Publications by authors named "Lingli Zhang"

216 Publications

The clinical characteristics and prognosis of cytogenetically normal AML with single mutations of CEBPA.

Int J Lab Hematol 2021 Jul 3. Epub 2021 Jul 3.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: CEBPA mutation is a common mutation in normal karyotype AML. CEBPAdm AML has been recognized as a separate entity, but there is still controversy to the prognosis of CEBPAsm patients.

Methods: A total of 151 newly diagnosed cytogenetically normal AML patients treated at the Second Hospital Center of Shanxi Medical University from February 2017 to December 2019 were the subjects of the study. According to the number of mutations in the CEBPA gene, the patients were divided into three groups, CEBPAsm, CEBPAdm, and CEBPAwt patients. The clinical characteristics, gene mutations, response, and prognosis were retrospectively compared among the three groups.

Results: CEBPAsm patients had lower hemoglobin values compared to CEBPAdm (P = .049). There was no statistical difference between the CEBPAsm cases and the CEBPAdm cases in the mutation types and the distribution of mutation regions (P > .050). Compared with CEBPAdm, cases with CEBPAsm were more likely associated with multiple other gene mutations (P = .023). Patients with CEBPAdm had a higher CR, ORR, and OS than those CEBPAwt (P < .050). CEBPAsm patients had a similar OS with CEBPAdm and CEBPAwt patients (P = .281). These CEBPAsm patients with VAF<30% had lower OS than the patients with VAF≥30%. FLT3-ITD mutations could reduce CEBPAsm patients' OS (P = .019).

Conclusion: Our data first highlighted the impact of CEBPAsm VAF on OS, and the results showed the lower the VAF was, the shorter the OS tended to. The VAF of CEBPAsm could provide specific significance in some extent for the prognosis of patients.
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http://dx.doi.org/10.1111/ijlh.13612DOI Listing
July 2021

CORO1C is Associated With Poor Prognosis and Promotes Metastasis Through PI3K/AKT Pathway in Colorectal Cancer.

Front Mol Biosci 2021 10;8:682594. Epub 2021 Jun 10.

Department of Pathology, Wannan Medical College, Wuhu, China.

Trophoblast cell surface protein 2 (Trop2) is one of the cancer-related proteins that plays a vital role in biological aggressiveness and poor prognosis of colorectal cancer (CRC). The study of the Trop2 related network is helpful for us to understand the mechanism of tumorigenesis. However, the effects of the related proteins interacting with Trop2 in CRC remain unclear. Here, we found that coronin-like actin-binding protein 1C (CORO1C) could interact with Trop2 and the expression of CORO1C in CRC tissues was higher than that in paracarcinoma tissues. The expression of CORO1C was associated with histological type, lymph node metastasis, distant metastasis, AJCC stage, venous invasion, and perineural invasion. The correlation between CORO1C expression and clinical characteristics was analyzed demonstrating that high CORO1C expression in CRC patients were associated with poor prognosis. Furthermore, CORO1C knockdown could decrease the cell proliferation, colony formation, migration and invasion and tumor growth . The underlying mechanisms were predicted by bioinformatics analysis and verified by Western blotting. We found that PI3K/AKT signaling pathway was significantly inhibited by CORO1C knockdown and the tuomr-promoting role of CORO1C was leastwise partly mediated by PI3K/AKT signaling pathway. Thus, CORO1C may be a valuable prognostic biomarker and drug target in CRC patients.
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http://dx.doi.org/10.3389/fmolb.2021.682594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223509PMC
June 2021

POM121 promotes proliferation and metastasis in non-small-cell lung cancer through TGF-β/SMAD and PI3K/AKT pathways.

Cancer Biomark 2021 Jun 12. Epub 2021 Jun 12.

Department of Oncology, Huaian Hospital of Huaian, Huaian, Jiangsu, China.

Background: Nuclear pore membrane protein 121 (POM121) is a novel biomarker involved in tumorigenesis and metastasis. However, little is known about the role of POM121 in non-small-cell lung cancer (NSCLC).

Objective: The aim of this study was to detect the expression of POM121 in NSCLC and its relationship with clinicopathologic feature and cell biological behavior, and explore the underlying mechanisms.

Methods: The expression of POM121 in NSCLC tissues and para-carcinoma tissues was compared by quantitative real-time PCR and immunohistochemistry analysis. The relationship between POM121 protein and clinicopathological characteristics in NSCLC was investigated. Roles of POM121 in NSCLC cells were investigated by CCK-8 assay, clone formation assay, transwell migration and invasion assay, and in vivo experiments. Variations of signaling pathways were determined by qRT-PCR and Western blot.

Results: The POM121 expression in NSCLC tissues was significantly higher than that in para-carcinoma tissues, both at the mRNA and protein level. The POM121 expression was related to sex, advanced differentiation, tumor diameter, lymph node metastases, distant metastases, American Joint Committee on Cancer (AJCC) stage, venous invasion, and perineural invasion in NSCLC. Kaplan-Meier analysis indicated that NSCLC patients with high POM121 expression had poor overall survival. Downregulation of POM121 inhibited cell proliferation, clone formation, migration and invasion. TGF-β/SMAD and PI3K/AKT pathways were involved in POM121-induced functional changes in NSCLC cells.

Conclusion: POM121 plays an oncogenic role in NSCLC through TGF-β/SMAD and PI3K/AKT pathways. POM121 expression is a potential independent prognostic factor for NSCLC.
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http://dx.doi.org/10.3233/CBM-210001DOI Listing
June 2021

A high-resolution cell atlas of the domestic pig lung and an online platform for exploring lung single-cell data.

J Genet Genomics 2021 Apr 30. Epub 2021 Apr 30.

