Publications by authors named "Yanmei Zhang"

193 Publications

Voice Emotion Recognition by Mandarin-Speaking Children with Cochlear Implants.

Ear Hear 2021 Jul 7. Epub 2021 Jul 7.

Department of Otolaryngology, Head and Neck Surgery, Peking University First Hospital, Beijing, China.

Objectives: Emotional expressions are very important in social interactions. Children with cochlear implants can have voice emotion recognition deficits due to device limitations. Mandarin-speaking children with cochlear implants may face greater challenges than those speaking nontonal languages; the pitch information is not well preserved in cochlear implants, and such children could benefit from child-directed speech, which carries more exaggerated distinctive acoustic cues for different emotions. This study investigated voice emotion recognition, using both adult-directed and child-directed materials, in Mandarin-speaking children with cochlear implants compared with normal hearing peers. The authors hypothesized that both the children with cochlear implants and those with normal hearing would perform better with child-directed materials than with adult-directed materials.

Design: Thirty children (7.17-17 years of age) with cochlear implants and 27 children with normal hearing (6.92-17.08 years of age) were recruited in this study. Participants completed a nonverbal reasoning test, speech recognition tests, and a voice emotion recognition task. Children with cochlear implants over the age of 10 years also completed the Chinese version of the Nijmegen Cochlear Implant Questionnaire to evaluate the health-related quality of life. The voice emotion recognition task was a five-alternative, forced-choice paradigm, which contains sentences spoken with five emotions (happy, angry, sad, scared, and neutral) in a child-directed or adult-directed manner.

Results: Acoustic analyses showed substantial variations across emotions in all materials, mainly on measures of mean fundamental frequency and fundamental frequency range. Mandarin-speaking children with cochlear implants displayed a significantly poorer performance than normal hearing peers in voice emotion perception tasks, regardless of whether the performance is measured in accuracy scores, Hu value, or reaction time. Children with cochlear implants and children with normal hearing were mainly affected by the mean fundamental frequency in speech emotion recognition tasks. Chronological age had a significant effect on speech emotion recognition in children with normal hearing; however, there was no significant correlation between chronological age and accuracy scores in speech emotion recognition in children with implants. Significant effects of specific emotion and test materials (better performance with child-directed materials) in both groups of children were observed. Among the children with cochlear implants, age at implantation, percentage scores of nonverbal intelligence quotient test, and sentence recognition threshold in quiet could predict recognition performance in both accuracy scores and Hu values. Time wearing cochlear implant could predict reaction time in emotion perception tasks among children with cochlear implants. No correlation was observed between the accuracy score in voice emotion perception and the self-reported scores of health-related quality of life; however, the latter were significantly correlated with speech recognition skills among Mandarin-speaking children with cochlear implants.

Conclusions: Mandarin-speaking children with cochlear implants could have significant deficits in voice emotion recognition tasks compared with their normally hearing peers and can benefit from the exaggerated prosody of child-directed speech. The effects of age at cochlear implantation, speech and language development, and cognition could play an important role in voice emotion perception by Mandarin-speaking children with cochlear implants.
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http://dx.doi.org/10.1097/AUD.0000000000001085DOI Listing
July 2021

The central nervous system can directly regulate breast cancer progression and blockage by quercetin.

Ann Transl Med 2021 Jun;9(12):999

Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

Background: Neuroinflammation involving the central nervous system (CNS), such as depression, is associated with a significantly increased risk of cancer and cancer-specific mortality due to breast cancer. It is of great significance to learn about the regulatory process of CNS in breast cancer progression.

Methods: We established a depressive MMTV-PyVT mouse model. The expression levels of neurotransmitters in the serum of depression animal models were assessed by enzyme-linked immunosorbent assay (ELISA). Changes of the microglia cells in the mice's brains were evaluated by immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). Breast cancer progression was assessed by immunohistochemistry (IHC) analysis. To further investigate the mechanism by which ant-depressant drugs disrupt breast cancer progression, protein sequencing and network pharmacology were applied to identify related targets. Furthermore, we used conditioned medium from BV-2 microglia to culture breast cancer cells and treated the cells with quercetin at different concentrations; cell viability was assessed by the MTT assay.

Results: Our results show a possible regulatory target between neuroinflammation in the CNS and development of breast cancer, along with the reversal effect of quercetin on breast cancer progression.

Conclusions: Chronic stress may be an indicator of breast cancer and that quercetin could be an effective treatment for breast cancer patients with chronic stress.
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http://dx.doi.org/10.21037/atm-21-2558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267261PMC
June 2021

Polymorphism of Antifolate Drug Resistance in From Local Residents and Migrant Workers Returned From the China-Myanmar Border.

Front Cell Infect Microbiol 2021 24;11:683423. Epub 2021 Jun 24.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.

Drug-resistant  malaria impedes efforts to control, eliminate, and ultimately eradicate malaria in Southeast Asia. resistance to antifolate drugs derives from point mutations in specific parasite genes, including the dihydropteroate synthase (), dihydrofolate reductase (), and GTP cyclohydrolase I () genes. This study aims to investigate the prevalence and spread of drug resistance markers in populating the China-Myanmar border. Blood samples were collected from symptomatic patients with acute infection. Samples with single-clone infections were sequenced for and genesand genotyped for 6 flanking microsatellite markers. Copy number variation in the gene was also examined. Polymorphisms were observed in six different codons of the  gene (382, 383, 512, 549, 553, and 571) and six different codons of the  gene (13, 57, 58, 61, 99, 117) in two study sites. The quadruple mutant haplotypes 57I/L/58R/61M/117T of gene were the most common (comprising 76% of cases in Myitsone and 43.7% of case in Laiza). The double mutant haplotype 383G/553G of  gene was also prevalent at each site (40.8% and 31%). Microsatellites flanking the gene differentiated clinical samples from wild type and quadruple mutant genotypes ( = 0.259-0.3036), as would be expected for a locus undergoing positive selection. The lack of copy number variation of suggests that SP-resistant may harbor alternative mechanisms to secure sufficient folate.
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http://dx.doi.org/10.3389/fcimb.2021.683423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265503PMC
July 2021

Fangchinoline Inhibits Human Esophageal Cancer by Transactivating ATF4 to Trigger Both Noxa-Dependent Intrinsic and DR5-Dependent Extrinsic Apoptosis.

Front Oncol 2021 14;11:666549. Epub 2021 Jun 14.

Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Esophageal squamous cell carcinoma (ESCC) is a recalcitrant cancer. The Chinese herbal monomer fangchinoline (FCL) has been reported to have anti-tumor activity in several human cancer cell types. However, the therapeutic efficacy and underlying mechanism on ESCC remain to be elucidated. In the present study, for the first time, we demonstrated that FCL significantly suppressed the growth of ESCC both and . Mechanistic studies revealed that FCL-induced G1 phase cell-cycle arrest in ESCC which is dependent on p21 and p27. Moreover, we found that FCL coordinatively triggered Noxa-dependent intrinsic apoptosis and DR5-dependent extrinsic apoptosis by transactivating ATF4, which is a novel mechanism. Our findings elucidated the tumor-suppressive efficacy and mechanisms of FCL and demonstrated FCL is a potential anti-ESCC agent.
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http://dx.doi.org/10.3389/fonc.2021.666549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236818PMC
June 2021

Increasing proportions of relapsing parasite species among imported malaria in China's Guangxi Province from Western and Central Africa.

Travel Med Infect Dis 2021 Jun 21;43:102130. Epub 2021 Jun 21.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, 650500, China. Electronic address:

Background: Travel-related malaria in non-endemic areas returning from endemic areas presents important challenges to diagnosis and treatment. Imported malaria to newly malaria-free countries poses further threats of malaria re-introduction and potential resurgence. For those traveling to places with high Plasmodium falciparum prevalence, prophylaxis against this parasite is recommended, whereas causal prophylaxis against relapsing malaria is often overlooked.

Methods: We analyzed a cluster of imported malaria among febrile patients in Shanglin County, Guangxi Province, China, who had recent travel histories to Western and Central Africa. Malaria was diagnosed by microscopy and subsequently confirmed by species- and subspecies-specific PCR. Plasmodium vivax was genotyped using a barcode consisting of 42 single nucleotide polymorphisms.

Results: Investigations of 344 PCR-confirmed malaria cases revealed that in addition to Plasmodium falciparum being the major parasite species, the relapsing parasites Plasmodium ovale and P. vivax accounted for ~40% of these imported cases. Of the 114 P. ovale infections, 65.8% and 34.2% were P. ovale curtisi and P. ovale wallikeri, respectively, with the two subspecies having a ~2:1 ratio in both Western and Central Africa. Phylogenetic analysis of 14 P. vivax isolates using a genetic barcode demonstrated that 11 formed a distinct clade from P. vivax populations from Eastern Africa.

Conclusion: This study provides support for active P. vivax transmission in areas with the predominant Duffy-negative blood group. With relapsing malaria making a substantial proportion of the imported malaria, causal prophylaxis should be advocated to travelers with a travel destination to Western and Central Africa.
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http://dx.doi.org/10.1016/j.tmaid.2021.102130DOI Listing
June 2021

Loop-mediated isothermal amplification (LAMP) assays targeting 18S ribosomal RNA genes for identifying P. vivax and P. ovale species and mitochondrial DNA for detecting the genus Plasmodium.

Parasit Vectors 2021 May 24;14(1):278. Epub 2021 May 24.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, 650500, Yunnan, People's Republic of China.

Background: Loop-mediated isothermal amplification (LAMP) has been widely used to diagnose various infectious diseases. Malaria is a globally distributed infectious disease attributed to parasites in the genus Plasmodium. It is known that persons infected with Plasmodium vivax and P. ovale are prone to clinical relapse of symptomatic blood-stage infections. LAMP has not previously been specifically evaluated for its diagnostic performance in detecting P. ovale in an epidemiological study, and no commercial LAMP or rapid diagnostic test (RDT) kits are available for specifically diagnosing infections with P. ovale.

Methods: An assay was designed to target a portion of mitochondrial DNA (mtDNA) among Plasmodium spp., the five human Plasmodium species and two other assays were designed to target the nuclear 18S ribosomal DNA gene (18S rDNA) of either P. vivax or P. ovale for differentiating the two species. The sensitivity of the assays was compared to that of nested PCR using defined concentrations of plasmids containing the target sequences and using limiting dilutions prepared from clinical isolates derived from Chinese workers who had become infected in Africa or near the Chinese border with Myanmar.

Results: The results showed that 10 copies of the mitochondrial target or 10 and 10 copies of 18S rDNA could be detected from Plasmodium spp., P. vivax and P. ovale, respectively. In 279 clinical samples, the malaria Pan mtDNA LAMP test performed well when compared with a nested PCR assay (95% confidence interval [CI] sensitivity 98.48-100%; specificity 90.75-100%). When diagnosing clinical cases of infection with P. vivax, the 18S rDNA assay demonstrated an even great sensitivity (95.85-100%) and specificity (98.1-100%). The same was true for clinical infections with P. ovale (sensitivity 90.76-99.96%; specificity 98.34-100%). Using plasmid-positive controls, the limits of detection of Malaria Pan, 18S rDNA P. vivax and 18S rDNA P. ovale LAMP were 100-, 100- and tenfold lower than those of PCR, respectively.

Conclusion: The novel LAMP assays can greatly aid the rapid, reliable and highly sensitive diagnosis of infections of Plasmodium spp. transmitted among people, including P. vivax and P. ovale, cases of which are most prone to clinical relapse.
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http://dx.doi.org/10.1186/s13071-021-04764-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147439PMC
May 2021

The Direct Semi-Quantitative Detection of 18 Pathogens and Simultaneous Screening for Nine Resistance Genes in Clinical Urine Samples by a High-Throughput Multiplex Genetic Detection System.

Front Cell Infect Microbiol 2021 12;11:660461. Epub 2021 Apr 12.

Department of Laboratory Medicine, Huadong Hospital, Affiliated With Fudan University, Shanghai, China.

Background: Urinary tract infections (UTIs) are one the most common infections. The rapid and accurate identification of uropathogens, and the determination of antimicrobial susceptibility, are essential aspects of the management of UTIs. However, existing detection methods are associated with certain limitations. In this study, a new urinary tract infection high-throughput multiplex genetic detection system (UTI-HMGS) was developed for the semi-quantitative detection of 18 pathogens and the simultaneously screening of nine resistance genes directly from the clinical urine sample within 4 hours.

Methods: We designed and optimized a multiplex polymerase chain reaction (PCR) involving fluorescent dye-labeled specific primers to detect 18 pathogens and nine resistance genes. The specificity of the UTI-HMGS was tested using standard strains or plasmids for each gene target. The sensitivity of the UTI-HMGS assay was tested by the detection of serial tenfold dilutions of plasmids or simulated positive urine samples. We also collected clinical urine samples and used these to perform urine culture and antimicrobial susceptibility testing (AST). Finally, all urine samples were detected by UTI-HMGS and the results were compared with both urine culture and Sanger sequencing.

