Publications by authors named "Qiang Guo"

595 Publications

CircRNA expression profiling and bioinformatics analysis indicate the potential biological role and clinical significance of circRNA in influenza A virus-induced lung injury.

J Biosci 2021 ;46

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215000, China.

Circular RNA (circRNA) plays an important role in the regulation of multiple biological processes. However, circRNA profiling and the potential biological role of circRNA in influenza A virus (IAV)-induced lung injury have not been investigated. In the present study, circRNA expression profiles in lung tissues from mice with and without IAV-induced lung injury were analyzed using high-throughput sequencing, and differentially expressed circRNAs were verified by quantitative PCR. The gene homology of candidate circRNAs was investigated and the expression of plasma circRNAs from patients with IAV-induced acute respiratory distress syndrome (ARDS) was detected. The target microRNAs (miRNAs) of circRNAs were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. In total, 781 circRNAs were differentially expressed between ARDS mice and control (467 were up-regulated and 314 were down-regulated). Moreover, the candidate circRNAs (Slco3a1, Nfatc2, Wdr33, and Dmd) expression showed the same trend with the sequencing results. The isoforms of circRNA Slco3a1 and Wdr33 were highly conserved between humans and mice. Plasma circRNA Slco3a1 and Wdr33 presented differential expression in patients with IAV-induced ARDS compared to control. The circRNAmiRNA interaction network and GO and KEGG analyses indicated the potential biological role of circRNAs in the development of IAV-induced lung injury. Taken together, a large number of differentially expressed circRNAs were identified in our study. CircRNA Slco3a1 and Wdr33 had significantly different expression in specimens from mice and humans, and showed a potential biological role in IAV-induced lung injury by bioinformatics analysis.
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January 2021

Prognostic Nomogram for Postoperative Patients With Gastroesophageal Junction Cancer of No Distant Metastasis.

Front Oncol 2021 16;11:643261. Epub 2021 Apr 16.

Department of Thoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Background: Gastroesophageal junction (GEJ) was one of the most common malignant tumors. However, the value of clinicopathological features in predicting the prognosis of postoperative patients with GEJ cancer and without distant metastasis was still unclear.

Methods: The 3425 GEJ patients diagnosed and underwent surgical resection without distant metastasis in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015 were enrolled,and they were randomly divided into training and validation cohorts with 7:3 ratio. Univariate and multivariate Cox regression analysis were used to determine the predictive factors that constituted the nomogram. The predictive accuracy and discriminability of Nomogram were determined by the area under the curve (AUC), C index, and calibration curve, and the influence of various factors on prognosis was explored.

Results: 2,400 patients were designed as training cohort and 1025 patients were designed as validation cohort. The percentages of the distribution of demographic and clinicopathological characteristics in the training and validation cohorts tended to be the same. In the training cohort, multivariate Cox regression analysis revealed that the age, tumor grade, T stage and N stage were independent prognostic risk factors for patients with GEJ cancer without distant metastasis. The C index of nomogram model was 0.667. The AUC of the receiver operating characteristic (ROC) analysis for 3- and 5-year overall survival (OS) were 0.704 and 0.71, respectively. The calibration curve of 3- and 5-year OS after operation showed that there was the best consistency between nomogram prediction and actual observation. In the validation cohort, the C index of nomogram model, the AUC of 3- and 5-year OS, and the calibration curve were similar to the training cohort.

Conclusions: Nomogram could evaluate the prognosis of patients with GEJ cancer who underwent surgical resection without distant metastasis.
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http://dx.doi.org/10.3389/fonc.2021.643261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085428PMC
April 2021

Pathological polyQ expansion does not alter the conformation of the Huntingtin-HAP40 complex.

Structure 2021 Apr 26. Epub 2021 Apr 26.

Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; Institute of Neuropathology, University Medical Center Göttingen, 37099 Göttingen, Germany; Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, 37075 Göttingen, Germany. Electronic address:

The abnormal amplification of a CAG repeat in the gene coding for huntingtin (HTT) leads to Huntington's disease (HD). At the protein level, this translates into the expansion of a polyglutamine (polyQ) stretch located at the HTT N terminus, which renders HTT aggregation prone by unknown mechanisms. Here we investigated the effects of polyQ expansion on HTT in a complex with its stabilizing interaction partner huntingtin-associated protein 40 (HAP40). Surprisingly, our comprehensive biophysical, crosslinking mass spectrometry and cryo-EM experiments revealed no major differences in the conformation of HTT-HAP40 complexes of various polyQ length, including 17QHTT-HAP40 (wild type), 46QHTT-HAP40 (typical polyQ length in HD patients), and 128QHTT-HAP40 (extreme polyQ length). Thus, HTT polyQ expansion does not alter the global conformation of HTT when associated with HAP40.
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http://dx.doi.org/10.1016/j.str.2021.04.003DOI Listing
April 2021

Profiling Oncogenic Germline Mutations in Unselected Chinese Lung Cancer Patients.

Front Oncol 2021 7;11:647598. Epub 2021 Apr 7.

Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, China.

Introduction: Emerging evidence has suggested that inherited factors are also involved in lung cancer development. However, most studies focused on well-elucidated cancer predisposition genes, the majority of which are tumor suppressor genes. The profile of germline mutations in oncogenic driver genes remains unrevealed, which might also provide potential clinical implications for lung cancer management.

Methods: Sequencing data from 36,813 unselected lung cancer patients who underwent somatic mutation profiling were retrospectively reviewed. All recruited patients had matched white blood cell samples sequenced in parallel using a capture-based panel including eight key lung cancer driver genes ( (, , and (). Likely pathogenic/pathogenic (LP/P) variants were called according to the classification criteria of the American College of Medical Genetics and Genomics. Variants of uncertain significance (VUS) located in the kinase domains of driver genes and occurring recurrently (n ≥3) were also included for further analyses.