Institute of Pediatrics, Department of Pediatric Surgery, Shenzhen Children's Hospital, Shenzhen 518038, China; Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. Electronic address:

The genetically engineered pig is regarded as an optimal source of human organs for transplantation and an excellent model for human disease research, given its comparable physiology to human beings. A myriad of single-cell RNA sequencing (scRNA-seq) data on humans has been reported, but such data on pigs are scarce. Here, we apply scRNA-seq technology to study the cellular heterogeneity of 3-month-old pig lungs, generating the single-cell atlas of 13,580 cells covering 16 major cell types. Based on these data, we systematically characterize the similarities and differences in the cellular cross-talk and expression patterns of respiratory virus receptors in each cell type of pig lungs compared with human lungs. Furthermore, we analyze pig lung xenotransplantation barriers and reported the cell-type expression patterns of 10 genes associated with pig-to-human immunobiological incompatibility and coagulation dysregulation. We also investigate the conserved transcription factors (TFs) and their candidate target genes and constructed five conserved TF regulatory networks in the main cell types shared by pig and human lungs. Finally, we present a comprehensive and openly accessible online platform, ScdbLung. Our scRNA-seq atlas of the domestic pig lung and ScdbLung database can guide pig lung research and clinical applicability.
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http://dx.doi.org/10.1016/j.jgg.2021.03.012DOI Listing
April 2021

Development of an evaluation indicator system for the rational use of proton pump inhibitors in pediatric intensive care units: An application of Delphi method.

Medicine (Baltimore) 2021 Jun;100(24):e26327

Department of Pharmacy.

Abstract: Proton pump inhibitors are frequently used to prevent gastrointestinal bleeding in critically ill patients. But there is little information in the instructions about the usages for children. It is important to monitor the appropriate use of proton pump inhibitors, especially in pediatrics. Therefore, we developed an evaluation indicator system for the rational use of proton pump inhibitors in pediatric intensive care units.First, a systematic review was conducted to developed the initial indicators. Then 2 rounds of Delphi surveys were conducted to collecting opinions from a panel of independent experts, and the indicator system was modified to form the final indicators according to the opinions. Finally, the analytic hierarchy procedure was used to determine the weight of each indicator.A total of 6 guidelines and 2 studies met the inclusion and exclusion criteria. Based on literature and discussion among experts, an initial indicator system including 4 first-rank indicators and 12 second-rank indicators was formed. After 2 rounds of Delphi surveys, 2 indicators were added, 5 indicators were deleted, and 1 indicator was revised, so the final indicator system contained a total of 13 indicators including 3 first-rank indicators (drug selection, drug usage and dosage, duration of drug therapy) and 10 second-rank indicators (the proportion of PPIs used in children, children under 1 year old, children who is using glucocorticoids, children with nonsteroidal anti-inflammatory drugs, children with gastroesophageal reflux disease, children with sepsis, children with ventilators in PICU; the strength of PPIs' use, the proportion of omeprazole in children using PPIs during the same period; the average days of PPIs used in children). By analyzing scores, all coefficients met the standard, indicating the indicators were scientific and credible.Through a two-round Delphi survey, 3 first-rank indicators and ten second-rank indicators were developed, which will help drug administrative departments to promote the rational use of PPIs for children in PICUs. What is more, our study can constitute a methodological reference for the development of other indicator systems.
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http://dx.doi.org/10.1097/MD.0000000000026327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213291PMC
June 2021

Impacts of Diagnosis-Related Groups Payment on the Healthcare Providers' Behavior in China: A Cross-Sectional Study Among Physicians.

Risk Manag Healthc Policy 2021 1;14:2263-2276. Epub 2021 Jun 1.

College of Business Administration, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.

Purpose: Currently, China is piloting diagnosis-related groups (DRG) payment system in 30 cities. The main aim of this study was to explore the respondents' impressions regarding the hospitals' policies and physicians' behavior change brought by the DRG payment system, and investigate whether and how the hospitals' policies affect the physicians' behavior.

Methods: We distributed questionnaires designed for this study to 200 physicians. Data analysis consisted of descriptive statistics, -test, and network analysis.

Results: Respondents stated that the hospitals had adopted several policies in response to DRG payment and DRG payment could reduce overtreatment and improve efficiency. However, it also led to several negative effects including an increased explanation to the patients, hindering new technologies, case splitting, and cherry picking. In addition, there was no evidence that harmful effects such as refusing patients and premature discharge existed. Overall, the benefits outweighed the drawbacks of DRG. Moreover, the hospitals' policies could effectively change physician behaviors. Our results indicated that promoting the implementation of clinical pathways had the most positive impact, while limiting costs and length of stay is not recommended.

Conclusion: In general, Chinese physicians who participated in the questionnaire possessed relatively positive attitudes towards the DRG payment system. Nevertheless, some of the negative impacts cannot be ignored. Meanwhile, the hospitals' policies should be implemented with adequate consideration of the impact on physicians' behavior.
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http://dx.doi.org/10.2147/RMHP.S308183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180304PMC
June 2021

The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation.

Cell Biosci 2021 May 17;11(1):88. Epub 2021 May 17.

School of Physical Education & Sports Science, South China Normal University, 55 Zhongshan Road West, Tianhe District, Guangzhou, 510631, Guangdong, China.

Bone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.
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http://dx.doi.org/10.1186/s13578-021-00601-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130302PMC
May 2021

Total variation with modified group sparsity for CT reconstruction under low SNR.

Authors:
Lingli Zhang

J Xray Sci Technol 2021 Apr 26. Epub 2021 Apr 26.

Chongqing Key Laboratory of Complex Data Analysis & Artificial Intelligence, Chongqing University of Arts and Sciences, Chongqing, China.

Background And Objective: Since the stair artifacts may affect non-destructive testing (NDT) and diagnosis in the later stage, an applicable model is desperately needed, which can deal with the stair artifacts and preserve the edges. However, the classical total variation (TV) algorithm only considers the sparsity of the gradient transformed image. The objective of this study is to introduce and test a new method based on group sparsity to address the low signal-to-noise ratio (SNR) problem.

