglobulin (Ig)M anti-M antibody and present a literature review. CASE REPORT: A 61-year-old male patient who underwent blood transfusion developed fever, chills, soy sauce-colored urine, and changes in laboratory test results, including persistently decreased hemoglobin levels, neutrophilia, elevated lactate dehydrogenase level, acute kidney injury, mild acute liver injury, and activation of the coagulation system, indicating acute hemolytic transfusion reaction (AHTR). Antibody screening and major crossmatching results indicated weak positive at 37°C for both posttransfusion and pretransfusion sample. Subsequent serological examinations indicated the presence of IgM anti-M antibodies in plasma but the direct antiglobulin and elution tests were negative. Antibody hemolytic activity assay confirmed AHTR caused by anti-M. The transfused red blood cells were MM and the patient is NN. These signs and symptoms disappeared rapidly and required no additional interventions before discharge. CONCLUSION: The accurate diagnosis of anti-M antibody-mediated acute hemolysis is essential for guiding treatment decisions.

Metal-Organic Framework Membrane Constructor: A Tool for High-Throughput Construction of Metal-Organic Framework Membrane Models.

With the rapid development of metal-organic framework (MOF) membranes for separation applications, computational screening of their separation performance has attracted increasing interest in the design and fabrication of such materials. Although bulk crystal models in MOF databases are often used to represent MOF membrane structures, membrane models in slab geometries are still essential for researchers to simulate the separation performance, particularly to understand the effects of the surface/interface structure, pore sieving, and exposed lattice plane on guest permeability. However, to date, no database or method has been established to provide researchers with numerous membrane models, restricting the further development of related theoretical studies. Herein, we propose an algorithm and develop a tool called the "MOF-membrane constructor" to realize the high-throughput construction of membrane models based on the MOF crystal structures. Using this tool, membrane models can be generated with desired sizes, reasonable surface terminations, and assigned exposed crystal planes. The tool can also deduce the most prominent surface in the Bravais-Friedel-Donnay-Harker morphology or identify the pores in MOF crystals and automatically determine an exposed plane for each membrane model. Thus, an MOF-membrane database can be established rapidly according to user simulation requirements. This study can considerably improve the efficiency of building MOF membrane models and may be beneficial for the future development of simulation studies on MOF membranes.

A single-center, retrospective analysis of 17 cases of hemolytic disease of the fetus and newborn caused by anti-M antibodies.

OBJECTIVE: We aimed to summarize the laboratory findings and clinical features of hemolytic disease of the fetus and newborn (HDFN). METHODS: We retrospectively analyzed the data for 17 infants with anti-M-induced HDFN (anti-M-HDFN) diagnosed between June 2013 and May 2019. Their maternal history, neonatal diagnosis on admission, and laboratory test results were compared with those of 15 infants with HDFN involving the ABO blood group system, 15 infants with HDFN involving the Rh system, and 15 premature infants. RESULTS: In the anti-M-HDFN group, 94.12% (16/17), 35.29% (6/17), and 17.65% (3/17) had free antibodies in plasma, a positive direct antiglobulin test, and a positive elution test, respectively. In 12 infants, free antibody reactions were stronger at 4°C than at 37°C, and the antibody titer at 4°C ranged from 1 to 512. All 17 infants with anti-M-HDFN developed anemia: 14 were treated with blood transfusion and 1 with neonatal exchange transfusion. Sixteen infants improved, and one died. Anti-M-HDFN had a higher rate of maternal stillbirth, lower gestational age, lower birthweight, and higher incidence of respiratory distress than other HDFN types. CONCLUSION: Anti-M may cause HDFN. It may present with varying degrees of anemia, low regenerative anemia, and low bilirubin levels. In addition, infants with anti-M-HDFN may have a negative elution test and direct antiglobulin test. These tests are helpful in examining antibody responses at a low temperature of 4°C.

Engineered cell-overexpression of circular RNA hybrid hydrogels promotes healing of calvarial defects.

Craniomaxillofacial bone defects seriously affect the physical and mental health of patients. Bone marrow mesenchymal stem cells (BMSCs) are "gold standard" cells used for bone repair. However, the collection of BMSCs is invasive, and the osteogenic capacity is limited with age. Human umbilical cord mesenchymal stem cells (hUCMSCs) are promising alternative seed cells for bone tissue engineering. Our group previously used high-throughput sequencing technology and bioinformatics methods to detect circ-CTTN (hsa-circ_0003376) molecules, which may play an essential role in the osteogenic differentiation of hUCMSCs. In this study, osteogenic induction in vitro showed that the overexpressing circ-CTTN (OE group) exhibits a more pronounced osteogenic phenotype. The levels of osteogenesis-related genes in the OE group were highly expressed. The gelatin-methacrylate (GelMA) hydrogel possessed excellent biocompatibility and was used to load hUCMSCs. In the rat calvarial defect, the OE group presented a larger bone healing volume and denser bone trabecular distribution than other groups. So far, the overexpression of circ-CTTN could enhance the osteogenic differentiation of hUCMSCs and accelerate bone reconstruction. Our research could provide a new strategy and a strong theoretical basis for promoting hUCMSC clinical application in bone tissue engineering.

