Publications by authors named "Hui Guo"

1,065 Publications

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Interferon Gamma-Induced Interferon Regulatory Factor 1 Activates Transcription of HHLA2 and Induces Immune Escape of Hepatocellular Carcinoma Cells.

Inflammation 2021 Sep 18. Epub 2021 Sep 18.

Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, No. 287, Changhuai Road, Bengbu, 233004, Anhui, People's Republic of China.

Immunosuppression developed by cancer cells remains a leading cause of treating failure of immunotherapies. This study aimed to explore the function of human endogenous retrovirus-H long terminal repeat-associating 2 (HHLA2), an immune checkpoint molecule from the B7 family, in the immune escape in hepatocellular carcinoma (HCC). Mouse models with primary HCC or with xenograft tumors were established. The portion of tumor-associated macrophages (TAMs) and the level of PD-L1 in the tumor tissues were examined. THP-1 cells were treated with PMA to obtain a macrophage-like phenotype. The PMA-treated THP-1 cells were co-cultured with the HCC cells in Transwell chambers to examine the function of HHLA2 in chemotactic migration and polarization of macrophages. HHLA2 expression was correlated with infiltration of immune cells, especially macrophages, and was linked to poor prognosis of patients with HCC. HHLA2 knockdown reduced incidence rate of primary HCC in mice. It also reduced tumor metastasis, the portion of M2 macrophages, and the expression of PD-L1 in primary and xenograft tumors. In vitro, HHLA2 upregulation increased expression of PD-L1 in HCC cells indirectly by inducing M2 polarization and chemotactic migration of macrophages. Interferon gamma (IFNG) enhanced expression of interferon regulatory factor 1 (IFR1) in HCC cells, and IFR1 bound to the promoter region of HHLA2 to activate HHLA2 expression. This study suggested that the IFNG/IFR1/HHLA2 axis in HCC induces M2 polarization and chemotactic migration of macrophages, which leads to immune escape and development of HCC.
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http://dx.doi.org/10.1007/s10753-021-01547-3DOI Listing
September 2021

Corrigendum: LncRNA NBR2 Inhibits the Malignancy of Thyroid Cancer, Associated With Enhancing the AMPK Signaling.

Front Oncol 2021 27;11:759471. Epub 2021 Aug 27.

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

[This corrects the article DOI: 10.3389/fonc.2020.00956.].
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http://dx.doi.org/10.3389/fonc.2021.759471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430396PMC
August 2021

CCNB2/SASP/Cathepsin B & PGE2 Axis Induce Cell Senescence Mediated Malignant Transformation.

Int J Biol Sci 2021 13;17(13):3538-3553. Epub 2021 Aug 13.

Department of Neurosurgery, Shanghai Deji Hospital, Qingdao University, Shanghai 200331, China.

Glioma is the most frequent and aggressive adult brain tumor with maximum mortality. However, the gene alteration and mechanism underlying malignant transformation of glioma remain largely unknown. We aimed to find key factors regulating tumor progression and malignant transformation of glioma. Here we compared the gene expression profiles of 693 glioma patients by HGG vs. LGG model, and identified a key factor CCNB2 for malignant transformation in glioma. CCNB2 induced a senescence-associated secretory phenotype (SASP) of glioma cells, and the malignant progression, such as invasion and excessive proliferation was mediated by secreting SASP cytokines, Cathepsin B and PGE2. These findings demonstrated a previously undiscovered link between senescence, CCNB2/SASP/Cathepsin B & PGE2 axis and malignant transformation in glioma. This might provide novel insights on developing new therapeutic regimens for abrogating aggressiveness of glioma.
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http://dx.doi.org/10.7150/ijbs.63430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416730PMC
August 2021

Revealing the binding properties between resorcinol and DNA.

Luminescence 2021 Sep 9. Epub 2021 Sep 9.

College of Chemistry, Nanchang University, Nanchang, Jiangxi, China.

Resorcinol (1,3-dihydroxybenzene) is a common coupling agent in permanent hair dyes, which has arrested people's attention for its potential hazard to the human health. However, the action mechanism of resorcinol and human DNA has not been elucidated yet. In this research, the binding property between resorcinol and calf thymus DNA (ct-DNA) was first studied through various spectral and molecular docking techniques. Spectral studies showed that the initial fluorescence quenching of resorcinol against DNA was a static one. The result of ΔH < 0 and ΔS > 0 was produced from thermodynamic experiment data, thus it could be concluded that electrostatic force was the major driving force, while the binding constant K was 1.56×10 M at 298 K. The electrostatic binding network between resorcinol and ct-DNA was established explicitly through competitive substitution analysis and other spectral approaches. The result of FT-IR absorption spectra indicated resorcinol had bound to DNA phosphate skeleton. Molecular docking clearly revealed the binding occurred between hydroxyl groups of resorcinol and phosphorus oxygen bonds (P-O) of the DNA skeleton. These findings may deepen our understanding of the action mechanism between resorcinol and ct-DNA and provide some useful data for the effect of resorcinol on human diseases.
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http://dx.doi.org/10.1002/bio.4140DOI Listing
September 2021

The autism risk gene CNTN4 modulates dendritic spine formation.

