Publications by authors named "Yong Ji"

492 Publications

Genome-wide association study of signature genetic alterations among pseudomonas aeruginosa cystic fibrosis isolates.

PLoS Pathog 2021 Jun 23;17(6):e1009681. Epub 2021 Jun 23.

Department of Microbiology and Immunology, Seoul, Republic of Korea.

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes diverse human infections including chronic airway infection in patients with cystic fibrosis (CF). Comparing the genomes of CF and non-CF PA isolates has great potential to identify the genetic basis of pathogenicity. To gain a deeper understanding of PA adaptation in CF airways, we performed a genome-wide association study (GWAS) on 1,001 PA genomes. Genetic variations identified among CF isolates were categorized into (i) alterations in protein-coding regions, either large- or small-scale, and (ii) polymorphic variation in intergenic regions. We introduced each CF-associated genetic alteration into the genome of PAO1, a prototype PA strain, and validated the outcomes experimentally. Loci readily mutated among CF isolates included genes encoding a probable sulfatase, a probable TonB-dependent receptor (PA2332~PA2336), L-cystine transporter (YecS, PA0313), and a probable transcriptional regulator (PA5438). A promoter region of a heme/hemoglobin uptake outer membrane receptor (PhuR, PA4710) was also different between the CF and non-CF isolate groups. Our analysis highlights ways in which the PA genome evolves to survive and persist within the context of chronic CF infection.
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http://dx.doi.org/10.1371/journal.ppat.1009681DOI Listing
June 2021

Molecular processes mediating hyperhomocysteinemia-induced metabolic reprogramming, redox regulation and growth inhibition in endothelial cells.

Redox Biol 2021 May 24:102018. Epub 2021 May 24.

Center for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United States; Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA, United States. Electronic address:

Hyperhomocysteinemia (HHcy) is an established and potent independent risk factor for degenerative diseases, including cardiovascular disease (CVD), Alzheimer disease, type II diabetes mellitus, and chronic kidney disease. HHcy has been shown to inhibit proliferation and promote inflammatory responses in endothelial cells (EC), and impair endothelial function, a hallmark for vascular injury. However, metabolic processes and molecular mechanisms mediating HHcy-induced endothelial injury remains to be elucidated. This study examined the effects of HHcy on the expression of microRNA (miRNA) and mRNA in human aortic EC treated with a pathophysiologically relevant concentration of homocysteine (Hcy 500 μM). We performed a set of extensive bioinformatics analyses to identify HHcy-altered metabolic and molecular processes. The global functional implications and molecular network were determined by Gene Set Enrichment Analysis (GSEA) followed by Cytoscape analysis. We identified 244 significantly differentially expressed (SDE) mRNA, their relevant functional pathways, and 45 SDE miRNA. HHcy-altered SDE inversely correlated miRNA-mRNA pairs (45 induced/14 reduced mRNA) were discovered and applied to network construction using an experimentally verified database. We established a hypothetical model to describe the biochemical and molecular network with these specified miRNA/mRNA axes, finding: 1) HHcy causes metabolic reprogramming by increasing glucose uptake and oxidation, by glycogen debranching and NAD/CoA synthesis, and by stimulating mitochondrial reactive oxygen species production via NNT/IDH2 suppression-induced NAD/NADP-NADPH/NADP metabolism disruption; 2) HHcy activates inflammatory responses by activating inflammasome-pyroptosis mainly through ↓miR193b→↑CASP-9 signaling and by inducing IL-1β and adhesion molecules through the ↓miR29c→↑NEDD9 and the ↓miR1256→↑ICAM-1 axes, as well as GPCR and interferon α/β signaling; 3) HHcy promotes cell degradation by the activation of lysosome autophagy and ubiquitin proteasome systems; 4) HHcy causes cell cycle arrest at G1/S and S/G2 transitions, suppresses spindle checkpoint complex and cytokinetic abscission, and suppresses proliferation through ↓miRNA335/↑VASH1 and other axes. These findings are in accordance with our previous studies and add a wealth of heretofore-unexplored molecular and metabolic mechanisms underlying HHcy-induced endothelial injury. This is the first study to consider the effects of HHcy on both global mRNA and miRNA expression changes for mechanism identification. Molecular axes and biochemical processes identified in this study are useful not only for the understanding of mechanisms underlying HHcy-induced endothelial injury, but also for discovering therapeutic targets for CVD in general.
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http://dx.doi.org/10.1016/j.redox.2021.102018DOI Listing
May 2021

Patellar retraction versus eversion on functional outcomes in total knee replacement: a randomized controlled study protocol.

J Orthop Surg Res 2021 Jun 14;16(1):381. Epub 2021 Jun 14.

Department of Orthopaedics, Jingjiang People's Hospital, No. 28, Zhongzhou Road, Jingjiang, Taizhou City, 214500, Jiangsu Province, China.

Background: Patellar mobilization technique during total knee replacement (TKR) has been debated, with some suggesting that lateral retraction, rather than eversion, of the patella may be beneficial. This randomized controlled trial was to investigate the effects of patellar eversion on functional outcomes in TKR.

Methods And Analysis: This single-center, prospective, randomized controlled test will be conducted in Jingjiang People's Hospital. Primary end-stage osteoarthritis patients that prepared for unilateral TKR were randomized to one of two patellar exposure techniques during the primary total knee arthroplasty: lateral retraction or eversion. The informed consent will be acquired in each patient. The primary outcome was operation time, length of hospital stay, and straight leg raising time. Second outcomes including Insall-Salvati ratio; range of motion at 1 month, 3 months, and 1 year following TKR; visual analog scale (VAS) at 1 month, 3 months; and Knee Society Score (KSS) score at 1 year following TKR. The significance level was defaulted as P < .05.

Results: Results will be published in relevant peer-reviewed journals.

Conclusion: Our study aims to systematically assess the functional outcomes of patellar eversion for TKR patients, which will provide clinical guidance for TKR patients.
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http://dx.doi.org/10.1186/s13018-021-02518-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204409PMC
June 2021

Evaluation of dry eye subtypes and characteristics using conventional assessments and dynamic tear interferometry.

Br J Ophthalmol 2021 Jun 9. Epub 2021 Jun 9.

Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea

Background/aims: To evaluate subtypes and characteristics of dry eye (DE) using conventional tests and dynamic tear interferometry, and to investigate determinants of disease severity in each DE subtype.

Methods: 309 patients diagnosed with DE and 69 healthy controls were prospectively enrolled. All eyes were evaluated using Ocular Surface Disease Index (OSDI), Schirmer's test I (ST1) and Meibomian gland dysfunction (MGD) grade were analysed. The tear interferometric pattern and lipid layer thickness were determined using DR-1α and LipiView II, respectively.

