Publications by authors named "Qian Jiang"

941 Publications

Algae biochar enhanced methanogenesis by enriching specific methanogens at low inoculation ratio during sludge anaerobic digestion.

Bioresour Technol 2021 Jul 4;338:125493. Epub 2021 Jul 4.

School of Environmental and Civil Engineering, Jiangnan University, Wuxi 214122, China; Jiangsu Key Laboratory of Anaerobic Biotechnology, Wuxi 214122, China; Jiangsu Collaborative Innovation Center of Water Treatment Technology and Material, Suzhou 215011, China. Electronic address:

Carbon materials are promising in improving the performance of anaerobic digestion, however, interactive mechanisms between the carbon-based enhancement and operating parameters remained unclear. Using anaerobic digested sludge as inoculum, the effects of Taihu blue algae biochar (ABC) on methanogenesis at different inoculation ratios were investigated during sludge anaerobic digestion. Results showed that ABC enhanced methane productions at the lower inoculation ratios (4% and 1%, v/v), but not at the higher ratio (10%, v/v). Mechanism analysis demonstrated methanogenic improvements at the lower inoculation ratios were not owing to initial organic loading rate increments. Otherwise, ABC addition at the lower inoculation ratios were more favorable for the enrichment of Methanosarcina than the higher ratio, which might be benefit for methanogenesis through directed interspecies electron transfer. Thus, for the improvement of sludge anaerobic digestion, the microbial enrichments at different inoculation ratios would be more important than the merely biochar addition.
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http://dx.doi.org/10.1016/j.biortech.2021.125493DOI Listing
July 2021

Genome assembly of the Chinese maize elite inbred line RP125 and its EMS mutant collection provide new resources for maize genetics research and crop improvement.

Plant J 2021 Jul 12. Epub 2021 Jul 12.

Maize Research Institute, Sichuan Agricultural University, ChengDu, 611130, China.

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 megabases) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. We obtained a total of 5,818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: 'missing a small part' in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein that is specifically required for iron transport. Increased accumulation of iron and ROS as well as ferroptosis-like cell death were detected in endosperm of qk1. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.
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http://dx.doi.org/10.1111/tpj.15421DOI Listing
July 2021

Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris.

Proteomics Clin Appl 2021 Jul 9:e2000094. Epub 2021 Jul 9.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Purpose: To characterize the proteome of the iris in primary angle closure glaucoma (PACG).

Experimental Design: In this cross-sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analysed using liquid chromatography-tandem mass spectrometry on an Orbitrap Q Exactive Plus mass spectrometer. Verification of proteins of interest was conducted using selected reaction monitoring on a triple quadrupole mass spectrometer. The main outcome was proteins with a log two-fold difference in expression in iris between PACG and controls.

Results: There were 3,446 non-redundant proteins identified in human iris, of which 416 proteins were upregulated and 251 proteins were downregulated in PACG compared with controls. Thirty-two upregulated proteins were either components of the extracellular matrix (ECM) (fibrillar collagens, EMILIN-2, fibrinogen, fibronectin, matrilin-2), matricellular proteins (thrombospondin-1), proteins involved in cell-matrix interactions (integrins, laminin, histidine-rich glycoprotein, paxillin), or protease inhibitors known to modulate ECM turnover (α-2 macroglobulin, tissue factor pathway inhibitor 2, papilin). Two giant proteins, titin and obscurin, were up- and down-regulated, respectively, in the iris in PACG compared with controls.

Conclusions And Clinical Relevance: This proteomic study shows that ECM composition and homeostasis are altered in the iris in PACG.
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http://dx.doi.org/10.1002/prca.202000094DOI Listing
July 2021

βA3/A1-crystallin regulates apical polarity and EGFR endocytosis in retinal pigmented epithelial cells.

Commun Biol 2021 Jul 8;4(1):850. Epub 2021 Jul 8.

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

The retinal pigmented epithelium (RPE) is a monolayer of multifunctional cells located at the back of the eye. High membrane turnover and polarization, including formation of actin-based apical microvilli, are essential for RPE function and retinal health. Herein, we demonstrate an important role for βA3/A1-crystallin in RPE. βA3/A1-crystallin deficiency leads to clathrin-mediated epidermal growth factor receptor (EGFR) endocytosis abnormalities and actin network disruption at the apical side that result in RPE polarity disruption and degeneration. We found that βA3/A1-crystallin binds to phosphatidylinositol transfer protein (PITPβ) and that βA3/A1-crystallin deficiency diminishes phosphatidylinositol 4,5-biphosphate (PI(4,5)P), thus probably decreasing ezrin phosphorylation, EGFR activation, internalization, and degradation. We propose that βA3/A1-crystallin acquired its RPE function before evolving as a structural element in the lens, and that in the RPE, it modulates the PI(4,5)P pool through PITPβ/PLC signaling axis, coordinates EGFR activation, regulates ezrin phosphorylation and ultimately the cell polarity.
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http://dx.doi.org/10.1038/s42003-021-02386-6DOI Listing
July 2021

Interferon-α as maintenance therapy can significantly reduce relapse in patients with favorable-risk acute myeloid leukemia.

Leuk Lymphoma 2021 Jul 1:1-8. Epub 2021 Jul 1.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

To evaluate the efficacy of interferon-α (IFN-α) as maintenance therapy in patients with favorable-risk acute myeloid leukemia (AML), this retrospective study enrolled 84 patients with favorable-risk AML: 42 patients who received IFN-α maintenance therapy and 42 patients who did not (control). The median follow-up time and duration of IFN-α treatment was 26 (6-54) months and 18 (2-24) months, respectively. The 4-year estimated relapse-free survival (RFS) after the last consolidation chemotherapy was 86.8% (95% confidence interval (CI), 75.8-97.8%) in the IFN-α group and 55.7% (95% CI, 37.2-74.3%) in the control group (=.007). The 4-year estimated overall survival was 94.4% (95% CI, 86.8-102%) and 76.4% (95% CI, 61.9-90.9%) in IFN-α and control groups, respectively (=.040). The Cox regression analysis showed that IFN-α treatment was the only independent factor affecting RFS (=.004). Maintenance therapy with IFN-α may prevent relapse in favorable-risk AML after consolidation chemotherapy.
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http://dx.doi.org/10.1080/10428194.2021.1948027DOI Listing
July 2021

Large-scale phenotypic drug screen identifies neuroprotectants in zebrafish and mouse models of retinitis pigmentosa.