Hum Mol Genet 2021 Aug 20. Epub 2021 Aug 20.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

Contactin 4 (CNTN4) is a crucial synaptic adhesion protein that belongs to the contactin superfamily. Evidence from both human genetics and mouse models suggests that synapse formation and structural deficits strongly correlate with neurodevelopmental disorders, including autism. In addition, several lines of evidence suggest that CNTN4 is associated with the risk of autism. However, the biological functions of CNTN4 in neural development and disease pathogenesis are poorly understood. In this study, we investigated whether and how CNTN4 is autonomously involved in the development of dendrites and dendritic spines in cortical neurons. Disruption of Cntn4 decreased the number of excitatory synapses, which led to a reduction in neural activity. Truncated proteins lacking the signal peptide, FnIII domains, or GPI domain lacked the ability to regulate dendritic spine formation, indicating that CNTN4 regulates dendritic spine density through a mechanism dependent on FnIII domains. Importantly, we revealed that autism-related variants lacked the ability to regulate spine density and neural activity. In conclusion, our study suggests that CNTN4 is essential for promoting dendrite growth and dendritic spine formation and that disruptive variants of CNTN4 interfere with abnormal synapse formation and may increase the risk of autism.
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http://dx.doi.org/10.1093/hmg/ddab233DOI Listing
August 2021

Discovery of Small Molecule Entry Inhibitors Targeting the Fusion Peptide of SARS-CoV-2 Spike Protein.

ACS Med Chem Lett 2021 Aug 28;12(8):1267-1274. Epub 2021 Jul 28.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.

SARS-CoV-2 entry into host cells relies on the spike (S) protein binding to the human ACE2 receptor. In this study, we investigated the structural dynamics of the viral S protein at the fusion peptide (FP) domain and small molecule binding for therapeutics development. Following comparative modeling analysis and docking studies of our previously identified fusion inhibitor chlorcyclizine, we performed a pharmacophore-based virtual screen and identified two novel chemotypes of entry inhibitors targeting the FP. The compounds were evaluated in the pseudoparticle viral entry assay and SARS-CoV-2 cytopathic effect assay and showed single-digital micromole inhibition against SARS-CoV-2 as well as SARS-CoV-1 and MERS. The characterization of the FP binding site of SARS-CoV-2 S protein provides a promising target for the structure-based development of small molecule entry inhibitors as drug candidates for the treatment of COVID-19.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353886PMC
August 2021

A Five-Genes Based Diagnostic Signature for Sepsis-Induced ARDS.

Pathol Oncol Res 2021 29;27:580801. Epub 2021 Jul 29.

Department of Emergency, Hebei General Hospital, Shijiazhuang, China.

Acute respiratory distress syndrome (ARDS) is a frequent and serious complication of sepsis without specific and sensitive diagnostic signatures. The mRNA profiles, including 60 blood samples with sepsis-induced ARDS and 86 blood samples with sepsis alone, were obtained from the Gene Expression Omnibus (GEO). The differently expressed genes (DEGs) were analyzed by package of R language. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out using the package of R. Eventually, multivariate logistic regression model was established through the function of R, and support vector machine (SVM) model was constructed via the package of R. A total of 242 DEGs in GSE32707 and 102 DEGs in GSE66890 were identified. Notably, five genes exhibited significant differences between the two datasets and were considered to be closely associated with the occurrence of ARDS induced by sepsis. Furthermore, functional enrichment analysis based on the DEGs showed there were 80 overlapped GO terms and one KEGG pathway which were significantly enriched in the two datasets. The logistic regression model and SVM model constructed could efficiently distinguish sepsis patients with or without ARDS. In brief, our study suggested that NKG7, SPTA1, FGL2, RGS2, and IFI27 might be potential diagnostic signatures for sepsis-induced ARDS, which contributed to the future exploration in mechanism of ARDS occurrence and development.
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http://dx.doi.org/10.3389/pore.2021.580801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357742PMC
July 2021

Reflections on the article "Led Astray": Thinking checklist to improve the diagnostic process of abdominal pain.

Asian J Surg 2021 Aug 7. Epub 2021 Aug 7.

Department of Emergency, Hebei General Hospital, Shijiazhuang, 050051, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.07.060DOI Listing
August 2021

Recent ultra-rare inherited variants implicate new autism candidate risk genes.

Nat Genet 2021 08 26;53(8):1125-1134. Epub 2021 Jul 26.

Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.

Autism is a highly heritable complex disorder in which de novo mutation (DNM) variation contributes significantly to risk. Using whole-genome sequencing data from 3,474 families, we investigate another source of large-effect risk variation, ultra-rare variants. We report and replicate a transmission disequilibrium of private, likely gene-disruptive (LGD) variants in probands but find that 95% of this burden resides outside of known DNM-enriched genes. This variant class more strongly affects multiplex family probands and supports a multi-hit model for autism. Candidate genes with private LGD variants preferentially transmitted to probands converge on the E3 ubiquitin-protein ligase complex, intracellular transport and Erb signaling protein networks. We estimate that these variants are approximately 2.5 generations old and significantly younger than other variants of similar type and frequency in siblings. Overall, private LGD variants are under strong purifying selection and appear to act on a distinct set of genes not yet associated with autism.
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http://dx.doi.org/10.1038/s41588-021-00899-8DOI Listing
August 2021

SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis.

J Cell Mol Med 2021 Sep 24;25(17):8432-8441. Epub 2021 Jul 24.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

High myopia is one of the leading causes of visual impairment worldwide with high heritability. We have previously identified the genetic contribution of SLC39A5 to nonsyndromic high myopia and demonstrated that disease-related mutations of SLC39A5 dysregulate the TGF-β pathway. In this study, the mechanisms underlying SLC39A5 involvement in the pathogenesis of high myopia are determined. We observed the morphogenesis and migration abnormalities of the SLC39A5 knockout (KO) human embryonic kidney cells (HEK293) and found a significant injury of ECM constituents. RNA-seq and qRT-PCR revealed the transcription decrease in COL1A1, COL2A1, COL4A1, FN1 and LAMA1 in the KO cells. Further, we demonstrated that TGF-β signalling, the regulator of ECM, was inhibited in SLC39A5 depletion situation, wherein the activation of receptor Smads (R-Smads) via phosphorylation was greatly blocked. SLC39A5 re-expression reversed the phenotype of TGF-β signalling and ECM synthesis in the KO cells. The fact that TGF-β signalling was zinc-regulated and that SLC39A5 was identified as a zinc transporter urged us to check the involvement of intracellular zinc in TGF-β signalling impairment. Finally, we determined that insufficient zinc chelation destabilized Smad proteins, which naturally inhibited TGF-β signalling. Overall, the SLC39A5 depletion-induced zinc deficiency destabilized Smad proteins, which inhibited the TGF-β signalling and downstream ECM synthesis, thus contributing to the pathogenesis of high myopia. This discovery provides a deep insight into myopic development.
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http://dx.doi.org/10.1111/jcmm.16803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419198PMC
September 2021

Effect of a Template Case Report Based on Cognitive Task Analysis on Emergency Thinking Ability of Resident Doctors in Standardized Training.