Results: Dynamic interferometric analysis revealed 56.6% of patients with DE exhibited Jupiter patterns, indicative of aqueous-deficiency, while 43.4% exhibited crystal patterns, indicative of lipid deficiency. These findings were in accordance with classification based on ST1 scores and MGD grade. Conventional assessment indicated 286 patients exhibited evidence of evaporative DE (EDE) due to MGD, while only 11 exhibited signs of pure aqueous-deficient DE (pure ADDE, only ST1 ≤5 mm). Interestingly, of 286 patients with EDE, 144 were categorised into the mixed-ADDE/EDE group, in which ST1 was identified as a strong negative determinant of OSDI. In contrast, 72.2% of patients with mixed-ADDE/EDE exhibited Jupiter patterns (Jupiter mixed), while 27.8% exhibited crystal patterns (crystal mixed). OSDI values were significantly higher in the crystal-mixed group than in the Jupiter mixed, in which OSDI scores were independently associated with ST1 values only.

Conclusions: Our findings indicate that majority of EDE patients also exhibit aqueous deficiency, which can aggravate symptoms even in patients with lipid-deficient mixed-ADDE/EDE. Conventional assessments should be combined with interferometric tear analysis to determine the most appropriate treatment for each DE patient.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318624DOI Listing
June 2021

Histidine Triad Nucleotide Binding Protein 1 Attenuates Cardiac Hypertrophy via Suppressing Homeobox A5 Expression.

Circulation 2021 Jun 8. Epub 2021 Jun 8.

Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China.

Cardiac hypertrophy is an important pre-pathology of heart failure, which will ultimately lead to heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. The aim of this study is to elucidate the effects and mechanisms of histidine triad nucleotide binding protein 1 (HINT1) in cardiac hypertrophy and heart failure. HINT1 was down-regulated in human hypertrophic heart samples compared with non-hypertrophic samples by mass spectrometry analysis. knockout mice were challenged with TAC (transverse aortic constriction) surgery. Cardiac specific overexpression of HINT1 mice by intravenous injection of adeno-associated viral (AAV9) encoding Hint1 under the cardiac troponin T (cTnT) promoter were subjected to TAC. Unbiased transcriptional analyses were used to identify the downstream targets of HINT1. AAV9 bearing shRNA against () was administrated to investigate whether the effects of on cardiac hypertrophy were HOXA5 dependent. RNA-Seq analysis was performed to recapitulate possible changes in transcriptome profile. Co-immunoprecipitation assays and cellular fractionation analyses were conducted to examine the mechanism by which HINT1 regulates the expression of HOXA5. The reduction of HINT1 expression was observed in the hearts from hypertrophic patients and pressure overloaded-induced hypertrophic mice, respectively. In deficient mice, cardiac hypertrophy was deteriorated after TAC. Conversely, cardiac specific overexpression of HINT1 alleviated cardiac hypertrophy and dysfunction. Unbiased profiler PCR-array showed Homeobox A5 (HOXA5) is one target for HINT1, and the cardioprotective role of HINT1 was abolished by HOXA5 knockdown . Hoxa5 was identified to affect hypertrophy through TGF-β signal pathway. Mechanically, HINT1 inhibited PKCβ1 membrane translocation and phosphorylation via direct interaction, attenuating MEK/ERK/YY1 signal pathway, down-regulating HOXA5 expression and eventually attenuating cardiac hypertrophy. HINT1 protects against cardiac hypertrophy through suppressing HOXA5 expression. These findings indicate that HINT1 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051094DOI Listing
June 2021

Bioinformatics analysis, codon optimization and expression of ovine pregnancy associated Glycoprotein-7 in HEK293 cells.

Theriogenology 2021 May 27;172:27-35. Epub 2021 May 27.

Institute of Animal Husbandry and Veterinary Science, Xinjiang Academy of Agriculture and Reclamation Science, Shihezi, 832000, PR China.

Pregnancy-associated glycoproteins (PAGs) are widely used as powerful markers for early pregnancy diagnosis in livestock. To improve expression efficiency of recombinant ovine pregnancy-associated glycoprotein-7 (ovPAG-7) in HEK293 cells, the codon usage bias of the ovPAG-7 gene was analyzed using bioinformatic approaches, after which the DNA sequence encoding ovPAG-7 was designed, synthesized, and expressed in HEK293. The structure and function of ovPAG-7 were predicted using bioinformatics software and online databases. The results showed that the effective number of codons (NEC) of the ovPAG-7 gene was 56.82, indicating that the ovPAG-7 gene was weakly biased. ovPAG-7 gene had 26 biased codons (relative synonymous codon usage (RSCU) > 1), 15 of which were biased towards G/C at the third position. After codon optimization, the codon adaptation index of the ovPAG-7 gene increased from 0.74 to 0.96, and its GC content changed from 46.6 to 58.6%. The amino acid sequence encoded by the optimized gene was entirely consistent with those published in Gen Bank. Western blot analysis indicated that the recombinant ovPAG-7 protein with a relative molecular mass of 48 kDa was successfully expressed in HEK293 cells. The bioinformatics prediction results showed that ovPAG-7 protein contained 3 N-glycosylation sites, 13 B-cell epitopes, and a signal peptide consisting of 15 amino acids at the N terminus. The secondary structure of the ovPAG-7 protein was predicted to consist of random coils (46.85%), extended strands (32.05%), α-helices (16.16%), and β-turns (4.93%). This study provided a tool for the screening of monoclonal antibodies and functional research on ovPAG-7.
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http://dx.doi.org/10.1016/j.theriogenology.2021.05.027DOI Listing
May 2021

S-nitrosylation of c-Jun N-terminal kinase mediates pressure overload-induced cardiac dysfunction and fibrosis.

Acta Pharmacol Sin 2021 May 19. Epub 2021 May 19.

Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, 201203, China.

Cardiac fibrosis (CF) is an irreversible pathological process that occurs in almost all kinds of cardiovascular diseases. Phosphorylation-dependent activation of c-Jun N-terminal kinase (JNK) induces cardiac fibrosis. However, whether S-nitrosylation of JNK mediates cardiac fibrosis remains an open question. A biotin-switch assay confirmed that S-nitrosylation of JNK (SNO-JNK) increased significantly in the heart tissues of hypertrophic patients, transverse aortic constriction (TAC) mice, spontaneously hypertensive rats (SHRs), and neonatal rat cardiac fibroblasts (NRCFs) stimulated with angiotensin II (Ang II). Site to site substitution of alanine for cysteine in JNK was applied to determine the S-nitrosylated site. S-Nitrosylation occurred at both Cys116 and Cys163 and substitution of alanine for cysteine 116 and cysteine 163 (C116/163A) inhibited Ang II-induced myofibroblast transformation. We further confirmed that the source of S-nitrosylation was inducible nitric oxide synthase (iNOS). 1400 W, an inhibitor of iNOS, abrogated the profibrotic effects of Ang II in NRCFs. Mechanistically, SNO-JNK facilitated the nuclear translocation of JNK, increased the phosphorylation of c-Jun, and induced the transcriptional activity of AP-1 as determined by chromatin immunoprecipitation and EMSA. Finally, WT and iNOS mice were subjected to TAC and iNOS knockout reduced SNO-JNK and alleviated cardiac fibrosis. Our findings demonstrate an alternative mechanism by which iNOS-induced SNO-JNK increases JNK pathway activity and accelerates cardiac fibrosis. Targeting SNO-JNK might be a novel therapeutic strategy against cardiac fibrosis.
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http://dx.doi.org/10.1038/s41401-021-00674-9DOI Listing
May 2021

Genetic fate-mapping reveals surface accumulation but not deep organ invasion of pleural and peritoneal cavity macrophages following injury.

