Publications by authors named "Fang Dong"

561 Publications

Comprehensive analysis of suppressor of cytokine signaling proteins in human breast Cancer.

BMC Cancer 2021 Jun 13;21(1):696. Epub 2021 Jun 13.

Department of Pathology, Soochow University Medical School, Suzhou, 215123, China.

Background: Abnormal expression of suppressor of cytokine signaling (SOCS) proteins regulates tumor angiogenesis and development in cancers. In this study, we aimed to perform a comprehensive bioinformatic analysis of SOCS proteins in breast invasive carcinoma (BRCA).

Methods: The gene expression, methylation level, copy number, protein expression and patient survival data related to SOCS family members in BRCA patients were obtained from the following databases: Oncomine, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), PCViz, cBioPortal and Kaplan-Meier plotter. Correlation analyses, identification of interacting genes and construction of regulatory networks were performed by functional and pathway enrichment analyses, weighted gene coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA).

Results: Data related to 1109 BRCA tissues and 113 normal breast tissue samples were extracted from the TCGA database. SOCS2 and SOCS3 exhibited significantly lower mRNA expression levels in BRCA tissues than in normal tissues. BRCA patients with high mRNA levels of SOCS3 (p < 0.01) and SOCS4 (p < 0.05) were predicted to have significantly longer overall survival (OS) times. Multivariate analysis showed that SOCS3 was an independent prognostic factor for OS. High mRNA expression levels of SOCS2 (p < 0.001), SOCS3 (p < 0.001), and SOCS4 (p < 0.01), and a low expression level of SOCS5 (p < 0.001) were predicted to be significantly associated with better recurrence-free survival (RFS). Multivariate analysis showed that SOCS2 was an independent prognostic factor for RFS. Lower expression levels of SOCS2 and SOCS3 were observed in patients with tumors of more advanced clinical stage (p < 0.05). Functional and pathway enrichment analyses, together with WGCNA and GSEA, showed that SOCS3 and its interacting genes were significantly involved in the JAK-STAT signaling pathway, suggesting that JAK-STAT signaling might play a critical role in BRCA angiogenesis and development. Western blot results showed that overexpression of SOCS3 inhibited the activity of the JAK-STAT signaling pathway in vitro.

Conclusions: SOCS family proteins play a very important role in BRCA. SOCS3 may be a prognostic factor and SOCS2 may be a potential therapeutic target in breast cancer.
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http://dx.doi.org/10.1186/s12885-021-08434-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201682PMC
June 2021

Case Report: A Novel Compound Heterozygous Mutation in in a Chinese Child With Very Early-Onset Inflammatory Bowel Disease.

Front Pediatr 2021 25;9:678390. Epub 2021 May 25.

Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Very early-onset inflammatory bowel disease (VEO-IBD) is defined as IBD diagnosed in children younger than 6 years of age. VEO-IBD is often associated with a monogenic etiology or primary immune deficiency. Here, we report the case of a 7-month-old Chinese girl diagnosed with VEO-IBD who had a variant in the interleukin-10 receptor A () gene. The patient presented with recurrent fevers, abdominal pain, diarrhea, perianal abscesses, and oral ulcers. Whole-exome sequencing (WES) identified a novel compound heterozygote mutation, c.395T>G (p.Leu132Arg)/ex.1del (p.?), in the gene of the patient. The missense mutation c.395T>G (p.Leu132Arg) was inherited from her mother, and ex.1del (p.?) was inherited from her father. Neither mutation has been reported previously. The IL-10RA function of the patient was defective, as demonstrated by a failure of signal transducer and activator of transcription 3 (STAT3) activation in peripheral blood mononuclear cells (PBMCs) stimulated with recombinant IL-10. The patient underwent matched unrelated peripheral blood hematopoietic stem cell transplantation (HSCT), and the clinical manifestations were dramatically improved. In summary, we identified a novel compound heterozygote mutation, c.395T>G (p.Leu132Arg)/ex.1del (p.?), in that caused VEO-IBD in a Chinese child, which further expands the mutational spectrum of .
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http://dx.doi.org/10.3389/fped.2021.678390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185152PMC
May 2021

The H3K36me2 methyltransferase NSD1 modulates H3K27ac at active enhancers to safeguard gene expression.

Nucleic Acids Res 2021 Jun 9. Epub 2021 Jun 9.

Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.

Epigenetics, especially histone marks, functions beyond the DNA sequences to regulate gene expression. Depletion of NSD1, which catalyzes H3K36me2, leads to both up- and down-regulation of gene expression, indicating NSD1 is associated with both active and repressed gene expression. It's known that NSD1 regulates the deposition and expansion of H3K27me3, a repressive mark for gene expression, to keep active gene transcription. However, how NSD1 functions to repress gene expression is largely unknown. Here, we find that, when NSD1 is knocked out in mouse embryonic stem cells (mESCs), H3K27ac increases correlatively with the decrease of H3K36me2 at active enhancers, which is associated with mesoderm differentiation genes, leading to elevated gene expression. Mechanistically, NSD1 recruits HDAC1, the deacetylase of H3K27ac, to chromatin. Moreover, HDAC1 knockout (KO) recapitulates the increase of H3K27ac at active enhancers as the NSD1 depletion. Together, we propose that NSD1 deposits H3K36me2 and recruits HDAC1 at active enhancers to serve as a 'safeguard', preventing further activation of active enhancer-associated genes.
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http://dx.doi.org/10.1093/nar/gkab473DOI Listing
June 2021

A Cloud Computing Platform for Scalable Relative and Absolute Binding Free Energy Predictions: New Opportunities and Challenges for Drug Discovery.

J Chem Inf Model 2021 Jun 4. Epub 2021 Jun 4.

Shenzhen Jingtai Technology Co., Ltd. (XtalPi), Floor 3, Sf Industrial Plant, No. 2 Hongliu Road, Fubao Community, Fubao Street, Futian District, Shenzhen 518045, China.

