Publications by authors named "Chen Wan"

174 Publications

Effects of aging on the histology and biochemistry of rat tendon healing.

BMC Musculoskelet Disord 2021 Nov 15;22(1):949. Epub 2021 Nov 15.

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, 400038, China.

Introduction: Tendon diseases and injuries are a serious problem for the aged population, often leading to pain, disability and a significant decline in quality of life. The purpose of this study was to determine the influence of aging on biochemistry and histology during tendon healing and to provide a new strategy for improving tendon healing.

Method: A total of 24 Sprague-Dawley rats were equally divided into a young and an aged group. A rat patellar tendon defect model was used in this study. Tendon samples were collected at weeks 2 and 4, and hematoxylin-eosin, alcian blue and immunofluorescence staining were performed for histological analysis. Meanwhile, reverse transcription-polymerase chain reaction (RT-PCR) and western blot were performed to evaluate the biochemical changes.

Results: The histological scores in aged rats were significantly lower than those in young rats. At the protein level, collagen synthesis-related markers Col-3, Matrix metalloproteinase-1 and Metallopeptidase Inhibitor 1(TIMP-1) were decreased at week 4 in aged rats compared with those of young rats. Though there was a decrease in the expression of the chondrogenic marker aggrecan at the protein level in aged tendon, the Micro-CT results from weeks 4 samples showed no significant difference(p>0.05) on the ectopic ossification between groups. Moreover, we found more adipocytes accumulated in the aged tendon defect with the Oil Red O staining and at the gene and protein levels the markers related to adipogenic differentiation.

Conclusions: Our findings indicate that tendon healing is impaired in aged rats and is characterized by a significantly lower histological score, decreased collagen synthesis and more adipocyte accumulation in patellar tendon after repair.
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http://dx.doi.org/10.1186/s12891-021-04838-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594129PMC
November 2021

MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength.

Biomaterials 2021 Nov 5;279:121242. Epub 2021 Nov 5.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400000, China. Electronic address:

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSC) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSC derived exosomes (BMMSC-exos). Local injection of BMMSC-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSC-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121242DOI Listing
November 2021

ALT neuroblastoma chemoresistance due to telomere dysfunction-induced ATM activation is reversible with ATM inhibitor AZD0156.

Sci Transl Med 2021 08;13(607)

Cancer Center, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Cancers overcome replicative immortality by activating either telomerase or an alternative lengthening of telomeres (ALT) mechanism. ALT occurs in ~25% of high-risk neuroblastomas, and progression in patients with ALT neuroblastoma during or after front-line therapy is frequent and often fatal. Temozolomide + irinotecan is commonly used as salvage therapy for neuroblastoma. Patient-derived cell lines and xenografts established from patients with relapsed ALT neuroblastoma demonstrated de novo resistance to temozolomide + irinotecan [SN-38 in vitro, < 0.05; in vivo mouse event-free survival (EFS), < 0.0001] vs. telomerase-positive neuroblastomas. We observed that ALT neuroblastoma cells manifested constitutive ataxia-telangiectasia mutated (ATM) activation due to spontaneous telomere dysfunction which was not observed in telomerase-positive neuroblastoma cells. We demonstrated that induction of telomere dysfunction resulted in ATM activation that, in turn, conferred resistance to temozolomide + SN-38 (4.2-fold change in IC, < 0.001). ATM knockdown (shRNA) or inhibition using a clinical-stage small-molecule inhibitor (AZD0156) reversed resistance to temozolomide + irinotecan in ALT neuroblastoma cell lines in vitro ( < 0.001) and in four ALT xenografts in vivo (EFS, < 0.0001). AZD0156 showed modest to no enhancement of temozolomide + irinotecan activity in telomerase-positive neuroblastoma cell lines and xenografts. Ataxia telangiectasia and Rad3 related (ATR) inhibition using AZD6738 did not enhance temozolomide + SN-38 activity in ALT neuroblastoma cells. Thus, ALT neuroblastoma chemotherapy resistance occurs via ATM activation and is reversible with ATM inhibitor AZD0156. Combining AZD0156 with temozolomide + irinotecan warrants clinical testing for neuroblastoma.
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http://dx.doi.org/10.1126/scitranslmed.abd5750DOI Listing
August 2021

Species distribution models for predicting the habitat suitability of Chinese fire-bellied newt under climate change.