Results: Seven different LP/P variants in , , or were identified in 0.03% of lung cancer patients (n = 14) and 25 different VUS in the kinase domains of seven driver genes (except ) were found with a prevalence of 0.3% (n = 117).Collectively, germline mutations were most frequently seen in (n = 31, 0.084%), followed by (n = 23, 0.062%), (n = 22, 0.06%), (n = 22, 0.06%) and (n = 17, 0.046%). LP/P variants and VUS fell the most commonly in (n = 10, 72%) and (n = 31, 26%), respectively. Of the 10 patients with LP/P germline mutation, 70% also acquired somatic driver mutation exon21 p.L858R or exon19 deletion at baseline; while the three patients with pathogenic germline mutation displayed distinct baseline somatic profiles of rare mutation or exon2 p.G12C. We discovered 11 germline mutations that also occurred somatically, including four LP/P variants and seven VUS.

Conclusion: We present the first study to systemically characterize the germline mutation in oncogenic driver genes in a large cohort of unselected patients with lung cancers.
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http://dx.doi.org/10.3389/fonc.2021.647598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058453PMC
April 2021

P-type transparent conducting characteristics of delafossite Ca doped CuScO prepared by hydrothermal synthesis.

Dalton Trans 2021 Apr;50(15):5262-5268

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan 430070, P. R. China. and Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.

Ca doped CuScO2 (CSO) delafossite oxides of 3-4 μm were synthesized through the hydrothermal method using Cu(NO3)2·3H2O, Sc(NO3)3·xH2O as the precursor at 240 °C for 24 h in this work. The influence of the process parameters (reaction temperature, Cu/Sc molar ratios, EG (ethylene glycol) quantity, NaOH mineralizer, reactant concentration) on the structure and morphology of CSO was studied systematically. The crystal structure, morphology, and chemical composition of these Ca doped CSO (0, 1 at%, 3 at%, and 5 at%) sheets were analyzed by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). With increasing Ca dopant, the Ca doped CSO sheets become much thinner; the thickness decreased from 568 nm (CSO) to 190 nm (3 at% Ca doped CSO). Moreover, the conductivity of Ca doped CSO sheets decreased with increasing Ca dopant. The CSO powders (19.91 S m-1) have higher conductivity than Ca doped CSO sheets (9.89, 15.69, and 16.51 S m-1) at room temperature. All these CSO based samples exhibit a weak absorption ability with the absorptance around 20-40% in the visible light region (400-780 nm). The optical band gap values exhibited a blue shift with increasing Ca dopant. The calculated band gaps of Ca-doped CSO sheets are 3.88 eV, 3.91 eV, 3.90 eV and 3.93 eV, respectively. This result indicates that all these CSO based samples have potential applications as p-type transparent materials in optoelectronic devices, owing to their comparable optical transmittance in the UV-vis region.
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http://dx.doi.org/10.1039/d1dt00362cDOI Listing
April 2021

In situ architecture of neuronal α-Synuclein inclusions.

Nat Commun 2021 04 14;12(1):2110. Epub 2021 Apr 14.

Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.

The molecular architecture of α-Synuclein (α-Syn) inclusions, pathognomonic of various neurodegenerative disorders, remains unclear. α-Syn inclusions were long thought to consist mainly of α-Syn fibrils, but recent reports pointed to intracellular membranes as the major inclusion component. Here, we use cryo-electron tomography (cryo-ET) to image neuronal α-Syn inclusions in situ at molecular resolution. We show that inclusions seeded by α-Syn aggregates produced recombinantly or purified from patient brain consist of α-Syn fibrils crisscrossing a variety of cellular organelles. Using gold-labeled seeds, we find that aggregate seeding is predominantly mediated by small α-Syn fibrils, from which cytoplasmic fibrils grow unidirectionally. Detailed analysis of membrane interactions revealed that α-Syn fibrils do not contact membranes directly, and that α-Syn does not drive membrane clustering. Altogether, we conclusively demonstrate that neuronal α-Syn inclusions consist of α-Syn fibrils intermixed with membranous organelles, and illuminate the mechanism of aggregate seeding and cellular interaction.
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http://dx.doi.org/10.1038/s41467-021-22108-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046968PMC
April 2021

A comparison of non-intubated video-assisted thoracic surgery with spontaneous ventilation and intubated video-assisted thoracic surgery: a meta-analysis based on 14 randomized controlled trials.

J Thorac Dis 2021 Mar;13(3):1624-1640

Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, China.

Background: Video-assisted thoracic surgery (VATS) generally involves endotracheal intubation under general anesthesia. However, inevitably, this may cause intubation-related complications and prolong the postoperative recovery process. Gradually, non-intubated video-assisted thoracic surgery (NIVATS) is increasingly being utilized. However, its safety and efficacy remain controversial.

Methods: Randomized controlled trials (RCTs) published up to August 2020 were selected from the Cochrane Library, Web of Science, PubMed, Embase, and ClinicalTrials.gov databases and included in this study according to the inclusion criteria. Two reviewers screened these RCTs and independently extracted the relevant data. After assessing the risk of bias in these RCTs, a meta-analysis was performed using Review Manager 5.3. Pooled data were meta-analyzed using a random-effects model.

Results: Meta-analysis data demonstrated that the mean difference (MD) in the length of hospital stay between non-intubated patients and intubated patients was -1.41 days, with a 95% confidence interval (CI) of -2.47 to -0.34 (P=0.01). The visual analogue scale (VAS) score between the two groups showed a MD of -0.34 (95% CI: -0.58 to -0.10; P=0.006). Patients who underwent NIVATS presented with lower rates of overall complications [odds ratio (OR) 0.41; 95% CI: 0.25 to 0.67; P=0.0004], air leak (OR 0.45; 95% CI: 0.24 to 0.87; P=0.02), pharyngeal discomfort (OR 0.08; 95% CI: 0.04 to 0.17; P<0.00001), hoarseness (OR 0.06; 95% CI: 0.02 to 0.21; P<0.00001), and gastrointestinal reactions (OR 0.23; 95% CI: 0.10 to 0.53; P=0.0005) compared to intubated patients. The anesthesia satisfaction scores in the NIVATS group were significantly higher than those of the VATS group (MD 0.50; 95% CI: 0.12 to 0.88; P=0.009). However, there were no statistically significant differences in the length of operation time (MD 0.90 hours; 95% CI: -0.23 to 2.03; P=0.12) and surgical field satisfaction (1 point) (OR 0.73; 95% CI: 0.34 to 1.59; P=0.43) between the two groups.