Free energy perturbation (FEP) has become widely used in drug discovery programs for binding affinity prediction between candidate compounds and their biological targets. However, limitations of FEP applications also exist, including, but not limited to, high cost, long waiting time, limited scalability, and breadth of application scenarios. To overcome these problems, we have developed XFEP, a scalable cloud computing platform for both relative and absolute free energy predictions using optimized simulation protocols. XFEP enables large-scale FEP calculations in a more efficient, scalable, and affordable way, for example, the evaluation of 5000 compounds can be performed in 1 week using 50-100 GPUs with a computing cost roughly equivalent to the cost for the synthesis of only one new compound. By combining these capabilities with artificial intelligence techniques for goal-directed molecule generation and evaluation, new opportunities can be explored for FEP applications in the drug discovery stages of hit identification, hit-to-lead, and lead optimization based not only on structure exploitation within the given chemical series but also including evaluation and comparison of completely unrelated molecules during structure exploration in a larger chemical space. XFEP provides the basis for scalable FEP applications to become more widely used in drug discovery projects and to speed up the drug discovery process from hit identification to preclinical candidate compound nomination.
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http://dx.doi.org/10.1021/acs.jcim.0c01329DOI Listing
June 2021

Scaffold Hopping Transformations Using Auxiliary Restraints for Calculating Accurate Relative Binding Free Energies.

J Chem Theory Comput 2021 Jun 24;17(6):3710-3726. Epub 2021 May 24.

Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.

screening of drug-target interactions is a key part of the drug discovery process. Changes in the drug scaffold via contraction or expansion of rings, the breaking of rings, and the introduction of cyclic structures from acyclic structures are commonly applied by medicinal chemists to improve binding affinity and enhance favorable properties of candidate compounds. These processes, commonly referred to as scaffold hopping, are challenging to model computationally. Although relative binding free energy (RBFE) calculations have shown success in predicting binding affinity changes caused by perturbing R-groups attached to a common scaffold, applications of RBFE calculations to modeling scaffold hopping are relatively limited. Scaffold hopping inevitably involves breaking and forming bond interactions of quadratic functional forms, which is highly challenging. A novel method for handling ring opening/closure/contraction/expansion and linker contraction/expansion is presented here. To the best of our knowledge, RBFE calculations on linker contraction/expansion have not been previously reported. The method uses auxiliary restraints to hold the atoms at the ends of a bond in place during the breaking and forming of the bonds. The broad applicability of the method was demonstrated by examining perturbations involving small-molecule macrocycles and mutations of proline in proteins. High accuracy was obtained using the method for most of the perturbations studied. The rigor of the method was isolated from the force field by validating the method using relative and absolute hydration free energy calculations compared to standard simulation results. Unlike other methods that rely on λ-dependent functional forms for bond interactions, the method presented here can be employed using modern molecular dynamics software without modification of codes or force field functions.
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http://dx.doi.org/10.1021/acs.jctc.1c00214DOI Listing
June 2021

Single Hormone Receptor-Positive Metaplastic Breast Cancer: Similar Outcome as Triple-Negative Subtype.

Front Endocrinol (Lausanne) 2021 23;12:628939. Epub 2021 Apr 23.

Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Metaplastic breast cancer (MBC) is a rare and aggressive subtype of the breast. To understand the characteristics and prognosis of single hormone receptor-positive (HR+) MBC (estrogen receptor-positive [ER+]/progesterone receptor-negative [PR-] and ER-/PR+), we compared these tumors to double HR+ tumors as well as HR- tumors.

Patients And Methods: The Surveillance, Epidemiology, and End Results database was used to analyze MBC between 1975 and 2016. The effect of HR status was evaluated using a multivariate Cox regression model.

Results: We included 3369 patients with a median follow-up time of 42 months (range 0-322 months). In this study, 280 (8.3%) cases were double HR+ tumors, 2597 (77.1%) were double HR- tumors, and 492 (14.6%) cases were single HR+ tumors, of which 159 (4.7%) cases were ER-/PR+ tumors and 333 (9.9%) were ER+/PR- tumors. On multivariate Cox analysis, the prognosis was related to age, race/ethnicity, tumor grade, TNM stage, and surgery. HR status remained no impact on breast cancer-specific survival (BCSS). In the Kaplan-Meier curve, HR status was not associated with better BCSS or overall survival (OS). In patients without HER2 overexpression, the BCSS and OS of ER+/PR- and ER-/PR+ tumors were not significantly different from that of ER-/PR- and ER+/PR+ tumors. The difference remains no significant in patients with HER2 overexpression.

Conclusions: In comparison with both ER-/PR- and ER+/PR+ tumors, we have identified clinically and biologically distinct features of single HR+ tumors. In patients with or without HER2 overexpression, the prognosis of single HR+ tumors was similar to ER-/PR- and ER+/PR+ tumors.
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http://dx.doi.org/10.3389/fendo.2021.628939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105402PMC
April 2021

Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations.

Cell Discov 2021 May 11;7(1):32. Epub 2021 May 11.

Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China.

Substitution of lysine 36 with methionine in histone H3.3 (H3.3K36M) is an oncogenic mutation that inhibits SETD2-mediated histone H3K36 tri-methylation in tumors. To investigate how the oncohistone mutation affects the function of SETD2 at the nucleosome level, we determined the cryo-EM structure of human SETD2 associated with an H3.3K36M nucleosome and cofactor S-adenosylmethionine (SAM), and revealed that SETD2 is attached to the N-terminal region of histone H3 and the nucleosome DNA at superhelix location 1, accompanied with the partial unwrapping of nucleosome DNA to expose the SETD2-binding site. These structural features were also observed in the previous cryo-EM structure of the fungal Set2-nucleosome complex. By contrast with the stable association of SETD2 with the H3.3K36M nucleosome, the EM densities of SETD2 could not be observed on the wild-type nucleosome surface, suggesting that the association of SETD2 with wild-type nucleosome might be transient. The linker histone H1, which stabilizes the wrapping of nucleosome DNA at the entry/exit sites, exhibits an inhibitory effect on the activities of SETD2 and displays inversely correlated genome distributions with that of the H3K36me3 marks. Cryo-EM analysis of yeast H3K36 methyltransferase Set2 complexed with nucleosomes further revealed evolutionarily conserved structural features for nucleosome recognition in eukaryotes, and provides insights into the mechanism of activity regulation. These findings have advanced our understanding of the structural basis for the tumorigenesis mechanism of the H3.3K36M mutation and highlight the effect of nucleosome conformation on the regulation of histone modification.
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http://dx.doi.org/10.1038/s41421-021-00261-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110526PMC
May 2021

Genome profiling of mismatch repair genes in eight types of tumors.