Ecol Evol 2021 Aug 27;11(15):10147-10154. Epub 2021 Jun 27.

Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life Sciences Nanjing Normal University Nanjing China.

Climate change influences species geographical distribution and diversity pattern. The Chinese fire-bellied newt () is an endemic species distributed in East-central China, which has been classified as near-threatened species recently due to habitat destruction and degradation and illegal trade in the domestic and international pet markets. So far, little is known about the spatial distribution of the species. Based on bioclimatic data of the current and future climate projections, we modeled the change in suitable habitat for by ten algorithms, evaluated the importance of environmental factors in shaping their distribution, and identified distribution shifts under climate change scenarios. In this study, 46 records of from East China and 8 bioclimatic variables were used. Among the ten modeling algorithms, four (GAM, GBM, Maxent, and RF) were selected according to their predictive abilities. The current habitat suitability showed that had a relatively wide but fragmented distribution, and it encompassed 41,862 km. The models suggested that precipitation of warmest quarter (bio18) and mean temperature of wettest quarter (bio6) had the highest contribution to the model. This study revealed that is sensitive to climate change, which will lead to a large range shift. The projected spatial and temporal pattern of range shifts for should provide a useful reference for implementing long-term conservation and management strategies for amphibians in East China.
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http://dx.doi.org/10.1002/ece3.7822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328465PMC
August 2021

Intraoperative optical coherence tomography for the assessment of posterior capsular integrity in pediatric cataract surgery.

J Cataract Refract Surg 2021 Jul 29. Epub 2021 Jul 29.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China Center for Precision Medicine, Sun Yat-sen University.

Purpose: To study the morphology of the posterior lens cortex and posterior capsules (PCs) in pediatric patients with posterior lens opacities using intraoperative optical coherence tomography (iOCT).

Setting: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Design: A prospective observational study.

Methods: Pediatric patients with posterior lens opacities were imaged using iOCT during cataract surgery. The morphology of the posterior lens cortex and PC, along with the common patterns to indicate PC integrity, were assessed. Moreover, posterior capsule rent during surgery was observed.

Results: A total of 62 eyes from 53 patients were included. The mean age of patients was 3.8 years. Four morphological variants of posterior lens opacity were observed: Type I (54.8%, 34/62) with intact PC; Type II (32.3%, 20/62) with intact PC, which protruded into the anterior vitreous; Type III (4.8%, 3/62) with deficient PC and an inability to delineate PC and type IV (8.1%, 5/62) with dense opacity and an inability to characterize the posterior cortex and PC. Phacoemulsification could be performed in types I and II. In types III and IV, manual nucleus removal was performed instead of phacoemulsification. Three cases (100%) of type III PC dehiscence developed during surgery, while no cases developed PC dehiscence of other types.

Conclusion: The morphology of the PC and posterior lens cortex in pediatric posterior lens opacities could be categorized and PC integrity could be assessed using iOCT, which was useful to guide surgical strategies and increase safety in preexisting posterior capsular dehiscence in pediatric cataract surgery.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000763DOI Listing
July 2021

Proteomics and metabonomics analyses of Covid-19 complications in patients with pulmonary fibrosis.

Sci Rep 2021 07 16;11(1):14601. Epub 2021 Jul 16.

Department of Endocrinology, the People's Hospital of Guangxi Zhuang Autonomous Region, 6 Taoyuan Road, Nanning, 530021, Guangxi, People's Republic of China.