Results: UTI-HMGS showed high levels of sensitivity and specificity for the detection of uropathogens when compared with culture and sequencing. In addition, ten species of bacteria and three species of fungi were detected semi-quantitatively to allow accurate discrimination of significant bacteriuria and candiduria. The sensitivity of the UTI-HMGS for the all the target genes could reach 50 copies per reaction. In total, 531 urine samples were collected and analyzed by UTI-HMGS, which exhibited high levels of sensitivity and specificity for the detection of uropathogens and resistance genes when compared with Sanger sequencing. The results from UTI-HMGS showed that the detection rates of 15 pathogens were significantly higher (P<0.05) than that of the culture method. In addition, there were 41(7.72%, 41/531) urine samples were positive for difficult-to-culture pathogens, which were missed detected by routine culture method.

Conclusions: UTI-HMGS proved to be an efficient method for the direct semi-quantitative detection of 18 uropathogens and the simultaneously screening of nine antibiotic resistance genes in urine samples. The UTI-HMGS could represent an alternative method for the clinical detection and monitoring of antibiotic resistance.
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http://dx.doi.org/10.3389/fcimb.2021.660461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072482PMC
July 2021

Genomic population structure of Shanghai isolates and identification of genomic features uniquely linked with pathogenicity.

Virulence 2021 12;12(1):1258-1270

Department of Laboratory Medicine, Research Center on Aging and Medicine, Fudan University, Shanghai, China.

Severe -linked gastric disorders are especially prevalent in the East Asia region. The ability of to cause different clinical outcomes is thought to be associated with unique sets of its genetic features. However, only few genetic features have been definitively linked to specific gastrointestinal pathologies. Genome heterogeneity of clinical strains from patients with four different gastric disorders was studied to explore the population structure and molecular genomic features and their association with pathogenicity. Population analysis showed that 92.9% of the Shanghai isolates were clustered in the East Asia group. Among 2,866 genes detected in all genomes, 1,146 genes formed the core genome, whereas 209 unique genes were detected in individual disease groups. The unique genes of peptic ulcer and gastric cancer groups represented the inorganic ion transport and metabolism function gene clusters. Sixteen virulence genes were detected with statistically different detection rates among the four disease groups. Furthermore, 127 clustered regularly interspaced short palindromic repeats were found with significantly different rates in the four disease groups. A total of 337 putative genomic islands were identified, and three genomic islands were individually found in more than 10% of strains. The genomic islands included several metabolism-associated genes and many genes with unknown function. In total, 88 sequence types were detected among the 112 Shanghai isolates. Our study provides an essential milestone in the mapping of specific genomic features and their functions to identify factors needed to induce specific gastric disorders in
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http://dx.doi.org/10.1080/21505594.2021.1920762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081043PMC
December 2021

The Nuclear Farnesoid X Receptor Reduces p53 Ubiquitination and Inhibits Cervical Cancer Cell Proliferation.

Front Cell Dev Biol 2021 6;9:583146. Epub 2021 Apr 6.

Department of Pharmacology, Shantou University Medical College, Shantou, China.

The role of farnesoid X receptor (FXR) in cervical cancer and the underlying molecular mechanism remain largely unknown. Therefore, this study aimed to assess the mechanism of FXR in cervical cancer. Western blot, qRT-PCR, and immunohistochemistry demonstrated that FXR was significantly reduced in squamous cell carcinoma tissues, although there were no associations of metastasis and TNM stage with FXR. In Lenti-FXR cells obtained by lentiviral transfection, the overexpression of FXR reduced cell viability and colony formation. Compared with the Lenti-Vector groups, the overexpression of FXR induced early and late apoptosis and promoted G1 arrest. With time, early apoptosis decreased, and late apoptosis increased. In tumor xenograft experiments, overexpression of FXR upregulated small heterodimer partner (SHP), murine double minute-2 (MDM2), and p53 in the nucleus. Co-immunoprecipitation (Co-IP) showed that SHP directly interacted with MDM2, which is important to protect p53 from ubiquitination. Nutlin3a increased MDM2 and p53 amounts in the Lenti-Vector groups, without effects in the Lenti-FXR groups. Silencing SHP reduced MDM2 and p53 levels in the Lenti-FXR groups, and Nutlin3a counteracted these effects. Taken together, these findings suggest that FXR inhibits cervical cancer via upregulation of SHP, MDM2, and p53.
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http://dx.doi.org/10.3389/fcell.2021.583146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056046PMC
April 2021

TWIST2 and the PPAR signaling pathway are important in the progression of nonalcoholic steatohepatitis.

Lipids Health Dis 2021 Apr 20;20(1):39. Epub 2021 Apr 20.

Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, P. R. China.

Background: To investigate the roles of the transcription factors twist family bHLH transcription factor 1 (TWIST1), twist family bHLH transcription factor 2 (TWIST2), and peroxisome proliferator activated receptor gamma (PPARγ) in the progression of nonalcoholic steatohepatitis.

Methods: The protein levels of TWIST1, TWIST2 and PPARγ were determined in the serum of nonalcoholic fatty liver disease (NAFLD) patients and healthy controls by enzyme-linked immunosorbent assay (ELISA). An in vivo model for fatty liver was established by feeding C57BL/6 J mice a high-fat diet (HFD). An in vitro model of steatosis was established by treating LO-2 cells with oleic acid (OA). RNA sequencing was performed on untreated and OA-treated LO-2 cells followed by TWIST1, TWIST2 and PPARγ gene mRNA levels analysis, Gene Ontology (GO) enrichment and pathway analysis.

Results: The TWIST2 serum protein levels decreased significantly in all fatty liver groups (P < 0.05), while TWIST1 varied. TWIST2 tended to be lower in mice fed an HFD and was significantly lower at 3 months. Similarly, in the in vitro model, the TWIST2 protein level was downregulated significantly at 48 and 72 h after OA treatment. RNA sequencing of LO-2 cells showed an approximately 2.3-fold decrease in TWIST2, with no obvious change in TWIST1 and PPARγ. The PPAR signaling pathway was enriched, with 4 genes upregulated in OA-treated cells (P = 0.0018). The interleukin (IL)-17 and tumor necrosis factor (TNF) signaling pathways were enriched in OA-treated cells.