Conclusions: NIVATS is a safe and feasible form of intervention that can reduce the postoperative pain and complications of various systems and shorten hospital stay duration without prolonging the operation time.
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http://dx.doi.org/10.21037/jtd-20-3039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024812PMC
March 2021

Network reconstruction of social networks based on the public information.

Chaos 2021 Mar;31(3):033123

Institute of Accounting and Finance, Shanghai University of Finance and Economics, Shanghai 200433, People's Republic of China.

The structure of a social network plays a crucial role for dynamic analysis, which is invisible in most scenes. In this paper, we present a model for reconstructing the social network by taking into account the public opinion diffusion dynamic model for specific agenda. First, the initial polarity attitude of users i for the agenda, o, is set in the range [-1,1], where negative and positive attitudes are set as -1 and 1, respectively, while 0 means that user i's attitude is uncertain. Second, we present an optimization model for detecting the relationship among each pair of users based on the generated public observable information. The experimental results for four synthetic networks and three real-world social networks show that the reconstruction accuracy depends on the uncertainty of the initial attitudes greatly. This work is helpful for revealing the structure of social networks in terms of public information.
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http://dx.doi.org/10.1063/5.0038816DOI Listing
March 2021

LRRK2 inhibition potentiates PARP inhibitor cytotoxicity through inhibiting homologous recombination-mediated DNA double strand break repair.

Clin Transl Med 2021 Mar;11(3):e341

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.

PARP inhibitors induce DNA lesions, the repair of which are highly dependent on homologous recombination (HR), and preferentially kill HR- deficient cancers. However, cancer cells have developed several mechanisms to transform HR and confer drug resistance to PARP inhibition. Therefore, there is a great clinical interest in exploring new therapies that induce HR deficiency (HRD), thereby sensitizing cancer cells to PARP inhibitors. Here, we found that GSK2578215A, a high-selective and effective leucine-rich repeat kinase 2 (LRRK2) inhibitor, or LRRK2 depletion suppresses HR preventing the recruitment of RAD51 to DNA damage sites through disruption of the interaction of RAD51 and BRCA2. Moreover, LRRK2 inhibition or depletion increases the susceptibility of ovarian cancer cells to Olaparib in vitro and in vivo. In clinical specimens, LRRK2 high expression is high related with advanced clinical characteristics and poor survival of ovarian cancer patients. All these findings indicate ovarian cancers expressing high levels of LRRK2 are more resistant to treatment potentially through promoting HR. Furthermore, combination treatment with an LRRK2 and PARP inhibitor may be a novel strategy to improve the effectiveness of LRRK2 expression ovarian cancers.
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http://dx.doi.org/10.1002/ctm2.341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908045PMC
March 2021

Effect of the kappa angle on depth of focus after implantation of the TECNIS Symfony intraocular lens.

Int Ophthalmol 2021 Mar 22. Epub 2021 Mar 22.

Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, 23 Bundesgasse, Harbin, Heilongjiang Province, China.

Purpose: To evaluate the clinical effect of TECNIS Symfony intraocular lens (IOL) implantation and identify the effect of kappa angle on the depth of focus (DOF) after implantation.

Methods: This prospective clinical study included consecutive patients who underwent cataract surgery and TECNIS Symfony IOL implantation at the Daqing Oilfield General Hospital from January 2019 to September 2019. Patients were divided into three groups according to the preoperative kappa angle (r): A (0 < r ≤ 0.2), B (0.2 < r ≤ 0.4), and C (r > 0.4). Uncorrected visual acuity was performed preoperatively and at 7 days, 1 month, and 3 months postoperatively. Synthetical optometry, higher-order aberrations, and defocus examinations were performed at 3 months postoperatively. Single-factor analysis of variance and Spearman correlation coefficient were used for data analysis.

Results: The uncorrected visual acuity values of the three groups were significantly improved postoperatively, compared with preoperative values (p < 0.001). Three months postoperatively, the best-corrected visual acuity values of the three groups were 0.11 ± 0.02 logarithm of the minimum angle of resolution (logMAR), 0.09 ± 0.03 logMAR, and 0.11 ± 0.03 logMAR, respectively. Spherical equivalent (SE) values were 0.37 ± 0.08 D, 0.41 ± 0.06 D, and 0.42 ± 0.06 D, respectively. Best-corrected visual acuity and SE did not significantly differ among the three groups (F = 1.254, p = 0.135; F = 0.849, p = 0.228). There was no significant difference in SE between the three groups (F = 1.658, p = 0.312). Moreover, higher-order aberrations did not significantly differ among the three groups (p > 0.05). The kappa angle was negatively correlated with the postoperative DOF (r = -4.341, p = 0.026). Three months postoperatively, 54.55% of patients exhibited DOF ≥ 3 D, while 92.42% of patients exhibited DOF ≥ 2 D. The ranges of DOF in the three groups were 3.18 ± 0.27 D, 2.83 ± 0.80 D, and 2.57 ± 0.89 D, respectively; the difference among the three groups was statistically significant (F = 5.689, p = 0.037).

Conclusion: Most patients achieved full-range vision after TECNIS Symfony IOL implantation, but the DOF narrowed for those with an excessively large kappa angle, which indicates a need for careful selection.
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http://dx.doi.org/10.1007/s10792-021-01809-xDOI Listing
March 2021

Primary Cardiac Angiosarcoma.

Authors:
Shiqi Guo Qiang Guo

Int Heart J 2021 Mar 17;62(2):458-462. Epub 2021 Mar 17.

Department of Critical Care Medicine, Dushu Lake District of The First Affiliated Hospital of Soochow University (Medical Center of Soochow University, Dushu Lake Hospital Affiliated to Soochow University).

In this study, we present the case of a 34-year-old man who was diagnosed with primary cardiac angiosarcoma 1 month after hospital admission. Cardiac angiosarcoma is a relatively rare disease that can be easily misdiagnosed as pneumonia or other diseases. Although surgery is the preferred treatment to prolong survival time, highly malignant tumors with local infiltration and systemic metastasis can lead to poor prognosis.
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http://dx.doi.org/10.1536/ihj.20-581DOI Listing
March 2021

miR-320a/SP1 negative reciprocal interaction contributes to cell growth and invasion in colorectal cancer.