Pulmonary fibrosis is a devastating disease, and the pathogenesis of this disease is not completely clear. Here, the medical records of 85 Covid-19 cases were collected, among which fibrosis and progression of fibrosis were analyzed in detail. Next, data independent acquisition (DIA) quantification proteomics and untargeted metabolomics were used to screen disease-related signaling pathways through clustering and enrichment analysis of the differential expression of proteins and metabolites. The main imaging features were lesions located in the bilateral lower lobes and involvement in five lobes. The closed association pathways were FcγR-mediated phagocytosis, PPAR signaling, TRP-inflammatory pathways, and the urea cycle. Our results provide evidence for the detection of serum biomarkers and targeted therapy in patients with Covid-19.
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http://dx.doi.org/10.1038/s41598-021-94256-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285535PMC
July 2021

Distribution and determinants of hospital efficiency and relative productivity in county-level hospitals in rural China: an observational study.

BMJ Open 2021 07 2;11(7):e042326. Epub 2021 Jul 2.

Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China

Background: Cataract surgery is very important to prevent blindness, but its productivity and efficiency in China are unknown. Our study aimed to evaluate the geographical distribution of cataract surgeons and prospectively identify the factors associated with the increased productivity in cataract surgery and efficiency in outpatient ophthalmic services in rural Chinese hospitals.

Methods: Data were prospectively collated from various hospital datasets and the census registered by the geographical unit county. Prior to mapping, the geographical location data of counties were cross-linked with the equivalent ophthalmologist and service output data to create categories and map multiple data attributes. Descriptive statistical analyses were performed to characterise the data stratified by county. Linear regression analyses were used to explore the factors associated with the increased productivity/efficiency.

Results: The ophthalmologists, surgical productivity of ophthalmologists and outpatient efficacy of ophthalmologists significantly varied across counties. During the period between 2016 and 2018, the median (IQR) change in surgical productivity of and outpatient efficacy of ophthalmologists were 31.627 (-3.33 to 29.94) and 118.08 (-132.30 to 740.89). In the simple regression analysis for predictors of a high productivity change, only the increased number of phaco machine had statistical significance (p=0.003). In addition, only the gross domestic product per capita in 2016 was associated with an increased improvement in efficiency of outpatient services (p=0.008).

Conclusions: This study demonstrated that the ophthalmologist productivity and the efficiency of outpatient services were unequally geographically distributed, and their predictors were identified. Further studies to elucidate the extent of the problem and improve the health service delivery models are required.
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http://dx.doi.org/10.1136/bmjopen-2020-042326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256740PMC
July 2021

Comparison of Visual Neuroadaptations After Multifocal and Monofocal Intraocular Lens Implantation.

Front Neurosci 2021 14;15:648863. Epub 2021 Jun 14.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Visual neuroadaptation is believed to play an important role in determining the final visual outcomes following intraocular lens (IOL) implantation. To investigate visual neuroadaptation in patients with age-related cataracts (ARCs) after phacoemulsification with multifocal and monofocal IOL implantation, we conducted a prospective, controlled clinical trial in Zhongshan Ophthalmology Center. This study included 22 patients with bilateral ARCs: 11 patients underwent phacoemulsification and multifocal IOL (Mu-IOL) implantation, and 11 patients underwent phacoemulsification and monofocal IOL (Mo-IOL) implantation. Visual disturbances (glare and halos), visual function (including visual acuity, retinal straylight, contrast sensitivity, and visual evoked potentials) and visual cortical function (fractional amplitude of low-frequency fluctuations, fALFF) in Bowman's areas 17-19 as the region of interest were assessed before and after surgeries. The results showed that the fALFF values of the visual cortex in the Mu-IOL group decreased at 1 week postoperatively and recovered to baseline at 3 months and then improved at 6 months, compared with preoperative levels (at a whole-brain threshold of < 0.05, AlphaSim-corrected, voxels > 228, repeated measures analysis of variance). Significantly increased fALFF values in the visual cortex were detected 1 week after surgery in the Mo-IOL group and decreased to baseline at 3 and 6 months. The fALFF of the lingual gyrus was negatively correlated with visual disturbances ( < 0.05). To conclude, early postoperative visual neuroadaptation was detected in the Mu-IOL group by resting-state fMRI analysis. The different changing trends of postoperative fALFF values in the two groups indicated distinct neuroadaptations patterns after Mu-IOL and Mo-IOL implantation.
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http://dx.doi.org/10.3389/fnins.2021.648863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236945PMC
June 2021

Reduced Functional Connectivity in Children With Congenital Cataracts Using Resting-State Electroencephalography Measurement.