Conclusions: The results provide evidence that the TWIST2 and PPAR signaling pathways are important in NAFLD and shed light on a potential mechanism of steatosis.
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http://dx.doi.org/10.1186/s12944-021-01458-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059034PMC
April 2021

Efficient induction of neural progenitor cells from human ESC/iPSCs on Type I Collagen.

Sci China Life Sci 2021 Mar 16. Epub 2021 Mar 16.

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.

A stable, rapid and effective neural differentiation method is essential for the clinical applications of human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in treating neurological disorders and diseases. Herein, we established a novel and robust monolayer differentiation method to produce functional neural progenitor cells (NPCs) from human ESC/iPSCs on Type I Collagen. The derived cells not only displayed the requisite markers, but also behaved similarly to classic NPCs both in vitro and in vivo. Upon transplantation into traumatic brain injury model, the derived NPCs facilitated recovery from injury. We also found that SMAD signaling stayed down throughout the differentiation process on Type I Collagen, and the pluripotent signals were rapidly downregulated along with raising up of neural early markers on the third day. Meanwhile, ATAC-seq data showed the related mediation of distinct transcriptome and global chromatin dynamics during NPC induction. Totally, our results thus provide a convenient way to generate NPCs from human ESC/iPSCs for neural diseases' treatment.
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http://dx.doi.org/10.1007/s11427-020-1897-0DOI Listing
March 2021

Overexpressed NEDD8 as a potential therapeutic target in esophageal squamous cell carcinoma.

Cancer Biol Med 2021 Mar 18. Epub 2021 Mar 18.

Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.

Objective: The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target. We aimed to study whether NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) might serve as a therapeutic target in esophageal squamous cell carcinoma (ESCC).

Methods: The clinical relevance of NEDD8 expression was evaluated by using The Cancer Genome Atlas (TCGA) database and tissue arrays. NEDD8-knockdown ESCC cells generated with the CRISPR/Cas9 system were used to explore the anticancer effects and mechanisms. Quantitative proteomic analysis was used to examine the variations in NEDD8 knockdown-induced biological pathways. The cell cycle and apoptosis were assessed with fluorescence activated cell sorting. A subcutaneous-transplantation mouse tumor model was established to investigate the anticancer potential of NEDD8 silencing .

Results: NEDD8 was upregulated at both the mRNA and protein expression levels in ESCC, and NEDD8 overexpression was associated with poorer overall patient survival (mRNA level: = 0.028, protein level: = 0.026, log-rank test). Downregulation of NEDD8 significantly suppressed tumor growth both and . Quantitative proteomic analysis revealed that downregulation of NEDD8 induced cell cycle arrest, DNA damage, and apoptosis in ESCC cells. Mechanistic studies demonstrated that NEDD8 knockdown led to the accumulation of cullin-RING E3 ubiquitin ligases (CRLs) substrates through inactivation of CRLs, thus suppressing the malignant phenotype by inducing cell cycle arrest and apoptosis in ESCC. Rescue experiments demonstrated that the induction of apoptosis after NEDD8 silencing was attenuated by DR5 knockdown.

Conclusions: Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown, and validated NEDD8 as a potential target for ESCC therapy.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0484DOI Listing
March 2021

Sphagnum Inspired g-C N Nano/Microspheres with Smaller Bandgap in Heterojunction Membranes for Sunlight-Driven Water Purification.

Small 2021 03 15;17(12):e2007122. Epub 2021 Feb 15.

Polymer Materials & Engineering Department, School of Materials Science & Engineering, Chang'an University, Xian, 710064, China.

Membrane separation is recognized as one of the most effective strategies to treat the complicated wastewater system for economic development. However, serious membrane fouling has restricted its further application. Inspired by sphagnum, a 0D/2D heterojunction composite membrane is engineered by depositing graphitic carbon nitride nano/microspheres (CNMS) with plentiful wrinkles onto the polyacrylic acid functionalized carbon nanotubes (CNTs-PAA) membrane through hydrogen bond force. Through coupling unique structure and chemistry properties, the CNTs-PAA/CNMS heterojunction membrane presents superhydrophilicity and underwater superoleophobicity. Furthermore, thanks to the J-type aggregates during the solvothermal process, it is provided with a smaller bandgap (1.77 eV) than the traditional graphitic carbon nitride (g-C N ) sheets-based membranes (2.4-2.8 eV). This feature endows the CNTs-PAA/CNMS membrane with superior visible-light-driven self-cleaning ability, which can maintain its excellent emulsion separation (with a maximum flux of 5557 ± 331 L m h bar and an efficiency of 98.5 ± 0.6%), photocatalytic degradation (with an efficiency of 99.7 ± 0.2%), and antibacterial (with an efficiency of ≈100%) ability even after cyclic experimental processes. The excellent self-cleaning performance of this all-in-one membrane represents its potential value for water purification.
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http://dx.doi.org/10.1002/smll.202007122DOI Listing
March 2021

Cullin3-TNFAIP1 E3 Ligase Controls Inflammatory Response in Hepatocellular Carcinoma Cells via Ubiquitination of RhoB.

Front Cell Dev Biol 2021 21;9:617134. Epub 2021 Jan 21.

Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China.

Rho family GTPase RhoB is the critical signaling component controlling the inflammatory response elicited by pro-inflammatory cytokines. However, the underlying mechanisms of RhoB degradation in inflammatory response remain unclear. In this study, for the first time, we identified that TNFAIP1, an adaptor protein of Cullin3 E3 ubiquitin ligases, coordinated with Cullin3 to mediate RhoB degradation through ubiquitin proteasome system. In addition, we demonstrated that downregulation of TNFAIP1 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in TNFα-stimulated hepatocellular carcinoma cells through the activation of p38/JNK MAPK pathway via blocking RhoB degradation. Our findings revealed a novel mechanism of RhoB degradation and provided a potential strategy for anti-inflammatory intervention of tumors by targeting TNFAIP1-RhoB axis.
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http://dx.doi.org/10.3389/fcell.2021.617134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859282PMC
January 2021

Tumor-associated antigen Prame targets tumor suppressor p14/ARF for degradation as the  receptor protein of CRL2 complex.

Cell Death Differ 2021 Jun 27;28(6):1926-1940. Epub 2021 Jan 27.

Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.