Patient Prefer Adherence 2021 15;15:1585-1591. Epub 2021 Jul 15.

Department of Emergency, Hebei General Hospital, Shijiazhuang, 050051, People's Republic of China.

Objective: To explore the effect of a template case report based on cognitive task analysis on the emergency thinking ability of resident doctors in standardized training.

Methods: The doctors were split into two groups, according to the date they joined the emergency department (n = 40, each group): the observation and control groups. In the observation group, the resident doctors' teachers in standardized training adopted the cognitive task analysis method to determine the primary links of emergency thinking, made case templates, and carried out training based on the case template report. In the control group, traditional teaching methods were used by the teachers.

Results: In the observation and control groups, the scores at departure were 88.10 ± 3.88 and 75.23 ± 7.19, respectively ( < 0.05), and the student's ability improvement rates were 92.5% and 75.0% ( < 0.01). In addition, the awareness rate of "know how to study" and "know how to work in emergency" in the observation group was 90% and 90%, respectively. The rate of doctors that considered "missed diagnosis and misdiagnosis can be reduced" was 85%, and the rate of doctors that considered "help to learn in other departments in the future" was 80%.

Conclusion: Template case reports based on the cognitive task analysis for emergency thinking training can help resident doctors in standardized training improve their emergency thinking ability.
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http://dx.doi.org/10.2147/PPA.S302025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289461PMC
July 2021

HECT E3 Ubiquitin Ligase Nedd4 Is Required for Antifungal Innate Immunity.

J Immunol 2021 08 19;207(3):868-877. Epub 2021 Jul 19.

Biomedical Science Graduate Program, Ohio State University, Columbus, OH; and

is the most common cause of fungal infections in humans, and disseminated candidiasis has become one of the leading causes of hospital-acquired bloodstream infections with a high mortality rate. However, little is known about the host-pathogen interactions and the mechanisms of antifungal immunity. Here, we report that Nedd4 (neuronal precursor cell-expressed developmentally downregulated 4) is essential for signaling through Dectin-1 and Dectin-2/3. We showed that mice that lack Nedd4 globally or only in the myeloid compartment are highly susceptible to systemic infection, which correlates with heightened organ fungal burden, defective inflammatory response, impaired leukocyte recruitment to the kidneys, and defective reactive oxygen species expression by granulocytes. At the molecular level, macrophages displayed impaired activation of TGF-β-activating kinase-1 and NF-κB, but normal activation of spleen tyrosine kinase and protein kinase C-δ on yeast and hyphal infections. These data suggest that Nedd4 regulates signaling events downstream of protein kinase C-δ but upstream of or at TGF-β-activating kinase-1.
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http://dx.doi.org/10.4049/jimmunol.2100083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324540PMC
August 2021

Congenital Asplenia Interrupts Immune Homeostasis and Leads to Excessive Systemic Inflammation in Zebrafish.

Front Cell Infect Microbiol 2021 28;11:668859. Epub 2021 Jun 28.

Institute of Three Gorges Ecological Fisheries of Chongqing, College of Fisheries, Southwest University, Chongqing, China.

Splenectomy or congenital asplenia in humans increases susceptibility to infections. We have previously reported that congenital asplenia in zebrafish reduces resistance to infection. However, the molecular mechanism of systemic immune response in congenitally asplenic individuals is largely unexplored. In this study, we found that pro-inflammatory cytokines were more highly induced in congenitally asplenic zebrafish than wild-type after pathogenic infection and lipopolysaccharide exposure. In addition, a higher aggregation of apoptotic cells was observed in congenitally asplenic zebrafish than that in wild-type. Next, we examined the transcriptome profiles of whole kidneys from wild-type and congenitally asplenic zebrafish to investigate the effects of congenital asplenia on innate and adaptive immune responses induced by the inactivated . Congenital asplenia inactivated the splenic anti-inflammatory reflex, disrupted immune homeostasis, and induced excessive inflammation as evidenced by the highly induced stress response-related biological processes, inflammatory and apoptosis-associated pathways, and pro-inflammatory cytokines/chemokines in congenitally asplenic zebrafish compared with wild-type after vaccination. In addition, complement component genes (, , , , and ) and several important immune-related genes (, , , , , , , , and ) were downregulated in congenitally asplenic zebrafish. Furthermore, congenital asplenia impaired adaptive immunity as demonstrated by downregulation of biological processes and signaling pathways involved in adaptive immune response after vaccination in congenitally asplenic zebrafish. The expression of was also significantly reduced in the congenitally asplenic zebrafish when compared with wild-type. Together, our study provides an in-depth understanding of spleen function in controlling immune homeostasis and may offer insight into the pathological response in splenectomized or congenitally asplenic patients after infections.
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http://dx.doi.org/10.3389/fcimb.2021.668859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274418PMC
July 2021

Identification of a seven-long non-coding RNA signature associated with Jab1/CSN5 in predicting hepatocellular carcinoma.

Cell Death Discov 2021 Jul 10;7(1):178. Epub 2021 Jul 10.