Front Neurosci 2021 14;15:657865. Epub 2021 Apr 14.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Objectives: Numerous task-based functional magnetic resonance imaging studies indicate the presence of compensatory functional improvement in patients with congenital cataracts. However, there is neuroimaging evidence that shows decreased sensory perception or cognition information processing related to visual dysfunction, which favors a general loss hypothesis. This study explored the functional connectivity between visual and other networks in children with congenital cataracts using resting state electroencephalography.

Methods: Twenty-one children with congenital cataracts (age: 8.02 ± 2.03 years) and thirty-five sex- and age-matched normal sighted controls were enrolled to investigate functional connectivity between the visual cortex and the default mode network, the salience network, and the cerebellum network during resting state electroencephalography (eyes closed) recordings.

Result: The congenital cataract group was less active, than the control group, in the occipital, temporal, frontal and limbic lobes in the theta, alpha, beta1 and beta2 frequency bands. Additionally, there was reduced alpha-band connectivity between the visual and somatosensory cortices and between regions of the frontal and parietal cortices associated with cognitive and attentive control.

Conclusion: The results indicate abnormalities in sensory, cognition, motion and execution functional connectivity across the developing brains of children with congenital cataracts when compared with normal controls. Reduced frontal alpha activity and alpha-band connectivity between the visual cortex and salience network might reflect attenuated inhibitory information flow, leading to higher attentional states, which could contribute to adaptation of environmental change in this group of patients.
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http://dx.doi.org/10.3389/fnins.2021.657865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079630PMC
April 2021

Transcriptomic analysis of the poultry red mite, Dermanyssus gallinae, across all stages of the lifecycle.

BMC Genomics 2021 Apr 7;22(1):248. Epub 2021 Apr 7.

Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh, Midlothian, EH26 0PZ, UK.

Background: The blood feeding poultry red mite (PRM), Dermanyssus gallinae, causes substantial economic damage to the egg laying industry worldwide, and is a serious welfare concern for laying hens and poultry house workers. In this study we have investigated the temporal gene expression across the 6 stages/sexes (egg, larvae, protonymph and deutonymph, adult male and adult female) of this neglected parasite in order to understand the temporal expression associated with development, parasitic lifestyle, reproduction and allergen expression.

Results: RNA-seq transcript data for the 6 stages were mapped to the PRM genome creating a publicly available gene expression atlas (on the OrcAE platform in conjunction with the PRM genome). Network analysis and clustering of stage-enriched gene expression in PRM resulted in 17 superclusters with stage-specific or multi-stage expression profiles. The 6 stage specific superclusters were clearly demarked from each other and the adult female supercluster contained the most stage specific transcripts (2725), whilst the protonymph supercluster the fewest (165). Fifteen pairwise comparisons performed between the different stages resulted in a total of 6025 Differentially Expressed Genes (DEGs) (P > 0.99). These data were evaluated alongside a Venn/Euler analysis of the top 100 most abundant genes in each stage. An expanded set of cuticle proteins and enzymes (chitinase and metallocarboxypeptidases) were identified in larvae and underpin cuticle formation and ecdysis to the protonymph stage. Two mucin/peritrophic-A salivary proteins (DEGAL6771g00070, DEGAL6824g00220) were highly expressed in the blood-feeding stages, indicating peritrophic membrane formation during feeding. Reproduction-associated vitellogenins were the most abundant transcripts in adult females whilst, in adult males, an expanded set of serine and cysteine proteinases and an epididymal protein (DEGAL6668g00010) were highly abundant. Assessment of the expression patterns of putative homologues of 32 allergen groups from house dust mites indicated a bias in their expression towards the non-feeding larval stage of PRM.

