Epigallocatechin-3-gallate Synergistically Enhanced Arecoline-Induced Cytotoxicity by Redirecting Cycle Arrest to Apoptosis.

Carcinogens, such as arecoline, play a crucial role in cancer progression and continuous gene mutations by generating reactive oxygen species (ROS). Antioxidants can reduce ROS levels and potentially prevent cancer progression but may paradoxically enhance the survival of cancer cells. This study investigated whether epigallocatechin-3-gallate (EGCG), an antioxidant from green tea, could resolve this paradox. Prostate cancer cells (PC-3 cell line) were cultured and treated with arecoline combined with NAC (N-acetylcysteine) or EGCG; the combined effects on intracellular ROS levels and cell viability were examined using the MTT and DCFDA assays, respectively. In addition, apoptosis, cell cycle, and protein expression were investigated using flow cytometry and western blot analysis. Our results showed that EGCG, similar to NAC (N-acetylcysteine), reduced the intracellular ROS levels, which were elevated by arecoline. Moreover, EGCG not only caused cell cycle arrest but also facilitated cell apoptosis in arecoline-treated cells in a synergistic manner. These were evidenced by elevated levels of cyclin B1 and p27, and increased fragmentation of procaspase-3, PARP, and DNA. Our findings highlight the potential use of EGCG for cancer prevention and therapy.

A Proteomics-Based Identification of the Biological Networks Mediating the Impact of Epigallocatechin-3-Gallate on Trophoblast Cell Migration and Invasion, with Potential Implications for Maternal and Fetal Health.

Trophoblast migration and invasion play crucial roles in placental development. However, the effects of (-)-epigallocatechin-3-gallate (EGCG) on trophoblast cell functions remain largely unexplored. In this study, we investigated the impact of EGCG on the survival of trophoblast cells and employed a proteomics analysis to evaluate its influence on trophoblast cell migration and invasion. Be-Wo trophoblast cells were treated with EGCG, and a zone closure assay was conducted to assess the cell migration and invasion. Subsequently, a proteomics analysis was performed on the treated and control groups, followed by a bioinformatics analysis to evaluate the affected biological pathways and protein networks. A quantitative real-time PCR and Western blot analysis were carried out to validate the proteomics findings. Our results showed that EGCG significantly suppressed the trophoblast migration and invasion at a concentration not affecting cell survival. The proteomics analysis revealed notable differences in the protein expression between the EGCG-treated and control groups. Specifically, EGCG downregulated the signaling pathways related to EIF2, mTOR, and estrogen response, as well as the processes associated with the cytoskeleton, extracellular matrix, and protein translation. Conversely, EGCG upregulated the pathways linked to lipid degradation and oxidative metabolism. The quantitative PCR showed that EGCG modulated protein expression by regulating gene transcription, and the Western blot analysis confirmed its impact on cytoskeleton and extracellular matrix reorganization. These findings suggest EGCG may inhibit trophoblast migration and invasion through multiple signaling pathways, highlighting the potential risks associated with consuming EGCG-containing products during pregnancy. Future research should investigate the impact of EGCG intake on maternal and fetal proteoforms.

Innovative Hybrid-Alignment Annotation Method for Bioinformatics Identification and Functional Verification of a Novel Nitric Oxide Synthase in Trichomonas vaginalis.