Cell Cycle 2021 Jun 9;20(11):1091-1106. Epub 2021 May 9.

Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.

Mismatch repair (MMR) plays an important role in the occurrence and development of tumors. At present, it is widely believed that MMR is a protective mechanism of tumors that plays a critical role in the progresses of cancer. In this study, 34 genes related to MMR selected from Gene Ontology (GO) database were scored by single sample Gene sets enrichment analysis (ssGSEA), and eight cancers were screened from 23 TCGA solid cancers to investigate the clinical significance of MMR score. MMR had different effects on the prognosis of the eight tumors, with a protective effect in three cancers and functioning as a risk factor in the remaining five cancers. We used unsupervised clustering to divide the patients into four clusters. We found that the immune and metabolic status of the four clusters were extremely different, among which cluster1 had the lowest tumor purity and the most complex microenvironment; this may explain its poor prognosis and immunotherapy effect. In summary, MMR scores can improve the predictive ability and provide effective guidance for immunotherapy in individual type of tumors.
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http://dx.doi.org/10.1080/15384101.2021.1922160DOI Listing
June 2021

Gene knockout in highly purified mouse hematopoietic stem cells by CRISPR/Cas9 technology.

J Immunol Methods 2021 May 4;495:113070. Epub 2021 May 4.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. Electronic address:

The CRISPR/Cas9 system has been used for genome editing of human and mouse cells. In this study, we established a protocol for gene knockout (KO) in mouse hematopoietic stem cells (HSCs). HSCs were highly purified from the bone marrow of tamoxifen-treated Cas9-EGFP/Cre-ER transgenic mice, maintained in serum-free polyvinyl alcohol culture with cytokines, lentivirally transduced with sgRNA-Crimson, and transplanted into lethally irradiated mice with competitor cells. Previous studies of Pax5 KO mice have shown B cell differentiation block. To verify our KO HSC strategy, we deleted Pax5 gene in 600 CD201CD150CD48c-KitSca-1Lin cells (HSC1 cells), highly enriched in myeloid-biased HSCs, and CD201CD150CD48 c-KitSca-1Lin cells (HSC2 cells), highly enriched in lymphoid-biased HSCs. As predicted, both Pax5 KO HSC1 and HSC2 cells showed few B cells in the peripheral blood and the accumulation of pro-B cells in the bone marrow of recipient mice. Our data suggesetd that myeloid-biased and lymphoid-biased HSCs share a common B cell differentiation pathway. This population-specific KO strategy will find its applications for gene editing in a varity of somatic cells, particuarly rare stem and progenitor cells from different tissues.
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http://dx.doi.org/10.1016/j.jim.2021.113070DOI Listing
May 2021

Alleviation of neurological disease by RNA editing.

Methods 2021 Apr 30. Epub 2021 Apr 30.

Shenzhen Eye Hospital affiliated to Jinan University, Shenzhen, PR China. Electronic address:

The development of CRISPR/Cas genome editing tools has revolutionized the life sciences by providing transformative applications in many biological fields, including the field of neurological disorders. Compared with previous CRISPR-Cas systems targeting DNA, a new field of RNA editing using CRISPR-Cas13 systems is gaining immense popularity. CRISPR-Cas13 is a robust, precise, versatile and safe RNA guided RNA-targeting system, which uniquely targets single-strand RNA. Recently, RNA-targeted gene editing tools have been refined by the introduction of an AAV (adeno-associated virus)-based CRISPR-Cas13 system for in vivo therapeutic cell fate conversion, which has been used to treat animal models of Parkinson's disease. This flavor of gene editing showed promising effects on glia-to-neuron conversion in both intact and damaged mature retinas in a mouse model. Herein, we summarize the CRISPR-Cas13 system and its potential for applications in neurological diseases, focusing on the method of applying the AAV-mediated CRISPR-Cas13 system to the conversion of glia-to-neuron.
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http://dx.doi.org/10.1016/j.ymeth.2021.04.023DOI Listing
April 2021

Efficacy and safety of Chinese patent medicine (Kang-ai injection) as an adjuvant in the treatment of patients with hepatocellular carcinoma: a meta-analysis.

Pharm Biol 2021 Dec;59(1):472-483

Dispensing Room for Intravenous Transfusion, Weifang People's Hospital, Weifang, China.

Context: Kang-ai injection (KAI) is an authorized herbal medicine used in cancer treatment. However, its clinical efficacy in hepatocellular carcinoma (HCC) has not been investigated thoroughly.

Objective: To systematically evaluate the efficacy and safety of KAI in patients with HCC.

Materials And Methods: The Web of Science, PubMed, Cochrane Library, EMBASE, CBM, CNKI, VIP and Wanfang databases were systematically searched (date range: inception to December 2020) using the key terms 'Kang-ai injection' and 'hepatocellular carcinoma'. The current analysis included controlled clinical trials that compared the efficacy and safety of the combination of KAI and conventional treatment (CT) with CT alone for HCC. The current study estimated the pooled risk ratio (RR) with 95% confidence intervals (CI).

Results: Data pertaining to 35 trials with 2501 HCC patients were analysed. The results revealed that the combination of KAI and CT was associated with significantly superior objective response rate (RR = 1.57, 95% CI = 1.43-1.73), disease control rate (RR = 1.18, 95% CI = 1.10-1.26), and quality of life (RR = 2.40, 95% CI = 1.79-3.23), compared to CT alone. The administration of KAI significantly alleviated most of the adverse effects caused by CT, including nausea and vomiting, liver damage, peripheral neurotoxicity, fever, abdominal pain, alopecia, increased bilirubin levels, leukopoenia, and reduction in haemoglobin levels ( < 0.05, for all).

Conclusions: The current meta-analysis indicates that a combination of CT and KAI could be more effective in improving the clinical efficacy of the treatment of HCC, compared to CT alone.
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http://dx.doi.org/10.1080/13880209.2021.1915340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081330PMC
December 2021

Radiation-induced bystander effects impair transplanted human hematopoietic stem cells via oxidative DNA damage.

Blood 2021 Jun;137(24):3339-3350

State Key Laboratory of Experimental Hematology, National Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine and Department of Stem Cell & Regenerative Medicine, Chinese Academy of Medical Sciences-Peking Union Medical College, Tianjin, China.