Department of Systems Biology, The University of Texas - MD Anderson Cancer Center, Houston, TX, USA.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, accounting for over 700,000 deaths each year. The lack of predictive and prognostic biomarkers for HCC, with effective therapy, remains a significant challenge for HCC management. Long non-coding RNAs (lncRNAs) play a key role in tumorigenesis and have clinical value as potential biomarkers in the early diagnosis and prediction of HCC. Jun activation domain-binding protein 1 (Jab1, also known as COP9 signalosome subunit 5, CSN5) is a potential oncogene that plays a critical role in the occurrence of HCC. Here, we performed a comprehensive analysis for Jab1/CSN5-associated lncRNAs to predict the prognosis of HCC. The differentially expressed (DE) lncRNAs between in HCC were analyzed based on the TCGA RNA-seq data. We detected 1031 upregulated lncRNAs in 371 HCC tissues and identified a seven-lncRNA signature strongly correlated with Jab1/CSN5 (SNHG6, CTD3065J16.9, LINC01604, CTD3025N20.3, KB-1460A1.5, RP13-582O9.7, and RP11-29520.2). We further evaluated the prognostic significance of these lncRNAs by GEPIA ( http://gepia.cancer-pku.cn/ ). The expression data in 364 liver tumors indicated that this seven-lncRNA signature could better predict worse survival in HCC patients. Moreover, 35 clinical HCC samples were evaluated to assess the validity and reproducibility of the bioinformatic analysis. We found that the targeted lncRNAs were upregulated, with a strong association with Jab1/CSN5 and prognostic value in HCC. Functional enrichment analysis by Gene Ontology (GO) showed that these seven prognostic lncRNAs exhibit oncogenic properties and are associated with prominent hallmarks of cancer. Overall, our findings demonstrate the clinical implication of Jab1/CSN5 with the seven-lncRNAs in predicting survival for patients with HCC.
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http://dx.doi.org/10.1038/s41420-021-00560-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272716PMC
July 2021

Pure modulation and accurate measurement of optical beam's tilt and displacement.

Rev Sci Instrum 2021 Jun;92(6):064504

State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Opto-Electronics, Shanxi University, Taiyuan 030006, China.

We developed a tilt modulation technique of a laser beam with a wedged crystal. Combined with a phase-compensating crystal, a pure tilt modulation with a wide bandwidth (actually determined by the bandwidth of electro-optic crystals) is realized. By Fourier transformation with a lens, the tilt signal is transformed into displacement. With homodyne detection using a local oscillator of the first-order Hermite-Gauss mode (HG) and a 4F phase-monitoring system, we measure the displacement and tilt of a laser probe beam. This technique can be used in metrology, such as Newtonian gravitational constant determination and gravitational wave detection, or the calibration of a spatial sensor, such as tilt/displacement sensors.
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http://dx.doi.org/10.1063/5.0050550DOI Listing
June 2021

NT157 Inhibits HCC Migration via Downregulating the STAT3/Jab1 Signaling Pathway.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211027916

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Purpose: The high fatality-to-case ratio of hepatocellular carcinoma is directly related to metastasis. The signal transducer and activator of transcription-3 is a key mediator of the cytokine and growth factor signaling pathways and drives the transcription of genes responsible for cancer-associated phenotypes. However, so far, no specific inhibitor for signal transducer and activator of transcription-3 has been used in clinical practice. Therefore, targeting the signal transducer and activator of transcription-3 for cancer therapy is highly desired to improve outcomes in patients with hepatocellular carcinoma.

Experimental Design: Using the small-molecule inhibitor NT157, the effect of signal transducer and activator of transcription-3 inhibition on cell migration was tested in hepatocellular carcinoma cell lines and a lung metastasis model of the disease.

Results: NT157 significantly inhibited the migration of hepatocellular carcinoma cell lines and lung metastasis of hepatocellular carcinoma . Mechanistically, it inhibited the phospho-signal transducer and activator of transcription-3 in a dose- and time-dependent manner. Furthermore, NT157 treatment suppressed the c-Jun activation domain-binding protein-1 levels in the nucleus but no significant decrease was observed in its expression in the cytoplasm. Finally, high mRNA expression levels of signal transducer and activator of transcription-3 and c-Jun activation domain-binding protein-1 in hepatocellular carcinoma were associated with significantly low survival rates.

Conclusion: NT157 inhibits hepatocellular carcinoma migration and metastasis by downregulating the signal transducer and activator of transcription-3/c-Jun activation domain-binding protein-1 signaling pathway and targeting it may serve as a novel therapeutic strategy for the clinical management of hepatocellular carcinoma in the future.
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http://dx.doi.org/10.1177/15330338211027916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274079PMC
July 2021

Effect of Immune-Related Adverse Events and Pneumonitis on Prognosis in Advanced Non-Small Cell Lung Cancer: A Comprehensive Systematic Review and Meta-analysis.

Clin Lung Cancer 2021 May 28. Epub 2021 May 28.

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, Shaanxi, China; Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, Shaanxi, China.

Objective: The correlation between immune-related adverse events (irAEs) and prognosis remains controversial in advanced non-small cell lung cancer (NSCLC). The aim of this study was to systematically evaluate the effect of irAEs, especially checkpoint inhibitor pneumonitis (CIP), on the survival and treatment response in advanced NSCLC.

Methods: The primary outcomes were overall survival (OS) and objective response rate (ORR). Databases were searched for relevant studies, and meta-analysis was conducted with RevMan.