Conclusions: This study is the first evaluation of temporal gene expression across all stages of PRM and has provided insight into developmental, feeding, reproduction and survival strategies employed by this mite. The publicly available PRM resource on OrcAE offers a valuable tool for researchers investigating the biology and novel interventions of this parasite.
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http://dx.doi.org/10.1186/s12864-021-07547-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028124PMC
April 2021

miR-93-5p promotes insulin resistance to regulate type 2 diabetes progression in HepG2 cells by targeting HGF.

Mol Med Rep 2021 05 24;23(5). Epub 2021 Mar 24.

Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, P.R. China.

Insulin resistance is a common feature of type 2 diabetes mellitus (T2DM). However, the mechanisms underlying insulin resistance are not completely understood. The present study aimed to investigate the effect of microRNA (miR)‑93‑5p on insulin resistance in T2DM cells. Human hepatocellular carcinoma (HCC; HepG2) cells were cultured in medium with high glucose content (30 mM glucose) to establish an insulin‑resistant cell model (IR group). Glucose consumption and glycogen synthesis assays were performed to assess glucose consumption and glycogen synthesis, respectively. By performing immunoprecipitation assays, the abundance of the Met‑insulin receptor complex was detected in HepG2 cells. miR‑93‑5p and hepatocyte growth factor (HGF) mRNA expression levels were measured via reverse transcription‑quantitative PCR, and HGF protein expression levels were measured via western blotting. A dual‑luciferase reporter assay was conducted to investigate the interaction between miR‑93‑5p and HGF. Cell Counting Kit‑8, BrdU and caspase‑3 activity assays were performed to evaluate cell viability, proliferation and apoptosis, respectively, in insulin‑resistant HepG2 cells following transfection with small interfering RNA‑HGF, HGF overexpression vector, miR‑93‑5p mimic or miR‑93‑5p inhibitor. The results demonstrated that miR‑93‑5p expression was significantly increased and HGF expression was significantly decreased in HCC tissues isolated from patients with or without T2DM compared with adjacent healthy tissues isolated from patients without T2DM. Compared with the IR group, miR‑93‑5p overexpression significantly increased cell proliferation, glucose consumption and glycogen synthesis, but significantly inhibited apoptosis in insulin‑resistant HepG2 cells. By contrast, compared with the IR group, HGF overexpression significantly inhibited cell proliferation, glucose consumption and glycogen synthesis, but significantly enhanced cell apoptosis in insulin‑resistant HepG2 cells. Following co‑transfection with HGF overexpression vector and miR‑93‑5p mimic, miR‑93‑5p mimic‑mediated induction of HepG2 cell proliferation, glucose consumption and glycogen synthesis in insulin‑resistant HepG2 cells was inhibited. Collectively, the results of the present study indicated that miR‑93‑5p enhanced insulin resistance to regulate T2DM progression in HepG2 cells by targeting HGF.
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http://dx.doi.org/10.3892/mmr.2021.11968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974269PMC
May 2021

Understanding the feeding ecology of Cynoglossus joyneri in Haizhou Bay based on stable isotope analysis.

Ying Yong Sheng Tai Xue Bao 2021 Mar;32(3):1080-1086

College of Fishery, Ocean University of China, Qingdao 266003, Shandong, China.