Nat Commun 2021 05 17;12(1):2863. Epub 2021 May 17.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

During injury, monocytes are recruited from the circulation to inflamed tissues and differentiate locally into mature macrophages, with prior reports showing that cavity macrophages of the peritoneum and pericardium invade deeply into the respective organs to promote repair. Here we report a dual recombinase-mediated genetic system designed to trace cavity macrophages in vivo by intersectional detection of two characteristic markers. Lineage tracing with this method shows accumulation of cavity macrophages during lung and liver injury on the surface of visceral organs without penetration into the parenchyma. Additional data suggest that these peritoneal or pleural cavity macrophages do not contribute to tissue repair and regeneration. Our in vivo genetic targeting approach thus provides a reliable method to identify and characterize cavity macrophages during their development and in tissue repair and regeneration, and distinguishes these cells from other lineages.
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http://dx.doi.org/10.1038/s41467-021-23197-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129080PMC
May 2021

Clinical features in coronavirus disease 2019 (COVID-19) patients with early clearance and prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.

Ann Transl Med 2021 Apr;9(8):665

Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), the pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding has not been well characterized.

Methods: In our study, 652 patients in Wuhan Designated Hospital were recruited, and their clinical and laboratory findings were extracted and analyzed.

Results: The median duration of SARS-CoV-2 RNA detection was 23 days [interquartile range (IQR), 18 days] from symptom onset. Compared to patients with early viral RNA clearance (<23 days after illness onset), we found that patients with late viral RNA clearance (≥23 days) had a higher proportion of clinical features, as follows: symptoms, including fever, dry cough, and sputum production; comorbidities, including hypertension, chronic kidney disease, uremia, chronic liver disease, anemia, hyperlipidemia, and bilateral lung involvement; complications, such as liver injury; delayed admission to hospital; laboratory parameters at baseline, including higher eosinophils, uric acid, cholesterol, triglycerides, and lower hemoglobin; and less treatment with arbidol, chloroquine, or any antivirals. After generalized linear regression, prolonged SARS-CoV-2 RNA shedding was independently associated with younger age; delayed admission to hospital; symptoms including fever, shivering, and sputum production; comorbidities including hypertension, diabetes, cardiovascular disease, anemia, hyperlipidemia, uremia, and lung involvement; and higher alanine aminotransferase (ALT), uric acid, and cholesterol levels at baseline.

Conclusions: In conclusion, the factors mentioned above are associated with the negative conversion of SARS-CoV-2 RNA. A deeper insight into virological dynamics will be helpful for establishing patient discharge and quarantine release criteria.
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http://dx.doi.org/10.21037/atm-21-445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106067PMC
April 2021

Risk factors for hypothyroidism and thyroid hormone replacement after hemithyroidectomy in papillary thyroid carcinoma.

Langenbecks Arch Surg 2021 Jun 10;406(4):1223-1231. Epub 2021 May 10.

Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Purpose: Thyroid lobectomy is now preferred over total thyroidectomy to preserve thyroid function and reduce complications in patients with low-risk papillary thyroid carcinoma (PTC). One inevitable consequence of thyroidectomy includes hypothyroidism. This study aimed to evaluate the risk factors for hypothyroidism and thyroid hormone replacement after hemithyroidectomy in patients with PTC.

Methods: We retrospectively studied 353 patients with PTC who underwent hemithyroidectomy with or without central neck dissection from January 2012 to January 2019. We excluded patients who had hypo- or hyperthyroidism preoperatively and those who underwent total or subtotal thyroidectomy. We analyzed various risk factors related to postoperative hypothyroidism and thyroid hormone supplementation.

Results: Of the patients, 54.7% showed hypothyroidism after hemithyroidectomy (n=193 with n=157, subclinical hypothyroidism; n=36, overt hypothyroidism). Ninety-one percent of postoperative hypothyroidism cases developed within 7 months postoperatively. Eventually, 43.1% (n=152) of patients received levothyroxine after hemithyroidectomy. Preoperative high thyroid-stimulating hormone (TSH) level and low free thyroxine (fT4) level were significantly associated with postoperative hypothyroidism and the need for thyroid hormone supplementation postoperatively.

Conclusion: Preoperative TSH and fT4 levels are predictive risk factors of hypothyroidism and need for supplementation of levothyroxine after hemithyroidectomy in patients with PTC. Finally, approximately 43% of patients need levothyroxine supplementation after hemithyroidectomy, and individual preoperative counseling is necessary for these patients.
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http://dx.doi.org/10.1007/s00423-021-02189-7DOI Listing
June 2021

Implications of cardiac markers in risk-stratification and management for COVID-19 patients.

Crit Care 2021 04 26;25(1):158. Epub 2021 Apr 26.

Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.

Background: COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients.

Methods: A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression.

Results: Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50-68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4-4.8]).

Conclusions: COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.
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http://dx.doi.org/10.1186/s13054-021-03555-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074282PMC
April 2021

The Dopaminergic Neuronal System Regulates the Inflammatory Status of Mouse Lacrimal Glands in Dry Eye Disease.

Invest Ophthalmol Vis Sci 2021 Apr;62(4):14

Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Comparison of the parasympathetic and sympathetic neurons, including the dopaminergic neural system, in dry eye (DE)-induced pathophysiology has not been elucidated well. This study investigated the presence of dopamine receptors (DRs) and their functional roles in the lacrimal glands (LGs) of DE-induced mice.

Methods: After DE was induced in B6 mice for 2 weeks, the expression of tyrosine hydroxylase (TH), dopamine, and DRs (DR1, DR2, etc.) in the LGs and corneas were measured by quantitative RT-PCR, immunoblot, and ELISA. Using flow cytometry and ELISA, immune cell infiltration and inflammatory cytokine expression were determined in DE-induced LGs with or without DR blockers, SCH-23390 (DR1i), or melperone (DR2i). Corneal erosion scores were also investigated.