Results: A total of 51 studies involving 12,600 participants were included. The development of irAEs had an advantageous effect on OS and ORR in advanced NSCLC (OS: hazard ratio [HR], 0.56 [95% confidence interval [CI] 0.46 to 0.67]; ORR: odds ratio [OR], 3.13 [2.41 to 4.06]). The occurrence of endocrine and skin irAEs had advantageous effects on both OS and ORR (endocrine OS, HR, 0.47 [-0.37 to 0.59]; endocrine ORR: OR, 1.90 [1.27 to 2.84]; skin OS: HR, 0.48 [0.38 to 0.61]; skin ORR: OR, 4.30 [2.68 to 6.91]). Severe-grade irAEs resulted in shorter OS than low-grade irAEs (HR, 1.49 [1.06, 2.09]), and multiple irAEs resulted in better ORR compared with 1 irAE (OR, 2.04 [1.41 to 2.94]). The occurrence of CIP had no significant effect on OS (HR, 1.14 [0.70 to 1.86]), but it was associated with better ORR (OR, 2.12 [1.06 to 4.25]). Severe-grade CIP had no effect on OS or ORR, but CIP leading to treatment discontinuation resulted in shorter OS (HR, 2.35 [1.17 to 4.72]).

Conclusion: The development of irAEs had advantageous effects on survival and response in advanced NSCLC. CIP had no effect on survival, but it predicted better response.
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http://dx.doi.org/10.1016/j.cllc.2021.05.004DOI Listing
May 2021

A Novel Variation in the Mitochondrial Complex I Assembly Factor NDUFAF5 Causes Isolated Bilateral Striatal Necrosis in Childhood.

Front Neurol 2021 10;12:675616. Epub 2021 Jun 10.

Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Bilateral striatal necrosis (BSN) is characterized by symmetrical degeneration, predominantly of the caudate and putamen nucleus, in the basal ganglia. It is associated with numerous acquired and hereditary neuro-developmental and motor dysfunction-related pathological conditions. BSN results in high morbidity and mortality among infants and children, and its diagnosis is clinically challenging due to several overlapping disease phenotypes. Therefore, a precise genetic diagnosis is urgently needed for accurate genetic counseling and improved prognostic outcomes as well. To identify novel missense mutations in the gene as a cause of childhood BSN in members of a Chinese family and summarize the clinical characteristics of patients with the gene mutations. This study included a large family living in a remote northwestern area of China. Three siblings developed a neurological disorder characterized by generalized dystonia within the first decade of their lives. Cerebral computed tomography (CT) and magnetic resonance imaging (MRI) showed bilateral lesions of the putamen. Biochemical and genetic approaches were used to identify the cause of BSN. Sequence analysis showed no pathogenic variation in , and genes and in the entire mitochondrial genome as well. Whole-exome sequencing revealed compound heterozygous mutations consisting of :c.425A > C(p.E142A) and c.836T > G (p.M279R). The father, a healthy sister, and a healthy brother of the affected siblings carried the c.836T > G mutation, and the mother carried the c.425A > C mutation. These variants were absent in 100 ethnically matched non-BSN controls. analysis demonstrated that the E142A and M279R mutations in NDUFAF5 protein significantly perturbed the normal conformation of the protein due to alterations in the hydrogen bonding patterns around the evolutionarily conserved catalytic domains, leading to its loss of function in the early stage of mitochondrial complex I assembly. We identified a novel compound heterozygous mutation (c.425A > C and c.836T > G) in the gene as the potential cause of autosomal recessive childhood BSN, which extended the pathogenic variation spectrum of the gene. This study provides substantial evidence for further improvement of genetic counseling and better clinical management of BSN affected individuals.
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http://dx.doi.org/10.3389/fneur.2021.675616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223072PMC
June 2021

High-Sensitive Cardiac Troponin T for Prediction of Cardiovascular Outcomes in Stable Maintenance Hemodialysis Patients: A 3-Year Prospective Study.

Kidney Blood Press Res 2021 24;46(4):484-494. Epub 2021 Jun 24.

Department of Nephrology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Hemodialysis patients, who are often excluded from cardiovascular (CV) clinical trials, are associated with higher CV morbidity and mortality. The risk stratification scheme for these patients is lacking. Therefore, this investigation examined the independent CV prognostic value of high-sensitive cardiac troponin T (hs-cTnT) and added prognostic value over echocardiographic parameters and other clinical risk predictors in asymptomatic stable maintenance hemodialysis (MHD) patients.

Methods: 181 patients with end-stage renal disease undergoing MHD were eligible from the dialysis center of Tongren Hospital, Shanghai Jiao Tong University School of Medicine between October 2017 and September 2018. These patients were followed until September 2020 or until death. The median follow-up was 31 (IQR: 21-33) months. Outcome measures were all-cause mortality, first fatal or nonfatal CV events (CVEs), and 4-point composite major adverse CVEs (MACE). We performed multivariable Cox regression analysis using demographic, clinical, laboratory, and echocardiographic data to identify predictors of CV outcomes. We also evaluated the increased discriminative value associated with the addition of echocardiographic parameters and hs-cTnT using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results: During follow-up, 37 patients died, 84 patients suffered one or more CVEs, and 78 patients developed 4-point MACE. In univariable analyses, age, dialysis vintage, diastolic blood pressure, parathyroid hormone concentrations, hs-cTnT, B-type natriuretic peptide, left ventricular mass index (LVMI), and E/E' predicted all end points. hs-cTnT remained a strong predictor for each end point in multivariate analysis, whereas LVMI and E/E' did not. The addition of hs-cTnT on top of clinical and echocardiographic variables was associated with improvements in reclassification for CVEs (NRI = 44.6% [15.9-74.3%], IDI = 15.9% [5.7-31.0%], all p < 0.001), all-cause mortality (NRI = 35.5% [10.1-50.2%], p < 0.001, IDI = 4.4% [1.3-8.5%], p = 0.005), and 4-point MACE (NRI = 47.2% [16.1-64.9%], p < 0.001, IDI = 16.9% [5.5-37.3%], p = 0.005). Adding echocardiographic variables on top of clinical variables and hs-cTnT was not associated with significant improvements in NRI and IDI (all p > 0.05).