Both the annotation and identification of genes in pathogenic parasites are still challenging. Although, as a survival factor, nitric oxide (NO) has been proven to be synthesized in Trichomonas vaginalis (TV), nitric oxide synthase (NOS) has not yet been annotated in the TV genome. We developed a witness-to-suspect strategy to identify incorrectly annotated genes in TV via the Smith-Waterman and Needleman-Wunsch algorithms through in-depth and repeated alignment of whole coding sequences of TV against thousands of sequences of known proteins from other organisms. A novel NOS of TV (TV NOS), which was annotated as hydrogenase in the NCBI database, was successfully identified; this TV NOS had a high witness-to-suspect ratio and contained all the NOS cofactor-binding motifs (NADPH, tetrahydrobiopterin (BH4), heme and flavin adenine dinucleotide (FAD) motifs). To confirm this identification, we performed in silico modeling of the protein structure and cofactor docking, cloned the gene, expressed and purified the protein, performed mass spectrometry analysis, and ultimately performed an assay to measure enzymatic activity. Our data showed that although the predicted structure of the TV NOS protein was not similar to the structure of NOSs of other species, all cofactor-binding motifs could interact with their ligands with high affinities. We clearly showed that the purified protein had high enzymatic activity for generating NO in vitro. This study provides an innovative approach to identify incorrectly annotated genes in TV and highlights a novel NOS that might serve as a virulence factor of TV.

Erythrocyte degradation, metabolism, secretion, and communication with immune cells in the blood during sepsis: A review.

Sepsis is a health issue that affects millions of people worldwide. It was assumed that erythrocytes were affected by sepsis. However, in recent years, a number of studies have shown that erythrocytes affect sepsis as well. When a pathogen invades the human body, it infects the blood and organs, causing infection and sepsis-related symptoms. Pathogens change the internal environment, increasing the levels of reactive oxygen species, influencing erythrocyte morphology, and causing erythrocyte death, i.e., eryptosis. Characteristics of eryptosis include cell shrinkage, membrane blebbing, and surface exposure of phosphatidylserine (PS). Eryptotic erythrocytes increase immune cell proliferation, and through PS, attract macrophages that remove the infected erythrocytes. Erythrocyte-degraded hemoglobin derivatives and heme deteriorate infection; however, they could also be metabolized to a series of derivatives. The result that erythrocytes play an anti-infection role during sepsis provides new perspectives for treatment. This review focuses on erythrocytes during pathogenic infection and sepsis.

Research and experimental verification of the molecular mechanism of berberine in improving premature ovarian failure based on network pharmacology.

Based on the research methods of network pharmacology, this study analyzed the improvement effect of berberine (BBR) on premature ovarian failure (POF) and its molecular mechanism. Carry out GO and KEGG enrichment analysis by R language to obtain the potential targets and pathways of BBR in the improvement of POF. Use SD rats and ovarian granulosa cells (GCs) for experimental verification. ELISA was used to measure the content of related hormones in the serum, CCK-8 was used to measure cell viability, western blot was used to measure the content of the target protein in the ovaries and GCs, and q-RT-PCR was used to detect the expression of the target genes in the ovaries and GCs. Predicted by network pharmacology: PTEN, AKT1, FoxO1, FasL, and Bim are the targets with the highest relative correlation between BBR and POF. The results of experiments show that the treatment of low and medium doses of BBR can increase the ovarian index of rats; BBR can increase the levels of Estradiol (E2) and Anti-Mullerian hormone (AMH) in the serum of rats and reduce the levels of Follicle stimulating hormone (FSH) and Luteinizing hormone (LH). BBR can increase the cell viability of GCs; BBR can inhibit the PTEN/AKT1/FoxO1 signaling pathway and its phosphorylation level and reduce the expression of Fas/FasL and Bim mRNA. Overall, BBR can promote the ovarian to maintain normal hormone levels, protect GCs, and enhance the function of POF.

Endovascular aortic repair is a cost-effective option for in-hospital patients with abdominal aortic aneurysm.