Results: The mRNA and protein levels of TH significantly increased in DE-induced LGs. The dopamine concentration of LGs was 9.51 pmol in DE (versus naive: 1.39 pmol; P < 0.001). Both DR1 and DR2 mRNA expression were significantly enhanced in desiccating stress compared with those in naive (3.7- and 2.1-fold, P < 0.001). Interestingly, DR1 and DR2 immunostaining patterns stained independently in DE-induced LGs. CD3+ and CD19+ cell infiltration was significantly increased by DR2i (P < 0.001) but not by DR1i. Furthermore, IFN-γ, IL-17, and TNF-α were significantly upregulated by DR2i compared with the blow-only condition. The severity of corneal erosion and inflammation was also aggravated by DR2i.

Conclusions: Upregulation of DR1 and DR2 was observed in DE-induced mouse LGs. As the inflammatory conditions are aggravated by the inhibition of DRs, especially DR2, their activity may be an important factor preserving ocular surface homeostasis.
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http://dx.doi.org/10.1167/iovs.62.4.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039574PMC
April 2021

ADCK1 activates the β-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells.

Cell Death Dis 2021 04 6;12(4):354. Epub 2021 Apr 6.

Department of Oncology, Jingjiang People's Hospital Affiliated with Yangzhou University, 214500, Jingjiang, China.

As a result of mutations in the upstream components of the Wnt/β-catenin signaling pathway, this cascade is abnormally activated in colon cancer. Hence, identifying the activation mechanism of this pathway is an urgent need for the treatment of colon cancer. Here, we found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Upregulation of ADCK1 expression promoted the colony formation and infiltration of cancer cells. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation. Molecular mechanistic studies demonstrated that ADCK1 interacted with TCF4 (T-cell factor 4) to activate the β-catenin/TCF signaling pathway. In conclusion, our research revealed the functions of ADCK1 in the development of colon cancer and provided potential therapeutic targets.
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http://dx.doi.org/10.1038/s41419-021-03624-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024291PMC
April 2021

Clinical characteristics of Lewy body dementia in Chinese memory clinics.

BMC Neurol 2021 Mar 31;21(1):144. Epub 2021 Mar 31.

Department of neurology, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing, China.

Background: Lewy body dementia (LBD), consisting of dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is the second most common type of neurodegenerative dementia in older people. The current study aimed to investigate the clinical characteristics of LBD in Chinese memory clinics.

Methods: A total of 8405 dementia medical records were reviewed, revealing 455 patients with LBD. Demographic data, neuropsychological scores, and the scale for Medial Temporal lobe Atrophy (MTA) were then analyzed from nine memory clinics in the China Lewy Body Disease Collaborative Alliance.

Results: The clinical proportion of LBD among the subjects and among all dementia types was 5.4% (4.9-5.9%) and 7.3% (6.7-8.0%), respectively, with a mean onset age of 68.6 ± 8.4 years. Patients with DLB comprised 5.6% (n = 348, age of onset 69.1 ± 8.3), while PDD comprised 1.7% (n = 107, age of onset 66.7 ± 8.8) of all dementia cases. There were slightly more males than females with DLB (n = 177, 50.9%) and PDD (n = 62, 57.9%). Patients with DLB had a poorer performance compared to those with PDD on the MMSE (16.8 ± 7.1 vs. 19.5 ± 5.7, p = 0.001), the MoCA (11.4 ± 6.6 vs. 14.0 ± 5.8, p<0.001), the CDR (1.8 ± 0.7 vs. 1.6 ± 0.7, p = 0.002), and the MTA (1.8 ± 0.7 vs. 1.2 ± 0.6, p = 0.002). Diagnostic differences for LBD exist among the centers; their reported proportions of those with DLB ranged from 0.7 to 11.4 and those with PDD ranged from 0.0 to 2.9%.

Conclusions: Variations of diagnoses exists in different regions and the clinical proportion of LBD is likely to be underestimated in China and other regions.
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http://dx.doi.org/10.1186/s12883-021-02169-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010972PMC
March 2021

Incidence and risk factors of dementia and the primary subtypes in northern rural China.

Medicine (Baltimore) 2021 Apr;100(13):e25343

Department of Neurology and Tianjin Key Laboratory of Cerebrovascular Disease and Neurodegenerative Disease, Tianjin Dementia Institute, Tianjin Huanhu Hospital.

Abstract: This study was carried out to estimate the incidence and to determine socio-demographic risk factors for dementia among individuals residing in rural northern China.The current prospective, population-based study was conducted between 2011 and 2016. Follow-up interviews were conducted annually from 2014 to 2016. The study involved 1511 dementia-free individuals aged 60 years or above from rural China. Standard criteria were used to make diagnoses for dementia and Alzheimer disease (AD).At least one follow up survey was completed with 1181 study participants. At the 5-year follow-up, 127 individuals had developed dementia, 75 had developed AD, and 32 had developed vascular dementia (VaD). With a total of 5649.2 risk years for the sample, the estimated incidence rates per 1000 person-years were 22.48 (95% CI: 18.62, 26.35) for dementia and 13.28 (95% CI: 10.29, 16.26) for AD. Incidence rates for dementia and AD increased with age across the 10-year age groups. Poor education (illiteracy) was an independent risk factor for both AD and VaD. Being engaged in social activities was an independent protective factor for VaD.The incidence of dementia in rural China was found to be higher than previously reported. Incidence of dementia increased with age, and AD was the most frequent type of dementia. Poor education was associated with a higher risk of VaD and AD. Engagement in social activities was an independent protective factor for VaD.
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http://dx.doi.org/10.1097/MD.0000000000025343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021353PMC
April 2021

Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2.

Sci Rep 2021 Mar 26;11(1):6986. Epub 2021 Mar 26.

Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea.

We investigated the clinical and genetic features of patients with severe phenotype of granular corneal dystrophy type 2 (GCD2) associated with compound heterozygosity in the transforming growth factor-β-induced (TGFBI) gene. Patients with severe GCD2 underwent ophthalmic examination (best-corrected visual acuity test, intraocular pressure measurement, slit-lamp examination, and slit-lamp photograph analysis) and direct Sanger sequencing of whole-TGFBI. The patient's family was tested to determine the pedigrees. Five novel mutations (p.(His174Asp), p.(Ile247Asn), p.(Tyr88Cys), p.(Arg257Pro), and p.(Tyr468*)) and two known mutations (p.(Asn544Ser) and p.(Arg179*)) in TGFBI were identified, along with p.(Arg124His), in the patients. Trans-phase of TGFBI second mutations was confirmed by pedigree analysis. Multiple, extensive discoid granular, and increased linear deposits were observed in the probands carrying p.(Arg124His) and other nonsense mutations. Some patients who had undergone phototherapeutic keratectomy experienced rapid recurrence (p.(Ile247Asn) and p.(Asn544Ser)); however, the cornea was well-maintained in a patient who underwent deep anterior lamellar keratoplasty (p.(Ile247Asn)). Thus, compound heterozygosity of TGFBI is associated with the phenotypic variability of TGFBI corneal dystrophies, suggesting that identifying TGFBI second mutations may be vital in patients with extraordinarily severe phenotypes. Our findings indicate the necessity for a more precise observation of genotype-phenotype correlation and additional care when treating TGFBI corneal dystrophies.
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http://dx.doi.org/10.1038/s41598-021-86414-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997986PMC
March 2021

Triptolide inhibits human telomerase reverse transcriptase by downregulating translation factors SP1 and c-Myc in Epstein-Barr virus-positive B lymphocytes.