Methods: This study proposes a weighted total variation with overlapping group sparsity model. This model combines the Gaussian kernel and overlapping group sparsity into TV model denoted as GOGS-TV, which considers the structure sparsity of the image to be reconstructed to deal with the stair artifacts. On one hand, TV is the accepted commercial algorithm, and it can work well in many situations. On the other hand, the Gaussian kernel can associate the points around each pixel. Quantitative assessments are implemented to verify this merit.

Results: Numerical simulations are performed to validate the presented method, compared with the classical simultaneous algebraic reconstruction technique (SART) and the state-of-the-art TV algorithm. It confirms the significantly improved SNR of the reconstruction images both in suppressing the noise and preserving the edges using new GOGS-TV model.

Conclusions: The proposed GOGS-TV model demonstrates its advantages to reduce stair artifacts especially in low SNR reconstruction because this new model considers both the sparsity of the gradient image and the structured sparsity. Meanwhile, the Gaussian kernel is utilized as a weighted factor that can be adapted to the global distribution.
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http://dx.doi.org/10.3233/XST-200833DOI Listing
April 2021

The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18-59 years: A phase I randomized, double-blinded, controlled trial.

Vaccine 2021 05 9;39(20):2746-2754. Epub 2021 Apr 9.

Institute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development for Severe Infectious Diseases, Kunming 650118, China.

Background: This study examined the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine.

Method: In a phase I randomized, double-blinded, placebo-controlled trial involving 192 healthy adults 18-59 years old, two injections of three doses (50 EU, 100 EU, 150 EU) of an inactivated SARS-CoV-2 vaccine or placebo were administered intramuscularly at a 2- or 4-week interval. The safety and immunogenicity of the vaccine were evaluated.

Results: Vaccination was completed in 191 subjects. Forty-four adverse reactions occurred within 28 days, most commonly mild pain and redness at the injection site or slight fatigue. At days 14 and 28, the seroconversion rates were 87.5% and 79.2% (50 EU), 100% and 95.8% (100 EU), and 95.8% and 87.5% (150 EU), respectively, with geometric mean titers (GMTs) of 18.1 and 10.6, 54.5 and 15.4, and 37.1 and 18.5, respectively, for the schedules with 2-week and 4-week intervals. Seroconversion was associated with synchronous upregulation of antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. No cytokines and immune cells related to immunopathology were observed. Transcriptome analysis revealed the genetic diversity of immune responses induced by the vaccine.

Interpretation: In a population aged 18-59 years in this trial, this inactivated SARS-CoV-2 vaccine was safe and immunogenic.

Trial Registration: CTR20200943 and NCT04412538.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040531PMC
May 2021

Prevalence and influencing factors of depression of caregivers in children with epilepsy in southwestern China: a cross-sectional study.

Medicine (Baltimore) 2021 Mar;100(10):e23571

Department of Pharmacy, Evidence-based Pharmacy Center, West China second hospital, Sichuan University. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education.

Abstract: This study investigated the epidemiological status of depression and its influencing factors among caregivers of children with epilepsy in southwestern China.This was a cross-sectional study. Caregivers of children with epilepsy were recruited from February to June 2018 at the Pediatric Neurology Department of the West China Second Hospital. Depression status was assessed using the Zung Self-Rating Depression Scale. Multiple linear regression analysis was used to assess correlations between depression status and its influencing factors.A total of 319 participants were included. The mean Zung Self-Rating Depression Scale score was 36.37 ± 10.178 and 5.3% (17/319) of participants were classified as depressed. Regression analysis showed that place of residence (B = 0.114; standard error = 0.643; P = .039), attitude towards seizures (B = -0.121; standard error = 1.215; P = .029), medical expenses payment (B = -0.111; standard error = 2.002; P = .044), and children's medication adherence (B = -0.124; standard error = 0.393; P = .025) were related to depression.Some caregivers of children with epilepsy in southwestern China experience depression. Health care providers should pay particular attention to caregivers who live in rural areas, who fear seizures, who experience difficulty paying medical expenses, and whose children show low medication adherence.
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http://dx.doi.org/10.1097/MD.0000000000023571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969277PMC
March 2021

A 12-genus bacterial signature identifies a group of severe autistic children with differential sensory behavior and brain structures.

Clin Transl Med 2021 02;11(2):e314

Department of Developmental and Behavioural Pediatric & Child Primary Care, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.1002/ctm2.314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893807PMC
February 2021

An overview of the characteristics and quality assessment criteria in systematic review of pharmacoeconomics.

PLoS One 2021 8;16(2):e0246080. Epub 2021 Feb 8.

Department of Pharmacy/Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.

Background: The systematic review of economic evaluations plays a critical role in making well-informed decisions about competing healthcare interventions. The quality of these systematic reviews varies due to the lack of internationally recognized methodological evaluation standards.

Methods: Nine English and Chinese databases including the Cochrane Library, PubMed, EMbase (Ovid), NHS economic evaluation database (NHSEED) (Ovid), Health Technology Assessment (HTA) database, Chinese National Knowledge Infrastructure (CNKI), WangFang, VIP Chinese Science & Technology Periodicals (VIP) and Chinese Biomedical Literature Database (CBM) were searched. Two reviewers independently screened studies and extracted data. The methodological quality of the literature was measured with modified AMSTAR. Data were narrative synthesized.

Results: 165 systematic reviews were included. The overall methodological quality of the literature was moderate according to the AMSTAR scale. In these articles, thirteen quality assessment tools and 32 author self-defined criteria were used. The three most widely used tools were the Drummond checklist (19.4%), the BMJ checklist (15.8%), the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement (12.7%). Others included the Quality of Health Economic Studies (QHES), the Consensus on Health Economic Criteria (CHEC), the checklist of Center for Reviews and Dissemination (CRD), the Philips checklist, the World Health Organization (WHO) checklist, the checklist of Critical Appraisal Skills Program (CASP), the Pediatric Quality Appraisal Questionnaire (PQAQ), the Joanna Briggs Institute (JBI) checklist, Spanish and Chinese guidelines. The quantitative scales used in these literature were the QHES and PQAQ.