Protein Preferentially Expressed Antigen in Melanoma (Prame), a tumor-associated antigen, has been found to frequently overexpress in various cancers, which indicates advanced cancer stages and poor clinical prognosis. Moreover, previous reports noted that Prame functions as a substrate recognizing receptor protein of Cullin RING E3 ligases (CRLs) to mediate potential substrates degradation through Ubiquitin Proteasome System (UPS). However, none of the Prame specific substrate has been identified so far. In this study, proteomic analysis of RBX1-interacting proteins revealed p14/ARF, a well-known tumor suppressor, as a novel ubiquitin target of RBX1. Subsequently, immunoprecipitation and in vivo ubiquitination assay determined Cullin2-RBX1-Transcription Elongation Factor B Subunit 2 (EloB) assembled CRL2 E3 ligase complex to regulate the ubiquitination and subsequent degradation of p14/ARF. Finally, through siRNA screening, Prame was identified as the specific receptor protein responsible for recognizing p14/ARF to be degraded. Additionally, via bioinformatics analysis of TCGA database and clinical samples, Prame was determined to overexpress in tumor tissues vs. paired adjacent tissues and associated with poor prognosis of cancer patients. As such, downregulation of Prame expression significantly restrained cancer cell growth by inducing G2/M phase cell cycle arrest, which could be rescued by simultaneously knocking down of p14/ARF. Altogether, targeting overexpressed Prame in cancer cells inactivated RBX1-Cullin2-EloB-Prame E3 ligase (CRL2) and halted p14/ARF degradation to restrain tumor growth by inducing G2/M phase cell cycle arrest.
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http://dx.doi.org/10.1038/s41418-020-00724-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184998PMC
June 2021

Impact of shoulder subluxation on peripheral nerve conduction and function of hemiplegic upper extremity in stroke patients: A retrospective, matched-pair study.

Neurol Res 2021 Jun 5;43(6):511-519. Epub 2021 Jan 5.

Rehabilitation Medical Center, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu, People's Republic of China.

: To investigate the impact of shoulder subluxation (SS) on peripheral nerve conduction and function of the hemiplegic upper extremity (HUE) in poststroke patients.: Thirty post-stroke patients were selected (SS group: 15 patients, non-SS group: 15 patients, respectively). Evaluation of nerve conduction in upper limbs: the compound muscle action potential (CMAP) amplitude and latency of suprascapular, axillary, musculocutaneous, radial, median, and ulnar nerves; the motor and sensory conduction velocity and the sensory nerve action potential (SNAP) amplitude of median, ulnar, and radial nerves. The Brunnstrom stage scale was used to evaluate the HUE motor function.: Compared with the healthy side, the CMAP and SNAP amplitudes of tested nerves on the HUE in both groups were lower, and the CMAP latency of the suprascapular, axillary and musculocutaneous nerves on the HUE in the SS group was longer (P < 0.05). Compared with the HUE in non-SS group, the CMAP amplitude of tested nerves (except ulnar) was decreased more (P < 0.05), the motor conduction velocity of the median nerve was lower (P < 0.05), and the Brunnstrom stage of the HUE was lower in SS group (P < 0.05).: Stroke may lead to extensive abnormal nerve conduction on the HUE, and SS may aggravate the abnormality, which may disturb the recovery of upper limb function.
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http://dx.doi.org/10.1080/01616412.2020.1870360DOI Listing
June 2021

Cancer-secreted exosomal miR-1468-5p promotes tumor immune escape via the immunosuppressive reprogramming of lymphatic vessels.

Mol Ther 2021 04 1;29(4):1512-1528. Epub 2021 Jan 1.

Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangdong Provincial Key Laboratory of Proteomics, Guangzhou 510515, China. Electronic address:

Cancer-associated lymphatic endothelial cells (LECs) are an active barrier to the effector arm of the anti-tumor immune response; however, it remains unclear how LECs become immunosuppressive in the tumor microenvironment (TME). Exosomal microRNAs (miRNAs) have recently been implicated in intercellular crosstalk within the TME. Here, we report a mechanistic model via which cervical cancer-secreted, exosome-encapsulated microRNA (miR)-1468-5p promotes lymphatic PD-L1 upregulation and lymphangiogenesis to impair T cell immunity. Subsequently, exosomal miR-1468-5p epigenetically activates the JAK2/STAT3 pathway in LECs by directly targeting homeobox containing 1 (HMBOX1) in the SOCS1 promoter, activating an immunosuppressive program that allows cancer cells to escape anti-cancer immunity. Furthermore, clinical data reveal that high serum exosomal miR-1468-5p levels correlate with TME immunosuppressive status and poor prognosis in cervical cancer (CCa) patients. Taken together, our results suggest that cancer-secreted exosomal miR-1468-5p instructs LECs to form an integrated immunosuppressive TME component and may be a prognostic biomarker and therapeutic target for CCa.
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http://dx.doi.org/10.1016/j.ymthe.2020.12.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058488PMC
April 2021

Specific effects of neglect and physical abuse on adolescent aggressive behaviors by gender: A multicenter study in rural China.

J Affect Disord 2021 02 9;281:271-278. Epub 2020 Dec 9.

Department of Maternal, Child and Adolescent Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Background: Neglect and physical abuse may be typical risk factors for aggressive behavior in adolescents. However, findings on their specific effects and sex differences are still unclear. This study aimed to examine the specific effects of neglect and physical abuse on adolescent aggressive behaviors and to further explore the potential sex-specific effect.

Methods: A multicenter school-based survey was conducted in rural China. A total of 15,957 students aged 11-20 years completed self-report questionnaires to record aggressive behaviors, neglect and physical abuse, and other related information. Participants were grouped into those who experienced none, one of, or both neglect and physical abuse for statistical analyses.

Results: Of the participants, 37.0% experienced both neglect and physical abuse, 30.0% experienced neglect only, and 9.8% experienced physical abuse only. Higher risk for physical aggression (OR=1.24, 95% CI=1.06-1.45), and lower risk for verbal aggression (OR=0.83, 95% CI=0.72-0.94) and hostility (OR=0.81, 95% CI=0.69-0.94) were found in the physical abuse only group as compared to the neglect only group. No sex difference was found between neglect or physical abuse and general aggressive behaviors (P>0.05), except that females were more likely to exert physical aggression than males when exposed to neglect and physical abuse (P<0.05).

Limitations: Cross-sectional design, retrospective self-report data, and not including other maltreatment subtypes.

Conclusions: Neglect and physical abuse may each have distinct sensitivity for different subtypes of aggression. Targeted treatment for diverse aggressive symptoms is suggested, and strategies to prevent both neglect and physical abuse across gender would yield comprehensive benefits.
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http://dx.doi.org/10.1016/j.jad.2020.12.019DOI Listing
February 2021

Systematic Review and Pharmacological Considerations for Chloroquine and Its Analogs in the Treatment for COVID-19.