Oncol Lett 2021 Apr 10;21(4):280. Epub 2021 Feb 10.

Department of General Surgery, Jingjiang People's Hospital, Jingjiang, Jiangsu 214500, P.R. China.

Epstein-Barr virus (EBV) mainly causes infectious mononucleosis and is associated with several neoplasms, including Burkitt's lymphoma, nasopharyngeal carcinoma and lymphoproliferative disease. Human telomerase reverse transcriptase (hTERT) regulates enzymatic activity of telomerase and is closely associated with tumorigenesis and senescence evasion. Triptolide (TP) is a diterpenoid triepoxide, with a broad-spectrum anticancer and immunosuppressive bioactivity profile. The present study investigated whether TP inhibited hTERT expression and suppressed its activity. The mRNA and protein levels of hTERT were examined by reverse transcription-quantitative PCR and western blotting. The activity of hTERT promoter was determined by dual-luciferase reporter assay. Cell Counting Kit-8 assays were performed to analyze cell proliferation. The present study used EBV-positive B lymphoma cells as a model system, and the results demonstrated that TP significantly decreased hTERT transcription and protein expression. Mechanistically, TP attenuated the hTERT promoter activity by downregulating the expression levels of specificityprotein 1 and c-Myc transcription factors. Consistently, inhibition of hTERT via shRNA transfection efficiently enhanced the suppression of cell proliferation by TP. Furthermore, TP increased virus latent replication and promoted the lytic cycle of EBV in EBV-positive B lymphoma cells, increasing the number of lytic cells and inhibiting the viability of tumor cells. Taken together, the results of the present study revealed a molecular mechanism of the pharmacological inhibition of tumor cell proliferation by TP, encouraging the translation of TP-based therapeutics in EBV-positive B lymphoma treatment.
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http://dx.doi.org/10.3892/ol.2021.12541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905526PMC
April 2021

A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia.

Alzheimers Res Ther 2021 03 17;13(1):62. Epub 2021 Mar 17.

Department of Geriatric psychiatry, Wuxi Mental Health Center, Wuxi, China.

Background: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China.

Methods: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored.

Results: A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group.

Conclusions: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated.

Trial Registration: ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.
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http://dx.doi.org/10.1186/s13195-021-00795-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967962PMC
March 2021

Immunological Feature and Transcriptional Signaling of Ly6C Monocyte Subsets From Transcriptome Analysis in Control and Hyperhomocysteinemic Mice.

Front Immunol 2021 25;12:632333. Epub 2021 Feb 25.

Department of Pharmacology, Center for Metabolic Disease Research, Lewis Kats School of Medicine, Temple University, Philadelphia, PA, United States.

Background: Murine monocytes (MC) are classified into Ly6C and Ly6C MC. Ly6C MC is the pro-inflammatory subset and the counterpart of human CD14CD16 intermediate MC which contributes to systemic and tissue inflammation in various metabolic disorders, including hyperhomocysteinemia (HHcy). This study aims to explore molecule signaling mediating MC subset differentiation in HHcy and control mice.

Methods: RNA-seq was performed in blood Ly6C and Ly6C MC sorted by flow cytometry from control and HHcy cystathionine β-synthase gene-deficient () mice. Transcriptome data were analyzed by comparing Ly6C vs. Ly6C in control mice, Ly6C vs. Ly6C in mice, Ly6C vs. control Ly6C MC and Ly6C vs. control Ly6C MC by using intensive bioinformatic strategies. Significantly differentially expressed (SDE) immunological genes and transcription factor (TF) were selected for functional pathways and transcriptional signaling identification.

Results: A total of 7,928 SDE genes and 46 canonical pathways derived from it were identified. Ly6C MC exhibited activated neutrophil degranulation, lysosome, cytokine production/receptor interaction and myeloid cell activation pathways, and Ly6C MC presented features of lymphocyte immunity pathways in both mice. Twenty-four potential transcriptional regulatory pathways were identified based on SDE TFs matched with their corresponding SDE immunological genes. Ly6C MC presented downregulated co-stimulatory receptors (CD2, GITR, and TIM1) which direct immune cell proliferation, and upregulated co-stimulatory ligands (LIGHT and SEMA4A) which trigger antigen priming and differentiation. Ly6C MC expressed higher levels of macrophage (MΦ) markers, whereas, Ly6C MC highly expressed lymphocyte markers in both mice. HHcy in mice reinforced inflammatory features in Ly6C MC by upregulating inflammatory TFs ( and ) and strengthened lymphocytes functional adaptation in Ly6C MC by increased expression of CD3, DR3, ICOS, and . Finally, we established 3 groups of transcriptional models to describe Ly6C to Ly6C MC subset differentiation, immune checkpoint regulation, Ly6C MC to MΦ subset differentiation and Ly6C MC to lymphocyte functional adaptation.

Conclusions: Ly6C MC displayed enriched inflammatory pathways and favored to be differentiated into MΦ. Ly6C MC manifested activated T-cell signaling pathways and potentially can adapt the function of lymphocytes. HHcy reinforced inflammatory feature in Ly6C MC and strengthened lymphocytes functional adaptation in Ly6C MC.
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http://dx.doi.org/10.3389/fimmu.2021.632333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947624PMC
February 2021

Upregulation of NUCKS1 in Lung Adenocarcinoma is Associated with a Poor Prognosis.

Cancer Invest 2021 May 12;39(5):435-444. Epub 2021 Mar 12.

Department of Thoracic Surgery, The Affiliated Hospital, Qingdao University, Qingdao, China.