Cancer Cell Int 2021 Mar 17;21(1):175. Epub 2021 Mar 17.

Department of Gastroenterology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650000, China.

Background: Transcription factors (TFs) may be engaged in reciprocal regulatory circuits with certain miRNAs to maintain cellular homeostasis. Disequilibrium of the reciprocities by certain tumor-related stimuli may give rise to deregulation of downstream cellular signaling pathways, thus promoting malignant tumor phenotypes. Specificity Protein 1 (SP1) is the most representative member of the tumor-related transcription factors. Previous studies disclosed that SP1 can transcriptionally regulate miRNAs and coding genes to facilitate tumor progression. In our study, we used bioinformatic analysis to predict several SP1-binding sites within the miR-320a promoter and found that SP1 is a predicted target gene of miR-320a. Therefore, we hypothesize a reciprocal regulatory link between SP1 and miR-320a that participates in colorectal cancer (CRC) development METHODS: We performed bioinformatic analysis, quantitative polymerase chain reaction (qPCR), immunoblotting, dual-luciferase reporter assays, and a series of in vitro and in vivo functional assays to describe a novel SP1/miR-320a reciprocal interaction in CRC RESULTS: First, we found that miR-320a was significantly downregulated in CRC tissues and cell lines. Consistent with findings in other cancers, miR-320a exhibited inhibitory effects on cell growth and invasion of CRC in vitro and in vivo. Moreover, we identified SP1 as a target gene of miR-320a, and ectopic SP1 expression partly abolished miR-320a-induced inhibitory effects. Conversely, we confirmed that SP1 interacts with the miR-320a promoter, leading to depression of miR-320a. This illustrates a double-negative feedback loop between miR-320a and SP1. Additionally, based on the fact that SP1 promotes MACC1 transcription, we determined via immunoblotting that the oncogenic MACC1/MET signaling pathway was inactivated in the context of miR-320a-induced SP1 downregulation CONCLUSION: Taken together, our study is the first to describe a miR-320a/SP1 negative reciprocal interaction, which contributes to cell growth and invasion in CRC through modulation of the MACC1/MET signaling pathway.
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http://dx.doi.org/10.1186/s12935-021-01874-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972346PMC
March 2021

Hemispherectomy Outcome Prediction Scale: Development and validation of a seizure freedom prediction tool.

Epilepsia 2021 May 13;62(5):1064-1073. Epub 2021 Mar 13.

Department of Pediatrics, BC Children's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.

Objective: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy.

Methods: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques.

Results: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-deoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom.

Significance: Children most likely to benefit from hemispheric surgery can be selected and counseled through the implementation of a scale derived from a multiple regression model. Importantly, children who are unlikely to experience seizure control can be spared from the complications and deficits associated with this surgery. The HOPS score is likely to help physicians in clinical decision-making.
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http://dx.doi.org/10.1111/epi.16861DOI Listing
May 2021

Correction: Small molecule induces mitochondrial fusion for neuroprotection via targeting CK2 without affecting its conventional kinase activity.

Signal Transduct Target Ther 2021 Mar 12;6(1):120. Epub 2021 Mar 12.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.

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http://dx.doi.org/10.1038/s41392-021-00533-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955056PMC
March 2021

Study on the role of methylation in nonsyndromic cleft lip with or without cleft palate using a monozygotic twin model.

Int J Pediatr Otorhinolaryngol 2021 Apr 25;143:110659. Epub 2021 Feb 25.

Department of Stomatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China. Electronic address:

Objective: The research on the etiology of nonsyndromic cleft lip with or without cleft palate(NSCL/P) is challenging, and DNA methylation has an impact on the formation of cleft lip and palate.

Subjects: In this study, one of a pair of monozygotic twins (T1) had nonsyndromic cleft lip (NSCL), and one of a pair of monozygotic twins (T2) had nonsyndromic cleft lip and palate (NSCLP). We determined the methylation profiles of more than 850,000 CpGs in the DNA of the blood samples from the two pairs of monozygotic twins.

Result: Methylation data indicated that 1184 differentially methylated CpG sites were found in the T1 group (651 hypermethylated and 533 hypomethylated) and 8099 differentially methylated CpG sites in the T2 group (1713 hypermethylated and 6386 hypomethylated) compared with the healthy twin.The common difference was 107 methylation sites.GO enrichment analysis showed that regulation of smooth muscle cell migration and actin cytoskeleton reorganization were the most prominent classes.KEGG pathway enrichment analysis showed that the TGF-β signaling pathway, Notch signaling pathway and Wnt signaling pathway are relevant to the formation of NSCL/P.Two selected genes (NTN1 and PLEKHA7) are involved in the formation of NSCL/P.

Conclusion: These findings provide some support for the hypothesis that abnormal DNA methylation may influence the formation of clefts.
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http://dx.doi.org/10.1016/j.ijporl.2021.110659DOI Listing
April 2021

[Therapeutic effect and mechanism of Shouhui Tongbian Capsules on slow transit constipation model mice].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(3):520-525

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Beijing 100191, China.

Shouhui Tongbian Capsules was used to explore the therapeutic effect and potential mechanism on slow transit constipation model mice induced by loperamide hydrochloride. In the experiment, loperamide hydrochloride-induced ICR mice were used as the model of slow transit constipation. Fifty ICR mice were divided into the blank group, model group and high, medium and low dose groups of Shouhui Tongbian Capsules extract(100, 200 and 400 mg·kg~(-1)). The model group and the administration groups were then modeled using loperamide hydrochloride intragastrically to obtain slow transit constipation. After successful modeling, high, medium and low doses of drugs were given to each drug group by intragastric administration. After 14 days of administration, the first defecation time, 6 h defecation grain number, 6 h defecation wet weight and dry weight, black feces discharged within 6 h and the fecal water content were measured. Intestinal tissues were taken for c-Kit and SCF immunohistochemical sections to detect the expression of c-Kit and SCF in the blank group, model group and high, medium and low dose groups of the medicinal extract of Shouhui Tongbian Capsules. The tissue changes in the intestinal wall of mice were detected by HE staining. At the same time, partial intestinal tissues were taken to test the activity of ATP synthase and isocitrate dehydrogenase in intestinal tissues of mice. RESULTS:: showed that Shouhui Tongbian Capsules effectively improved the symptoms of slow transit constipation in ICR mice and promoted intestinal movement. Shouhui Tongbian Capsules obviously shortened the time of discharging black stool for the first time, improved the intestinal propulsion rate, increased the water content and amount of feces, and improved the constipation symptoms. Mechanism study revealed that Shouhui Tongbian Capsules increased ATP synthase activity and mitochondrial isocitrate dehydrogenase activity in intestinal tissue, and up-regulated c-Kit/SCF signaling pathway to promote interstitial Cajal cells proliferation, intestinal nerve transmission, intestinal motility and transport capacity.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201125.401DOI Listing
February 2021