Total body irradiation (TBI) is commonly used in host conditioning regimens for human hematopoietic stem cell (HSC) transplantation to treat various hematological disorders. Exposure to TBI not only induces acute myelosuppression and immunosuppression, but also injures the various components of the HSC niche in recipients. Our previous study demonstrated that radiation-induced bystander effects (RIBE) of irradiated recipients decreased the long-term repopulating ability of transplanted mouse HSCs. However, RIBE on transplanted human HSCs have not been studied. Here, we report that RIBE impaired the long-term hematopoietic reconstitution of human HSCs as well as the colony-forming ability of human hematopoietic progenitor cells (HPCs). Our further analyses revealed that the RIBE-affected human hematopoietic cells showed enhanced DNA damage responses, cell-cycle arrest, and p53-dependent apoptosis, mainly because of oxidative stress. Moreover, multiple antioxidants could mitigate these bystander effects, though at different efficacies in vitro and in vivo. Taken together, these findings suggest that RIBE impair human HSCs and HPCs by oxidative DNA damage. This study provides definitive evidence for RIBE on transplanted human HSCs and further justifies the necessity of conducting clinical trials to evaluate different antioxidants to improve the efficacy of HSC transplantation for the patients with hematological or nonhematological disorders.
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http://dx.doi.org/10.1182/blood.2020007362DOI Listing
June 2021

High phosphate impairs arterial endothelial function through AMPK-related pathways in mouse resistance arteries.

Acta Physiol (Oxf) 2021 04 20;231(4):e13595. Epub 2020 Dec 20.

Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.

Aims: In patients with renal disease, high serum phosphate shows a relationship with cardiovascular risk. We speculate that high phosphate (HP) impairs arterial vasodilation via the endothelium and explore potential underlying mechanisms.

Methods: Isolated vessel relaxation, endothelial function, glomerular filtration rate (GFR), oxidative stress status and protein expression were assessed in HP diet mice. Mitochondrial function and protein expression were assessed in HP-treated human umbilical vein endothelial cells (HUVECs).

Results: High phosphate (1.3%) diet for 12 weeks impaired endothelium-dependent relaxation in mesenteric arteries, kidney interlobar arteries and afferent arterioles; reduced GFR and the blood pressure responses to acute administration of acetylcholine. The PPARα/LKB1/AMPK/eNOS pathway was attenuated in the endothelium of mesenteric arteries from HP diet mice. The observed vasodilatory impairment of mesenteric arteries was ameliorated by PPARα agonist WY-14643. The phosphate transporter PiT-1 knockdown prevented HP-mediated suppression of eNOS activity by impeding phosphorus influx in HUVECs. Endothelium cytoplasmic and mitochondrial reactive oxygen species (ROS) were increased in HP diet mice. Moreover HP decreased the expression of mitochondrial-related antioxidant genes. Finally, mitochondrial membrane potential and PGC-1α expression were reduced by HP treatment in HUVECs, which was partly restored by AMPKα agonist.

Conclusions: HP impairs endothelial function by reducing NO bioavailability via decreasing eNOS activity and increasing mitochondrial ROS, in which the AMPK-related signalling pathways may play a key role.
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http://dx.doi.org/10.1111/apha.13595DOI Listing
April 2021

Clinical characteristics and serotype distribution of invasive pneumococcal disease in pediatric patients from Beijing, China.

Eur J Clin Microbiol Infect Dis 2021 Mar 31. Epub 2021 Mar 31.

Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nan-Li-Shi Road, Beijing, 100045, China.

Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality. However, limited studies have reported clinical features of IPD cases among Chinese children. This study aimed to evaluate clinical characteristics as well as serotype distribution of hospitalized IPD children in Beijing, China. Children with confirmed IPD were retrospectively recruited from January 2014 to December 2019. Clinical data were gathered from medical records, and serotypes of Streptococcus pneumoniae isolates were detected. Clinical differences between deaths and survivors were also compared, and risk factors associated with death were determined. Of sixty-eight children diagnosed with IPD, 58 (85.3%) were < 5 years. 19F was the predominant serotype (23, 33.8%), followed by 19A (14, 20.6%), 14 (12, 17.6%), 23F (5, 7.4%), and non-vaccine serotype (NVT) 15A (3, 4.4%). The coverage rate of 13-valent pneumococcal conjugate vaccine (PCV) was 92.6% (63). After introduction of PCV-13, there was a significant increase of IPD due to NVTs (p = 0.047). Sixteen (23.5%) children died, and diagnoses of 11 (68.8%) were meningitis. Risk factors for death were < 2 years (odds ratio [OR] [95% confidence interval {CI}]: 6.64 [1.14-32.10]; p = 0.019), altered mental status (OR [95%CI]: 10.10 [2.11-48.31]; p = 0.004), and septic shock (OR [95%CI]: 6.61 [1.11-39.50]; p = 0.038). This study revealed that the case fatality rate of hospitalized IPD children was high in this hospital. Fatal cases were more likely to be children < 2 years, presented with changed mental status and septic shock. Notably, we found that NVTs increased after PCV13 availability in China.
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http://dx.doi.org/10.1007/s10096-021-04238-xDOI Listing
March 2021

Mechanistic Insights into Substrate Recognition and Catalysis of a New Ulvan Lyase of Polysaccharide Lyase Family 24.

Appl Environ Microbiol 2021 May 26;87(12):e0041221. Epub 2021 May 26.

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.