Elife 2021 Jun 29;10. Epub 2021 Jun 29.

Wilmer Eye Institute, Johns Hopkins University, Baltimore, United States.

Retinitis pigmentosa (RP) and associated inherited retinal diseases (IRDs) are caused by rod photoreceptor degeneration, necessitating therapeutics promoting rod photoreceptor survival. To address this, we tested compounds for neuroprotective effects in multiple zebrafish and mouse RP models, reasoning drugs effective across species and/or independent of disease mutation may translate better clinically. We first performed a large-scale phenotypic drug screen for compounds promoting rod cell survival in a larval zebrafish model of inducible RP. We tested 2,934 compounds, mostly human-approved drugs, across six concentrations, resulting in 113 compounds being identified as hits. Secondary tests of 42 high-priority hits confirmed eleven lead candidates. Leads were then evaluated in a series of mouse RP models in an effort to identify compounds effective across species and RP models, i.e., potential pan-disease therapeutics. Nine of eleven leads exhibited neuroprotective effects in mouse primary photoreceptor cultures, and three promoted photoreceptor survival in mouse retinal explants. Both shared and complementary mechanisms of action were implicated across leads. Shared target tests implicated -dependent cell death in our zebrafish RP model. Complementation tests revealed enhanced and additive/synergistic neuroprotective effects of paired drug combinations in mouse photoreceptor cultures and zebrafish, respectively. These results highlight the value of cross-species/multi-model phenotypic drug discovery and suggest combinatorial drug therapies may provide enhanced therapeutic benefits for RP patients.
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http://dx.doi.org/10.7554/eLife.57245DOI Listing
June 2021

Predictive model based on gene and laboratory data for intravenous immunoglobulin resistance in Kawasaki disease in a Chinese population.

Pediatr Rheumatol Online J 2021 Jun 26;19(1):95. Epub 2021 Jun 26.

Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020, China.

Background: Here, we investigated the predictive efficiency of a newly developed model based on single nucleotide polymorphisms (SNPs) and laboratory data for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) in a Chinese population.

Methods: Data relating to children with KD were acquired from a single center between December 2015 and August 2019 and used to screen target SNPs. We then developed a predictive model of IVIG resistance using previous laboratory parameters. We then validated our model using data acquired from children with KD attending a second center between January and December 2019.

Results: Analysis showed that rs10056474 GG, rs746994GG, rs76863441GT, rs16944 (CT/TT), and rs1143627 (CT/CC), increased the risk of IVIG-resistance in KD patients (odds ratio, OR > 1). The new predictive model, which combined SNP data with a previous model derived from laboratory data, significantly increased the area under the receiver-operator-characteristic curves (AUC) (0.832, 95% CI: 0.776-0.878 vs 0.793, 95%CI:0.734-0.844, P < 0.05) in the development dataset, and (0.820, 95% CI: 0.730-0.889 vs 0.749, 95% CI: 0.652-0.830, P < 0.05) in the validation dataset. The sensitivity and specificity of the new assay were 65.33% (95% CI: 53.5-76.0%) and 86.67% (95% CI: 80.2-91.7%) in the development dataset and 77.14% (95% CI: 59.9-89.6%) and 86.15% (95% CI: 75.3-93.5%) in the validation dataset.

Conclusion: Analysis showed that rs10056474 and rs746994 in the SMAD5 gene, rs76863441 in the PLA2G7 gene, and rs16944 or rs1143627 in the interleukin (IL)-1B gene, were associated with IVIG resistant KD in a Chinese population. The new model combined SNPs with laboratory data and improved the predictve efficiency of IVIG-resistant KD.
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http://dx.doi.org/10.1186/s12969-021-00582-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236184PMC
June 2021

Mental Health in Persons With Chronic Myeloid Leukemia During the SARS-CoV-2 Pandemic: The Need for Increased Access to Health Care Services.

Front Psychiatry 2021 8;12:679932. Epub 2021 Jun 8.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China.

Mental health problems in the general population have been reported during the SARS-CoV-2 pandemic; however, there were rare data in persons with chronic myeloid leukemia (CML). Therefore, we performed a cross-sectional study on mental health evaluated using the 9-item Patient Health Questionnaire (PHQ-9; depression), the 7-item Generalized Anxiety Disorder (GAD-7; anxiety), and the 22-item Impact of Event Scale-Revised (IES-R; distress), including subscales of avoidance, intrusion, and hyper-arousal in persons with CML, non-cancer persons, and immediate family members of persons with cancer as controls (≥16 years) by an online survey. Data from 3,197 persons with CML and 7,256 controls were collected. In multivariate analyses, CML was significantly associated with moderate to severe depression (OR = 1.6; 95% Confidence Interval [CI], 1.4, 1.9; < 0.001), anxiety (OR = 1.4 [1.1, 1.7]; = 0.001), distress (OR = 1.3 [1.1, 1.5]; < 0.001), and hyper-arousal (OR = 1.5 [1.3, 1.6]; < 0.001). Moreover, delay in regular monitoring was significantly associated with depression (OR 1.3 [1.0, 1.7]; = 0.024), anxiety (OR = 1.3 [1.0, 1.8]; = 0.044), avoidance (OR = 1.2 [1.0, 1.4]; = 0.017), and intrusion (OR = 1.2 [1.0, 1.4]; = 0.057); tyrosine kinase-inhibitor dose reduction or discontinuation, depression (OR = 1.9 [1.3, 2.8]; = 0.001), distress (OR = 2.0 [1.4, 2.8]; < 0.001), avoidance (OR = 1.6 [1.2, 2.1]; = 0.004), intrusion (OR = 1.6 [1.1, 2.1]; = 0.006), and hyper-arousal (OR = 1.3 [1.0, 1.8]; = 0.088). We concluded that persons with CML during the SARS-CoV-2 pandemic have worse mental health including depression, anxiety, and distress symptoms. Decreasing or stopping monitoring or dose resulted in adverse mental health consequences.
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http://dx.doi.org/10.3389/fpsyt.2021.679932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217438PMC
June 2021

Novel Bioactive Glass-Modified Hybrid Composite Resin: Mechanical Properties, Biocompatibility, and Antibacterial and Remineralizing Activity.