We analyzed the feeding ecology of by carbon and nitrogen stable isotope analysis based on the samples collected from the bottom trawl surveys during spring and autumn of 2018 in Haizhou Bay, China. The results showed that the δC and δN values of ranged from -20.75‰ to -15.91‰ and from 5.98‰ to 12.02‰, respectively. The mean values of the δC and δN were (-17.79±1.00)‰ and (9.37±1.33)‰, respectively. There was a significantly negative correlation between the δC values and standard length and a positive correlation between the δN values and standard length. The mean trophic level of was (3.43±0.97). There was a significantly positive correlation between the trophic level and standard length. The dominant prey groups of were fish, crabs, shrimps, mollusca, polychaeta, plankton and particle organic matter (POM). The trophic contribution of shrimps was the highest among these prey groups. The trophic contribution of fish, crabs and shrimps was higher in autumn than those in spring. This study would help to understand the role of in the material cycling and energy flow in Haizhou Bay ecosystem, and provide scientific basis for the protection and rational utilization of this species.
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http://dx.doi.org/10.13287/j.1001-9332.202103.036DOI Listing
March 2021

Microperipheral Iridectomy for Troublesome Posterior Synechiolysis in Secondary Intraocular Lens Implantation.

J Ophthalmol 2021 23;2021:6634871. Epub 2021 Feb 23.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

Purpose: To introduce an effective method for separating extensive posterior synechiae and those located under or adjacent to surgical incisions.

Methods: Pediatric patients who had been subjected to cataract surgery and developed troublesome posterior synechiae requiring secondary intraocular lens (IOL) implantation were recruited. All patients underwent microperipheral iridectomy at the 12 o'clock position. Then, an ophthalmic viscosurgical device was injected into the posterior chamber through the iris fistula to mechanically separate the posterior synechiae, using scissors to cut robust posterior synechiae if necessary. The results of posterior synechiolysis and the position of the implanted IOL were analyzed.

Results: Sixteen patients (median age, 51.56 months; range, 28-80 months) were included. The scope of posterior synechia in clock was 4.42 (range, 1-10). All troublesome posterior synechiae were successfully separated using the microperipheral iridectomy method, and all patients underwent IOL implantation in the ciliary sulcus. There was one case of peripheral iridectomy-related early intraoperative bleeding; no bleeding was observed at the end of surgery.

Conclusions: Microperipheral iridectomy is a useful method for the management of troublesome posterior synechiae during secondary IOL implantation in pediatric patients, which makes secondary IOL implantation an easier and safer method in some challenging cases.
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http://dx.doi.org/10.1155/2021/6634871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929652PMC
February 2021

The E-Nurture Project: A Hybrid Virtual Neonatal Follow Up Model for 2021.

Children (Basel) 2021 Feb 12;8(2). Epub 2021 Feb 12.

Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.

Neonatal follow-up has long focused on a model of surveillance and identification of short-term outcomes. This model has long become outdated, with evidence documenting the need for longer follow-up with known school-based challenges and significant gaps in knowledge by educators. This article reviews the history of neonatal follow-up and demonstrates a novel approach to neonatal follow-up, built largely with a hybrid virtual platform, which then became essential with the declaration of the pandemic in 2020.
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http://dx.doi.org/10.3390/children8020139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918063PMC
February 2021

Three dimension printing talar prostheses for total replacement in talar necrosis and collapse.

Int Orthop 2021 09 5;45(9):2313-2321. Epub 2021 Mar 5.

The First Affiliated Hospital of Military Medical University of the Army, Chongqing, China.

Background: Reconstructing bone structures and stabilizing adjacent joints are clinical challenges in treating talar necrosis and collapse (TNC). 3D printing technology has been demonstrated to improve the accuracy of talar replacement. This study aimed to evaluate anatomical talar replacement and the clinical results.

Methods: Nine patients with TNC were enrolled between 2016 and 2020. The prosthetic shape and size were designed by CT post-processing and mirror symmetry technology. The clinical outcomes included radiographic parameters of the forefoot, hindfoot, and ankle alignment, ankle activity, recurrent pain, and peri-operative complications.