Ulvan is an important marine polysaccharide. Bacterial ulvan lyases play important roles in ulvan degradation and marine carbon cycling. Until now, only a small number of ulvan lyases have been characterized. Here, a new ulvan lyase, Uly1, belonging to polysaccharide lyase family 24 (PL24) from the marine bacterium Catenovulum maritimum, is characterized. The optimal temperature and pH for Uly1 to degrade ulvan are 40°C and pH 9.0, respectively. Uly1 degrades ulvan polysaccharides in the endolytic manner, mainly producing ΔRha3S, consisting of an unsaturated 4-deoxy-l--hex-4-enopyranosiduronic acid and a 3-O-sulfated α-l-rhamnose. The structure of Uly1 was resolved at a 2.10-Å resolution. Uly1 adopts a seven-bladed β-propeller architecture. Structural and site-directed mutagenesis analyses indicate that four highly conserved residues, H128, H149, Y223, and R239, are essential for catalysis. H128 functions as both the catalytic acid and base, H149 and R239 function as the neutralizers, and Y223 plays a supporting role in catalysis. Structural comparison and sequence alignment suggest that Uly1 and many other PL24 enzymes may directly bind the substrate near the catalytic residues for catalysis, different from the PL24 ulvan lyase LOR_107, which adopts a two-stage substrate binding process. This study provides new insights into ulvan lyases and ulvan degradation. Ulvan is a major cell wall component of green algae of the genus Many marine heterotrophic bacteria can produce extracellular ulvan lyases to degrade ulvan for a carbon nutrient. In addition, ulvan has a range of physiological bioactivities based on its specific chemical structure. Ulvan lyase thus plays an important role in marine carbon cycling and has great potential in biotechnological applications. However, only a small number of ulvan lyases have been characterized over the past 10 years. Here, based on biochemical and structural analyses, a new ulvan lyase of polysaccharide lyase family 24 is characterized, and its substrate recognition and catalytic mechanisms are revealed. Moreover, a new substrate binding process adopted by PL24 ulvan lyases is proposed. This study offers a better understanding of bacterial ulvan lyases and is helpful for studying the application potentials of ulvan lyases.
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http://dx.doi.org/10.1128/AEM.00412-21DOI Listing
May 2021

Knockdown of Chitinase 3-Like-1 Inhibits Cell Proliferation, Promotes Apoptosis, and Enhances Effect of Anti-Programmed Death Ligand 1 (PD-L1) in Diffuse Large B Cell Lymphoma Cells.

Med Sci Monit 2021 Mar 25;27:e929431. Epub 2021 Mar 25.

Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).

BACKGROUND Enzymatically inactive chitinase-like protein CHI3L1 is overexpressed in diffuse large B cell lymphoma (DLBCL) patients with PD-L1 imbalance and promotes tumor progression in the microenvironment. Based on this, we investigated how CHI3L1 acts on the proliferation and apoptosis of DLBCL and whether there is a synergy of CHI3L1 in combination with anti-PD-L1 antibodies in vivo. MATERIAL AND METHODS CHI3L1 was detected by quantitative real-time PCR (RT-PCR) and western blot (WB) in B-lymphoma cell lines. CHI3L1 interference plasmids were constructed, and the levels of proliferation, cell cycle, apoptosis, and cell survival were examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model by RT-PCR, WB, CCK-8, and flow cytometry. RESULTS CHI3L1 was significantly expressed in SU-DHL-4 cells. CHI3L1-interfered RNA ShRNA-CHI3L1-1 was chosen to be used in the next experiment because it had a better interference effect. Dampened cell proliferation level, arrested cell cycle, reduced protein expressions of cyclin D1 and cyclin D2, and promoted cell apoptosis level were observed after SU-DHL-4 was transfected with ShRNA-CHI3L1-1. Furthermore, we also noticed increased expression of Bcl-2, decreased expressions of bax, cleaved caspase 3 and cleaved PARP, promoted cell survival-related protein p53, and reduced survivin. CONCLUSIONS This study demonstrated that knockdown of CHI3L1 inhibits cancer cell proliferation by regulating cell cycles, promotes cancer cell apoptosis, and enhances the pro-apoptotic effect of anti-PD-L1 antibody both in vivo and in vitro in DLBCL.
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http://dx.doi.org/10.12659/MSM.929431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008972PMC
March 2021

The incorporation loci of H3.3K36M determine its preferential prevalence in chondroblastomas.

Cell Death Dis 2021 03 24;12(4):311. Epub 2021 Mar 24.

Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, 310058, Hangzhou, Zhejiang, China.

The histone H3.3K36M mutation, identified in over 90% of chondroblastoma cases, reprograms the H3K36 methylation landscape and gene expression to promote tumorigenesis. However, it's still unclear how the H3K36M mutation preferentially occurs in the histone H3 variant H3.3 in chondroblastomas. Here, we report that H3.3K36M-, but not H3.1K36M-, mutant cells showed increased colony formation ability and differentiation defects. H3K36 methylations and enhancers were reprogrammed to different status in H3.3K36M- and H3.1K36M-mutant cells. The reprogramming of H3K36 methylation and enhancers was depended on the specific loci at which H3.3K36M and H3.1K36M were incorporated. Moreover, targeting H3K36M-mutant proteins to the chromatin inhibited the H3K36 methylation locally. Taken together, these results highlight the roles of the chromatic localization of H3.3K36M-mutant protein in the reprogramming of the epigenome and the subsequent induction of tumorigenesis, and shed light on the molecular mechanisms by which the H3K36M mutation mainly occurs in histone H3.3 in chondroblastomas.
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http://dx.doi.org/10.1038/s41419-021-03597-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991640PMC
March 2021

Etiology and Ureteral Reconstruction Strategy for Iatrogenic Ureteral Injuries: A Retrospective Single-Center Experience.

Urol Int 2021 19;105(5-6):470-476. Epub 2021 Mar 19.

Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China.

Objective: To analyze the etiology, characteristics, and ureteral reconstruction strategies of iatrogenic ureteric injuries in a high-volume center.

Methods: Between September 2010 and August 2019, we retrospectively collected patients who underwent ureteral reconstruction due to iatrogenic ureteric injuries. Patient profiles, laboratory data, imaging studies, perioperative data, and complications were recorded.

Results: Sixty-eight patients were enrolled in this study. The upper, middle, and lower thirds of the ureter were affected in 30, 2, and 36 cases, respectively. Of the 68 ureteric injuries, 69.1% occurred during urological procedures, followed by gynecological procedures, general surgery, radiotherapy, and orthopedic surgery. The majority of urological injuries (41, 87.2%) occurred due to stone removal. There was a significant difference in the age, sex, and location of ureteric injuries between the urological and nonurological groups. The median follow-up time was 17.9 months. The overall symptom remission rate was 91.2% and ranged from 87.5 to 100% for different reconstructive surgeries.

Conclusions: Urological procedures were the most common cause of iatrogenic ureteric injury; thus, extra care should be taken. Timely detection and appropriate treatment of the ureteric injuries are necessary. Treatment strategies should be depended on the location and length of injury.
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http://dx.doi.org/10.1159/000511141DOI Listing
March 2021

Correction to: The Impact of Smoking, Sex, Infection, and Comedication Administration on Oral Olanzapine: A Population Pharmacokinetic Model in Chinese Psychiatric Patients.