To evaluate the clinicopathologic features and survival analysis of NUCKS1 expression in human lung adenocarcinoma (LA), we used bioinformatic methods to obtain NUCKS1 gene status and correlated it with prognosis in LA. We compared NUCKS1 expression in 70 samples of LA with intrinsically normal lung alveoli (NLA) by immunohistochemistry, and analyzed their clinicopathologic features. NUCKS1 was overexpressed in LA components(LACs) relative to NLA, and was significantly correlated to patient with 5-year disease-free survival (DFS) and overall survival(OS). Elevated NUCKS1 expression in LACs was shown to be an independent prognostic indicator for OS and a biomarker in LA.
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http://dx.doi.org/10.1080/07357907.2021.1899199DOI Listing
May 2021

An efficient system for intestinal on-site butyrate production using novel microbiome-derived esterases.

J Biol Eng 2021 Mar 6;15(1). Epub 2021 Mar 6.

Department of Microbiology and Immunology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Short-chain fatty acids, especially butyrate, play beneficial roles in sustaining gastrointestinal health. However, due to limitations associated with direct consumption of butyrate, there has been interest in using prodrugs of butyrate. Tributyrin (TB), a triglyceride composed of three butyrate molecules and a glycerol, is a well-studied precursor of butyrate. We screened a metagenome library consisting of 5760 bacterial artificial chromosome clones, with DNA inserts originating from mouse microbiomes, and identified two clones that efficiently hydrolyse TB into butyrate. Nucleotide sequence analysis indicated that inserts in these two clones are derived from unknown microbes. BLASTp analysis, however, revealed that each insert contains a gene homologous to acetylesterase or esterase genes, from Clostridium spp. and Bacteroides spp., respectively. Predicted structures of these two proteins both contain serine-histidine-aspartate catalytic triad, highly conserved in the family of esterases. Escherichia coli host expressing each of the two candidate genes invariably produced greater amounts of butyrate in the presence of TB. Importantly, administration of TB together with cloned E. coli cells alleviated inflammatory symptoms in a mouse model of acute colitis. Based on these results, we established an efficient on-site and real-time butyrate production system that releases butyrate in a controlled manner inside the intestine.
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http://dx.doi.org/10.1186/s13036-021-00259-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936488PMC
March 2021

Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair.

Science 2021 02;371(6532)

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Organ homeostasis is orchestrated by time- and spatially restricted cell proliferation. Studies identifying cells with superior proliferative capacities often rely on the lineage tracing of a subset of cell populations, which introduces a potential selective bias. In this work, we developed a genetic system [proliferation tracer (ProTracer)] by incorporating dual recombinases to seamlessly record the proliferation events of entire cell populations over time in multiple organs. In the mouse liver, ProTracer revealed more hepatocyte proliferation in distinct zones during liver homeostasis, injury repair, and regrowth. Clonal analysis showed that most of the hepatocytes labeled by ProTracer had undergone cell division. By genetically recording proliferation events of entire cell populations, ProTracer enables the unbiased detection of specific cellular compartments with enhanced regenerative capacities.
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http://dx.doi.org/10.1126/science.abc4346DOI Listing
February 2021

Lung Auscultation of Hospitalized Patients with SARS-CoV-2 Pneumonia via a Wireless Stethoscope.

Int J Med Sci 2021 28;18(6):1415-1422. Epub 2021 Jan 28.

Department of Cardiology , Shanghai General Hospital, Shanghai Jiaotong University School of medicine (originally named "Shanghai First People's Hospital"), Shanghai, China.

SARS-CoV-2 (originally named COVID-2019) pneumonia is currently prevalent worldwide. The number of cases has increased rapidly but the auscultatory characteristics of affected patients and how to use it to predict who is most likely to survive or die are not available. This study aims to describe the auscultatory characteristics and its clinical relativity of SARS-CoV-2 pneumonia by using a wireless stethoscope. A cross-sectional, observational, single-center case series of 30 consecutive hospitalized patients with confirmed SARS-CoV-2 pneumonia at Leishenshan Hospital in Wuhan, China, were enrolled from March 9 to April 5, 2020. Clinical, laboratory, radiological, treatment data and lung auscultation were collected and analyzed. Lung auscultation was acquired by a wireless electronic stethoscope. Auscultatory characteristics of the moderate, severe, and critically ill patients were compared. Kinds of crackles including fine crackles and wheezing were heard and recorded in these patients. Velcro crackles were heard in most critically ill patients (6/10). Besides, patients with Velcro crackles were all dead (6/6). There was no positive lung auscultatory finding in the moderate group and little positive lung auscultatory findings (4/10) in the severe group. Velcro crackles can be auscultated by this newly designed electronic wireless stethoscope in most critically ill patients infected by SARS-CoV-2 and predicts a poor prognosis. Moderate and severe patients without positive auscultatory findings may have a better prognosis.
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http://dx.doi.org/10.7150/ijms.54987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893566PMC
April 2021

High-Expressed Macrophage Scavenger Receptor 1 Predicts Severity Clinical Outcome in Transplant Patient in Idiopathic Pulmonary Fibrosis Disease.

J Immunol Res 2021 31;2021:6690100. Epub 2021 Jan 31.

Department of Cardiothoracic Surgery in Affiliated Wuxi People's Hospital, Wuxi, China.

Background: Lung transplantation has been performed worldwide and admitted as an effective treatment for patients with various end-stage lung diseases. However, limit reliable clinical indicators exist to identify patients at high risk for allograft failure in lung transplant recipients. The recent advances in the knowledge of immunological aspects of the pulmonary diseases, for that innate macrophage activation, are induced by pathogen or pathogen-derived molecules and widely accepted as the critical evidence among the pathogenesis of lung inflammation and fibrosis. This study was aimed at evaluating the clinical significance of CD86- and macrophage scavenger receptor 1- (MSR1-) positive cells during the development of idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH), and their potential roles in the prediction of the outcomes after lung transplantation were examined.

Methods: Tissues from lung transplantation for 37 IPF and 15 PAH patients from the Department of Cardiothoracic Surgery in Wuxi People's Hospital from December 2015 to December 2016 were analyzed by immunohistochemistry (IHC) for detecting the expression and CD86 and MSR1 and correlated with clinical events after lung transplantation.

Results: IHC results showed that the expression of MSR1, IL-13, and arginase-1 (Arg1) but not CD86 in the lung section of IPF patients was dramatically enhanced when compared with that of PAH patients. The expression of MSR1, IL-13, and Arg1 but not CD86 in the lung from IPF patients with smoking was significantly increased when compared with that from nonsmoking subjects. In addition, the expression of MSR1-positive cells in IPF subjects with infection was dramatically enhanced than that in noninfection subjects. MSR1-positive macrophages were negatively associated with FEV1 and with FVC but not associated with TLC and with TL. However, CD86-positive macrophages were not significantly associated with the above lung function-related factors. Furthermore, MSR1 had a higher area under the ROC curve (AUC) than CD86 for IPF diagnosis. Survival analysis indicated that high levels of MSR1-positive macrophages had a worse prognostic effect for IPF patients with lung transplantation.