[Identification of intestine direct targets of Shouhui Tongbian Capsules using "target fishing" strategy].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(3):505-510

State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University Beijing 100191,China.

"Target fishing" strategy was used to investigate the direct targets and mechanism of Shouhui Tongbian Capsules on relaxing bowel. Magnetic beads cross-linked with the chemical constituents from Shouhui Tongbian Capsules were prepared. The potential target proteins were captured from the total protein lysates of rat intestine using the beads. The captured proteins were further identified by LC-MS/MS, and the associated pathways were analyzed by Cytoscape. RESULTS:: showed that 138 potential target proteins were identified, which were involved in eight signaling pathways, including tricarboxylic acid cycle, pyrimidine metabolism, sulfur metabolism, fatty acid degradation, alanine/aspartate/glutamate metabolism, arginine/proline metabolism, valine/leucine/isoleucine degradation, and β-alanine metabolism. Taken together, Shouhui Tongbian Capsules may exert relaxing bowel effect by acting on multiple signaling pathways to promote intestinal gurgling, inhibit inflammation, as well as improve intestinal barrier function, intestinal water secretion, and intestinal flora.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201125.403DOI Listing
February 2021

Profiling of Serum Exosome MiRNA Reveals the Potential of a MiRNA Panel as Diagnostic Biomarker for Alzheimer's Disease.

Mol Neurobiol 2021 Feb 24. Epub 2021 Feb 24.

Department of Pathophysiology, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People's Republic of China.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the older adults. Although much effort has been made in the analyses of diagnostic biomarkers, such as amyloid-β, tau, and neurofilament light chain, identifying peripheral blood-based biomarkers is in extremely urgent need for their minimal invasiveness and more convenience. Here we characterized the miRNA profile by RNA sequencing in human serum exosomes from AD patients and healthy controls (HC) to investigate its potential for AD diagnosis. Subsequently, Gene Ontology analysis and pathway analysis were performed for the targeted genes from the differentially expressed miRNAs. These basic functions were differentially enriched, including cell adhesion, regulation of transcription, and the ubiquitin system. Functional network analysis highlighted the pathways of proteoglycans in cancer, viral carcinogenesis, signaling pathways regulating pluripotency of stem cells, and cellular senescence in AD. A total of 24 miRNAs showed significantly differential expression between AD and HC with more than ± 2.0-fold change at p value < 0.05 and at least 50 reads for each sample. Logistic regression analysis established a model for AD prediction by serum exosomal miR-30b-5p, miR-22-3p, and miR-378a-3p. Sequencing results were validated using quantitative reverse transcription PCR. The data showed that miR-30b-5p, miR-22-3p, and miR-378a-3p were significantly deregulated in AD, with area under the curve (AUC) of 0.668, 0.637, and 0.718, respectively. The combination of the three miRs gained a better diagnostic capability with AUC of 0.880. This finding revealed a miR panel as potential biomarker in the peripheral blood to distinguish AD from HC.
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http://dx.doi.org/10.1007/s12035-021-02323-yDOI Listing
February 2021

Side chain engineering of copolymers based on benzotriazole (BTA) and dithieno[2,3-d;2',3'-d']benzo[1,2-b;4,5-b']dithiophenes (DTBDT) enables a high PCE of 14.6.

Nanotechnology 2021 Feb 22. Epub 2021 Feb 22.

National Center for Nanoscience and Technology, Haidian District, 100190, CHINA.

Dithieno[2,3-d;2',3'-d']benzo[1,2-b;4,5-b']dithiophenes (DTBDT) is a kind of prospective candidate for constructing donor-π-acceptor (D-π-A) copolymer donors applied in organic solar cells (OSCs), but restricted for its relatively poor photovoltaic performance compared with benzo[1,2-b;4,5-b']dithiophenes (BDT)-based analogue. Herein, three conjugated polymers (PE51, PE52 and PE53) based DTBDT and benzo[d][1,2,3]triazole (BTA) bearing different length of side alkyl chain unit were synthesized. The change of alkyl chain length can effectively affect energy level distribution, molecular stacking, miscibility and morphology with the non-fullerene acceptor of Y6, resulting in gradually increased open-circuit voltage (VOC) from 0.79 to 0.83 V, improved short-current density (JSC) and fill-factor (FF) reached up to 25.36 mA cm-2 and 71.94% in PE52-based device (with moderate alkyl chain). Impressively, compared with BDT-based analogue J52-Cl, the significantly enhanced crystallinity and intermolecular interaction of PE52 had effectively boosted the charge transport characteristic and optimized the surface morphology, thereby increasing the power conversion efficiency (PCE) from 12.3% to 14.6%, which is the highest PCE among DTBDT-based polymers and BTA-based polymers. Our results show that not only high efficiency could be achieved via using DTBDT as D unit, but also the length of the alkyl chain on BTA has a significant impact on photovoltaic performance for DTBDT-based polymers.
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http://dx.doi.org/10.1088/1361-6528/abe896DOI Listing
February 2021

The Dual Effects of Reactive Oxygen Species on the Mandibular Alveolar Bone Formation in SOD1 Knockout Mice: Promotion or Inhibition.

Oxid Med Cell Longev 2021 3;2021:8847140. Epub 2021 Feb 3.

Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

The status of reactive oxygen species (ROS) correlates closely with the normal development of the oral and maxillofacial tissues. Oxidative stress caused by ROS accumulation not only affects the development of enamel and dentin but also causes pathological changes in periodontal tissues (periodontal ligament and alveolar bone) that surround the root of the tooth. Although previous studies have shown that ROS accumulation plays a pathologic role in some oral and maxillofacial tissues, the effects of ROS on alveolar bone development remain unclear. In this study, we focused on mandibular alveolar bone development of mice deficient in superoxide dismutase1 (SOD1). Analyses were performed using microcomputerized tomography (micro-CT), TRAP staining, immunohistochemical (IHC) staining, and enzyme-linked immunosorbent assay (ELISA). We found for the first time that slightly higher ROS in mandibular alveolar bone of SOD1(-/-) mice at early ages (2-4 months) caused a distinct enlargement in bone size and increased bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and osteopontin (OPN). With ROS accumulation to oxidative stress level, increased trabecular bone separation (Tb.Sp) and decreased expression of ALP, Runx2, and OPN were found in SOD1(-/-) mice at 6 months. Additionally, dosing with N-acetylcysteine (NAC) effectively mitigated bone loss and normalized expression of ALP, Runx2, and OPN. These results indicate that redox imbalance caused by SOD1 deficiency has dual effects (promotion or inhibition) on mandibular alveolar bone development, which is closely related to the concentration of ROS and the stage of growth. We present a valuable model here for investigating the effects of ROS on mandibular alveolar bone formation and highlight important roles of ROS in regulating tissue development and pathological states, illustrating the complexity of the redox signal.
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http://dx.doi.org/10.1155/2021/8847140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878083PMC
February 2021

Geometric Analysis of the Distolingual Root and Canal in Mandibular First Molars: A Micro-computed Tomographic Study.

J Endod 2021 May 18;47(5):779-786. Epub 2021 Feb 18.

Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.

Introduction: The purpose of this study was to comprehensively assess by micro-computed tomographic imaging the anatomic features of distolingual (DL) roots and canals in mandibular first molars collected from 1 population.

Methods: One hundred two specimens were examined for the location and initial direction of the DL canal and the relationship between the distance of apical deviation and the angle of root curvature.

Results: All DL roots had only 1 canal. A new 7-category classification system is proposed for the DL roots of mandibular first molars. Most DL roots were type IV (28 teeth), type III (26 teeth), and type V (25 teeth). The average canal curvature in all root types was over 25°. There was a positive correlation between the angles of root and canal curvature for types II, IV, and V (P < .05) but not for types I and III (P > .05). In the buccolingual view, most DL roots were straight, whereas in the mesiodistal view the root curvature was close to the maximum value. The orifice of the DL canal was 4 times further from the line that bisects a line between the mesiobuccal and mesiolingual canal orifices than the distobuccal canal. The angle between the mesiobuccal-mesiolingual line and the horizontal projection of the coronal third of the DL canal on the pulp floor was 8.1° ± 10.0° and 6.1° ± 8.2° for teeth from the left and right side, respectively. The angle between the inserted simulated file and the cementoenamel junction was 57.9° ± 6.3°. Seventy-three percent of the DL canals had no constriction in the apical area. The DL canals were narrow and had a conical frustum-like shape with a 0.04 taper at the apical portion.

Conclusions: The novel classification of the DL roots helps to better understand the clinically challenging anatomy of the root and canal.
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http://dx.doi.org/10.1016/j.joen.2021.02.006DOI Listing
May 2021

Small molecule induces mitochondrial fusion for neuroprotection via targeting CK2 without affecting its conventional kinase activity.

Signal Transduct Target Ther 2021 Feb 19;6(1):71. Epub 2021 Feb 19.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.

Mitochondrial fusion/fission dynamics plays a fundamental role in neuroprotection; however, there is still a severe lack of therapeutic targets for this biological process. Here, we found that the naturally derived small molecule echinacoside (ECH) significantly promotes mitochondrial fusion progression. ECH selectively binds to the previously uncharacterized casein kinase 2 (CK2) α' subunit (CK2α') as a direct cellular target, and genetic knockdown of CK2α' abolishes ECH-mediated mitochondrial fusion. Mechanistically, ECH allosterically regulates CK2α' conformation to recruit basic transcription factor 3 (BTF3) to form a binary protein complex. Then, the CK2α'/BTF3 complex facilitates β-catenin nuclear translocation to activate TCF/LEF transcription factors and stimulate transcription of the mitochondrial fusion gene Mfn2. Strikingly, in a mouse middle cerebral artery occlusion (MCAO) model, ECH administration was found to significantly improve cerebral injuries and behavioral deficits by enhancing Mfn2 expression in wild-type but not CK2α' mice. Taken together, our findings reveal, for the first time, that CK2 is essential for promoting mitochondrial fusion in a Wnt/β-catenin-dependent manner and suggest that pharmacologically targeting CK2 is a promising therapeutic strategy for ischemic stroke.
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http://dx.doi.org/10.1038/s41392-020-00447-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893052PMC
February 2021

Tectorigenin attenuates the OGD/R-induced HT-22 cell damage through regulation of the PI3K/AKT and the PPARγ/NF-κB pathways.

Hum Exp Toxicol 2021 Feb 16:960327121993213. Epub 2021 Feb 16.

Department of Anesthesiology, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, China.