Conclusions: Evidence showed that pharmacoeconomic systematic reviews' methodology remained to be improved, and the quality assessment criteria were gradually unified. Multiple scales can be used in combination to evaluate the quality of economic research in different settings and types.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246080PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870091PMC
July 2021

Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy.

Diabetes Metab Syndr Obes 2021 18;14:227-240. Epub 2021 Jan 18.

Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People's Republic of China.

Background: Abnormal lipid deposition in the progress of diabetic nephropathy (DN) plays an important role in a number of studies that have shown that SGLT2 inhibitor (SGLT2i) empagliflozin plays an important role in lipid metabolism, but its mechanism is still unclear.

Methods: We aimed to explore the effect of empagliflozin on lipid levels in kidney cancer patients with DN and postoperative patients without DN kidney carcinoma; the patients with DN showed ectopic lipid deposition. In type 2 diabetes model mice induced by streptozotocin (STZ) and a high-fat diet, combined AMPK plus empagliflozin or empagliflozin inhibitor plus compound C was applied, followed by analyses of the blood, urine and kidney indexes to observe the correlation between SGLT2i and AMPK and lipid metabolism in diabetic kidney disease. We determined whether DN in patients with renal tubular atrophy involved lipid metabolism.

Results: In clinical specimens, the adiponectin receptor AdipoR1 was reduced, and the phosphorylation acetyl-CoA carboxylase (p-ACC) was increased. In vitro and in vivo pathological immunofluorescence and Western blotting confirmed that, under the condition of high glucose, malpighian tubules displayed ectopic lipid deposition and expressed related lipid parameters accompanied by fibrosis. Empagliflozin intervention reduced lipid deposition fibrosis and renal tubular atrophy, and the addition of compound C promoted disease progression. Moreover, siAdipoR1 transfection proved that AdipoR1 affected P-AMPK and then p-ACC affected lipid metabolism in renal tubular cells.

Conclusion: According to the above experimental results, empagliflozin could reduce lipid metabolism of DN through AdipoR1/P-AMPK/P-ACC pathway and delay DN progress.
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http://dx.doi.org/10.2147/DMSO.S289712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822229PMC
January 2021

Use of tyrosine kinase inhibitors for paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia: a systematic review and meta-analysis.

BMJ Open 2021 01 19;11(1):e042814. Epub 2021 Jan 19.

Department of Pharmacy/Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

Objectives: To investigate the effectiveness and safety of tyrosine kinase inhibitors (TKIs) in the management of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL).

Design: A systematic review and meta-analysis.

Data Sources: Electronic searches were conducted on CENTRAL, MEDLINE, EMBASE, SIOP, ASPHO, ASCO, ASH and four Chinese databases from inception to 8 March 2020. Language of publications was restricted in English and Chinese.

Eligibility Criteria: Prospective and retrospective comparative studies were included.

Data Extraction And Synthesis: Two authors independently assessed and extracted data. Quality of studies was assessed by the Cochrane Collaboration's tool and Newcastle-Ottawa Scale. Subgroup analysis was performed by comparing different types of TKIs. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results: Two randomised controlled trials (RCTs) and four cohort studies enrolling 536 patients were included. For RCTs, the pooled HR was 0.68 (95% CI 0.26 to 1.78) in overall survival (OS), 0.63 (95% CI 0.28 to 1.42) in event-free survival (EFS), respectively, comparing TKI arm with non-TKI arm for treatment of paediatric Ph+ALL. There was significant difference in OS and EFS between imatinib arm and dasatinib arm (HR 2.26, 95% CI 1.02 to 5.01; HR 2.36; 95% CI 1.27 to 4.39, respectively). For cohort studies, the pooled HR was 0.25 (95% CI 0.14 to 0.47) in OS, 0.25 (95% CI 0.12 to 0.56) in EFS, respectively, comparing TKI arm with non-TKI arm. There was no significance difference in adverse drug reaction between TKI group and without TKI group (risk ratio (RR) 0.82, 95% CI 0.63 to 1.08 in RCT; RR 1.01, 95% CI 0.64 to 1.59 in cohort studies; respectively), and imatinib versus dasatinib (RR 0.97, 95% CI 0.77 to 1.23). The quality of evidence was rated as low for OS, EFS and adverse drug reaction (ADR).

Conclusions: The combination of TKIs with chemotherapy is likely to improve the OS and EFS rates in paediatric Ph+ALL, and dasatinib is superior than imatinib. Large sample size and prospective controlled studies are warranted.

Prospero Registration Number: CRD42018104107.
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http://dx.doi.org/10.1136/bmjopen-2020-042814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817804PMC
January 2021

The efficacy and safety of prokinetics in critically ill adults receiving gastric feeding tubes: A systematic review and meta-analysis.

PLoS One 2021 11;16(1):e0245317. Epub 2021 Jan 11.

Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Background: Intolerance to gastric feeding tubes is common among critically ill adults and may increase morbidity. Administration of prokinetics in the ICU is common. However, the efficacy and safety of prokinetics are unclear in critically ill adults with gastric feeding tubes. We conducted a systematic review to determine the efficacy and safety of prokinetics for improving gastric feeding tube tolerance in critically ill adults.

Methods: Randomized controlled trials (RCTs) were identified by systematically searching the Medline, Cochrane and Embase databases. Two independent reviewers extracted the relevant data and assessed the quality of the studies. We calculated pooled relative risks (RRs) for dichotomous outcomes and the mean differences (MDs) for continuous outcomes with the corresponding 95% confidence intervals (CIs). We assessed the risk of bias using the Cochrane risk-of-bias tool and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to rate the quality of the evidence.