Front Pharmacol 2020 28;11:554172. Epub 2020 Oct 28.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

COVID-19 has been announced pandemic by WHO and over 17,000,000 people infected (Till April 21st 2020). The disease is currently under control in China, with a curative rate of 86.8%. Chloroquine (CQ) is an old anti-malarial drug with good tolerability, which had proved to be effective in previous SARS-coronavirus, which spread and disappeared between 2002-2003. In vitro studies demonstrated the efficacy of CQ in curing COVID-19. Consequently, analytical PBPK modeling, a further preliminary clinical trial has proved the efficacy and safety of CQ in China., and multiple clinical trials were registered and approved to investigate the activity of other analogs of CQ against COVID-19. We have listed all the clinical trials and made a meta-analysis of published data of hydroxychloroquine (HCQ). HCQ could increase the CT improvement and adverse reactions (ADRs) significantly though there was considerable heterogeneity among current researches. Actually, CQ and its analogs have unique pharmacokinetic characteristics, which would induce severe side effects in some circumstances. We have then summarized pharmacological considerations for these drugs so as to provide to the busy clinicians to avoid potential side effects when administered CQ or its analogs to COVID-19 patients, especially in the elderly, pediatrics, and pregnancies.
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http://dx.doi.org/10.3389/fphar.2020.554172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655531PMC
October 2020

Study on the anti-infection ability of vancomycin cationic liposome combined with polylactide fracture internal fixator.

Int J Biol Macromol 2021 Jan 9;167:834-844. Epub 2020 Nov 9.

Department of Pharmacology, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong 515041, China. Electronic address:

A polylactide composite fracture fixator loaded with vancomycin cationic liposome ([email protected]) was prepared by reverse evaporation method. The method of cationic liposome encapsulating vancomycin could effectively improve antibacterial property and achieve drug sustained release effect, so as to reduce toxicity of antibiotics in vivo. Scanning electron microscope (SEM) was used to observe morphology and Fourier transform infrared spectroscopy (FTIR) was used to detect the composition of the internal fixator. In vitro drug release model, in vitro degradation model and body fluid osteogenesis model were designed in this study. On the other hand, the experiments of inhibition zone and MC3T3-E1 osteoblasts in mice were conducted to explore antibacterial property, cell activity and adhesion of the [email protected] composite internal fixator. Alkaline phosphatase (ALP) staining method and alizarin red assay were used to detect the osteogenic induction ability of the composite internal fixator. Finally, mice fracture models were established to verify osteogenic and anti-infection abilities of the composite internal fixator in vivo. The results showed that MC3T3-E1 cells had better adhesion and proliferation abilities on the [email protected] composite internal fixator than on the PLA fixator, which indicated that the [email protected] composite internal fixator possessed excellent osteogenic and anti-infection abilities both in vivo and in vitro. Therefore, the above experiments showed that the fracture internal fixator combined with vancomycin cationic liposome had better biocompatibility, antibacterial ability and osteogenic ability, which provides a promising anti-infection material for the clinical field of fracture.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.039DOI Listing
January 2021

Hydroxyapatite-modified micro/nanostructured titania surfaces with different crystalline phases for osteoblast regulation.

Bioact Mater 2021 Apr 20;6(4):1118-1129. Epub 2020 Oct 20.

College of Materials, Xiamen University, Xiamen, 361005, China.

Surface structures and physicochemical properties critically influence osseointegration of titanium (Ti) implants. Previous studies have shown that the surface with both micro- and nanoscale roughness may provide multiple features comparable to cell dimensions and thus efficiently regulate cell-material interaction. However, less attention has been made to further optimize the physicochemical properties (e.g., crystalline phase) and to further improve the bioactivity of micro/nanostructured surfaces. Herein, micro/nanostructured titania surfaces with different crystalline phases (amorphous, anatase and anatase/rutile) were prepared and hydroxyapatite (HA) nanorods were deposited onto the as-prepared surfaces by a spin-assisted layer-by-layer assembly method without greatly altering the initial multi-scale morphology and wettability. The effects of crystalline phase, chemical composition and wettability on osteoblast response were investigated. It is noted that all the micro/nanostructured surfaces with/without HA modification presented superamphiphilic. The activities of MC3T3-E1 cells suggested that the proliferation trend on the micro/nanostructured surfaces was greatly influenced by different crystalline phases, and the highest proliferation rate was obtained on the anatase/rutile surface, followed by the anatase; but the cell differentiation and extracellular matrix mineralization were almost the same among them. After ultrathin HA modification on the micro/nanostructured surfaces with different crystalline phases, it exhibited similar proliferation trend as the original surfaces; however, the cell differentiation and extracellular matrix mineralization were significantly improved. The results indicate that the introduction of ultrathin HA to the micro/nanostructured surfaces with optimized crystalline phase benefits cell proliferation, differentiation and maturation, which suggests a favorable biomimetic microenvironment and provides the potential for enhanced implant osseointegration in vivo.
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http://dx.doi.org/10.1016/j.bioactmat.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577196PMC
April 2021

LINC00460 Enhances Bladder Carcinoma Cell Proliferation and Migration by Modulating miR-612/FOXK1 Axis.

Pharmacology 2021 7;106(1-2):79-90. Epub 2020 Oct 7.

Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China,

Introduction: LincRNA (long intergenic noncoding RNA) has been indicated as a mediator in tumorigenesis of bladder carcinoma. This study was performed to evaluate the role of LINC00460 in bladder carcinoma progression.

Methods: Expression levels of LINC00460 in bladder carcinoma tissues and cell lines were analyzed via qRT-PCR. MTT, EdU (5-ethynyl-2'-deoxyuridine) staining, and colony formation assays were utilized to evaluate cell viability and proliferation. The wound healing assay was performed to evaluate bladder cancer cell migration, and the transwell assay was used to evaluate cell invasion. The microRNA (miRNA) target of LINC00460 and the corresponding target gene were validated via the dual luciferase activity assay. The tumorigenic function of LINC00460 was determined via establishment of a xenotransplanted tumor model.