Front Bioeng Biotechnol 2021 1;9:661734. Epub 2021 Jun 1.

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Secondary caries seriously limits the lifetime of composite resin. However, integrating all desirable properties (i.e., mechanical, antibacterial, bioactivity, and biocompatibility) into one composite resin is still challenging. Herein, a novel bioactive glass (BAG)-modified hybrid composite resin has been successfully developed to simultaneously achieve excellent mechanical properties, good biocompatibility, and antibacterial and remineralizing capabilities. When the mass fractions of BAG particles were added from 8 to 23 wt %, the original mechanical properties of the composite resin, including flexural strength and compressive strength, were not obviously affected without compromising the degree of conversion. Although the BAG incorporation of mass fractions of 16 wt % to 23 wt % in composite resins reduced cell viability, the viability could be recovered to normal by adjusting the pH value. Moreover, the BAG-modified composite resins that were obtained showed good antibacterial effects against and enhanced remineralizing activity on demineralized dentin surfaces with increasing incorporation of BAG particles. The possible mechanisms for antibacterial and remineralizing activity might be closely related to the release of bioactive ions (Ca, Si), suggesting that its antibacterial and biological properties can be controlled by modulating the amounts of bioactive ions. The capability to balance the mechanical properties, cytotoxicity, antibacterial activity, and bioactivity makes the BAG-modified composite resin a promising prospect for clinical application. Our findings provide insight into better design and intelligent fabrication of bioactive composite resins.
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http://dx.doi.org/10.3389/fbioe.2021.661734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205519PMC
June 2021

3D genome alterations associated with dysregulated HOXA13 expression in high-risk T-lineage acute lymphoblastic leukemia.

Nat Commun 2021 06 17;12(1):3708. Epub 2021 Jun 17.

The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China.

3D genome alternations can dysregulate gene expression by rewiring enhancer-promoter interactions and lead to diseases. We report integrated analyses of 3D genome alterations and differential gene expressions in 18 newly diagnosed T-lineage acute lymphoblastic leukemia (T-ALL) patients and 4 healthy controls. 3D genome organizations at the levels of compartment, topologically associated domains and loop could hierarchically classify different subtypes of T-ALL according to T cell differentiation trajectory, similar to gene expressions-based classification. Thirty-four previously unrecognized translocations and 44 translocation-mediated neo-loops are mapped by Hi-C analysis. We find that neo-loops formed in the non-coding region of the genome could potentially regulate ectopic expressions of TLX3, TAL2 and HOXA transcription factors via enhancer hijacking. Importantly, both translocation-mediated neo-loops and NUP98-related fusions are associated with HOXA13 ectopic expressions. Patients with HOXA11-A13 expressions, but not other genes in the HOXA cluster, have immature immunophenotype and poor outcomes. Here, we highlight the potentially important roles of 3D genome alterations in the etiology and prognosis of T-ALL.
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http://dx.doi.org/10.1038/s41467-021-24044-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211852PMC
June 2021

Effect of chlorhexidine-loaded poly(amido amine) dendrimer on matrix metalloproteinase activities and remineralization in etched human dentin in vitro.

J Mech Behav Biomed Mater 2021 09 10;121:104625. Epub 2021 Jun 10.

Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China. Electronic address:

To investigate the effect of chlorhexidine (CHX)-loaded carboxyl-terminated poly (amido amine) dendrimer (CHX-PAMAM-COOH) on matrix metalloproteinase (MMP) activities and remineralization in human dentin, CHX-PAMAM-COOH was prepared and characterized by Fourier-transform infrared spectroscopy. The inhibitory effects of CHX, PAMAM-COOH, and CHX-PAMAM-COOH on soluble recombinant human matrix metalloproteinase (rhMMP-2) and dentin-bound endogenous MMP activity were measured using an MMP Activity Assay Kit. In situ zymography was performed to evaluate the gelatinase activity in dentin pretreated with CHX, PAMAM-COOH, and CHX-PAMAM-COOH. The remineralization of etched dentin pretreated with CHX, PAMAM-COOH, and CHX-PAMAM-COOH was evaluated by field emission-scanning electron microscopy (SEM) and energy disperse spectroscopy (EDS) after incubation in artificial saliva for 14 days. The results of the rhMMP-2 activity assay showed that the MMP-2 activity in the CHX-PAMAM-COOH group and the CHX group decreased significantly to 5.58 ± 0.85% (P < 0.05) and 4.86 ± 1.12% (P < 0.05), respectively, but that in the PAMAM-COOH group increased significantly to 213.38 ± 0.11% (P < 0.05). The results of total MMP activity and in situ zymography showed a significant reduction in endogenous gelatinase activity in dentin in the CHX-PAMAM-COOH group and the CHX group. The SEM and EDS results showed that rod-like crystals were formed on the etched dentin surface in the PAMAM-COOH group and the CHX-PAMAM-COOH group, and their Ca/P ratios were 1.73 and 1.71, respectively. In conclusion, CHX-PAMAM-COOH can inhibit dentin-bound endogenous MMPs and induce remineralization in etched dentin simultaneously. However, it is important to note that the catalytic role of PAMAM dendrimers may have an undesired excitatory effect on MMP activity, which cannot be ignored if PAMAM dendrimers were used alone in the oral environment.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104625DOI Listing
September 2021

An integrated gene catalog and over 10,000 metagenome-assembled genomes from the gastrointestinal microbiome of ruminants.

Microbiome 2021 06 12;9(1):137. Epub 2021 Jun 12.

Laboratory of Gastrointestinal Microbiology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.