Results: Fifteen RCTs met the inclusion criteria. A total of 10 RCTs involving 846 participants were eligible for the quantitative analysis. Most studies (10 of 13, 76.92%) showed that prokinetics had beneficial effects on feeding intolerance in critically ill adults. In critically ill adults receiving gastric feeding, prokinetic agents may reduce the ICU length of stay (MD -2.03, 95% CI -3.96, -0.10; P = 0.04; low certainty) and the hospital length of stay (MD -3.21, 95% CI -5.35, -1.06; P = 0.003; low certainty). However, prokinetics failed to improve the outcomes of reported adverse events and all-cause mortality.

Conclusion: As a class of drugs, prokinetics may improve tolerance to gastric feeding to some extent in critically ill adults. However, the certainty of the evidence suggesting that prokinetics reduce the ICU or hospital length of stay is low. Prokinetics did not significantly decrease the risks of reported adverse events or all-cause mortality among critically ill adults.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245317PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799841PMC
May 2021

Identification and validation of genetic locus Rfk1 for wheat fertility restoration in the presence of Aegilops kotschyi cytoplasm.

Theor Appl Genet 2021 Mar 3;134(3):875-885. Epub 2021 Jan 3.

College of Agronomy, Northwest A&F University, Yangling, Shaanxi, China.

Key Message: Major fertility restorer locus for Aegilops kotschyi cytoplasm in wheat, Rfk1, was mapped to chromosome arm 1BS. Most likely candidate gene is TraesCS1B02G197400LC, which is predicted to encode a pectinesterase/pectinesterase inhibitor. Cytoplasmic male sterility (CMS) is widely used for heterosis and hybrid seed production in wheat. Genes related to male fertility restoration in the presence of Aegilops kotschyi cytoplasm have been reported, but the fertility restoration-associated gene loci have not been investigated systematically. In this study, a BCF population derived from a backcross between KTP116A, its maintainer line TP116B, and its restorer line LK783 was employed to map fertility restoration by bulked segregant RNA-Seq (BSR-Seq). A major fertility allele restorer locus for Ae. kotschyi cytoplasm in wheat, Rfk1, was mapped to chromosome arm 1BS, and it was contributed by LK783. Morphological and cytological studies showed that male fertility restoration occurred mainly after the late uninucleate stage. Based on simple sequence repeat and single-nucleotide polymorphism genotyping, the gene locus was located between Xnwafu_6 and Xbarc137 on chromosome arm 1BS. To further isolate the specific region, six Kompetitive allele-specific polymerase chain reaction markers derived from BSR-Seq were developed to delimit Rfk1 within physical intervals of 26.0 Mb. After searching for differentially expressed genes within the candidate interval in the anthers and sequencing analysis, TraesCS1B02G197400LC was identified as a candidate gene for Rfk1 and it was predicted to encode a pectinesterase/pectinesterase inhibitor. Expression analysis also confirmed that it was specifically expressed in the anthers, and its expression level was higher in fertile lines compared with sterile lines. Thus, TraesCS1B02G197400LC was identified as the most likely candidate gene for Rfk1, thereby providing insights into the fertility restoration mechanism for K-type CMS in wheat.
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http://dx.doi.org/10.1007/s00122-020-03738-2DOI Listing
March 2021

Medium-Intensity Treadmill Exercise Exerts Beneficial Effects on Bone Modeling Through Bone Marrow Mesenchymal Stromal Cells.

Front Cell Dev Biol 2020 24;8:600639. Epub 2020 Nov 24.

School of Kinesiology, Shanghai University of Sport, Shanghai, China.

As a type of multipotential cells, bone marrow mesenchymal stromal cells (BMMSCs) can differentiate into chondrocytes, osteoblasts, and adipocytes under different loading condition or specific microenvironment. Previous studies have shown that BMMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. The appropriate physical activity and exercise could help attenuate bone loss, effectively stimulate bone formation, increase bone mineral density (BMD), prevent the progression of osteoporosis, and reduce the risk of bone fractures. Bone morphogenetic protein (BMP) is originally discovered as a protein with heterotopic bone-inducing activity in the bone matrix that exerts a critical role in multiple stages of bone metabolism. In the present study, the medium-intensity treadmill exercise enhanced bone formation and increased and mRNA expression as well as activation of the BMP-Smad signaling pathway . In order to investigate the effect of a BMP-Smad signaling pathway, we injected mice with activated enzyme inhibitors (LDN-193189HCL) and subjected the mice to treadmill exercise intervention. LDN-193189HCL attenuated the BMD and bone mass mediated by medium-intensity exercise and BMP-Smad signaling pathway.
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http://dx.doi.org/10.3389/fcell.2020.600639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732523PMC
November 2020

An instrument for evaluating the clinical applicability of guidelines.

J Evid Based Med 2020 Oct 14. Epub 2020 Oct 14.

Department of Pharmacy/Evidence-Based Pharmacy Centre, West China Second University Hospital, Sichuan University, Chengdu, P.R. China.

Objective: To establish an instrument for evaluating the clinical applicability of guidelines from the guideline-users' perspective.

Methods: We established this instrument through forming a working group, forming an initial list of items based on a qualitative systematic review, establishing initial instrument via two rounds of modified Delphi surveys, and external review the initial instrument.

Results: The results of modified Delphi surveys establishing appraisal aspects, appraisal items, general information of the evaluator met the preset requirements. The instrument includes three parts: general information of the evaluator (12 items), evaluation of clinical applicability (12 items, including items on the availability, readability, acceptability, feasibility, and overall applicability of guideline), and scoring scheme.

Conclusions: The instrument for evaluating the clinical applicability of guidelines from the guideline-users' perspective provides criteria and methods for improving the clinical applicability of guidelines during development and updating.
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http://dx.doi.org/10.1111/jebm.12416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984040PMC
October 2020

Monitoring Treatment-Free Remission by Droplet Digital PCR in CML Patients with Deep Molecular Response to Tyrosine Kinase Inhibitor: An Analysis Based on Real-World Data.