Tectorigenin (TEC) is an effective compound that derived from many plants, such as . Evidence suggested that TEC has anti-tumor, anti-oxidant activity, anti-bacterial and anti-inflammatory effects. In addition, there has some evidence indicated that TEC is a potential anti-stroke compound; however, its specific roles and associated mechanism have not yet been elucidated. In the present study, we aimed to investigate the anti-inflammatory, anti-oxidant activity and anti-apoptosis effects of TEC on oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT-22 cells, and clarified the relevant mechanisms. Here, we observed that TEC significantly promoted cell survival, impeded cell apoptosis, inhibited ROS and inflammatory cytokines IL-1β, IL-6, TNF-α production in OGD/R-induced HT-22 cells. Moreover, TEC activated PI3K/AKT signal pathway, increased PPARγ expression and inhibited NF-κB pathway activation in OGD/R-induced HT-22 cells. Further studies indicated that PPARγ inhibitor GW9662 activated NF-κB pathway after TEC treatment in OGD/R-induced HT-22 cells. Also, PI3K/AKT inhibitor LY294002, PPARγ inhibitor GW9662 and NF-κB activator LPS both reversed the effects of TEC on OGD/R-induced HT-22 cell biology. Taken together, this research confirmed that TEC benefit to HT-22 cell survival and against OGD/R damage through the PI3K/AKT and PPARγ/NF-κB pathways. These results indicated that TEC might be an effective compound in the treatment for ischemic brain injury.
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http://dx.doi.org/10.1177/0960327121993213DOI Listing
February 2021

SPARC Knockdown Reduces Glutamate-Induced HT22 Hippocampal Nerve Cell Damage by Regulating Autophagy.

Front Neurosci 2020 26;14:581441. Epub 2021 Jan 26.

Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Haikou, China.

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein involved in the extracellular matrix and interactions between cells during neural development of the central nervous system (CNS). Oxidative glutamate toxicity is involved in CNS diseases, including epilepsy, Alzheimer's disease, and ischemic stroke. However, the molecular mechanism of nerve injury is not fully understood in CNS diseases. Herein, the glutamate-induced nerve damage model was used to explore the molecular mechanisms affecting nerve damage. The levels of SPARC and autophagy were increased in glutamate-induced HT22 hippocampal nerve injury. In summary, the current study confirmed that SPARC regulates autophagy in HT22 hippocampal nerve cells, and its knockdown reduces the glutamate-induced HT22 hippocampal nerve injury by inhibiting autophagy. These findings suggested that SPARC plays a crucial role in nerve injury of CNS diseases.
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http://dx.doi.org/10.3389/fnins.2020.581441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874057PMC
January 2021

Hippocampal Aromatase Knockdown Aggravates Ovariectomy-Induced Spatial Memory Impairment, Aβ Accumulation and Neural Plasticity Deficiency in Adult Female Mice.

Neurochem Res 2021 May 8;46(5):1188-1202. Epub 2021 Feb 8.

Department of Neurobiology, Army Medical University, Chongqing, China.

Ovarian estrogens (mainly 17β estradiol, E2) have been involved in the regulation of the structure of hippocampus, the center of spatial memory. In recent years, high levels of aromatase (AROM), the estrogen synthase, has been localized in hippocampus; and this hippocampus-derived E2 seems to be functional in synaptic plasticity and spatial memory as ovarian E2 does. However, the contribution of ovarian E2 and hippocampal E2 to spatial memory and neural plasticity remains unclear. In this study, AROM-specific RNA interference AAVs (shAROM) were constructed and injected into the hippocampus of control or ovariectomized (OVX) mice. Four weeks later the spatial learning and memory behavior was examined with Morris water maze, the expression of hippocampal Aβ related proteins, selected synaptic proteins and CA1 synapse density, actin polymerization related proteins and CA1 spine density were also examined. The results showed that while OVX and hippocampal shAROM contributed similarly to most of the parameters examined, shAROM induced more increase in BACE1 (amyloidogenic β-secretase), more decrease in neprilysin (Aβ remover) and Profilin-1 (actin polymerization inducer). More importantly, combined OVX and shAROM treatment displayed most significant impairment of spatial learning and memory as well as decrease in synaptic plasticity compared to OVX or shAROM alone. In conclusion, the above results clearly demonstrated the crucial role of hippocampal E2 in the regulation of the structure and function of hippocampus besides ovarian E2, indicating that hippocampal E2 content should also be taken into consideration during estrogenic replacement.
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http://dx.doi.org/10.1007/s11064-021-03258-5DOI Listing
May 2021

Silk fibroin hydrogel scaffolds incorporated with chitosan nanoparticles repair articular cartilage defects by regulating TGF-β1 and BMP-2.

Arthritis Res Ther 2021 02 2;23(1):50. Epub 2021 Feb 2.

Department of Hand and Foot Surgery, Linyi People's Hospital, Linyi, 276000, People's Republic of China.

Cartilage defects frequently occur around the knee joint yet cartilage has limited self-repair abilities. Hydrogel scaffolds have excellent potential for use in tissue engineering. Therefore, the aim of the present study was to assess the ability of silk fibroin (SF) hydrogel scaffolds incorporated with chitosan (CS) nanoparticles (NPs) to repair knee joint cartilage defects. In the present study, composite systems of CS NPs incorporated with transforming growth factor-β1 (TGF-β1; TGF-β1@CS) and SF incorporated with bone morphogenetic protein-2 (BMP-2; TGF-β1@CS/BMP-2@SF) were developed and characterized with respect to their size distribution, zeta potential, morphology, and release of TGF-β1 and BMP-2. Bone marrow stromal cells (BMSCs) were co-cultured with TGF-β1@CS/BMP-2@SF extracts to assess chondrogenesis in vitro using a cell counting kit-8 assay, which was followed by in vivo evaluations in a rabbit model of knee joint cartilage defects. The constructed TGF-β1@CS/BMP-2@SF composite system was successfully characterized and showed favorable biocompatibility. In the presence of TGF-β1@CS/BMP-2@SF extracts, BMSCs exhibited normal cell morphology and enhanced chondrogenic ability both in vitro and in vivo, as evidenced by the promotion of cell viability and the alleviation of cartilage defects. Thus, the TGF-β1@CS/BMP-2@SF hydrogel developed in the present study promoted chondrogenic ability of BMSCs both in vivo and in vitro by releasing TGF-β1 and BMP-2, thereby offering a novel therapeutic strategy for repairing articular cartilage defects in knee joints.
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http://dx.doi.org/10.1186/s13075-020-02382-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856775PMC
February 2021

The alteration of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in the knee joints of osteoarthritis mice.

J Histotechnol 2021 Jan 22:1-12. Epub 2021 Jan 22.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu, China.