Conclusion: Our study indicates the clinical significance of infection-related MSR1-positive cells in IPF progression, and it could be a prognostic marker in IPF after the lung transplant; development strategies to reduce the expression of MSR1-positive macrophages in IPF may be beneficial for the lung transplant.
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http://dx.doi.org/10.1155/2021/6690100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868147PMC
January 2021

Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial.

Stroke 2021 Mar 16;52(3):772-780. Epub 2021 Feb 16.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Jie Xu, A.W., X.M., G.Y., S.L., H.Z., X.C., Yilong Wang, X.Z., Yongjun Wang).

Background And Purpose: Edaravone dexborneol, comprised of 2 active ingredients, edaravone and (+)-borneol, has been developed as a novel neuroprotective agent with synergistic effects of antioxidant and anti-inflammatory in animal models. The present clinical trial aimed at testing the effects of edaravone dexborneol versus edaravone on 90-day functional outcome in patients with acute ischemic stroke (AIS).

Methods: A multicenter, randomized, double-blind, comparative, phase III clinical trial was conducted at 48 hospitals in China between May 2015 and December 2016. Inclusion criteria included patients diagnosed as AIS, 35 to 80 years of age, National Institutes of Health Stroke Scale Score between 4 and 24, and within 48 hours of AIS onset. AIS patients were randomized in 1:1 ratio into 2 treatment arms: 14-day infusion of edaravone dexborneol or edaravone injection. The primary end point was the proportion of patients with modified Rankin Scale score ≤1 on day 90 after randomization.

Results: One thousand one hundred sixty-five AIS patients were randomly allocated to the edaravone dexborneol group (n=585) or the edaravone group (n=580). The edaravone dexborneol group showed significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization, compared with the edaravone group (modified Rankin Scale score ≤1, 67.18% versus 58.97%; odds ratio, 1.42 [95% CI, 1.12-1.81]; =0.004). The prespecified subgroup analyses indicated that a greater benefit was observed in female patients than their male counterparts (2.26, 1.49-3.43 versus 1.14, 0.85-1.52).

Conclusions: When edaravone dexborneol versus edaravone was administered within 48 hours after AIS, 90-day good functional outcomes favored the edaravone dexborneol group, especially in female patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02430350.
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http://dx.doi.org/10.1161/STROKEAHA.120.031197DOI Listing
March 2021

A modified technique of transanal specimen extraction in the laparoscopic anterior rectal resection for upper rectal or lower sigmoid colon cancer: a retrospective study.

BMC Surg 2021 Feb 12;21(1):82. Epub 2021 Feb 12.

Department of General Surgery, The First People's Hospital of Foshan (Foshan Hospital of Sun Yat-Sen University), Foshan, China.

Background: In recent years, natural orifice specimen extraction surgery (NOSES) has become a field of special interest for colorectal surgeons. Some researchers have reported transanal specimen extraction in the laparoscopic anterior rectal resection, including intersphincteric resection (ISR) and rectal eversion-resection. However, these surgical procedures have certain limitations. Based on the proven expertise in laparoscopic surgery, our center has developed a modified technique of transanal specimen extraction. The aim of this study was to investigate the safety and feasibility of a modified technique of transanal specimen extraction in the laparoscopic anterior rectal resection.

Methods: From January 2011 to January 2014, the patients with upper rectal or lower sigmoid colon cancer who had undergone laparoscopic anterior rectal resection with specimen extraction by a modified transanal technique were enrolled in the observation group, and the patients who had undergone laparoscopic anterior rectal resection with specimen extraction via an abdominal incision by the same surgeons during the same period were enrolled in the control group.

Results: A total of 36 patients were included in the observation group and 128 patients were included in the control group. There were no significant differences (P > 0.05) between the two groups in terms of the mean operative time [144 ± 10 min vs. 141 ± 11 min], mean intraoperative blood loss [63 ± 6 ml vs. 61 ± 7 ml], and the mean time to anal exhaust [67 ± 7 h vs. 65 ± 8 h]. However, there were significant differences (P < 0.05) between the two groups in terms of the mean postoperative Visual Analogue Scale (VAS) pain scores [3.4 ± 1.1 vs. 4.5 ± 1.2], mean postoperative hospital stay [6.0 ± 1.1 days ± vs. 7.2 ± 1.2 days], and incidence of postoperative complications (4/36 vs. 15/128). Long-term follow-up results showed that there was no significant difference (P > 0.05) between the two groups in terms of the 3- or 5-year overall survival.

Conclusions: The modified technique of transanal specimen extraction in the laparoscopic anterior rectal resection fulfilled the principle of no-neoplasm touch technique, with advantages, such as minimal trauma, rapid recovery, and fewer complications. Long-term follow-up results also showed satisfactory oncological outcomes.
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http://dx.doi.org/10.1186/s12893-021-01085-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881460PMC
February 2021

Evaluation of Voice and Vocal Fold Vibration after Thyroidectomy Using Two-Dimensional Scanning Digital Kymography and High-Speed Videolaryngoscopy.

J Voice 2021 Feb 1. Epub 2021 Feb 1.

Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Hanyang University, Seoul, Republic of Korea. Electronic address:

Objective: Vocal dysfunction is one of the major factors that affect the health-related quality of life of patients after thyroidectomy. Conventionally, voice changes after thyroidectomy have been evaluated by videostroboscopy and acoustic analysis. Recently, two-dimensional scanning digital kymography (2D DKG) and high-speed videolaryngoscopy (HSV) have been developed and have shown usefulness in accurately evaluating vocal fold vibration. This study aimed to evaluate changes of vocal fold vibration and voice after thyroidectomy using 2D DKG and HSV.

Materials And Methods: We evaluated the voice and vocal fold movement of 24 female patients who underwent thyroidectomy in a single tertiary hospital from December 2018 to October 2019. We obtained serial 2D DKG and HSV data one day before thyroidectomy, and 1 week and 1 month after surgery. We analyzed the peak glottal area of HSV, amplitude symmetry index, phase symmetry index, and open quotient using the 2D DKG data. The parameters were calculated at three levels of the vocal fold (line 1=anterior, line 2=middle, line 3=posterior). In the same period, we performed a voice analysis evaluating voice frequency, jitter, shimmer, and noise to harmonic ratio. We also assessed maximum phonation time and subjective voice changes with voice handicap index-10 questionnaires.