Background: Gastrointestinal tract (GIT) microbiomes in ruminants play major roles in host health and thus animal production. However, we lack an integrated understanding of microbial community structure and function as prior studies. are predominantly biased towards the rumen. Therefore, to acquire a microbiota inventory of the discrete GIT compartments, In this study, we used shotgun metagenomics to profile the microbiota of 370 samples that represent 10 GIT regions of seven ruminant species.

Results: Our analyses reconstructed a GIT microbial reference catalog with > 154 million nonredundant genes and identified 8745 uncultured candidate species from over 10,000 metagenome-assembled genomes. The integrated gene catalog across the GIT regions demonstrates spatial associations between the microbiome and physiological adaptations, and 8745 newly characterized genomes substantially expand the genomic landscape of ruminant microbiota, particularly those from the lower gut. This substantially expands the previously known set of endogenous microbial diversity and the taxonomic classification rate of the GIT microbiome. These candidate species encode hundreds of enzymes and novel biosynthetic gene clusters that improve our understanding concerning methane production and feed efficiency in ruminants. Overall, this study expands the characterization of the ruminant GIT microbiota at unprecedented spatial resolution and offers clues for improving ruminant livestock production in the future.

Conclusions: Having access to a comprehensive gene catalog and collections of microbial genomes provides the ability to perform efficiently genome-based analysis to achieve a detailed classification of GIT microbial ecosystem composition. Our study will bring unprecedented power in future association studies to investigate the impact of the GIT microbiota in ruminant health and production. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01078-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199421PMC
June 2021

Variables associated with patient-reported outcomes in patients with myeloproliferative neoplasms.

Leuk Lymphoma 2021 Jun 8:1-13. Epub 2021 Jun 8.

Peking University People's Hospital, Beijing, China.

We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.
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http://dx.doi.org/10.1080/10428194.2021.1933481DOI Listing
June 2021

Enzyme-Treated Soybean Meal Replacing Extruded Full-Fat Soybean Affects Nitrogen Digestibility, Cecal Fermentation Characteristics and Bacterial Community of Newly Weaned Piglets.

Front Vet Sci 2021 20;8:639039. Epub 2021 May 20.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

The study investigated the impact of soybean protein from different processing on the performance, dietary nitrogen digestibility, cecal fermentation characteristics, and bacterial community in newly weaned piglets. The piglets were allocated to two dietary treatment and fed with the extruded full-fat soybean diet (EFS group) and enzyme-treated soybean meal diet (ESBM group), respectively. The piglets in ESBM group showed greater nitrogen digestibility and feed efficiency, and lower diarrhea rate in comparison to piglets in EFS group ( < 0.05). Cecal samples from piglets in ESBM group contained greater concentration of acetate, propionate and total SCFAs ( < 0.05), and lower contents of isobutyrate, isovalerate, total BCFAs, NH-N and putrescine ( < 0.05) than cecal samples from piglets in the EFS group. The cecal samples from piglets in ESBM group contained greater abundances of g_, g_, g_, and g_ than the cecal sample from piglets in the EFS group, which could promote to protect intestinal health. In summary, enzyme-treated soybean meal may enhance the growth performance of weaned piglets increasing the dietary nitrogen digestibility, preventing protein fermentation in the hindgut, which shed light on the mechanism in regulating gut health of dietary protein.
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http://dx.doi.org/10.3389/fvets.2021.639039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173081PMC
May 2021

Adolescents experienced more treatment failure than children with chronic myeloid leukemia receiving imatinib as frontline therapy: a retrospective multicenter study.

Ann Hematol 2021 Jun 5. Epub 2021 Jun 5.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

To explore the differences in the clinical features, treatment responses, and outcomes among children, adolescents, and adults with chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib as first-line therapy. Data from children (0-8 years for girls and 0-10 years for boys), adolescents (9-19 years for girls and 11-19 years for boys), and adults (age ≥ 20 years) with newly diagnosed CML-CP receiving imatinib as first-line therapy between 2006 and 2019 were retrospectively reviewed. In total, 135 children (cohort 1), 189 adolescents (cohort 2), and 658 adults (cohort 3: age 20-39 years, n = 305; cohort 4: age 40-59 years, n = 270; and cohort 5: age 60-83 years, n = 83) were included in this study. When compared with children, adolescents showed a significantly higher white blood cell count (P = 0.033) and basophil percentage in peripheral blood (P = 0.002) and a significantly higher prevalence of splenomegaly (P = 0.004). Both children and adolescents presented with more aggressive clinical features than adults. During median follow-ups of 28 months (range, 3-161 months) in children, 33 months (range, 3-152 months) in adolescents, and 48 months (range, 3-157 months) in adults, multivariate analysis showed that children and adolescents had higher probabilities of achieving complete cytogenetic response, major molecular response, and molecular response. Notably, compared with not only adults (cohort 3 vs. cohort 1: HR = 2.03 [1.03, 3.98], P = 0.040; cohort 4 vs. cohort 1: HR = 2.15 [1.07, 4.33], P = 0.033; cohort 5 vs. cohort 1: HR = 4.22 [1.94, 9.15], P < 0.001) but also adolescents (cohort 2 vs. cohort 1: HR = 2.36 [1.18, 4.72], P = 0.015), children had significantly longer failure-free survival. Age was not associated with progression-free survival or overall survival. Although they exhibited more aggressive clinical features at diagnosis, both children and adolescents achieved superior treatment responses than adults. Adolescents showed even more adverse features and a poor FFS than children.
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http://dx.doi.org/10.1007/s00277-021-04544-6DOI Listing
June 2021

Tuning the Chemical Properties of Co-Ti C T MXene Materials for Catalytic CO Reduction.

Small 2021 Jul 4;17(26):e2007509. Epub 2021 Jun 4.

Dalian National Laboratory for Clean Energy (DNL), Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, China.