Ann Clin Lab Sci 2020 Sep;50(5):591-599

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, China

Treatment-free remission (TFR) is emerging as a new therapy goal for chronic myeloid leukemia (CML) patients in the tyrosine kinase inhibitors (TKI) era. Data indicates the unfavorable success rate of TFR. This study aimed to compare and evaluate the clinical value of dd-PCR in predicting relapse in CML patients entering TFR. Using dd-PCR and RT-qPCR technology, dynamic BCR/ABL transcripts were detected in 13 CML patients who discontinued TKI treatment after sustaining undetectable BCR-ABL levels for a median time of 25 months. The results showed that in 13 patients, only 2 cases (22.2%) of 9 patients who executed planned discontinuation achieved TFR within 12 months. In the first 6 months, the detection rate of BCR/ABL transcripts by dd-PCR was higher than that by RT-qPCR and the two methods kept a positive correlation (r=0.9651, =0.0349). Meanwhile, the time of detectable BCR/ABL by dd-PCR were significantly shorter (<0.05), which was an average of 2.98 months earlier than RT-qPCR. The total TKI therapy and MR4.5 duration time related with TFR were longer in patients with intermediate or high Sokal risk scores (<0.05). The dd-PCR could be more sensitive than RT-qPCR for monitoring BCR/ABL transcripts of CML patients with deep molecular response to TKI. The technique can be used as a preferred method to detect the transcripts in the first 6 months after TKI cessation.
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September 2020

PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer.

Int J Nanomedicine 2020 28;15:7173-7184. Epub 2020 Sep 28.

Department of Orthopedic Surgery, Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangzhou, Guangdong Province 510080, People's Republic of China.

Objective: This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro.

Methods: A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG. The obtained HPAA-PEG-APT could form nanocomplexes with through electrostatic adsorption.

Results: The results of immunocytochemistry indicated that the complexes could target PSMA-expressing LNCaP cells. The ability of HPAA-PEG-APT to facilitate the delivery of into LNCaP cells was proven, and HPAA-PEG-APT/ demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/ complex significantly inhibited cancer growth and extended the survival time.

Conclusion: This study provided an aptamer-anchored HPAA-loaded gene system to deliver for better therapeutic efficacy of bone metastasis of prostate cancer.
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http://dx.doi.org/10.2147/IJN.S268398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533908PMC
December 2020

Association between childhood trauma and risk for obesity: a putative neurocognitive developmental pathway.

BMC Med 2020 10 15;18(1):278. Epub 2020 Oct 15.

Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, 200433, People's Republic of China.

Background: Childhood trauma increases the risk for adult obesity through multiple complex pathways, and the neural substrates are yet to be determined.

Methods: Participants from three population-based neuroimaging cohorts, including the IMAGEN cohort, the UK Biobank (UKB), and the Human Connectome Project (HCP), were recruited. Voxel-based morphometry analysis of both childhood trauma and body mass index (BMI) was performed in the longitudinal IMAGEN cohort; validation of the findings was performed in the UKB. White-matter connectivity analysis was conducted to study the structural connectivity between the identified brain region and subdivisions of the hypothalamus in the HCP.

Results: In IMAGEN, a smaller frontopolar cortex (FPC) was associated with both childhood abuse (CA) (β = - .568, 95%CI - .942 to - .194; p = .003) and higher BMI (β = - .086, 95%CI - .128 to - .043; p < .001) in male participants, and these findings were validated in UKB. Across seven data collection sites, a stronger negative CA-FPC association was correlated with a higher positive CA-BMI association (β = - 1.033, 95%CI - 1.762 to - .305; p = .015). Using 7-T diffusion tensor imaging data (n = 156), we found that FPC was the third most connected cortical area with the hypothalamus, especially the lateral hypothalamus. A smaller FPC at age 14 contributed to higher BMI at age 19 in those male participants with a history of CA, and the CA-FPC interaction enabled a model at age 14 to account for some future weight gain during a 5-year follow-up (variance explained 5.8%).

Conclusions: The findings highlight that a malfunctioning, top-down cognitive or behavioral control system, independent of genetic predisposition, putatively contributes to excessive weight gain in a particularly vulnerable population, and may inform treatment approaches.
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http://dx.doi.org/10.1186/s12916-020-01743-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559717PMC
October 2020

POM121 is a novel marker for predicting the prognosis of laryngeal cancer.

Histol Histopathol 2020 Nov 5;35(11):1285-1293. Epub 2020 Oct 5.

Department of Oncology, Huaian Hospital, Huaian, China.

The nuclear pore membrane protein 121 (POM121) is an important member of the nuclear pore complex which regulates nucleocytoplasmic transport, but little is known about the role of POM121 in laryngeal cancer. In this study, quantitative real-time polymerase chain reaction and immunohistochemistry were performed to detect POM121 expression in laryngeal tissues. The associations between POM121 and clinicopathological characteristics and overall survival in laryngocarcinoma patients were also analyzed. The mechanism of POM121 was preliminarily explored through gene set enrichment analysis (GSEA). mRNA and protein expression of POM121 in laryngocarcinoma tissues were higher than those in nontumor tissues. High POM121 expression was positively correlated with poor differentiation (χ²=42.391, P<0.001), advanced distant metastases (χ²=20.346, P<0.001) and TNM stage (χ²=23.436, P<0.001). Laryngocarcinoma patients with high POM121 level tended to have poor overall survival. GSEA confirmed that the mechanism of POM121 in laryngeal cancer may relate to sphingolipid metabolism, lysosome, fatty acid metabolism, ribosome, nucleotide excision repair and the PPAR signaling pathway. Overall, POM121 expression might be a prognostic biomarker in laryngeal cancer, and POM121 has the potential to present as a therapeutic target for laryngocarcinoma patients.
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http://dx.doi.org/10.14670/HH-18-267DOI Listing
November 2020

Corrigendum to "Adverse impact of ambient PM2.5 on expression and trafficking of surfactant protein A through reactive oxygen species damage to lamellar bodies" [Toxicology Letters 315 (2019) 47-54].