The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is gradually being recognized as an important family of mediators that, along with the matrix metalloproteinases (MMPs), control the degradation process in osteoarthritis (OA). The objective of this study was to uncover the detailed alterations of ADAMTS1, ADAMTS2, and ADAMTS5 in the knee joint of OA mice. The OA model was established by anterior cruciate ligament transection (ACLT) on the knee joints of C57BL/6 J mice. The mice showed representative phenotypes of ACLT-induced OA, including obvious deterioration of the cartilage, reductions in the collagen and proteoglycan components in the cartilage matrix of OA mice, and increased inflammation and osteoclast activity. By qPCR, the gene expression levels of were the top-ranked among in cartilage/chondrocytes, osteogenic tissue/osteoblasts, and cortical bone/osteocytes. Moreover, the protein expression levels of ADAMTS1, -2, and -5 were all increased in articular cartilage, the growth plate, and subchondral bone of the knee joint. The results suggest the important roles of ADAMTS1, -2, and -5 in OA disease, which will be helpful in further research on degenerative changes in OA.
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http://dx.doi.org/10.1080/01478885.2020.1861908DOI Listing
January 2021

STING promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the NF-κB signaling pathway.

Cell Death Dis 2021 01 4;12(1):13. Epub 2021 Jan 4.

Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.

Damaged deoxyribonucleic acid (DNA) is a primary pathologic factor for osteoarthritis (OA); however, the mechanism by which DNA damage drives OA is unclear. Previous research demonstrated that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) participates in DNA damage response. As a result, the current study aimed at exploring the role STING, which is the major effector in the cGAS-STING signaling casacde, in OA progress in vitro, as well as in vivo. In this study, the expression of STING was evaluated in the human and mouse OA tissues, and in chondrocytes exposed to interleukin-1 beta (IL-1β). The influences of STING on the metabolism of the extracellular matrix (ECM), apoptosis, and senescence, were assessed in STING overexpressing and knocking-down chondrocytes. Moreover, the NF-κB-signaling casacde and its role in the regulatory effects of STING on ECM metabolism, apoptosis, and senescence were explored. The STING knockdown lentivirus was intra-articularly injected to evaluate its therapeutic impact on OA in mice in vivo. The results showed that the expression of STING was remarkably elevated in the human and mouse OA tissues and in chondrocytes exposed to IL-1β. Overexpression of STING promoted the expression of MMP13, as well as ADAMTS5, but suppressed the expression of Aggrecan, as well as Collagen II; it also enhanced apoptosis and senescence in chondrocytes exposed to and those untreated with IL-1β. The mechanistic study showed that STING activated NF-κB signaling cascade, whereas the blockage of NF-κB signaling attenuated STING-induced apoptosis and senescence, and ameliorated STING-induced ECM metabolism imbalance. In in vivo study, it was demonstrated that STING knockdown alleviated destabilization of the medial meniscus-induced OA development in mice. In conclusion, STING promotes OA by activating the NF-κB signaling cascade, whereas suppression of STING may provide a novel approach for OA therapy.
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http://dx.doi.org/10.1038/s41419-020-03341-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791051PMC
January 2021

Syphilis-associated septic cardiomyopathy: case report and review of the literature.

Authors:
Shiqi Guo Qiang Guo

BMC Infect Dis 2021 Jan 7;21(1):33. Epub 2021 Jan 7.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Background: Septic cardiomyopathy has been observed in association with influenza, indicating that not only bacteria but also other infective agents can cause this condition. There has been no systematic study as to whether Treponema pallidum infection induces septic cardiomyopathy, and we are the first to report this possibility.

Case Presentation: We report two cases of a 48-year-old man and a 57-year-old man who were diagnosed with syphilis-related septic cardiomyopathy. The diagnosis of cardiomyopathy was made based on elevation of cardiogenic markers and decrease in ejection fraction evaluated by echocardiography. Screen for infective pathogens was negative except for syphilis, which supported our diagnosis. The two patients recovered following effective anti-syphilis treatment and advanced life support technology. Syphilis serology became negative after treatment.

Conclusion: Syphilis has the potential to cause septic cardiomyopathy. Clinicians should consider Treponema pallidum in cases of septic cardiomyopathy with unknown pathogens. However, the specific pathophysiological mechanism of syphilis-associated septic cardiomyopathy has not been elucidated, and more specific studies are needed.
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http://dx.doi.org/10.1186/s12879-020-05722-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790048PMC
January 2021

Double versus single T-tube drainage for frank cysto-biliary communication in patients with hepatic cystic echinococcosis: a retrospective cohort study with median 11 years follow-up.

BMC Surg 2021 Jan 6;21(1):12. Epub 2021 Jan 6.

Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, #137 South Liyushan Road, Urumqi, 830054, China.

Background: Partial peri-cystectomy (PPC) is one of the major surgical approaches for hepatic cystic echinococcosis (CE) and has been practiced in most centers worldwide. Cysto-biliary communication (fistula, leakage, rupture) is a problematic issue in CE patients. T-tube is a useful technique in situations where an exploration and decompression are needed for common bile duct (CBD). However, postoperative biliary complications for cystic cavity still remains to be studied in depth.

Methods: A retrospective cohort analysis of CE cases in our single center database from 2007 March to 2012 December was performed. Patients (n = 51) were divided into two cohorts: double T-tube drainage (one at CBD for decompression and one at the fistula for sustaining in cystic cavity, n = 23) group and single T-tube drainage cohort (only one at CBD for decompression, n = 28). Short-/long-term postoperative complications focusing on biliary system was recorded in detail and they were followed-up for median 11 years.

Results: Overall biliary complication rates for double and single T-tube drainages were 17.4% vs. 39.3% (P > 0.05). Short-term complications ranged from minor to major leakages, cavity infection and abscess formation, and prevalence was 17.4% vs. 21.4% (P > 0.05) respectively for double and single T-tube groups; most importantly, double T-tube drainage group had obvious advantages regarding long-term complications (P < 0.05), which was biliary stricture needing surgery and it was observed only in single T-tube drainage group.

Conclusions: Double T-tube drainage had better outcomes without procedure-specific postoperative biliary complications than single T-tube drainage. Meanwhile, we recommend long-term follow-up when comparing residual cavity related biliary complications in CE patients as it could happen lately.
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http://dx.doi.org/10.1186/s12893-020-01028-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789643PMC
January 2021