MXenes, a novel family of 2D materials, are energy materials that have gained considerable attention, particularly for their catalytic applications in emerging areas such as CO and N hydrogenation. Herein, for the first time, it is shown that the surface reducibility of Ti C T MXene can be tuned by N doping, which induces a change in the catalytic properties of supported Co nanoparticles. Pristine Co-Ti C T MXene favors CO production during CO hydrogenation, whereas CH production is favored when the MXene is subjected to simple N doping. X-ray photoelectron spectroscopy and transmission electron microscopy (TEM) reveal that surface rutile TiO nanoparticles appear on the Ti C T support upon N doping, which interact strongly with the supported Co nanoparticles. This interaction alters the reducibility of the supported Co nanoparticles at the interface with the TiO nanoparticles, shifting the product selectivity from CO to CH . This study successfully showcases a practical strategy, based on surface chemistry modulation of 2D MXenes, for regulating product distribution in CO hydrogenation.
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http://dx.doi.org/10.1002/smll.202007509DOI Listing
July 2021

High-Consistency Optical Fiber Fabry-Perot Pressure Sensor Based on Silicon MEMS Technology for High Temperature Environment.

Micromachines (Basel) 2021 May 28;12(6). Epub 2021 May 28.

Science and Technology on Electronic Test and Measurement Laboratory, North University of China, Taiyuan 030051, China.

This paper proposes a high-temperature optical fiber Fabry-Perot pressure sensor based on the micro-electro-mechanical system (MEMS). The sensing structure of the sensor is composed of Pyrex glass wafer and silicon wafer manufactured by mass micromachining through anodic bonding process. The separated sensing head and the gold-plated fiber are welded together by a carbon dioxide laser to form a fiber-optic Fabry-Perot high temperature pressure sensor, which uses a four-layer bonding technology to improve the sealing performance of the Fabry-Perot cavity. The test system of high temperature pressure sensor is set up, and the experimental data obtained are calculated and analyzed. The experimental results showed that the maximum linearity of the optical fiber pressure sensor was 1% in the temperature range of 20-400 °C. The pressure sensor exhibited a high linear sensitivity of about 1.38 nm/KPa at room temperature at a range of pressures from approximarely 0-to 1 MPa. The structure of the sensor is characterized by high consistency, which makes the structure more compact and the manufacturing process more controllable.
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http://dx.doi.org/10.3390/mi12060623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228703PMC
May 2021

Acid-Sensing Ion Channels and Mechanosensation.

Int J Mol Sci 2021 May 1;22(9). Epub 2021 May 1.

Department of Biomedical Sciences, School of Medicine, University of Missouri, Kansas City, MO 64108, USA.

Acid-sensing ion channels (ASICs) are mainly proton-gated cation channels that are activated by pH drops and nonproton ligands. They are part of the degenerin/epithelial sodium channel superfamily due to their sodium permeability. Predominantly expressed in the central nervous system, ASICs are involved in synaptic plasticity, learning/memory, and fear conditioning. These channels have also been implicated in multiple disease conditions, including ischemic brain injury, multiple sclerosis, Alzheimer's disease, and drug addiction. Recent research has illustrated the involvement of ASICs in mechanosensation. Mechanosensation is a form of signal transduction in which mechanical forces are converted into neuronal signals. Specific mechanosensitive functions have been elucidated in functional ASIC1a, ASIC1b, ASIC2a, and ASIC3. The implications of mechanosensation in ASICs indicate their subsequent involvement in functions such as maintaining blood pressure, modulating the gastrointestinal function, and bladder micturition, and contributing to nociception. The underlying mechanism of ASIC mechanosensation is the tether-gate model, which uses a gating-spring mechanism to activate ASIC responses. Further understanding of the mechanism of ASICs will help in treatments for ASIC-related pathologies. Along with the well-known chemosensitive functions of ASICs, emerging evidence has revealed that mechanosensitive functions of ASICs are important for maintaining homeostasis and contribute to various disease conditions.
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http://dx.doi.org/10.3390/ijms22094810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125064PMC
May 2021

Efficacy and safety of novel-targeted drugs in the treatment of pulmonary arterial hypertension: a Bayesian network meta-analysis.

Drug Deliv 2021 Dec;28(1):1007-1019

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.

Pulmonary arterial hypertension (PAH) is a severe and fatal clinical syndrome characterized by high blood pressure and vascular remodeling in the pulmonary arterioles, which is also a rapidly progressing disease of the lung vasculature with a poor prognosis. Although PAH medication made great advances in recent years, the efficacy and safety of the medication are unsatisfactory. Therefore, we aimed to update and expand previous studies to explore the efficacy and safety of PAH-targeted medications. Relevant articles were searched and selected from published or publicly available data in PubMed, Cochrane Library, CNKI, PsycInfo, and MEDLINE (from inception until October 1, 2020). To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO functional class (WHO FC) improvement, clinical worsening, death] and two safety outcomes [adverse events (AEs), serious adverse events (SAEs)] were selected. And 6MWD was regarded as the primary efficacy outcome. 50 trials included with 10 996participants were selected. In terms of efficacy, all targeted drugs were more effective than placebo. For 6MWD, Bosentan + Sildenafil, Sildenafil, Bosentan + Iloprost were better than others. Bosentan + Iloprost and Bosentan + Sildenafil were better for mPAP. Bosentan + Iloprost and Ambrisentan + Tadalafil were more effective in improving WHO FC. Bosentan + Tadalafil and Bosentan + Iloprost had the Ambrisentan probability to reduce the incidence of clinical worsening. It is demonstrated that Ambrisentan had clear benefits in reducing all-cause mortality. In terms of safety, no therapies had been shown to reduce the incidence of SAEs significantly, and Ambrisentan + Tadalafil significantly increased the incidence of AEs. Phosphodiesterase 5 inhibitor (PDE5i) + Endothelin Receptor Antagonists (ERA) seems to be better therapy for PAH. Prostacyclin analogs (ProsA) + ERA appear promising, though additional data is warranted. PROSPERO CRD42020218818.
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http://dx.doi.org/10.1080/10717544.2021.1927243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172220PMC
December 2021

Differentiation of lacrimal gland tumors using the multi-model MRI: classification and regression tree (CART)-based analysis.