MicroRNA-503 Exacerbates Myocardial Ischemia/Reperfusion Injury via Inhibiting PI3K/Akt- and STAT3-Dependent Prosurvival Signaling Pathways.

Acute myocardial infarction is a leading cause of death worldwide, while restoration of blood flow to previously ischemic myocardium may lead to ischemia/reperfusion (I/R) injury. Accumulated evidence shows that microRNAs play important roles in cardiovascular diseases. However, the potential role of microRNA-503 (miR-503) in myocardial I/R injury is little known. Thus, this study is aimed at determining whether and how miR-503 affects myocardial I/R injury in vivo and in vitro. A mouse model of myocardial I/R injury and H9c2 cell model of hypoxia/reoxygenation (H/R) injury were established. The postischemic cardiac miR-503 was downregulated in vivo and in vitro. Mechanistically, PI3K p85 and Bcl-2 are miR-503 targets. The post-ischemic cardiac PI3K p85 protein level was decreased in vivo. Agomir-503 treatment exacerbated H/R-induced injuries manifested as decreased cell viability, increased lactate dehydrogenase activity, and cell apoptosis. Agomir-503 treatment reduced cell viability under normoxia as well and reduced both PI3K p85 and Bcl-2 protein levels under either normoxia or H/R condition. It reduced phosphorylation of Stat3 (p-Stat3-Y705) and Akt (T450) in cells subjected to H/R. In contrast, Antagomir-503 treatment attenuated H/R injury and increased p-Stat3 (Y705) under normoxia and increased p-Akt (T450) under either normoxia or H/R condition. It is concluded that miR-503 exacerbated I/R injury via inactivation of PI3K/Akt and STAT3 pathways and may become a therapeutic target in preventing myocardial I/R injury.

The Protective Role of Hydrogen Sulfide and Its Impact on Gene Expression Profiling in Rat Model of COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, which is usually caused by exposure to noxious particles or gases. Hydrogen sulfide (H2S), as an endogenous gasotransmitter, is involved in the pathogenesis of COPD, but its role in COPD is little known. To investigate the role of H2S in COPD, a rat model of COPD was established by cigarette smoking (CS) and intratracheal instillation of lipopolysaccharide (LPS). Rats were randomly divided into 4 groups: control, CS + LPS, CS + LPS + sodium hydrosulfide (NaHS, H2S donor), and CS + LPS + propargylglycine (PPG, inhibitor of cystathionine-γ-lyase, and CTH). Lung function in vivo, histology analysis of lung sections, malondialdehyde (MDA) concentration, CTH protein, total superoxide dismutase (T-SOD), and catalase (CAT) activity in lung tissues were assessed. Gene expression profiling of lung was assessed by microarray analysis. The results showed that rats in the CS + LPS group had lower body weight and lung function but higher lung pathological scores, MDA concentration, CTH protein, T-SOD, and CAT activity compared with the control. Compared with CS + LPS group, NaHS treatment decreased lung pathological scores and MDA concentration, while PPG treatment decreased body weight of rats and T-SOD activity, and no significant differences were detected in pathological scores by PPG treatment. Microarray analysis identified multiple differentially expressed genes, and some genes regulated by H2S were involved in oxidative stress, apoptosis, and inflammation pathways. It indicates that H2S may play a protective role in COPD via antioxidative stress and antiapoptosis pathway.

The Causes and Consequences of miR-503 Dysregulation and Its Impact on Cardiovascular Disease and Cancer.

microRNAs (miRs) are short, non-coding RNAs that regulate gene expression by mRNA degradation or translational repression. Accumulated studies have demonstrated that miRs participate in various biological processes including cell differentiation, proliferation, apoptosis, metabolism and development, and the dysregulation of miRs expression are involved in different human diseases, such as neurological, cardiovascular disease and cancer. microRNA-503 (miR-503), one member of miR-16 family, has been studied widely in cardiovascular disease and cancer. In this review, we summarize and discuss the studies of miR-503 in vitro and in vivo, and how miR-503 regulates gene expression from different aspects of pathological processes of diseases, including carcinogenesis, angiogenesis, tissue fibrosis and oxidative stress; We will also discuss the mechanisms of dysregulation of miR-503, and whether miR-503 could be applied as a diagnostic marker or therapeutic target in cardiovascular disease or cancer.