Conclusions: Our data suggest that hs-cTnT is a powerful independent predictor of CV outcome and all-cause mortality in stable MHD patients. The additional use of echocardiography for improvement of risk stratification is not supported by our results.
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http://dx.doi.org/10.1159/000516658DOI Listing
June 2021

Immobilization of lipase by dialdehyde cellulose crosslinked magnetic nanoparticles.

Int J Biol Macromol 2021 Aug 18;185:287-296. Epub 2021 Jun 18.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, PR China.

Cellulose microcrystalline (MCC) was widely used in pharmaceutical and chemical industries because of its low degree of polymerization and large specific surface area. As its modified form, dialdehyde cellulose (DAC) was used for cross-linking and immobilizing Rhizopus lipase together with magnetic nanoparticles (MNPs) due to its active aldehyde groups. In this study, in order to maintain the original enzyme activity as much as possible and improve the stability of lipase, the Rhizopus lipase was successfully immobilized on the magnetic dialdehyde cellulose nanoparticles (MDC). Specifically, the immobilization conditions including dosage of DAC, concentration of enzyme, immobilization time and temperature together with pH value of the reaction medium were optimized. Maximum immobilization yield (60.03 ± 0.49%) and recovery activity (88.88 ± 0.61%) can be obtained under the optimal process conditions. The changes in secondary structures of immobilized enzyme revealed the increment in conformational rigidity, which can be reflected in temperature and pH stability as well as tolerance of organic reagents. Additionally, the recovery activity of immobilized enzyme still reached 50.60 ± 0.59% after 30 d of storage and 52.10 ± 0.57% retained after 6 cycles. These results indicated the ideal application prospect of MDC in immobilized enzymes.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.073DOI Listing
August 2021

Discovery of TMPRSS2 Inhibitors from Virtual Screening as a Potential Treatment of COVID-19.

ACS Pharmacol Transl Sci 2021 Jun 2;4(3):1124-1135. Epub 2021 Apr 2.

National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted researchers to pivot their efforts to finding antiviral compounds and vaccines. In this study, we focused on the human host cell transmembrane protease serine 2 (TMPRSS2), which plays an important role in the viral life cycle by cleaving the spike protein to initiate membrane fusion. TMPRSS2 is an attractive target and has received attention for the development of drugs against SARS and Middle East respiratory syndrome. Starting with comparative structural modeling and a binding model analysis, we developed an efficient pharmacophore-based approach and applied a large-scale in silico database screening for small-molecule inhibitors against TMPRSS2. The hits were evaluated in the TMPRSS2 biochemical assay and the SARS-CoV-2 pseudotyped particle entry assay. A number of novel inhibitors were identified, providing starting points for the further development of drug candidates for the treatment of coronavirus disease 2019.
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http://dx.doi.org/10.1021/acsptsci.0c00221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043206PMC
June 2021

Comprehensive analysis of lncRNA biomarkers in kidney renal clear cell carcinoma by lncRNA-mediated ceRNA network.

PLoS One 2021 8;16(6):e0252452. Epub 2021 Jun 8.

Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, P.R. China.

Introduction: Kidney renal clear cell carcinoma (KIRC) has a high incidence globally, and its pathogenesis remains unclear. Long non-coding RNA (lncRNA), as a molecular sponge, participates in the regulation of competitive endogenous RNA (ceRNA). We aimed to construct a ceRNA network and screened out possible lncRNAs to predict KIRC prognosis.

Material And Methods: All KIRC data were downloaded from the TCGA database and screened to find the possible target lncRNA; a ceRNA network was designed. Next, GO functional enrichment and KEGG pathway of differentially expressed mRNA related to lncRNA were performed. We used Kaplan-Meier curve analysis to predict the survival of these RNAs. We used Cox regression analysis to construct a model to predict KIRC prognosis.

Results: In the KIRC datasets, 1457 lncRNA, 54 miRNA and 2307 mRNA were screened out. The constructed ceRNA network contained 81 lncRNAs, nine miRNAs, and 17 mRNAs differentially expressed in KIRC. Survival analysis of all differentially expressed RNAs showed that 21 lncRNAs, four miRNAs, and two mRNAs were related to the overall survival rate. Cox regression analysis was performed again, and we found that eight lncRNAs were related to prognosis and used to construct predictive models. Three lnRNAs from independent samples were meaningful.

Conclusion: The construction of ceRNA network was involved in the process and transfer of KIRC, and three lncRNAs may be potential targets for predicting KIRC prognosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252452PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186793PMC
June 2021

Thymic stromal lymphopoietin participates in the TLR2-and TLR4-dependent immune response triggered by Aspergillus fumigatus in human corneal cells.

Exp Eye Res 2021 May 31;209:108644. Epub 2021 May 31.

Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, 250012, PR China. Electronic address:

Fungal keratitis constitutes a serious vision-threatening disease. Toll-like receptors (TLRs) comprise key mediators of innate immunity triggered by Aspergillus fumigatus (AF) in the cornea, but the messenger between innate and adaptive immunity remained unknown. Thymic stromal lymphopoietin (TSLP) represents a critical factor of adaptive immunity. Here we investigated the expression of TSLP in corneal epithelial and stromal cells challenged by AF and its relationship with TLRs. We stimulated corneal cells with TLR ligands zymosan or lipopolysaccharide (LPS), human recombinant TSLP, or AF hyphae for various periods, with or without prior TLR2, TLR4, or TSLP inhibition. TLR2, TLR4, TSLP, IL-8, and TNF-α release and expression were measured via enzyme-linked immunosorbent analysis, quantitative polymerase chain reaction, or western blot. Corneal cell stimulation with zymosan or LPS induced up-regulated TSLP expression. Enhanced TSLP expression was associated with AF treatment in human corneal cells; TLR2 or TLR4 inhibition impaired the AF-induced TSLP levels. Human recombinant TSLP augmented TLR2 and TLR4 expression; RNA interference of TSLP attenuated TLR, IL-8, and TNF-α expression stimulated by AF hyphae. These findings indicated that TSLP participates in the immune response of corneal cells triggered by AF, which is closely related to TLR function, and the innate immunity mediated by TLRs could be enhanced by TSLP. Innate immunity may therefore transmit inflammatory signals to adaptive immunity through activation of TSLP; in turn, adaptive immunity likely exerts certain regulatory effects on innate immunity via TSLP. That is, TSLP could interact with innate immunity mediated by TLR2 and TLR4 in human corneal cells challenged by AF and thus may serve as a messenger between the innate and adaptive immune responses in AF keratitis.
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http://dx.doi.org/10.1016/j.exer.2021.108644DOI Listing
May 2021