Acta Radiol 2021 May 31:2841851211021039. Epub 2021 May 31.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, PR China.

Background: Little is known about the value of dynamic contrast-enhanced (DCE) in combination with diffusion-weighted imaging (DWI) for the differentiation of lacrimal gland tumors.

Purpose: To evaluate the ability of DCE and DWI in differentiating lacrimal gland tumors.

Material And Methods: DCE and DWI were performed in 72 patients with lacrimal gland tumors. Time-intensity curve (TIC) patterns were categorized as type A, type B, type C, and type D. Apparent diffusion coefficient (ADC) was measured on DWI. Then, the diagnostic effectiveness of TIC in conjunction with ADC was assessed using classification and regression tree (CART) analysis.

Results: Type A tumors were all epithelial; they could be further separated into pleomorphic adenoma sand carcinomas. Type B tumors were all non-epithelial tumors, which could be further separated into benign inflammatory infiltrates (BIIs) and lymphomas. Type C tumors contained both carcinomas and non-epithelial tumors, which could be diagnosed into carcinomas, BIIs and lymphomas. Type D tumors were all PAs. The mean ADC of epithelial tumors was significantly higher than that of non-epithelial tumors, and the mean ADC values were significantly different between PAs and carcinomas. Besides, the mean ADC value of BIIs was higher than that of lymphomas. Therefore, the CART decision tree made by ADC and TIC had a predictive accuracy of 86.1%, differentiating lacrimal gland tumors effectively.

Conclusion: Combined DCE and DWI-MRI can efficiently differentiate lacrimal gland tumors which can be of help to ophthalmologists in the diagnosis and treatment of these tumors.
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http://dx.doi.org/10.1177/02841851211021039DOI Listing
May 2021

Control of neurogenic competence in mammalian hypothalamic tanycytes.

Sci Adv 2021 May 28;7(22). Epub 2021 May 28.

Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.

Hypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, can generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. In this study, we show that tanycyte-specific disruption of the NFI family of transcription factors () robustly stimulates tanycyte proliferation and tanycyte-derived neurogenesis. Single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analysis reveals that NFI (nuclear factor I) factors repress Sonic hedgehog (Shh) and Wnt signaling in tanycytes and modulation of these pathways blocks proliferation and tanycyte-derived neurogenesis in -deficient mice. -deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, fire action potentials, receive synaptic inputs, and selectively respond to changes in internal states. These findings identify molecular mechanisms that control tanycyte-derived neurogenesis, which can potentially be targeted to selectively remodel the hypothalamic neural circuitry that controls homeostatic physiological processes.
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http://dx.doi.org/10.1126/sciadv.abg3777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163082PMC
May 2021

Lovastatin attenuates sevoflurane-induced cognitive disorder in aged rats via reducing Aβ accumulation.

Neurochem Int 2021 Sep 25;148:105078. Epub 2021 May 25.

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China. Electronic address:

As a general anesthetic widely used in surgical, sevoflurane has been shown to cause cognitive and memory deficits in the elderly. It's important to find out agents that can counteract sevoflurane-induced cognitive dysfunction. This study is aimed to investigate the effect of lovastatin on sevoflurane-induced cognitive impairment in aged rats and reveal the potential mechanisms. BV-2 cells, rat hippocampal neurons or male aged rats were exposed to 2% sevoflurane for 5 h. The cells were pretreated with 10 μM lovastatin. The rats were intraperitoneally injected with 5 mg/kg/day lovastatin for three days. The results showed that lovastatin enhanced exosomal IDE secretion from sevoflurane-exposed BV-2 cells and promoted Aβ degradation. Lovastatin treatment also inhibited the increased expressions of β-secretase 1 (BACE1) and γ-secretase in hippocampal neurons under sevoflurane exposure in vitro. In animal experiments, the discrimination index in novel object recognition test and percentage of spontaneous alternation in Y-maze test were significantly elevated after lovastatin administration. In addition, Aβ plaque area and contents of soluble Aβ and Aβ in the hippocampal tissues were decreased upon lovastatin treatment. Furthermore, lovastatin reversed sevoflurane-induced Aβ accumulation via up-regulating IDE expression, and down-regulating amyloid precursor protein (APP)-related protein expression (β-C-terminal fragment (CTF), BACE1 and γ-secretase). In conclusion, lovastatin alleviates sevoflurane-induced cognitive deficient in aged rats via promoting Aβ degradation and reducing Aβ production. Lovastatin may be beneficial in preventing anesthetic-induced cognitive impairment.
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http://dx.doi.org/10.1016/j.neuint.2021.105078DOI Listing
September 2021

Recalcitrant paradoxical pustular psoriasis induced by infliximab: Two case reports.

World J Clin Cases 2021 May;9(15):3655-3661

Department of Dermatology, Midwest Center for Dermatology and Cosmetic Surgery, Clinton Township, MI 48038, United States.

Background: Paradoxical psoriasis induced by tumor necrosis factor alpha antagonists is a rare side effect of those drugs and has similarities with and differences from classical psoriasis in clinical and pathological characteristics. Treating severe paradoxical psoriasis is challenging because the reported cases are rare, with treatment experience being only anecdotal.

Case Summary: We report 2 cases of paradoxical psoriasis caused by infliximab. Both cases manifested with a significant number of pustular lesions and had protracted and complicated clinical courses. In case 1, secukinumab alone could not control the eruptions, but colchicine supplementation markedly decreased disease activity. In case 2 miscellaneous medications were administered, including the systemic drug acitretin, the immunosuppressive drug cyclosporine, and the biologic agent ustekinumab. However, multiple applications of those medications failed to prevent new lesions from occurring. Both cases showed moderate-to-high anti-nuclear antibody titers.

Conclusion: Based on these cases, moderate-to-high anti-nuclear antibody titer seems to be a risk factor for paradoxical psoriasis. In addition, extensive pustular presentation may be a negative prognostic indicator and may portend a protracted clinical course refractory to therapy.
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http://dx.doi.org/10.12998/wjcc.v9.i15.3655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130067PMC
May 2021

Delivery of siHIF-1α to Reconstruct Tumor Normoxic Microenvironment for Effective Chemotherapeutic and Photodynamic Anticancer Treatments.