Effects of 5 MeV Proton Irradiation on Nitrided SiO2/4H-SiC MOS Capacitors and the Related Mechanisms.

In this paper the effects of 5 MeV proton irradiation on nitrided SiO2/4H-SiC metal-oxide-semiconductor (MOS) capacitors are studied in detail and the related mechanisms are revealed. The density of interface states (Dit) is increased with the irradiation doses, and the annealing response suggests that the worse of Dit is mainly caused by displacement effect of proton irradiation. However, the X-rays photoelectron spectroscopy (XPS) measurement shows that the quantity proportion of breaking of Si≡N induced by displacement is only 8%, which means that the numbers of near interface electron traps (NIETs) and near interface hole traps (NIHTs) are not significantly changed by the displacement effect. The measurements of bidirectional high frequency (HF) C-V characteristics and positive bias stress stability show that the number of un-trapped NIETs and oxide electron traps decreased with increasing irradiation doses because they are filled by electrons resulted from the ionization effect of proton irradiation, benefiting to the field effective mobility (µFE) and threshold voltage stability of metal-oxide-semiconductor field-effect transistors (MOSFETs). The obviously negative shift of flat-band voltage (VFB) resulted from the dominant NIHTs induced by nitrogen passivation capture more holes produced by ionization effect, which has been revealed by the experimental samples with different nitrogen content under same irradiation dose.

miR-181c-5p Exacerbates Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4.

BACKGROUND: Activation of cell apoptosis is a major form of cell death during myocardial ischemia/reperfusion injury (I/RI). Therefore, examining ways to control cell apoptosis has important clinical significance for improving postischemic recovery. Clinical evidence demonstrated that miR-181c-5p was significantly upregulated in the early phase of myocardial infarction. However, whether or not miR-181c-5p mediates cardiac I/RI through cell apoptosis pathway is unknown. Thus, the present study is aimed at investigating the role and the possible mechanism of miR-181c-5p in apoptosis during I/R injury by using H9C2 cardiomyocytes. METHODS AND RESULTS: The rat origin H9C2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R, 6 hours hypoxia followed by 6 hours reoxygenation) to induce cell injury. The results showed that H/R significantly increased the expression of miR-181c-5p but not miR-181c-3p in H9C2 cells. In line with this, in an in vivo rat cardiac I/RI model, miR-181c-5p expression was also significantly increased. The overexpression of miR-181c-5p by its agomir transfection significantly aggravated H/R-induced cell injury (increased lactate dehydrogenase level and reduced cell viability) and exacerbated H/R-induced cell apoptosis (greater cleaved caspases 3 expression, Bax/Bcl-2 and more TUNEL-positive cells). In contrast, inhibition of miR-181c-5p in vitro had the opposite effect. By using computational prediction algorithms, protein tyrosine phosphatase nonreceptor type 4 (PTPN4) was predicted as a potential target gene of miR-181c-5p and was verified by the luciferase reporter assay. The overexpression of miR-181c-5p significantly attenuated the mRNA and protein expression of PTPN4 in H9C2 cardiomyocytes. Moreover, knockdown of PTPN4 significantly aggravated H/R-induced enhancement of LDH level, cleaved caspase 3 expression, and apoptotic cell death, which mimicked the proapoptotic effects of miR-181c-5p in H9C2 cardiomyocytes. CONCLUSIONS: These findings suggested that miR-181c-5p exacerbates H/R-induced cardiomyocyte injury and apoptosis via targeting PTPN4 and that miR-181c-5p/PTPN4 signaling may yield novel strategies to combat myocardial I/R injury.

Establishing a perinatal red blood cell transfusion risk evaluation model for obstetric patients: a retrospective cohort study.