Results: Highest frequency (F-high), frequency range (F-range), and fundamental frequency (F0) decreased at 1 week and 1 month after thyroidectomy compared with preoperative values (P = 0.003, 0.004, <0.001 and P = 0.002, 0.015, 0.001 at 1 week and 1 month, respectively). The open quotient of 2D DKG in lines 1 and 2 increased at 1 week after thyroidectomy (P = 0.011, 0.006) and recovered to preoperative levels at 1 month postoperatively (P = 0.189, 0.153). Other quantitative measures by 2D DKG and HSV did not show significant changes between the preoperative and postoperative periods. In a correlation analysis between vocal parameters from the acoustic analysis and the values obtained from 2D DKG and HSV, significant negative correlations were observed between peak glottal area and three factors (F-high, F-range, and F0) at 1 month after surgery (r = -0.589, -0.529, -0.708; P = 0.002, 0.008, <0.001, respectively). There were positive correlations between phase symmetry indexes in lines 1 and 2 and shimmer at 1 week after thyroidectomy (r = 0.489, 0.425; P = 0.015, 0.038, respectively). Phase symmetry index in line 3 showed a significant negative correlation with maximum phonation time at both 1 week and 1 month after surgery (r = -0.497, -0.439; P = 0.013, 0.032, respectively). However, there was no correlation between total score on the voice handicap index-10 questionnaires and quantitative measurements of vocal fold vibration.

Conclusion: 2D DKG and HSV may provide important information on vocal fold vibratory patterns after thyroidectomy, and measurements made with them were correlated with maximal phonation time and acoustic parameters such as F-high, F-range, F0, shimmer.
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http://dx.doi.org/10.1016/j.jvoice.2021.01.005DOI Listing
February 2021

MiR-325-3p mediate the CXCL17/CXCR8 axis to regulate angiogenesis in hepatocellular carcinoma.

Cytokine 2021 May 27;141:155436. Epub 2021 Jan 27.

Department of Hepatic & Pancreatic Surgery, The First People's Hospital of Foshan, Foshan 528000, Guangdong Province, PR China. Electronic address:

Introduction: MicroRNA-325-3p (miR-325-3p) is involved in the progression of a great number of tumors. However, the regulatory mechanism of miR-325-3p on hepatocellular carcinoma (HCC) remains unclear.

Aim: In this paper, we aim to investigate the underlying mechanism by which miR-325-3p regulate the progression of HCC.

Methods: RT-qPCR was performed to detect the levels of miR-325-3p, CXCL17, and CXCR8. Western bolt was conducted to determine the levels of pro-angiogenic factors VEGF, FGF2, Ang-1 and PDGF-B. Immunohistochemistry was carried to detect the distribution and expression of Ki-67 and CD34 in HCC tissues. MTT and colony formation were carried to evaluate cell proliferation, endothelial tube-formation assay was used detect tubule formation, and transwell assay was performed to evaluate cell migration and invasion ability. Dual-luciferase activity assay was used to verify the relationship between miR-325-3p and CXCL17.

Results: MiR-325-3p was down-regulated in HCC cells and tissues, miR-325-3p overexpression inhibited the proliferation, migration and invasion of HCC cells. Besides, miR-325-3p overexpression inhibited angiogenesis of HCC. CXCL17 is a direct target of miR-325-3p and partially mediates the effect of miR-325-3p on proliferation, migration, invasion and angiogenesis of HCC.

Conclusion: MiR-325-3p regulated angiogenesis of HCC via mediating CXCL17/CXCR8 axis, indicating miR-325-3p may serve as a promising therapy biomarker for HCC.
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http://dx.doi.org/10.1016/j.cyto.2021.155436DOI Listing
May 2021

The correction of conjunctivochalasis using high-frequency radiowave electrosurgery improves dry eye disease.

Sci Rep 2021 Jan 28;11(1):2551. Epub 2021 Jan 28.

Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

We aimed to determine the clinical impact of conjunctivochalasis (CCh) and its correction using high-frequency radiowave electrosurgery (HFR-ES), for signs and symptoms of dry eye disease (DED). Forty patients diagnosed with symptomatic CCh were prospectively enrolled. As a result, patients with CCh had moderate to severe DED and most of them exhibited meibomian gland dysfunction (MGD). Corneo-conjunctival fluorescein staining score (CFS) and all lid-parallel-conjunctival-folds scores (LIPCOFs) were positively correlated. Nasal LIPCOF significantly correlated with symptoms and tear volume. Central, temporal, and total LIPCOF significantly correlated with MG loss, MGD stage, and lipid layer thickness. Independent significant factors associated with total LIPCOF included CFS, tear break-up time, and MGD stage. One month following HFR-ES, CCh was completely resolved in all cases. Patient age and preoperative nasal LIPCOF were determinants of outcomes associated with postoperative improvements in symptoms. Ocular surface parameters significantly improved, but MGD-related signs did not. Collectively, CCh associated with MGD severity deteriorates not only tear film stability and reservoir capacity, leading to DED exacerbation. Therefore, CCh should be corrected in patients with DED and MGD. Younger patients with nasal CCh are likely to experience more symptomatic relief after HFR-ES. Particularly, management for MGD should be maintained after CCh correction.
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http://dx.doi.org/10.1038/s41598-021-82088-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844232PMC
January 2021

Long-term outcomes of prediction error after combined phacoemulsification and trabeculectomy in glaucoma patients.

BMC Ophthalmol 2021 Jan 26;21(1):60. Epub 2021 Jan 26.

Department of Ophthalmology, Chonnam National University Medical School and Hospital, 42 Jebong-ro, Dong-gu, Gwangju, 61469, South Korea.

Background: To investigate long-term outcomes of prediction error after phacotrabeculectomy and to determine risk factors that may cause unstable prediction error after phacotrabeculectomy in glaucoma patients.

Methods: A total 120 eyes of 120 patients who had underwent uncomplicated phacotrabeculectomy (combined group) or phacoemulsification (phaco-only group) were included. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) were measured before and after surgery, and anterior segment parameters including anterior chamber depth (ACD), lens vault (LV), and anterior vault (AV) measured using anterior-segment optical coherence tomography were compared between the two groups. The mean absolute error (MAE) at 3, 6, 12, and 24 months postoperatively were compared. Risk factors associated with unstable prediction error (MAE ≥ 0.5) were investigated in the combined group.

Results: In both groups, BCVA was improved and IOP was decreased significantly. MAE at 3, 6, 12, 24 months postoperatively were not significantly different between two groups. The risk factors for unstable prediction error after 12 months of phacotrabeculectomy were old age and LV. Whereas, the only factor predicting unstable prediction error after 24 months of phacotrabeculectomy was LV. The cut-off value of LV for predicting unstable refractive error analyzed by the ROC curve was 0.855 mm.

Conclusions: Phacotrabeculectomy may be an effective treatment with stable long-term outcomes of prediction error similar to phacoemulsification in patients with glaucoma. However, elderly patients or patients with large LV may be predisposed to unstable prediction error after phacotrabeculectomy.
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http://dx.doi.org/10.1186/s12886-021-01824-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839202PMC
January 2021