Results: LINC00460 was elevated in bladder carcinoma tissues and cell lines. Elevated LINC00460 was associated with shorter overall survival of bladder carcinoma patients. Overexpression of LINC00460 promoted cell viability, proliferation, invasion, and migration, while silencing of LINC00460 indicated the opposite effect on bladder carcinoma progression. LINC00460 could directly bind to miR-612 and inhibit miR-612 expression. Moreover, LINC00460 expression was negatively correlated with miR-612 in patients with bladder carcinoma. FOXK1 (Forkhead Box K1) was identified as the target of miR-612 and upregulated in patients with bladder carcinoma. Overexpression of FOXK1 attenuated interference of LINC00460-inhibited bladder carcinoma progression. Knockdown of LINC00460 suppressed in vivo bladder carcinoma growth.

Conclusions: LINC00460 promoted bladder carcinoma progression via sponging miR-612 to facilitate FOXK1 expression, suggesting that LINC00460 might have the potential of being explored as a therapeutic target for treatment of bladder carcinoma.
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http://dx.doi.org/10.1159/000509255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949225PMC
March 2021

Brother of regulator of imprinted sites inhibits cisplatin-induced DNA damage in non-small cell lung cancer.

Oncol Lett 2020 Nov 17;20(5):251. Epub 2020 Sep 17.

Center for Molecular Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310012, P.R. China.

Cisplatin (DDP) chemotherapy is the primary modality of treatment for non-small cell lung cancer (NSCLC). However, due to the occurrence of DDP resistance, only a limited number of patients benefit from this treatment regimen. Brother of Regulator of Imprinted Sites (BORIS) is expressed elevated in NSCLC. Whether BORIS is involved in the DDP resistance of NSCLC is currently undetermined. The association between expression and overall survival rate of 156 patients with NSCLC who received DDP chemotherapy was analyzed in the present study. In order to investigate the function of BORIS in DDP chemotherapy, was silenced or overexpressed in four NSCLC cell lines. The cell viabilities, apoptosis and DNA damage induced by DDP were evaluated in these cell lines. In addition, the regulations of DNA repair genes were assessed, including and . The present study demonstrated that high expression was associated with decreased overall survival rate in patients with NSCLC who received DDP chemotherapy. The patients who benefited and went into remission following DDP therapy expressed a relatively low level of , suggesting the potential function of BORIS in DDP resistance. Cell experiments revealed that NSCLC cells that had a higher proliferation rate and resisted DDP treatment expressed a relatively higher level of . Knockdown of in NSCLC cells induced DNA damage; inhibiting cell proliferation and sensitizing cells to DDP treatment. In contrast, overexpression suppressed DDP-induced DNA damage. Notably, the mismatch repair factor mutS homolog 6 () was regulated by BORIS, indicating its association with BORIS-associated DDP resistance in NSCLC. The findings of the present study suggest that BORIS suppresses DNA damage and promotes the progression of NSCLC and DDP resistance. The present study indicates the potential application of BORIS in NSCLC therapy and prognosis.
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http://dx.doi.org/10.3892/ol.2020.12114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509674PMC
November 2020

Exosome-derived miR-142-5p remodels lymphatic vessels and induces IDO to promote immune privilege in the tumour microenvironment.

Cell Death Differ 2021 02 14;28(2):715-729. Epub 2020 Sep 14.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Clinical response to immunotherapy is closely associated with the immunosuppressive tumour microenvironment (TME), and influenced by the dynamic interaction between tumour cells and lymphatic endothelial cells (LECs). Here, we show that high levels of miR-142-5p positively correlate with indoleamine 2,3-dioxygenase (IDO) expression in tumour-associated lymphatic vessels in advanced cervical squamous cell carcinoma (CSCC). The miR-142-5p is transferred by CSCC-secreted exosomes into LECs to exhaust CD8 T cells via the up-regulation of lymphatic IDO expression, which was abrogated by an IDO inhibitor. Mechanistically, miR-142-5p directly down-regulates lymphatic AT-rich interactive domain-containing protein 2 (ARID2) expression, inhibits DNA methyltransferase 1 (DNMT1) recruitment to interferon (IFN)-γ promoter, and enhances IFN-γ transcription by suppressing promoter methylation, thereby leading to elevated IDO activity. Furthermore, increased serum exosomal miR-142-5p levels and the consequent IDO activity positively correlate with CSCC progression. In conclusion, exosomes secreted by CSCC cells deliver miR-142-5p to LECs and induce IDO expression via ARID2-DNMT1-IFN-γ signalling to suppress and exhaust CD8 T cells. Our study suggests that LECs act as an integral component of the immune checkpoint(s) in the TME and may serve as a potential new target for CSCC diagnosis and treatment.
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http://dx.doi.org/10.1038/s41418-020-00618-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862304PMC
February 2021

Sequential Bilateral Cochlear Implantation With Prolonged Time Intervals.

J Speech Lang Hear Res 2020 09 28;63(9):3195-3207. Epub 2020 Aug 28.

Department of Otolaryngology, Head and Neck Surgery, Peking University First Hospital, Beijing, China.

Purpose The aim of the study was to assess whether sequential cochlear implantation (CI) with a prolonged interimplant interval ( = 15.2 years) between the first and second CIs benefited speech recognition and health-related quality of life. Method This prospective study included 14 prelingually deafened participants who received their second CI after a prolonged interimplant interval ( = 15.2 years). Additionally, speech recognition ability over a 12-month period of bilateral implant use was investigated. The results of the speech recognition test in both quiet and noisy conditions were statistically analyzed for each CI alone and both CIs together. Nijmegen Cochlear Implant Questionnaire scores were also collected at activation and at 12 months after activation. Results Improvements in speech recognition ability were observed following the use of the first implant alone and with the use of both implants together; however, progress was much slower with the use of the second implant alone, following its introduction. Furthermore, a significant difference in the trajectory of speech recognition ability was observed between the first and the second implanted ear. According to Nijmegen Cochlear Implant Questionnaire scores, all participants benefitted from bilateral CI after 12 months. Conclusions Prolonged interimplant intervals resulted in asymmetrical speech recognition abilities. A significant improvement in the speech recognition scores was observed with the first implanted ear, and much slower progress was observed with the second implanted ear. However, the "poorer" second implanted ear could provide a considerable beneficial effect on the improved speech recognition and health-related quality of life with the bilateral CI. Supplemental Material https://doi.org/10.23641/asha.12861152.
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http://dx.doi.org/10.1044/2020_JSLHR-20-00140DOI Listing
September 2020

[Research on modelling vestibular rehabilitation decision based on machine learning].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Jul;34(7):592-598

Department of Otorhinolaryngology Head and Neck Surgery,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology.