BACKGROUND: The ability to predict risk factors for blood transfusion after postpartum hemorrhage could enhance the performance of lifesaving procedures in patients who experience postpartum hemorrhage. Therefore, this study aimed to evaluate these risk factors and create a scoring system for blood transfusion evaluations and risk in obstetric patients. STUDY DESIGN AND METHODS: Diagnosis and blood transfusion data of 14,112 women who delivered between January 1, 2015, and December 31, 2015, were analyzed. A binary logistic regression model was used. We conducted univariate analyses of each risk factor as well as multivariable logistic regression analysis. Data of obstetric patients in 2016 validated the receiver operating characteristic curve. A risk prediction score was generated from the transfusion risk factor ß-coefficients in the multivariable logistic regression model. RESULTS: In total, 392 (2.94%) of 13,328 patients received transfusions. After multivariable adjustment, polyembryony, anemia, thrombocytopenia, preeclampsia, placenta previa, placental implantation, uterine scarring, uterine rupture, retained placenta, stillbirth, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) were significantly associated with perinatal transfusion. Heart disease and hemophilia were not related to transfusion risk. The blood transfusion risk evaluation table was well calibrated. CONCLUSIONS: Our retrospective analysis revealed that diagnoses including polyembryony, anemia, thrombocytopenia, preeclampsia, placenta previa, placenta implantation, uterine scarring, uterine rupture, retained placenta, stillbirth, and HELLP syndrome are significantly associated with perinatal transfusion and are risk factors for blood transfusion. The blood transfusion scoring system could be beneficial for evaluating blood transfusion risk.

XRCC3 Thr241Met and TYMS variable number tandem repeat polymorphisms are associated with time-to-metastasis in colorectal cancer.

BACKGROUND: Metastasis is a major cause of mortality in cancer. Identifying prognostic factors that distinguish patients who will experience metastasis in the short-term and those that will be free of metastasis in the long-term is of particular interest in current medical research. The objective of this study was to examine if select genetic polymorphisms can differentiate colorectal cancer patients based on timing and long-term risk of metastasis. METHODS: The patient cohort consisted of 402 stage I-III colorectal cancer patients with microsatellite instability (MSI)-low (MSI-L) or microsatellite stable (MSS) tumors. We applied multivariable mixture cure model, which is the proper model when there is a substantial group of patients who remain free of metastasis in the long-term, to 26 polymorphisms. Time-dependent receiver operator characteristic (ROC) curve analysis was performed to determine the change in discriminatory accuracy of the models when the significant SNPs were included. RESULTS: After adjusting for significant baseline characteristics, two polymorphisms were significantly associated with time-to-metastasis: TT and TC genotypes of the XRCC3 Thr241Met (p = 0.042) and the 3R/3R genotype of TYMS 5'-UTR variable number tandem repeat (VNTR) (p = 0.009) were associated with decreased time-to-metastasis. ROC curves showed that the discriminatory accuracy of the model is increased slightly when these polymorphisms were added to the significant baseline characteristics. CONCLUSIONS: Our results indicate XRCC3 Thr241Met and TYMS 5'-UTR VNTR polymorphisms are associated with time-to-metastasis, and may have potential biological roles in expediting the metastatic process. Once replicated, these associations could contribute to the development of precision medicine for colorectal cancer patients.

Imbalance of Endogenous Hydrogen Sulfide and Homocysteine in Chronic Obstructive Pulmonary Disease Combined with Cardiovascular Disease.

Background: Considerable studies showed associations between chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), we evaluated the role of endogenous hydrogen sulfide (H2S)/homocysteine (Hcy) in patients with COPD combined with CVD. Methods: Fifty one stable patients with COPD were enrolled (25 COPD, 26 COPD + CVD). Lung function, sputum, peripheral blood samples, serum H2S, Hcy, high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α) levels were measured. Dyspnea, symptoms and quality of life were quantified by modified Medical Research Council dyspnea scale (mMRC), COPD assessment test (CAT) and St. George's Respiratory Questionnaire (SGRQ). Results: Compared with COPD group, waist circumference and body mass index (BMI) were higher in COPD + CVD group, mMRC, CAT and activity scores were also higher, high density lipoprotein cholesterol (HDL-C) was lower, total cells, neutrophils (%) in sputum and serum hs-CRP level were higher, whereas macrophages (% ) in sputum was lower. H2S and Hcy levels from COPD + CVD group were higher than those from COPD group, but H2S/Hcy ratio was lower. With increasing COPD severity, H2S level was decreased, however, Hcy level was increased. H2S level was positively correlated with FEV1/FVC, FEV1% predicted, lymphocytes (%) and macrophages (%) in sputum, but negatively correlated with smoking pack-years and neutrophils (%) in sputum. Hcy level was positively correlated with BMI and total cells in sputum. The ratio of H2S/Hcy was also positively correlated with FEV1/FVC, but negatively correlated with total cells in sputum. Conclusion: The imbalance of H2S/Hcy may be involved in the pathogenesis of COPD combined with CVD and provide novel targets for therapy.

Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung.