BACKGROUND: To investigate the cost-effectiveness of endovascular aortic repair (EVAR) versus open aortic repair (OAR) for abdominal aortic aneurysm (AAA) using incremental costs per decreased in-hospital mortality rate gained through our patients' cohort. METHODS: Medical records and healthcare costs of patients with AAA hospitalized between 2010 and 2015 were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Multiple regression analysis was applied to adjust for confounding factors and to compare the differences in postoperative clinical outcomes between patients who received EVAR and OAR. The incremental cost-effectiveness ratio (ICER) of EVAR was determined based on the healthcare cost obtained from the analyzed data. RESULTS: A total of 2803 AAA patients were identified (n = 559 with ruptured AAA and n = 2244 unruptured AAA). Patients with ruptured AAA who underwent EVAR compared with OAR patients had shorter hospital and intensive care unit (ICU) stays (all p < 0.05). For patients with unruptured AAA, those who received EVAR compared with OAR, the adjusted odds ratio (aOR) of postoperative complications and in-hospital mortality were 0.371 and 0.447 (all p < 0.05). The total direct surgical costs and medical expenses during hospitalization in all AAA patients were higher for the EVAR group; however, ICER was <1 per capita gross domestic product. Stratification by age groups further suggested that ICER for patients with unruptured AAA who received EVAR, compared with OAR, decreased with age. CONCLUSION: Total direct medical costs were higher for AAA patients receiving EVAR regardless of rupture status; however, the cost is offset by lower odds of postoperative complications and in-hospital mortality. The observed decrease in ICER with age and EVAR use warrants further analysis. Our findings further validate the use of EVAR over OAR. These results provides supporting evidence for physicians and patients with AAA to inform shared decision making regarding endovascular or OAR options.

NH787 EMS mutant of rice variety Nagina22 exhibits higher phosphate use efficiency.

Rice (Oryza sativa L.), a major dietary source, is often cultivated in soils poor in available inorganic orthophosphate (Pi), which is a key nutrient for growth and development. Poor soils are amended by phosphorus (P) fertilizer, which is derived from the non-renewable rock phosphate reserves. Therefore, there is a need for developing rice varieties with high productivity under low P conditions. At the ICAR-IIRR, ethyl methanesulfonate (EMS) mutagenized rice genotype Nagina22 (N22) were screened for high grain yield in Pi-deprived soil, which led to the identification of ~ 10 gain-of-function mutants including NH787. Here, detailed comparative morphophysiological, biochemical, and molecular analyses of N22 and NH787 were carried out in hydroponics and potting soil under different Pi regimes. Under Pi-deprived condition, compared with N22, NH787 exhibited higher root and vegetative biomass, the number of tillers, and grain yield. The augmented agronomic traits of NH787 were corroborated with significantly higher photosynthetic rate, pollen fertility, stigma receptivity, and the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Further, several genes involved in the maintenance of Pi homeostasis (GPH) were differentially regulated. The study thus revealed a wide-spectrum influence of the mutation in NH787 that contributed towards its higher Pi use efficiency (PUE).

Early Screening of Risk for Multidrug-Resistant Organisms in the Emergency Department in Patients With Pneumonia and Early Septic Shock: Single-Center, Retrospective Cohort Study.

OBJECTIVES: Pneumonia is the fourth leading cause of death globally, with rapid progression during sepsis. Multidrug-resistant organisms (MDROs) are becoming more common with some healthcare-associated pneumonia events. Early detection of MDRO risk improves the outcomes; however, MDROs risk in pneumonia with sepsis is unknown. This study investigated the disease outcomes of pneumonia with septic shock in patients admitted in the emergency department (ED) intensive care unit (ICU), a population with a high prevalence of MDROs, after early screening of MDROs risk. METHODS: In this retrospective cohort study, patients with pneumonia and early septic shock (n = 533) admitted to the ED at the Taipei Tzu Chi Hospital from 2013 to 2019 were selected. The study population was divided into four subgroups after the MDROs risk and screening procedure were completed within 1 or 6 h of admission. ICU mortality and multidrug antibiotic therapy were compared. RESULTS: The high-risk MDROs groups had higher percentage of P aeruginosa than the low-risk group. Furthermore, the appropriate ED first antibiotics were higher in the 1-h subgroup than in the 6-h subgroup of the high-risk MDROs group. In multivariate analysis, the 6-h high-risk MDROs group had an adjusted odds ratio of 7.191 (95% CI: 2.911-17.767, P < 0.001) and 2.917 (95% CI: 1.456-5.847, P = 0.003) for ICU mortality and multidrug therapy in the ICU, respectively, after adjusting for other confounding factors. CONCLUSIONS: MDRO screening within 1 h is recommended following admission of patients with pneumonia and early septic shock in the ED, especially in areas with a high prevalence of MDROs.