Eur J Drug Metab Pharmacokinet 2021 May;46(3):373-374

The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, Beijing, 100088, China.

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http://dx.doi.org/10.1007/s13318-021-00680-6DOI Listing
May 2021

The Impact of Smoking, Sex, Infection, and Comedication Administration on Oral Olanzapine: A Population Pharmacokinetic Model in Chinese Psychiatric Patients.

Eur J Drug Metab Pharmacokinet 2021 May 6;46(3):353-371. Epub 2021 Mar 6.

The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, Beijing, 100088, China.

BACKGROUND AND OBJECTIVE: Prior olanzapine population pharmacokinetic (PPK) models have focused on the effects of sex and smoking on olanzapine clearance. This PPK model in Chinese adult psychiatric patients also investigated the influence of comedications and co-occurrence of infections on olanzapine clearance, and explored how to personalize oral olanzapine dosage in the clinical setting.

Methods: A total of 1546 serum concentrations from 354 patients were collected in this study. A one-compartment model with first-order absorption was employed to develop the PPK model using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, co-occurrence of infection and concomitant medications (including dangguilonghui tablets, a Chinese herbal medicine for constipation). Bootstrap validation (1000 runs) and external validation of 50 patients were employed to evaluate the final model. Simulations were performed to explore the personalization of olanzapine dosing after stratification by sex, smoking, and comedication with valproate.

Results: Typical estimates for the absorption rate constant (K), apparent clearance (CL/F), and apparent distribution volume (V/F) were 0.30 h, 12.88 L/h, and 754.41 L, respectively. Olanzapine clearance was increased by the following variables: 1.23-fold by male sex, 1.23-fold by smoking, 1.23-fold by comedication with valproate, 1.16-fold by sertraline, and 2.01-fold by dangguilonghui tablets. Olanzapine clearance was decreased by the following variables: 0.75-fold by co-occurrence of infection, 0.70-fold by fluvoxamine, and 0.78-fold by perphenazine. The model evaluation indicated that the final model's performance was good, stable, and precise.

Conclusion: This study contributes to the personalization of oral olanzapine dosing, but further studies should be performed to verify the effects of infection and comedications, including valproate and dangguilonghui.
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http://dx.doi.org/10.1007/s13318-021-00673-5DOI Listing
May 2021

Metaplastic breast cancer: Treatment and prognosis by molecular subtype.

Transl Oncol 2021 May 4;14(5):101054. Epub 2021 Mar 4.

Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Background: Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast. However, the effect of molecular subtype on treatment and prognosis of MBC remains unclear.

Patients And Methods: The Surveillance, Epidemiology, and End Results database was used to analyze patients with MBC between 2010 and 2016. Molecular subtype was stratified to TN group (ER and PR-/HER2-), HER2 group (ER and PR-/HER2+, ER/PR+ and HER2+), and HR group (ER/PR+ and HER2-). The breast cancer-specific survival (BCSS) differences were estimated using multivariate Cox regression model and Kaplan-Meier curves.

Results: We included 1665 patients with median follow-up time of 27 months (range 0-83 months). 1154 (69.3%), 65 (3.9%), and 446 (26.8%) patients presented in TN group, HER2 group, and HR group, respectively. On multivariate Cox analysis, the prognosis was related to age, tumor size, regional node metastasis, and surgery. Molecular subtype remained no impact on BCSS. Radiotherapy (RT) was associated with better prognosis. Patients cannot benefit from chemotherapy. In Kaplan-Meier curve, triple-negative (P = 0.047) and HR-positive (P = 0.006) patients receiving RT had a superior BCSS than that not RT. HER2-positive patients cannot benefit from RT. However, adjusted Kaplan-Meier survival model showed that triple-negative (P = 0.019) but not HER2-positive (P = 0.575) or HR-positive (P = 0.574) patients receiving RT had a superior BCSS than that not RT.

Conclusions: Molecular subtype is not associated with the better prognosis of MBC. Patients could benefit from RT. However, triple-negative but not HR-positive or HER2-positive patients have superior survival after receiving RT.
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http://dx.doi.org/10.1016/j.tranon.2021.101054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079171PMC
May 2021

The involvement of NLRP3 inflammasome in the treatment of neurodegenerative diseases.

Biomed Pharmacother 2021 Jun 2;138:111428. Epub 2021 Mar 2.

Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang 050051, PR China; Hebei Key Laboratory of Critical Disease Mechanism and intervention, Shijiazhuang 050051, PR China. Electronic address:

In an ageing society, neurodegenerative diseases have attracted attention because of their high incidence worldwide. Despite extensive research, there is a lack of conclusive insights into the pathogenesis of neurodegenerative diseases, which limit the strategies for symptomatic treatment. Therefore, better elucidation of the molecular mechanisms involved in neurodegenerative diseases can provide an important theoretical basis for the discovery of new and effective prevention and treatment methods. The innate immune system is activated during the ageing process and in response to neurodegenerative diseases. Inflammasomes are multiprotein complexes that play an important role in the activation of the innate immune system. They mediate inflammatory reactions and pyroptosis, which are closely involved in neurodegeneration. There are different types of inflammasomes, although the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is the most common inflammasome; NLRP3 plays an important role in the pathogenesis of neurodegenerative diseases. In this review, we will discuss the mechanisms that are involved in the activation of the NLRP3 inflammasome and its crucial role in the pathology of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. We will also review various treatments that target the NLRP3 inflammasome pathway and alleviate neuroinflammation. Finally, we will summarize the novel treatment strategies for neurodegenerative disorders.
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http://dx.doi.org/10.1016/j.biopha.2021.111428DOI Listing
June 2021

Clinical and molecular characteristics of Staphylococcus aureus isolated from Chinese children: association among the agr groups and genotypes, virulence genes and disease types.

World J Pediatr 2021 Apr 3;17(2):180-188. Epub 2021 Mar 3.

Bacteriology Laboratory, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China.

Background: This study was aimed to investigate the clinical and molecular epidemiology of Staphylococcus aureus (S. aureus) isolated from Chinese children and determine the possible relationship among the accessory gene regulator (agr) groups and genotypes, as well as among the virulence genes and disease types.

Methods: S. aureus strains were isolated from Beijing Children's Hospital between October 2017 and October 2019. The isolates and 19 virulence genes were characterized using multi-locus sequence typing, staphylococcal protein A (spa), staphylococcal cassette chromosome mec, and agr typing.