Hydrogen sulfide (H2S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H2S may be a crucial mediator in airway responsiveness and airway inflammation in a rat model of chronic exposure to cigarette smoke (CS). Rats randomly divided into control and CS-exposed groups were treated with or without sodium hydrosulfide (NaHS, donor of H2S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H2S-synthesizing enzyme) for 4-month exposure. Serum H2S level and CSE protein expression in lung tissue were higher, by 2.04- and 2.33-fold, respectively, in CS-exposed rats than in controls (P<0.05). Exogenous administration of NaHS to CS-exposed rats alleviated airway reactivity induced by acetylcholine (Ach) or potassium chloride (KCl) by 17.4% and 13.8%, respectively, decreased lung pathology score by 32.7%, inhibited IL-8 and TNF- α concentrations in lung tissue by 34.2% and 31.4%, respectively, as compared with CS-exposed rats (all P<0.05). However, blocking endogenous CSE with PPG in CS-exposed rats increased airway reactivity induced by Ach or KCl, by 24.1% and 24.5%, respectively, and aggravated lung pathology score, by 44.8%, as compared with CS-exposed rats (all P<0.01). Incubation in vitro with NaHS, 1-3 mmol/L, relaxed rat tracheal smooth muscle precontracted by Ach or KCl. However, the NaHS-induced relaxation was not blocked by glibenclamide (10⁻4 mol/L), L-NAME (10⁻4 mol/L), or ODQ (1 µmol/L) or denudation of epithelium. Endogenous H2S may have a protective role of anti-inflammation and bronchodilation in chronic CS-induced pulmonary injury.

Characterization of a phenazine-producing strain Pseudomonas chlororaphis GP72 with broad-spectrum antifungal activity from green pepper rhizosphere.

A new Pseudomonas strain, designated GP72, was isolated from green pepper rhizosphere and identified as a member of species Pseudomonas chlororaphis based on morphology; conventional biochemical and physiologic tests; Biolog GN system (Biolog Inc., Hayward, CA); and 16S rDNA sequence analysis. The secondary metabolites produced by this strain have shown broad-spectrum antifungal activity against various phytopathogens of agricultural importance in vitro. Two main antifungal substances produced by this strain proved to be phenazine-1-carboxylic acid and 2-hydroxyphenazine with further purification and structure elucidation based on ultraviolet-absorbent spectrum scanning, atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) spectrum, and (1)H,(13)C nuclear magnetic resonance spectrums. Strain GP72 could produce quorum-sensing signaling molecules of N-butanoyl-L-homoserine lactone and N-hexanoyl-L-homoserine lactone, which were found to accumulate with different quantities in King's medium B and pigment producing medium, respectively.

[Isolation and characterization of a new Pseudomonas strain against Phytophthora capsici].

One Pseudomonas strain GP72, which was against Phytophthora capsici, was isolated from green pepper rhizosphere in Jiangsu province. It had distinctively inhibitive effect on several kinds of pathogenic fungi; mostly of them are soilborne pathogens. Therefore, this strain may be used for an effective biocontrol strain in the crop protection. The morphological, biochemical and physiological characteristics, Biolog GN, G + C mol% content and 16S rDNA sequence analysis of this strain were studied. In comparison and conclusion of all the experimental data, GP72 is identified as Pseudomonas chlororaphis. The strain is single-cellular and motile by means of single polar flagellum. It was not able to accumulate ploy-beta-hydroxybutyrate. Compared to P. aureofaciens 30-84, the strain was able to survive at the concentration of 5% NaCl. It could strongly utilize 45 of 95 carbon-substrates; weakly utilize 6 of the whole carbon-substrates and never utilize 43 of the whole carbon-substrates resulting from analysis of Biolog GN, bearing the similarity probability of 98% with Pseudomonas chlororaphis and with the similarity index 0.72. The G + C content of the strain DNA was 65.1 mol% using the thermal denaturation method. A phylogenetic tree was constructed by comparing with the validly published 16S rDNA sequences of the related type strains from GenBank, using the Neighbor-Joining method of Saitou and Nei and the Clustal X program to do the multiple alignments. The tree topology was tested by a bootstrap analysis of 1000 samplings. The overall similarity value between strain GP72 and typical is the closest in the phylogenetic tree. For the latest taxonomical development has put genus Pseudomonas aureofaciens to the genus Pseudomonas chlororaphis, then it is appropriate to say that GP72 belongs to the genus Pseudomonas chlororaphis. This is the first time in China to report that a strain of Pseudomonas chlororaphis was isolated from green pepper rhizosphere, having a strong inhibitive effect on Phytophthora capsici and other soilborne pathogenic fungus. The other characteristics and the biocontrol mechanism are yet to be further studied.