A smartphone-combined ratiometric fluorescence probe for specifically and visibly detecting cephalexin.

A smartphone-combined dual-emission ratiometric fluorescence probe for specifically and visibly detecting cephalexin was first designed. In the probe, blue-emitting fluorescent carbon dots (CDs) was synthesized and covered with a layer of silica spacer. Red-emitting fluorescent CdTe QDs (r-QDs) was grafted onto the silica nanospheres as an analytical probe. Then, the cephalexin antibody was covalent grafted to the ratio sensor to increase the selectivity. The ratio of fluorescence intensity (FL) of r-QDs and CDs was quenched with the increasing concentration of cephalexin. The detection method has good linear response in the range of 1-500 µM and the detection limit was 0.7 µM. Then portable device based on smartphone detection was constructed according to the color change under UV lamp. The detection image was obtained through the smartphone camera, and the color picker APP installed in the smartphone captured the RGB value of the image. In addition, this method was also used to determine the amount of cephalexin in milk samples with recovery of 94.1%-102.2%. These results showed that it was a portable, simple and visible method to detect cephalexin in food analysis and environmental monitoring.

Endophytic fungus Phomopsis liquidambaris B3 induces rice resistance to RSRD caused by Fusarium proliferatum and promotes plant growth.

BACKGROUND: Rice spikelet rot disease (RSRD) is an emerging disease that significantly reduces rice yield and quality. In this study, we evaluated the potential use of the broad-spectrum endophytic fungus Phomopsis liquidambaris B3 as a biocontrol agent against RSRD. We also compared the control effects of different treatments, including chemical fungicides and treatment with multiple strains and single strains in combination or individually, against RSRD. The objective of this study was to find an effective and environmentally friendly control strategy to reduce the occurrence of RSRD and improve the rice yield. RESULTS: In pot experiments, the effect of B3 alone was better than that of fungicide or combined measures. The results showed that root colonization by B3 significantly reduced the incidence and disease index of RSRD by 41.0% and 53.8%, respectively. This was related to enhanced superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO) activity, and to significantly upregulated expression levels of OsAOX, OsLOX, OsPAL, and OsPR10 in rice. Moreover, B3 improved the diversity of the bacterial community rather than the fungal community in the rice rhizosphere. It also led to a decrease in Fusarium proliferatum colonization and fumonisin content in the grain. Finally, root development was markedly promoted after B3 inoculation, and the yield improved by 48.60%. The result of field experiments showed that the incidence of RSRD and the fumonisin content were observably reduced in rice receiving B3, by 24.41% and 37.87%, respectively. CONCLUSION: The endophytic fungus Phomopsis liquidambaris B3 may become an effective tool to relieve rice spikelet rot disease. © 2020 Society of Chemical Industry.

Mechanisms of the antiplatelet and analgesic effects of dextromethorphan and its metabolites.