Results: A total of 191 non-repetitive S. aureus clinical isolates were divided into 33 sequence types (STs), 18 clonal complexes (CCs), and 59 spa types. ST59 (39.8%), t437 (37.7%), and agr I (84.8%) were the predominant types. CC59, CC25, CC22, CC951, CC8, and CC398 belonged to agr I. CC5 and CC15 were assigned to agr II, and CC30 was characterized as agr III. CC121 was classified under agr IV. The eta, etb, and bbp genes were more prevalent in agr IV (P < 0.001 for each), while tst was more prevalent in agr group III compared to the other groups (P < 0.001). Nearly all isolates that harbored lukS/F-PV belonged to agr I (P = 0.005). However, the correlation between disease types and agr groups was not significant (P > 0.05).

Conclusions: An association among the agr groups and genotypes, as well as specific toxin genes, was observed among the S. aureus strains isolated from Chinese children. However, a statistical correlation was not found among the agr groups and disease types.
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http://dx.doi.org/10.1007/s12519-021-00421-4DOI Listing
April 2021

Antifungal activity of double Schiff bases of chitosan derivatives bearing active halogeno-benzenes.

Int J Biol Macromol 2021 May 27;179:292-298. Epub 2021 Feb 27.

Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

In this study, a series of chitosan derivatives bearing active halogenated aromatic imines were successfully synthesized via Schiff bases with the high degrees of substitution. Detailed structural characterization was carried out using Fourier transform infrared (FTIR) spectroscopy, solid-state C nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis. Besides, the antifungal activity against three common plant pathogenic fungi, including Botrytis cinerea, Fusarium oxysporum f. sp. cucumerinum, and Fusarium oxysporum f. sp. niveum, was investigated using in vitro hyphal measurements. The results showed that double Schiff bases of chitosan derivatives exhibited enhanced antifungal activity compared with chitosan, especially at 1.0 mg/mL. The double Schiff bases of chitosan bearing halogeno-benzenes showed >95% inhibitory indices at 1.0 mg/mL against Botrytis cinereal since halogens had the stronger electron-withdrawing property. The higher degree of substitution was another positive effect to improve the antifungal activity. This study provides a practical strategy to synthesize new double Schiff bases of chitosan derivatives bearing halogeno-benzenes, which could be developed into stronger antifungal agents.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.184DOI Listing
May 2021

The effects of BMMSC treatment on lung tissue degeneration in elderly macaques.

Stem Cell Res Ther 2021 Mar 1;12(1):156. Epub 2021 Mar 1.

Kunming Key Laboratory of Stem Cell and Regenerative Medicine, 920th Hospital of the PLA Joint Logistics Support Force, Kunming, 650032, Yunnan Province, China.

Background: Age-associated lung tissue degeneration is a risk factor for lung injury and exacerbated lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, among others). So, it is particularly important to find new anti-aging treatments.

Methods: We systematically screened and evaluated elderly senile multiple organ dysfunction macaque models to determine whether BMMSCs inhibited lung tissue degeneration.

Results: The average alveolar area, mean linear intercept (MLI), and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (p < 0.05), while the capillary density around the alveoli was significantly low than in young macaque models (p < 0.05). Intravenous infusion of BMMSCs reduced the degree of pulmonary fibrosis, increased the density of capillaries around the alveoli (p < 0.05), and the number of type II alveolar epithelium in elderly macaques (p < 0.05). In addition, the infusion reduced lung tissue ROS levels, systemic and lung tissue inflammatory levels, and Treg cell ratio in elderly macaque models (p < 0.05). Indirect co-cultivation revealed that BMMSCs suppressed the expression of senescence-associated genes, ROS levels, apoptosis rate of aging type II alveolar epithelial cells (A549 cells), and enhanced their proliferation (p < 0.05).

Conclusions: BMMSC treatment inhibited age-associated lung tissue degeneration.
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http://dx.doi.org/10.1186/s13287-021-02201-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923486PMC
March 2021

Congenital hepatic fibrosis in a young boy with congenital hypothyroidism: A case report.

World J Clin Cases 2021 Feb;9(6):1475-1482

Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.

Background: Congenital hepatic fibrosis (CHF) is a rare autosomal recessive disorder characterized by variable degrees of periportal fibrosis and malformation of bile ducts. CHF is generally accompanied by a variety of conditions or syndromes with other organ involvement.

Case Summary: We report a 5-year-4-month-old Chinese boy with congenital hypothyroidism (CH) diagnosed with CHF. The patient was diagnosed with CH by a newborn screening test and has since been taking levothyroxine. He has developed normally without neurocognitive deficits. Abnormal liver function was observed in the patient at the age of 4 years and 11 mo, and elevated levels of liver function indices were persistent for 5 mo. Radiological imaging indicated hepatospleno-megaly without narrowing of the portal vein but dilated splenic vein. A liver biopsy confirmed the pathological features of CHF. Genetic testing revealed two novel homozygous mutations, namely, c.2141-3T>C variant in related to CHF and c.2921G>A (p.R974H) in related to CH. The patient was treated with compound glycyrrhizin tablet, ursodeoxycholic acid, and levothyroxine after diagnosis. The patient achieved a favorable clinical outcome during a follow-up period of over 2 years.

Conclusion: Herein, we report the first case of a Chinese boy with comorbidity of CHF and CH, carrying both gene and gene novel mutations. Liver biopsy and genetic testing should be considered for the diagnosis of coexistent liver disease in CH patients with unexplained abnormal liver function.
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http://dx.doi.org/10.12998/wjcc.v9.i6.1475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896672PMC
February 2021

The Anti-apoptosis Effect of Single Electroacupuncture Treatment Suppressing Neuronal Autophagy in the Acute Stage of Ischemic Stroke Without Infarct Alleviation.

Front Cell Neurosci 2021 2;15:633280. Epub 2021 Feb 2.

Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

The main purpose of the study was to investigate the antiapoptotic effect of electroacupuncture (EA) in the acute stage of ischaemic stroke in rats. The cerebral ischemia model was established by middle cerebral artery occlusion (MCAO)/reperfusion in rats. A single EA treatment was performed at the acute stage of ischaemic stroke. The neurological function, brain water content, apoptotic cell number, and cerebral infarct volume were assessed in stroke rats. The expression of autophagy-related proteins (LC3II/I, Beclin1, P62, and LAMP1), Sirtuin 1 (SIRT1), p-JNK, p-ERK1/2, and cleaved caspase-3 (CCAS3) were measured by Western blot, immunofluorescence, and immunohistochemistry. Rapamycin (RAP, an activator of autophagy) was used to confirm the antiapoptotic effect of EA regulating autophagy. The brain edema infarct size and apoptotic cell number were increasing within 3 days following stroke, and brain edema reached its peak at 24 h after stroke. EA treatment at 24 h after ischaemic stroke obviously suppressed the number of apoptotic cells and brain edema. However, there were no significant differences in infarct volumes among EA-12 h, EA-24 h, and MCAO/R group. Moreover, EA treatment at 24 h after ischaemic stroke obviously suppressed the expression of CCAS3, LC3II/I, Beclin1 while increasing the level of P62 and LAMP1 and hence mediating autophagy, which was reversed by RAP. Meanwhile, the expression of SIRT1, p-ERK1/2, p-JNK were promoted by EA at 24 h after ischaemic stroke. In conclusion, EA treatment may suppress apoptosis possibly regulating autophagy in the acute period after ischaemic stroke, hence reducing brain injury.
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http://dx.doi.org/10.3389/fncel.2021.633280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884854PMC
February 2021

Unsupervised Eye Blink Artifact Detection from EEG with Gaussian Mixture Model.

IEEE J Biomed Health Inform 2021 Feb 9;PP. Epub 2021 Feb 9.

Eye blink is one of the most common artifacts in electroencephalogram (EEG) and significantly affects the performance of the EEG related applications, such as epilepsy recognition, spike detection, encephalitis diagnosis, etc. To achieve an accurate and efficient eye blink detection, a novel unsupervised learning algorithm based on a hybrid thresholding followed with a Gaussian mixture model (GMM) is presented in this paper. The EEG signal is priliminarily screened by a cascaded thresholding method built on the distributions of signal amplitude, amplitude displacement, as well as the cross channel correlation. Then, the channel correlation of the two frontal electrodes (FP1, FP2), the fractal dimension, and the mean of amplitude difference between FP1 and FP2, are extracted to characterize the filtered EEGs. The GMM trained on these features is applied for the eye blink detection. The performance of the proposed algorithm is studied on two EEG datasets collected by the Temple University Hospital (TUH) and the Children's Hospital, Zhejiang University School of Medicine (CHZU), where the datasets are recorded from epilepsy and encephalitis patients, and contain a lot of eye blink artifacts. Experimental results show that the proposed algorithm can achieve the highest detection precision and F1 score over the state-of-the-art methods.
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http://dx.doi.org/10.1109/JBHI.2021.3057891DOI Listing
February 2021

Minimally invasive ileal ureter replacement: Comparative analysis of robot-assisted laparoscopic versus conventional laparoscopic surgery.

Int J Med Robot 2021 Jun 24;17(3):e2230. Epub 2021 Feb 24.

Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Centre, Beijing, China.

Background: This study is an initial comparative analysis of perioperative and intermediate-term functional outcomes between patients who underwent robot-assisted laparoscopic (RALS) or conventional laparoscopic surgery (LS).

Materials And Methods: A total of 25 patients who underwent ileal ureter replacement (10 RALS and 15 LS) were followed by functional cine magnetic resonance urography (MRU) combined with a modified Whitaker test. Also, the characteristics, perioperative data and functional outcomes of the patients were compared.

Results: The estimated blood loss, postoperative hospital stay and time to oral intake were significantly lower in the RALS group. At the median 14-month follow-up, all the patients showed improved renal function and were symptom-free, with no signs of leakage or stenosis observed by cine MRU combined with a modified Whitaker test.

Conclusions: RALS with an extracorporeal bowel resection is feasible and appears to be safe, with quick postoperative recovery and encouraging outcomes.
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http://dx.doi.org/10.1002/rcs.2230DOI Listing
June 2021

Local continuous glial cell derived neurotrophic factor release using osmotic pump promotes parasympathetic nerve rehabilitation in an animal model of cavernous nerve injury induced erectile dysfunction.

Transl Androl Urol 2021 Jan;10(1):258-271

Andrology Center, Department of Urology, Peking University First Hospital, Peking University, Beijing, China.

Background: Nerve injury-related erectile dysfunction (ED) is one of the types that respond poorly to conventional ED treatments. Our previous experiments have demonstrated the paracrine of various neurotrophic factors (NTFs) by stem cells or other treatment modalities as a potential mechanism in the recovery of nerve injury-related ED. Glial cell derived neurotrophic factor (GDNF) is one of the essential NTFs for the regeneration of nerve fibers, especially for parasympathetic nerves. The aim of this study is to explore if local continuous GDNF administration is beneficial for the functional and histological recovery of nerve injury induced ED.

Methods: Eight-week-old male Sprague-Dawley rats were used for this study. Rats were randomly grouped into 5: Sham surgery (Sham), bilateral cavernous nerve injury (BCNI) and placebo treatment, BCNI and 0.1 µg/100 µL GDNF treatment (BCNI+GDNF 0.1), BCNI and 1 µg/100 µL GDNF treatment (BCNI+GDNF 1), BCNI and 10 µg/100 µL GDNF treatment (BCNI+GDNF 10). GDNF was administered using an osmotic pump technique which would deliver GDNF locally and continuously for 28 days without the need for external connections or frequent handling of animals. Recovery of sexual function, nerve fibers regeneration, and expression of neurotrophic receptors were examined and compared among groups after the treatment.

Results: Local continuous GDNF release treatment increased the average number of intromissions in the sexual behavior test and intracavernous pressure (ICP) in the erectile function test in a dose dependent manner. Osmotic pump implantation induced increased local GDNF concentration and mild inflammatory response. Gene expression of GDNF receptors in major pelvic ganglion (MPG) and nerve regeneration along the urethra were partially promoted by GDNF. These changes were associated with increased nerve fibers especially the parasympathetic nerve fibers in dorsal nerve of penis (DNP) in GDNF treated groups.

Conclusions: In conclusion, our project illustrated the promising effects of local continuous GDNF administration for the functional and histological recovery of nerve injury-induced ED.
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http://dx.doi.org/10.21037/tau-20-1110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844500PMC
January 2021