Toxicol Lett 2020 Oct 13;333:326. Epub 2020 Sep 13.

Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China; Department of Hematology and Oncology, Institute of Pediatrics, Shenzhen Children's Hospital, 518038, China. Electronic address:

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http://dx.doi.org/10.1016/j.toxlet.2020.09.001DOI Listing
October 2020

Immunonutrition for traumatic brain injury in children and adolescents: protocol for a systematic review and meta-analysis.

BMJ Open 2020 09 3;10(9):e037014. Epub 2020 Sep 3.

Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China

Introduction: Traumatic brain injury (TBI) is the leading cause of paediatric trauma death and disability worldwide. The 'Guidelines for the Management of Severe Traumatic Brain Injury (Fourth Edition)' recommend that nutritional goals should be achieved within 5-7 days of injury. Immune-enhancing nutrition or immunonutrition, referring to the addition of specialised nutrients, including glutamine, alanine, omega-3 fatty acids and nucleotides, to standard nutrition formulas, may improve surgical outcomes in the perioperative period. However, the role of immune-enhancing nutritional supplements for patients with paediatric TBI remains unclear. We will conduct a systematic review to determine the efficacy and safety of immunonutrition for patients with paediatric TBI and provide evidence for clinical decision-making.

Methods And Analysis: Studies reporting immune-enhancing nutrition treatments for patients with paediatric TBI will be included. Outcomes of interest include the length of hospital stay, wound infections, all-cause mortality, non-wound infection, including pneumonia, urinary tract infection and bacteraemia, and the reports adverse events. Duration of follow-up has no restriction. Primary studies consisting of randomised controlled trials (RCTs) and non-RCTs will be eligible for this review, and only studies published in English will be included. We will search the Medline, Embase and Cochrane Library databases from their inception dates to January 2020. We will also search clinicaltrials.gov and the WHO International Clinical Trials Registry Platform for additional information. Two reviewers will independently select studies and extract data. Risk-of-bias will be assessed with tools based on the Cochrane risk-of-bias criteria and Newcastle-Ottawa Quality Assessment Scale. A meta-analysis will be used to pool data when there are sufficient studies with homogeneity. Heterogeneity of the estimates across studies will be assessed; if necessary, a subgroup analysis will be performed to explore the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the level of evidence obtained from this systematic review.

Ethics And Dissemination: The proposed systematic review and meta-analysis will be based on published data, and thus ethical approval is not required. The results of this review will be published.

Prospero Registration Number: CRD42020154814.
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http://dx.doi.org/10.1136/bmjopen-2020-037014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473625PMC
September 2020

The transcriptional factor GATA-4 negatively regulates Hsp70 transcription in Crassostrea hongkongensis.

Mol Biol Rep 2020 Sep 3;47(9):7107-7114. Epub 2020 Sep 3.

Department of Ecology, Institute of Hydrobiology, School of Life Science and Technology, Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, Engineering Research Center of Tropical and Subtropical Aquatic Ecological Engineering, Ministry of Education, Jinan University, Guangzhou, 510632, People's Republic of China.

To better explore the application potential of heat shock protein Hsp70s in diverse areas including biomonitoring, a further investigation of the details of the regulatory mechanism governing Hsp70 transcription is required. A transcriptional factor ChGATA-4 that displayed affinity to the ChHsp70 promoter of Crassostrea hongkongensis was isolated and identified by DNA affinity purification as well as mass spectrometry analysis. The ChGATA-4 cDNA is 2162 bp in length and the open reading frame encodes a polypeptide containing 482 amino acids with a conserved zinc finger domain. The over-expression of ChGATA-4 significantly inhibited the expression of ChHsp70 promoter in heterologous HEK293T cells. However, the depletion of ChGATA-4 mRNA by RNAi technique resulted in significant increase of ChHsp70 transcription in oyster hemocytes. The RT-PCR results demonstrated that the transcription of both ChHsp70 and ChGATA-4 were induced by heat, Cd, or NP (Nonyl phenol) stress. This suggested a potential correlation between ChHsp70 and ChGATA-4 in the stress-mediated genetic regulatory cascade. This study demonstrated that ChGATA-4 acts in a negative manner in controlling ChHsp70 transcription in C. hongkongensis and promotes to further understand the mechanisms leading Hsp70 transcription.
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http://dx.doi.org/10.1007/s11033-020-05778-9DOI Listing
September 2020

Reconsolidation of a post-ingestive nutrient memory requires mTOR in the central amygdala.

Mol Psychiatry 2020 Sep 1. Epub 2020 Sep 1.

Developmental and Behavioral Pediatric Department, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Institute for Pediatric Research, Xin Hua Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

The central control of feeding behavior and metabolic homeostasis has been proposed to involve a form of post-ingestive nutrient learning independent of the gustatory value of food. However, after such learning, it is unknown which brain regions or circuits are activated to retrieve the stored memory and whether this memory undergoes reconsolidation that depends on protein synthesis after its reactivation through retrieval. In the present study, using a conditioned-flavor-preference paradigm by associating flavors with intra-gastric infusion of glucose to minimize the evaluation of the taste of food, we show that retrieval of the post-ingestive nutrient-conditioned flavor memory stimulates multiple brain regions in mice, including the central nucleus of the amygdala (CeA). Moreover, memory retrieval activated the mammalian target of rapamycin complex 1 (mTORC1) in the CeA, while site-specific or systemic inhibition of mTORC1 immediately after retrieval prevented the subsequent expression of the post-ingestive nutrient-associated flavor memory, leading to a long-lasting suppression of reinstatement. Taken together, our findings suggest that the reconsolidation process of a post-ingestive nutrient memory modulates food preferences.
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http://dx.doi.org/10.1038/s41380-020-00874-5DOI Listing
September 2020

An empirical study on the index system of rational drug use in children with primary nephrotic syndrome: A cross-sectional study.