Objective: In the present study, we investigated the effects of dextromethorphan (DM) and its metabolites, including dextrorphan (LK2), 3-methoxymorphinan (LK3), and 3-hydroxymorphinan (LK4), on platelet aggregation in vitro and the inflammatory pain caused by carrageenan in rats, and their underlying mechanisms. Materials and Methods: Rabbit platelets were pretreated with DM or its metabolites to assess their effects on platelet aggregation and related target mediators. In addition, the analgesic activity and the underlying mechanisms of DM and LK3 were investigated in a carrageenan-evoked thermal hyperalgesia rat model. Results: The inhibitory potency of DM and its metabolites on platelet aggregation induced by arachidonic acid or collagen was LK3> DM > LK4>> LK2 as demonstrated by the half-maximal inhibitory concentration values. Moreover, the mechanisms of the antiplatelet effect of DM and LK3 may involve the inhibition of intracellular calcium mobilization, expression of platelet surface glycoprotein IIb/IIIa, the formation of thromboxane B2, and elevation of platelet membrane fluidity. DM and LK3 also exhibited analgesic effects on carrageenan-evoked thermal hyperalgesia by suppressing the production of pro-inflammatory cytokines, nitric oxide, prostaglandin E2, and neutrophil infiltration in inflammatory sites. Conclusion: DM and its metabolites, especially LK3, exhibit both antiplatelet and analgesic effects, and may, therefore, potentially ameliorate platelet hyperactivity and inflammatory-related diseases.

Ignorance of pre-ED healthcare setting is a factor leading to inappropriate initial antibiotic treatment of sepsis in ED and poor outcomes in ICU.

OBJECTIVES: Appropriate initial antibiotic therapy is critical for successfully treating sepsis. In the emergency department (ED), clinicians often rely on septic symptoms to guide empirical therapy. The aim of this study was to investigate whether history of contacting pre-ED healthcare setting is easy to be neglected and whether the patients received more inappropriate initial antibiotic therapy and developed poorer outcomes. METHODS: Septic patients (n = 453) admitted from ED to the intensive care unit (ICU) between 2014 and 2017 were retrospectively selected. Appropriate antibiotic treatment or not was determined by checking whether the selected antibiotics can effectively eradicate the bacteria identified. Various indexes were compared between patients with appropriate and inappropriate initial antibiotic treatments, including septic symptoms (qSOFA scores) in ED, septic-severity change in ICU (SOFA-score ratios), and septic outcomes (APACHE II scores, stay length, 30-day survival probability). These indexes were also compared between pre-ED healthcare and pre-ED community patients. RESULTS: In comparison with pre-ED community patients, pre-ED healthcare patients received more inappropriate initial antibiotic treatment in ED, showing poorer outcomes in ICU, including septic severity, stay-lengths in ICU and 30-day survival probabilities. Pre-ED settings is more significant than qSOFA scores to predict the inappropriate initial antibiotic treatment. CONCLUSIONS: Pre-ED healthcare settings, which are indexes for infection with antibiotic resistant pathogens, are easy to be neglected in the first hour in ED. We suggested that standard operating procedure for getting enough information of pre-ED settings should be incorporated to the 1 h bundle of sepsis guideline.

WNK4-SPAK modulates lipopolysaccharide-induced macrophage activation.

Dysregulation of alveolar macrophage activation has been recognized as the major mechanism in the pathogenesis of acute lung injury. The aim of the present study was to investigate the role of NKCC1 regulating mechanism in modulating macrophage activation. Knockout (SPAK-/- and WNK4-/-) and knockin (WNK4D561A/+) mice were used in this study. LPS induced expression of p-NKCC1 and activation of NFκB in the primary culture of alveolar macrophages. WNK4 or SPAK knockout suppressed p-NKCC1 expression and inflammation cascade activation, whereas WNK4 knockin enhanced these responses. Intrapulmonary administration of LPS induced in vivo expression and phosphorylation of NKCC1 in alveolar inflammation cells and caused a shift in the cell population from macrophage to neutrophil predominance. WNK4 or SPAK knockout attenuated the LPS-induced alveolar cell-population shifting, macrophage NKCC1 phosphorylation, and acute lung injury, whereas WNK4 knockin augmented the inflammatory response. In summary, our results demonstrated the presence of NKCC1 in alveolar macrophage, which is inducible by lipopolysaccharide. Our results also showed showed that the WNK4-SPAK-NKCC1 cascade plays an important role in modulating macrophage activation to regulate LPS-induced lung inflammation and lung injury.