Long-Term Observation and Sequencing Analysis of SKPs-Derived Corneal Endothelial Cell-Like Cells for Treating Corneal Endothelial Dysfunction.

Cell Transplant 2021 Jan-Dec;30:9636897211017830

Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Corneal endothelial dysfunction is a principal cause of visual deficiency. Corneal transplantation is the most effective treatment for corneal endothelial dysfunction. However, a severe shortage of available donor corneas or human corneal endothelial cells (HCECs) remains a global challenge. Previously, we acquired corneal endothelial cell-like cells (CEC-like cells) derived from human skin-derived precursors (SKPs). CEC-like cells were injected into rabbit and monkey corneal endothelial dysfunction models and exerted excellent therapeutic effect. In this study, we prolonged the clinical observation in the monkey experiment for 2 years. Polymerase chain reaction (PCR) and DNA sequencing were carried out to confirm the existence of CEC-like cells. Histological examinations were carried out to show the corneal morphology. Further transcriptome sequencing was also carried out on HCEC, CEC-like cells before transplantation and after transplantation. We found that the monkeys cornea remained transparent and normal thickness. The total endothelial cell density decreased gradually, but tended to be stable and remained in a normal range during 2-year observation. The CEC-like cells persist during observation and could adapt to the microenvironment after transplantation. The gene expression pattern of CEC-like cells was similar to HCEC and changed slightly after transplantation. In conclusion, this study presented a brand-new insight into CEC-like cells and further provided a promising prospect of cell-based therapy for corneal endothelial dysfunction. The renewable cell source, novel derivation method and simple treatment strategy may be clinically applied in regenerative medicine in the future.
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http://dx.doi.org/10.1177/09636897211017830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182626PMC
May 2021

Molecular mechanism underlying transport and allosteric inhibition of bicarbonate transporter SbtA.

Proc Natl Acad Sci U S A 2021 Jun;118(22)

National Key Laboratory of Plant Molecular Genetics, Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China

SbtA is a high-affinity, sodium-dependent bicarbonate transporter found in the cyanobacterial CO-concentrating mechanism (CCM). SbtA forms a complex with SbtB, while SbtB allosterically regulates the transport activity of SbtA by binding with adenyl nucleotides. The underlying mechanism of transport and regulation of SbtA is largely unknown. In this study, we report the three-dimensional structures of the cyanobacterial sp. PCC 6803 SbtA-SbtB complex in both the presence and absence of HCO and/or AMP at 2.7 Å and 3.2 Å resolution. An analysis of the inward-facing state of the SbtA structure reveals the HCO /Na binding site, providing evidence for the functional unit as a trimer. A structural comparison found that SbtA adopts an elevator mechanism for bicarbonate transport. A structure-based analysis revealed that the allosteric inhibition of SbtA by SbtB occurs mainly through the T-loop of SbtB, which binds to both the core domain and the scaffold domain of SbtA and locks it in an inward-facing state. T-loop conformation is stabilized by the AMP molecules binding at the SbtB trimer interfaces and may be adjusted by other adenyl nucleotides. The unique regulatory mechanism of SbtA by SbtB makes it important to study inorganic carbon uptake systems in CCM, which can be used to modify photosynthesis in crops.
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http://dx.doi.org/10.1073/pnas.2101632118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179158PMC
June 2021

Delay in seeking medical care after the onset of symptoms in patients with sight-threatening diabetic retinopathy.

J Int Med Res 2021 May;49(5):3000605211013224

Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People's Republic of China.

Objective: To investigate the reasons for delays in seeking medical care in patients with diabetic retinopathy and associated risk factors.

Methods: We retrospectively reviewed data for patients with sight-threatening diabetic retinopathy (STDR) who attended a hospital in China. Various forms of STDR were identified, including severe non-proliferative DR, clinically significant macular edema and proliferative DR. Demographic, clinical and socioeconomic information was collected and the associated risk factors were evaluated.

Results: Of the 127 patients with STDR, 89.2% sought medical care within 1 month of developing symptoms. Those who sought treatment ≥6 months after symptoms developed had significantly lower income and less knowledge of diabetic complications than those who attended earlier. Multivariate logistic regression analysis showed that no or infrequent routine examination for diabetic complications were associated with long delays in seeking medical care (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.05-9.19; and OR 2.91, 95% CI 1.04-8.40, respectively).

Conclusions: Most patients with STDR sought medical care within 1 month of symptoms developing, but no or infrequent routine examination for diabetic complications was associated with long delays. These results stress the importance of educational programs regarding diabetic complications to encourage timely medical care and prevent poor outcomes.
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http://dx.doi.org/10.1177/03000605211013224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150428PMC
May 2021

Elevated RBP-Jκ and CXCL11 Expression in Colon Cancer is Associated with an Unfavorable Clinical Outcome.

Cancer Manag Res 2021 5;13:3651-3661. Epub 2021 May 5.