Medicine (Baltimore) 2020 Aug;99(32):e21564

Department of Pharmacy.

In the study's early stage, the research group had established an evaluation index system for the rational drug use of primary nephrotic syndrome in children. To assess the feasibility of the established index system, we conducted this empirical study.The cross-sectional study was conducted by using the Hospital Information System to extract some general clinical data of hospitalized children with primary nephrotic syndrome, which included registration number, age, sex, diagnosis and medication, etc. Utilize the SPSS23.0 software and Excel 2016 to descriptively analyze information.224 hospitalized children with primary nephrotic syndrome who met the inclusion criteria were included, ranging from 18 years old and 10 months to 11 months and 23 days, with an average age of 8.40, plus or minus 4.30 years. 148 males (66.07%) and 76 females (33.93%). The duration of hospitalization was 1-57 days, with an average hospitalization time of 10.59 days. The most common is respiratory infections, such as the bronchopneumonia, the mycoplasma pneumonia, etc. This study had successfully completed the measurement of the evaluation index system for the rational drug use of primary nephrotic syndrome in children.All indicators are feasible, but the operability and applicability need further research and improvement.
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http://dx.doi.org/10.1097/MD.0000000000021564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593002PMC
August 2020

Rituximab for treating inhibitors in people with inherited severe hemophilia.

Cochrane Database Syst Rev 2020 08 3;8:CD010810. Epub 2020 Aug 3.

Association for the Promotion of Multimedia Education, Zagreb, Croatia.

Background: Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. This is an update of a previously published Cochrane Review.

Objectives: To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B.

Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies. We also undertook further searches of other bibliographic databases and trial registries. Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 19 March 2020.

Selection Criteria: Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia.

Data Collection And Analysis: No randomized controlled trials matching the selection criteria were eligible for inclusion.

Main Results: No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified.

Authors' Conclusions: We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.
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http://dx.doi.org/10.1002/14651858.CD010810.pub4DOI Listing
August 2020

Comprehensive analysis of polygalacturonase gene family highlights candidate genes related to pollen development and male fertility in wheat (Triticum aestivum L.).

Planta 2020 Aug 1;252(2):31. Epub 2020 Aug 1.

College of Agronomy, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Main Conclusion: Four polygalacturonase gene family members were highlighted that contribute to elucidate the roles of polygalacturonase during the fertility conversion process in male-sterile wheat. Polygalacturonase (PG) belongs to a large family of hydrolases with important functions in cell separation during plant growth and development via the degradation of pectin. Specific expressed PGs in anthers may be significant for male sterility research and hybrid wheat breeding, but they have not been characterized in wheat (Triticum aestivum L.). In this study, we systematically studied the PG gene family using the latest published wheat reference genomic information. In total, 113 wheat PG genes were identified, which could be classified into six categories A-F according to their structure characteristics and phylogenetic comparisons with Arabidopsis and rice. Polyploidy and segmental duplications in wheat were proved to be mainly responsible for the expansion of the wheat PG gene family. RNA-seq showed that TaPGs have specific temporal and spatial expression characteristics, in which 12 TaPGs with spike-specific expression patterns were detected by qRT-PCR in different fertility anthers of KTM3315A, a thermo-sensitive cytoplasmic male-sterile wheat. Four of them specific upregulated (TaPG09, TaPG95, and TaPG93) or downregulated (TaPG87) at trinucleate stage of fertile anthers, and further aligning with the homologous in Arabidopsis revealed that they may undertake functions such as anther dehiscence, separation of pollen, pollen development, and pollen tube elongation, thereby inducing male fertility conversion in KTM3315A. These findings facilitate function investigations of the wheat PG gene family and provide new insights into the fertility conversion mechanism in male-sterile wheat.
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http://dx.doi.org/10.1007/s00425-020-03435-wDOI Listing
August 2020

Safety of azithromycin in pediatrics: a systematic review and meta-analysis.

Eur J Clin Pharmacol 2020 Dec 17;76(12):1709-1721. Epub 2020 Jul 17.

Department of Pharmacy/Evidence-based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.

Purpose: To evaluate the toxicity of azithromycin in neonates, infants, and children.

Methods: A systematic review was performed for relevant studies using Medline (Ovid), PubMed, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and International Pharmaceutical Abstracts. We calculated the pooled incidence of adverse drug reactions (ADRs) associated with azithromycin based on prospective studies (RCTs and prospective cohort studies) and analyzed the risk difference (RD) of ADRs between azithromycin and placebo or other antibiotics using meta-analysis of RCTs.

Results: We included 133 studies with 4243 ADRs reported in 197,675 neonates, infants, and children who received azithromycin. The safety of azithromycin as MDA in pediatrics was poorly monitored. The main ADRs were diarrhea and vomiting. In prospective non-MDA studies, the most common toxicity was gastrointestinal ADRs (938/1967; 47.7%). The most serious toxicities were cardiac (prolonged QT or irregular heart beat) and idiopathic hypertrophic pyloric stenosis (IHPS). Compared with placebo, azithromycin did not show increased risk ADRs based on RCTs (risk difference - 0.17 to 0.07). The incidence of QT prolonged was higher in the medium-dosage group (10-30 mg/kg/day) than that of low-dosage group (≤ 10 mg/kg/day) (82.0% vs 1.2%).

Conclusion: The safety of azithromycin as MDA needs further evaluation. The most common ADRs are diarrhea and vomiting. The risk of the most serious uncommon ADRs (cardiac-prolonged QT and IHPS) is unknown.
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http://dx.doi.org/10.1007/s00228-020-02956-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661415PMC
December 2020
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