Safety and efficacy of patients with refractory B-lymphoblastic leukemia treated with anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy and side effects of anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) regimen for refractory B-lymphoblastic leukemia. Methods: 10 patients with refractory B-lymphoblastic leukemia with minimal residual disease (MRD) negative after anti-CD19 CAR-T cell treatment, then bridging to allo-HSCT from November 2017 to March 2019 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Results: ①Among 10 patients, 5 were males and 5 females, with a median age of 23.6 (10-31) years. 9 patients were diagnosed refractory acute lymphoblastic leukemia and the other one was chronic lymphoblastic leukemia. 10 patients reached MRD negative 30 days after anti-CD19 CAR-T cell. ②The donors were identical sibling (2 cases) and haploidentical family member (8 cases) . The median time from MRD negative after CAR-T treatment to transplantation were 32.5 (20-60) days. ③10 patients obtained complete haploidentical engraftment. The median time of neutrophil implantation was 15 (15-21) days, and 19 (17-30) days of platelet implantation. ④ After conditioning, no hepatic venoocclusive disease and hemorrhagic cystitis occurred. One patient had leakage syndrome and got improved after intervention such as limited water entry, albumin supplementation and diuresis. 8 (80%) patients had fever, 2 cases experienced acute graft-versus-host disease (GVHD) grade Ⅱ, 1 case with aGVHD grade Ⅲ. Among 9 survivals, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 262 (150-540) days and the estimated 1-years overall survivaln (OS) and disease free survival (DFS) were (90.0±1.0) % and (85.7±1.3) %, respectively. Conclusion: Anti-CD19 CAR-T cell bridging to allo-HSCT regimen is a feasible choice with favorable outcome for refractory B-lymphoblastic leukemia.

Analysis of efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in treatment of relapsed/refractory acute myeloid leukemia / 白血病·淋巴瘤

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.

[Stable Carbon Isotope Compositions and Source Apportionments of Volatile Aromatic Compounds in the Urban Atmosphere of Taiyuan, China].

This study used Tenax TA absorption tubes to sample volatile aromatic compounds from different emission sources and functional zones in Taiyuan City, Shanxi Province, China. Thermal desorption-gas chromatography-isotope ratio mass spectrometry (TD-GC-IRMS) was subsequently employed to analyze the stable carbon isotope characteristics of the volatile aromatic compounds. The results revealed that the stable carbon isotope ratio (δ13C) of the volatile aromatic compounds emitted through diesel, gasoline, and solvent volatilization, vehicle exhaust, and domestic coal combustion ranged from (-30.79±0.98)‰ to (-29.10±0.14)‰, (-30.96±0.88)‰ to (-28.02±1.77)‰, (-32.13±0.59)‰ to (-27.67±0.49)‰, (-27.58±0.16)‰ to (-25.50±0.75)‰, and (-25.14±0.93)‰ to (-23.44±1.32)‰, respectively. The δ13C value of styrene was (-23.44±1.32)‰, which was only detected in the fumes emitted through domestic coal combustion. Additionally, the sample analysis based on data collected from four different functional zones of Taiyuan City revealed the following:① the δ13C values of the atmospheric volatile aromatic compounds in the mixed residential and traffic zone ranged from (-25.61±2.20)‰ to (-23.91±0.78)‰. Compared with other functional zones, the emissions in this zone were enriched with13C; and ② the δ13C values measured in the industrial zone ranged from (-29.15±1.06)‰ to (-24.53±1.07)‰; the emissions in this functional zone were relatively low in 13C compared with other zones. A comparison of the δ13C values of the atmospheric volatile aromatic compounds and emission sources indicated that the main sources of volatile aromatic compounds at the four sampling points in Taiyuan were vehicle exhausts and domestic coal combustion, while the air sampled in the industrial functional zone was heavily affected by the volatilization of solvents.

Staphylococcal phosphatidylinositol-specific phospholipase C potentiates lung injury via complement sensitisation.