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.

Introduction: This study aims at exploring the expression and significance of recombination signal-binding protein for immunoglobulin kappa J region (RBP-Jκ) and C-X-C motif chemokine 11 (CXCL11) in human colon cancer tissues.

Methods: The RBP-Jκ and CXCL11 expression levels were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) in patients with colon cancer, and their prognostic significance was evaluated.

Results: Through analyzing 342 samples of colon cancer patients treated at our institution, increased expression of RBP-Jκ and CXCL11 was found in human colon cancer specimens compared with matched paratumorous normal specimens (<0.001). A positive correlation was found between RBP-Jκ expression and CXCL11 expression (<0.001). High RBP-Jκ expression was significantly associated with poorly differentiated tumors (=0.005), invasion beyond propria muscularis (=0.025), lymph node metastases (=0.005), distant metastasis (<0.001), advanced tumor-node-metastasis (TNM) stage (=0.004), and a shorter overall survival (<0.001). An increase in CXCL11 protein expression was associated with poorly differentiated tumors (=0.015), invasion beyond propria muscularis (=0.029), lymph node metastases (=0.031), distant metastasis (=0.045), advanced TNM stage (=0.026), and a shorter overall survival of patients (<0.001). In multivariate Cox regression analysis, RBP-Jκ protein expression (=0.036), CXCL11 protein expression (=0.001), differentiation (<0.001), depth of invasion (=0.009), distant metastasis (<0.001), and TNM stage (<0.001) were independent prognostic indicators of colon cancer.

Conclusion: High expression of RBP-Jκ is closely associated with high CXCL11 expression, which represents a risk factor for the poor overall survival of colon cancer patients.
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http://dx.doi.org/10.2147/CMAR.S298580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107007PMC
May 2021

A rare case of ectopic ACTH syndrome with rhabdomyolysis.

BMC Endocr Disord 2021 May 10;21(1):98. Epub 2021 May 10.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, No.277 West Yanta Road, 710061, Xi'an, People's Republic of China.

Background: Manifestations of hypokalaemia in ectopic adrenocorticotropic hormonesyndrome(EAS) vary from mild muscle weakness to life-threatening arrhythmia. Herein, we present a rare case of EAS with concomitant rhabdomyolysis(RM) as a result of intractable hypokalaemia.

Case Presentation: A 64-year-old man was admitted for limb weakness and facial hyperpigmentation for 2 weeks. Lab tests revealed intractable hypokalaemia (lowest at 1.8 mmol/L) and metabolic alkalosis. The diagnosis of RM was based on a creatine kinase(CK)level of 5 times the upper limit. The elevated CK and myohemoglobin (Mb) levels returned to within the normal range after the alleviation of hypokalaemia. The patient was diagnosed with ACTH-dependent Cushing's syndrome (CS) based on unsuppressed serum cortisol after a low-dose dexamethasone suppression test(LDDST) and remarkably elevated ACTH levels. The diagnosis of EAS was made based on the results of a high-dose dexamethasone suppression test(HDDST) and bilateral inferior petrosal sinus sampling(BIPSS). Multiple lymph nodes in the left supraclavicular fossa, right root of neck, mediastinum and bilateral hili of the lung were found with abnormal uptake of Ga-DOTA-NOC. Mediastinoscopic lymph node biopsy was performed. The pathological diagnosis was small-cell and large-cell neuroendocrine carcinoma with positive ACTH staining. The patient was prescribed mifepristone and received one cycle of chemotherapy. The patient could not tolerate subsequent chemotherapy and died of dyscrasia.

Conclusions: RM is a rare complication of EAS with insidious onset and atypical clinical manifestations. Serum potassium levels should be vigilantly monitored to avoid RM in EAS.
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http://dx.doi.org/10.1186/s12902-021-00755-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111963PMC
May 2021

Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders.

J Autism Dev Disord 2021 May 10. Epub 2021 May 10.

National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Xiangya Road, Kaifu District, Changsha, 410013, Hunan, China.

The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.11%, 34.40%, 33.31%, 10.98% and 6.91% of patients with ID, EE, UDD, ASD and SCZ, respectively. Consistent with phenotype similarity and heterogeneity in different NPDs, they show different degree of genetic association. Cross-disorder analysis of DNMs prioritized 321 candidate genes (FDR < 0.05) and showed that genes shared in more disorders were more likely to exhibited specific expression pattern, functional pathway, genetic convergence, and genetic intolerance.
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http://dx.doi.org/10.1007/s10803-021-05031-7DOI Listing
May 2021

[Pleurodesis with an Autologous Blood Patch in the Treatment of Persistent Air Leak after Lung Resection].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):211-215

Department of Thoracic Surgery,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China.

Objective To evaluate the efficacy and risks of autologous blood patch pleurodesis in patients with persistent air leak(PAL)after lung resection. Methods A total of 97 patients with PAL after lung resection in Beijing Shijitan Hospital from October 2014 to October 2019 were retrospectively reviewed,including 53 treated by autologous blood patch pleurodesis and 44 by the conventional way.The therapeutic effect,adverse reactions and complications were analyzed. Results All the patients with PAL were cured with autologous blood patch pleurodesis.Most air leaks(81.1%)ceased within 48 hours after treatment,and the left 18.9% patients got cured after a repeat.The mean tube retention time and the mean in-hospital stay were 8.4 days and 10.0 days in the autologous blood patch pleurodesis group and 13.5 days and 15.3 days in the conventional treatment group.A prolonged drainage time(P=0.00)and in-hospital stay(P=0.00)were observed in the conventional treatment group.No severe complications were observed except two patients developed slight fever and cutaneous emphysema. Conclusion In our experience,the autologous blood patch pleurodesis is an effective way with low risk of adverse reactions in the treatment of PAL.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12784DOI Listing
April 2021
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