To evaluate the effect of the support vector machine(SVM) and artificial neutral network(ANN) on the treatment choice of vestibular rehabilitation. Total scores COMP and three ratios of sensory analysis: somatosensory(SOM), visual(VIS), vestibular(VEST) from the sensory organization test(SOT), and physical score(DHI-P), emotional score(DHI-E), functional score(DHI-F) from the dizziness handicap inventory(DHI) were chosen as input of SVM and ANN, rehabilitation program as output. According to the data source of the literatures, we constructed simulation database used as the sample set to conduct model training, and part of the clinical data was used to train the model accuracy. After trainings, the accuracy rate of ANN model was 52.3%, and that of SVM model was 83.4%. The error mainly comes from the serious overlap of each score data interval under the three diagnostic schemes, which easily leads to the misclassification of boundary sample points, which is also a difficult problem to overcome in clinical diagnosis. Vestibular rehabilitation decision based SVM is more accurate than ANN. The use of machine learning to assist decision-making of vestibular rehabilitation scheme has important prospective reference significance in promoting clinical medical informatization and improving medical quality.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.07.004DOI Listing
July 2020

NEDD8-conjugating enzyme UBC12 as a novel therapeutic target in esophageal squamous cell carcinoma.

Signal Transduct Target Ther 2020 07 10;5(1):123. Epub 2020 Jul 10.

Department of Laboratory Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, China.

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http://dx.doi.org/10.1038/s41392-020-00226-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351728PMC
July 2020

Comments on 'Association of FcϵRIβ polymorphisms with risk of asthma and allergic rhinitis: evidence based on 29 case-control studies'.

Biosci Rep 2020 07;40(7)

Department of Preventive Medicine, College of Basic Medical Sciences, Hubei University of Chinese Medicine, Hongshan District, Wuhan 430065, P.R. China.

Guo et al. (Bioscience Reports (2018) 38, BSR20180177) published a meta-analysis concerning the association between five single nucleotide polymorphisms (SNPs) in the high-affinity IgE receptor β chain (FcεRIβ) gene, namely E237G, -109 C/T, RsaI_in2, RsaI_ex7, and I181L, and risk of asthma and allergic rhinitis based on available 29 case-control studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of association of SNPs in FcεRIβ gene with allergic diseases risk. They found that FcεRIβ E237G (237G vs. 237E: OR = 1.28, 95% CI = 1.06-1.53) and -109 C/T (TT vs. CT+CC: OR = 1.58, 95% CI = 1.26-1.98) were risk factors for allergic diseases. Guo et al.'s findings are interesting, but we found that several issues should be clarified after carefully reading the paper. Here, we intended to comment on these data clarifications.
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http://dx.doi.org/10.1042/BSR20193424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374272PMC
July 2020

Molecular Surveillance and in vitro Drug Sensitivity Study of Isolates from the China-Myanmar Border.

Am J Trop Med Hyg 2020 09;103(3):1100-1106

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.

The emergence and spread of resistance in to the frontline treatment artemisinin-based combination therapies in Southeast Asia require close monitoring of the situation. Here, we collected 36 clinical samples of from the China-Myanmar border in 2014-2016, adapted these parasites to continuous culture, and performed in vitro drug assays on seven antimalarial drugs. Data for 23 parasites collected in 2010 and 2012 from the same area reported in an early study were used to assess longitudinal changes in drug sensitivity. Parasites remained highly resistant to chloroquine (CQ) and pyrimethamine, whereas they were generally sensitive to mefloquine (MFQ), lumefantrine (LMF), naphthoquine (NQ), and pyronaridine (PND). Parasites showed a similar temporal trend in sensitivity to CQ, NQ, and PND, with gradual reduction in the half-maximal inhibitory concentrations (ICs) after 2012. The ICs to the aminoalcohol drugs MFQ, LMF, and quinine (QN) all significantly declined in 2014, followed by various degrees of increase in 2016. Pyrimethamine displayed a continuous increase in IC over the years. The Dd2-like mutations were fixed or nearly fixed in the parasite population. The F1226Y mutation was detected in 80% parasites in 2016 and associated with reduced sensitivity to LMF and QN ( < 0.05). The N51I in and K540E/N and A581G in that are associated with antifolate resistance were either fixed or were approaching fixation in recent years. This study provides an updated picture and temporal trend of antimalarial drug resistance in the China-Myanmar border region, which will serve as a reference for antimalarial treatment.
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http://dx.doi.org/10.4269/ajtmh.20-0235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470591PMC
September 2020

Establishing metastatic patient-derived xenograft model for colorectal cancer.

Jpn J Clin Oncol 2020 Sep;50(10):1108-1116

ZJU-UoE Institute, School of Medicine, Zhejiang University, Haining, China.

Background: Patient-derived xenograft model is a powerful and promising tool for drug discovery and cancer biology studies. The application of previous metastatic colorectal cancer models has been greatly limited by its low success rate and long time to develop metastasis. Therefore, in this study, we aim to describe an optimized protocol for faster establishment of colorectal cancer metastatic patient-derived xenograft mouse models.

Methods: Smaller micro tissues (˂150 μm in diameter) mixed with Matrigel were engrafted subcutaneously into NSG mice to generate the passage 1 (P1) patient-derived xenograft. The micro tumours from P1 patient-derived xenograft were then excised and orthotopically xenografted into another batch of NSG mice to generate a metastatic colorectal cancer patient-derived xenograft, P2. Haematoxylin and eosin and immunohistochemistry staining were performed to compare the characters between patient-derived xenograft tumours and primary tumours.

Results: About 16 out of 18 P1 xenograft models successfully grew a tumour for 50.8 ± 5.1 days (success rate 89.9%). Six out of eight P1 xenograft models originating from metastatic patients successfully grew tumours in the colon and metastasized to liver or lung in the NSG recipients for 60.9 ± 4.5 days (success rate 75%). Histological examination of both P1 and P2 xenografts closely resembled the histological architecture of the original patients' tumours. Immunohistochemical analysis revealed similar biomarker expression levels, including CDH17, Ki-67, active β-catenin, Ki-67 and α smooth muscle actin when compared with the original patients' tumours. The stromal components that support the growth of patient-derived xenograft tumours were of murine origin.

Conclusions: Metastatic patient-derived xenograft mouse model could be established with shorter time and higher success rate. Although the patient-derived xenograft tumours were supported by the stromal cells of murine origin, they retained the dominant characters of the original patient tumours.
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http://dx.doi.org/10.1093/jjco/hyaa089DOI Listing
September 2020
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