Staphylococcus aureus is frequently isolated from patients with community-acquired pneumonia and acute respiratory distress syndrome (ARDS). ARDS is associated with staphylococcal phosphatidylinositol-specific phospholipase C (PI-PLC); however, the role of PI-PLC in the pathogenesis and progression of ARDS remains unknown. Here, we showed that recombinant staphylococcal PI-PLC possesses enzyme activity that causes shedding of glycosylphosphatidylinositol-anchored CD55 and CD59 from human umbilical vein endothelial cell surfaces and triggers cell lysis via complement activity. Intranasal infection with PI-PLC-positive S. aureus resulted in greater neutrophil infiltration and increased pulmonary oedema compared with a plc-isogenic mutant. Although indistinguishable proinflammatory genes were induced, the wild-type strain activated higher levels of C5a in lung tissue accompanied by elevated albumin instillation and increased lactate dehydrogenase release in bronchoalveolar lavage fluid compared with the plc- mutant. Following treatment with cobra venom factor to deplete complement, the wild-type strain with PI-PLC showed a reduced ability to trigger pulmonary permeability and tissue damage. PI-PLC-positive S. aureus induced the formation of membrane attack complex, mainly on type II pneumocytes, and reduced the level of CD55/CD59, indicating the importance of complement regulation in pulmonary injury. In conclusion, S. aureus PI-PLC sensitised tissue to complement activation leading to more severe tissue damage, increased pulmonary oedema, and ARDS progression.

Idiopathic portal hypertension presenting with hepatic nodular regenerative hyperplasia after splenectomy: a case report.

Idiopathic portal hypertension (IPH) is a rare disease, and its etiology and pathogenesis have not yet been fully clarified. The main clinical manifestations are non-cirrhotic intrahepatic portal hypertension, accompanied by splenomegaly, thrombocytopenia, and recurrent upper gastrointestinal bleeding. The liver histopathologic changes are diverse. Splenectomy is considered an effective treatment for hypersplenism. We report a patient who presented with splenomegaly, then underwent splenectomy to relieve thrombocytopenia based on routine treatment strategies. However, multiple space-occupying lesions were found in the liver about one year later. Thereafter, the lesions were confirmed as nodular regenerative hyperplasia (NRH) by liver biopsy, the patient was finally diagnosed with IPH. We consider that although splenectomy is generally recommended for IPH, under certain circumstances splenectomy may disturb blood flow in the liver, leading to the formation of NRH. Therefore, splenectomy in IPH patients should be chosen carefully.

The role of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia (R-SAA) . Method: The clinical data of 25 R-SAA patients receiving co-transplantation of mesenchymal stem cells combined with peripheral blood stem cells from sibling donors (10 cases) and unrelated donors (15 cases) from March 2010 to July 2018 in Zhengzhou University Affiliated Tumor Hospital were retrospectively analyzed. Antithymocyte globulin (ATG) treatment was ineffective/relapsed in 11 cases, and cyclosporine (CsA) treatment ineffective/relapsed in 14 cases. Results: There were 13 male and 12 female among these patients. One patient had a primary graft failure, one patient had a poorly engraftment of platelets, and the remaining 23 patients achieved hematopoietic engraftment. The median time of granulocyte engraftment was 12.5 (10-23) days and 15 (11-25) days for megakaryocyte. Incidences of grade Ⅰ/Ⅱ acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were 37.5% (9/24) and 21.7% (5/23) , respectively. There was no severe GVHD and no severe complications that related to transplantation. 21 of 25 (84%) patients were alive with a median follow-up of 22.9 (1.6-107.8) months. The 5-year overall survival rate after transplantation was (83.6±7.5) %. Conclusion: The combination of mesenchymal stem cells is reliable and safe in the treatment of R-SAA in peripheral blood stem cell transplantation of unrelated donors and sibling donors, which could significantly reduce the incidence of GVHD and severe transplantation-related complications.