Small 2021 06 25;17(25):e2100609. Epub 2021 May 25.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, P. R. China.

The tumor hypoxic microenvironment not only induces genetic and epigenetic changes in tumor cells, immature vessels formation for oxygen demand, but also compromises the efficiency of therapeutic interventions. On the other hand, conventional therapeutic approaches which kill tumor cells or destroy tumor blood vessels to block nutrition and oxygen supply usually facilitate even harsher microenvironment. Thus, simultaneously relieving the strained response of tumor cells and blood vessels represents a promising strategy to reverse the adverse tumor hypoxic microenvironment. In the present study, an integrated amphiphilic system (RSCD) is designed based on Angiotensin II receptor blocker candesartan for siRNA delivery against the hypoxia-inducible factor-1 alpha (HIF-1α), aiming at both vascular and cellular "relaxation" to reconstruct a tumor normoxic microenvironment. Both in vitro and in vivo studies have confirmed that the hypoxia-inducible HIF-1α expression is down-regulated by 70% and vascular growth is inhibited by 60%. The "relaxation" therapy enables neovascularization with more complete and organized structures to obviously increase the oxygen level inside tumor, which results in a 50% growth inhibition. Moreover, reconstruction of tumor microenvironment enhances tumor-targeted drug delivery, and significantly improves the chemotherapeutic and photodynamic anticancer treatments.
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http://dx.doi.org/10.1002/smll.202100609DOI Listing
June 2021

Risk factors evaluation of post-transplant lymphoproliferative disorders after allogeneic haematopoietic stem cell transplantation with comparison between paediatric and adult.

J Clin Pathol 2021 May 19. Epub 2021 May 19.

Pathology, Peking University People's Hospital, Beijing, China.

To describe the clincopathological features and evaluate risk factors of post-transplant lymphoproliferative disorder (PTLD) after allogeneic haematopoietic stem cell transplants (allo-HSCT), with comparison between paediatric and adult .Clinicopathological features of 81 cases of PTLD after allo-HSCT were analysed by histopatholgy, immunohistochemistry and in situ hybridisatioin.The cases included 58 males and 23 females with a median age of 26.7 years (range 6-55 years) and the PTLDs developed 1-60 months post-transplant (mean 5.9 months). The histological types indicated 10 cases of non-destructive PTLD, including 4 of plasmacytic hyperplasia, 5 of infectious mononucleosis and 1 of florid follicular hyperplasia. Fifty-six cases were polymorphic PTLD, and 15 were monomorphic PTLD, including thirteen of diffuse large B cell lymphoma, 1 of extranodal nasal type natural killer (NK)/T cell lymphoma and 1 of plasmablastic lymphoma. Foci and sheets of necrosis were observed in 31 cases. The infected ratio of Epstein-Barr virus (EBV) was 91.4%. Some cases were treated by reduction of immunosuppression, antiviral therapy, donor lymphocyte infusion or anti-CD20 monoclonal rituximab. Thirty-three cases died. Compared with that of adult, overall survival of paediatric recipient may be better.The first half year after allo-HSCT is very important for the development of PTLD. Type of PTLD, EBV infection and graft-versus-host disease are risk factors. The prognosis of PTLD is poor, and PTLD after allo-HSCT exhibits some features different from that after solid organ transplantation and some differences existing between adult and paediatric recipients.
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http://dx.doi.org/10.1136/jclinpath-2021-207492DOI Listing
May 2021

Epidemiological and clinical characteristics of suspected COVID-19 patients in the isolation ward in Guangzhou, China: a cohort study.

Ann Transl Med 2021 Apr;9(8):621

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Since there are reports of cases of 2019-coronavirus disease (COVID-19) asymptomatic carriers in China recently and fever is one of the main symptoms, we aimed to distinguish COVID-19 cases from other febrile patients with clinical examinations in this study.

Methods: A total of 134 suspected COVID-19 patients in the isolation ward of the First Affiliated Hospital of Guangzhou Medical University were recruited from January 23 to May 23, 2020. We analyze the pathogenic form and clinical characteristics.

Results: Among them, pathogens were identified in only 84 patients (62.7%), including 23 (17.1%) with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), 30 (22.3%) with other viruses, 31 (25.0%) with other pathogens and 3 (3.5%) with mixed infections. The commonly observed symptoms of COVID-19 patients were cough, fever, fatigue, and muscle aches, which were significantly different than the symptoms of nonviral infections (P<0.05) but from those of other viral infections (P>0.05). Furthermore, lactate dehydrogenase and the neutrophil/lymphocyte were found significantly high in COVID-19 patients compared to non-COVID-19 patients (P<0.05). The most common manifestations of COVID-19 patients were ground-glass opacities (100%) with or without lung consolidation, however, they also often showed involvement of several lobes of both lungs (P<0.05). Due to the clear differential diagnosis, the overall antibiotic use rate was 35.8% (31/87).

Conclusions: When diagnosing COVID-19, infections with other pathogens should not be ignored. Successful pathogen identification will support accurate treatment.
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http://dx.doi.org/10.21037/atm-20-6600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106086PMC
April 2021

Immunosuppression and Neuroinflammation in Stroke Pathobiology.

Exp Neurobiol 2021 Apr;30(2):101-112

Department of Neurosurgery, Wayne State University School of Medicine, Detroit 48201, MI, USA.

Over the preceding decades, there have been substantial advances in our knowledge of the pathophysiology of stroke. One such advance has been an increased understanding of the multifarious crosstalk in which the nervous and immune systems engage in order to maintain homeostasis. By interrupting the immune-nervous nexus, it is thought that stroke induces change in both systems. Additionally, it has been found that both innate and adaptive immunosuppression play protective roles against the effects of stroke. The release of danger-/damage-associated molecular patterns (DAMPs) activates Toll-like receptors (TLRs), contributing to the harmful inflammatory effects of ischemia/reperfusion injury after stroke; the Tyro3, Axl, and MerTK (TAM)/Gas6 system, however, has been shown to suppress inflammation via downstream signaling molecules that inhibit TLR signaling. Anti-inflammatory cytokines have also been found to promote neuroprotection following stroke. Additionally, adaptive immunosuppression merits further consideration as a potential endogenous protective mechanism. In this review, we highlight recent studies regarding the effects and mechanism of immunosuppression on the pathophysiology of stroke, with the hope that a better understanding of the function of both of innate and adaptive immunity in this setting will facilitate the development of effective therapies for post-stroke inflammation.
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http://dx.doi.org/10.5607/en20033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118752PMC
April 2021

Longitudinal virological changes and underlying pathogenesis in hospitalized COVID-19 patients in Guangzhou, China.

Sci China Life Sci 2021 Apr 28. Epub 2021 Apr 28.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been reported. However, the clinical outcome and pathogenesis remain unclear. In this study, we recruited 43 laboratory-confirmed COVID-19 patients. We found that prolonged viral RNA shedding or recurrence mainly occurred in severe/critical patients (P<0.05). The average viral shedding time in severe/critical patients was more than 50 days, and up to 100 days in some patients, after symptom onset. However, chest computed tomography gradually improved and complete absorption occurred when SARS-CoV-2 RT-PCR was still positive, but specific antibodies appeared. Furthermore, the viral shedding time significantly decreased when the A1,430G or C12,473T mutation occurred (P<0.01 and FDR<0.01) and increased when G227A occurred (P<0.05 and FDR<0.05). High IL1R1, IL1R2, and TNFRSF21 expression in the host positively correlated with viral shedding time (P<0.05 and false discovery rate <0.05). Prolonged viral RNA shedding often occurs but may not increase disease damage. Prolonged viral RNA shedding is associated with viral mutations and host factors.
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http://dx.doi.org/10.1007/s11427-020-1921-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093132PMC
April 2021

Economics influences therapy decisions in chronic myeloid leukaemia: should it?

J Cancer Res Clin Oncol 2021 Apr 22. Epub 2021 Apr 22.

Department of Immunology and Inflammation, Centre for Haematology Research, Imperial College London, London, SW7 2AZ, UK.

The question whether economic considerations should influence therapy decisions in persons with chronic myeloid leukaemia (CML) is complex touching on many metrics other than medicine including the perceptions, attitudes, and motivations of physicians, patients, their families, and payors', allocation of health care resources, and others. We discuss metrics whereby physicians, patients, and payors make CML therapy choices in settings where cost and availability are or are not considerations. We conclude that economic considerations strongly influence therapy decisions in CML. Whether this should be so and what impact it has on outcomes is also considered. Absent definitive data proving which therapy strategy is best allowing economic considerations to operate may not be as unreasonable or unethical as it appears. In some settings, it may be the best approach. However, because TKIs markedly prolong survival and may even cure some persons with CML, TKI therapy should be available to everyone with CML.
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http://dx.doi.org/10.1007/s00432-021-03607-5DOI Listing
April 2021

Effects of triangle grass decoction on bone metabolism in rats with chronic kidney disease complicated with mineral and bone abnormalities.

J Ethnopharmacol 2021 Jul 17;275:114126. Epub 2021 Apr 17.

Department of Nephrology, Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan, 528400, China. Electronic address:

Ethnopharmacological Relevance: Triangle grass is a liliaceous Chlorophytum perennial herb of ChlorophytumlaxumR.Br. It is distributed mainly in Guangdong and Guangxi Provinces of China. The initial use of triangle grass was mainly to treat bone pain and swelling caused by a fall injury. Triangle grass tablets (NO. Z20070544) are also used as a preparation in our hospital because of their analgesic, anti-inflammatory, anti-snake venom and microcirculation improvement properties and other pharmacological effects (Mei et al., 2006). Triangle grass tablets have been widely used in our hospital to treat patients with bone pain from chronic kidney disease-mineral and bone disorder (CKD-MBD). However, the effects and mechanism of triangle grass on bone metabolism in chronic kidney disease complicated with mineral and bone abnormalities are unclear.

Aim Of The Study: The aim of the present study was to investigate the effects of a triangle grass decoction on bone metabolism in CKD-MBD rats.

Materials And Methods: CKD-MBD model rats were subjected to 5/6 nephrectomy combined with 0.5 g NaHPO/rat. Serum blood urea nitrogen (BUN), creatinine (Cr), phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels were measured with an automatic biochemical analyser. Bone mineral density was determined with a Viva CT 40 system. Bone morphogenetic protein 7(BMP-7),runt-related transcription factor 2 (Runx2) and Osterix protein levels were measured by Western blot analysis. Kidney, vertebra and thoracic aorta tissue samples were assessed by histopathology and immunohistochemistry (IHC).

Results: The degrees of membrane thickening, necrosis, swelling and cast deposition were significantly reduced in high-dose rats and Low-dose rats. Serum BUN levels were significantly reduced in the Pre-H group (P < 0.05). Hypocalcaemia and hyperphos phataemia were detected in triangle grass (P < 0.05, P < 0.05). In addition, iPTH levels were significantly increased in the Pre-H group (P < 0.05). Alkaline phosphatase (ALP)levels were significantly decreased in the Pre-H group (P < 0.05). The bone mineral density was improved in the Pre-H and Pre-L groups. BMP-7 protein levels were significantly increased in the Pre-H group (P < 0.05). The pathological changes in muscle fibres in the thoracic aorta middle membranes were significantly alleviated in rats in the Pre-H and Pre-L groups. Changes in SM22α and SMα-act in protein levels were significantly attenuated in the Pre-H group (P < 0.05, P < 0.05). Changes in Runx2 and Osterix protein levels were also significantly attenuated in the Pre-H and Pre-L groups (P < 0.05, P < 0.05).

Conclusions: Triangle grass can simultaneously ameliorate vertebral bone loss and abnormal calcification in the thoracic aorta. Triangle grass has a definite effect on bone metabolism disorder in CKD-MBD rats.
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http://dx.doi.org/10.1016/j.jep.2021.114126DOI Listing
July 2021