Results: After a mean follow-up of 23.17 ± 6.65 months, degenerative arthritis and prosthetic dislocation and other complications were not observed on plain radiographs. Each 3D-printed talar prosthesis was placed in the original anatomical position. The parameters which have significant changes pre-operative and post-operative are as follows: talar height, 27.59 ± 5.99 mm and 34.56 ± 3.54 mm (95% CI - 13.05 to - 0.87, t = 2.94, P = 0.032) and Meary's angle, 11.73 ± 4.79° and 4.45 ± 1.82° (95% CI 1.29~22.44, t = 2.89, P = 0.034). The AOFAS hindfoot score improved from 26.33 ± 6.62 to 79.67 ± 3.14 at the final follow-up (95% CI 43.36~63.30, t = 13.75, P = 0.000). The VAS score decreased from 6.33 ± 1.03 to 0.83 ± 0.75 (95% CI 4.40~6.60, t = 12.84, P = 0.000). The post-operative satisfaction scores regarding pain relief, activities of daily living, and return to recreational activities were good to excellent, and the change of activity range was statistically significant.

Conclusions: The 3D printing patient-specific total talar prostheses allowed anatomical reconstruction in TNC. This novel treatment with 3D-printed prostheses could serve as a reliable patient-specific alternative in TNC.
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http://dx.doi.org/10.1007/s00264-021-04992-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494653PMC
September 2021

Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics.

Elife 2021 Feb 15;10. Epub 2021 Feb 15.

Department of Biology, Southern University of Science and Technology, Shenzhen, China.

Communications between actin filaments and integrin-mediated focal adhesion (FA) are crucial for cell adhesion and migration. As a core platform to organize FA proteins, the tripartite ILK/PINCH/Parvin (IPP) complex interacts with actin filaments to regulate the cytoskeleton-FA crosstalk. Rsu1, a Ras suppressor, is enriched in FA through PINCH1 and plays important roles in regulating F-actin structures. Here, we solved crystal structures of the Rsu1/PINCH1 complex, in which the leucine-rich-repeats of Rsu1 form a solenoid structure to tightly associate with the C-terminal region of PINCH1. Further structural analysis uncovered that the interaction between Rsu1 and PINCH1 blocks the IPP-mediated F-actin bundling by disrupting the binding of PINCH1 to actin. Consistently, overexpressing Rsu1 in HeLa cells impairs stress fiber formation and cell spreading. Together, our findings demonstrated that Rsu1 is critical for tuning the communication between F-actin and FA by interacting with the IPP complex and negatively modulating the F-actin bundling.
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http://dx.doi.org/10.7554/eLife.64395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909951PMC
February 2021

Spatial Genetic Structure and Demographic History of the Wild Boar in the Qinling Mountains, China.

Animals (Basel) 2021 Jan 29;11(2). Epub 2021 Jan 29.

Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210046, China.

Species dispersal patterns and population genetic structure can be influenced by geographical features. Qinling Mountains (QM) provide an excellent area for phylogeographic study. The phylogeography of Asian-wide wild boars revealed the colonization route. However, the impact of the QM on genetic diversity, genetic structure and population origin is still poorly understood. In this study, genetic analysis of wild boar in the QM was conducted based on the mitochondrial control region (943 bp) and twelve microsatellite loci of 82 individuals in 16 sampling locations. Overall genetic haplotype diversity was 0.86, and the nucleotide diversity was 0.0079. A total of 17 new haplotypes were detected. The level of genetic diversity of wild boars in QM was lower than in East Asia, but higher than in Europe. Phylogenetic analysis showed the weak genetic divergence in QM. Mismatch analysis, neutrality tests, and Bayesian Skyline Plot (BSP) results revealed that the estimates of effective population size were under demographic equilibrium in the past. Spatial analysis of molecular variance indicated no obvious phylogeographic structure.
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http://dx.doi.org/10.3390/ani11020346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912324PMC
January 2021

Visual outcomes of surgical and conservative treatment in children with small posterior polar cataracts and posterior lenticonus.

Int J Ophthalmol 2021 18;14(1):64-71. Epub 2021 Jan 18.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China.

Aim: To compare the visual outcomes of children with small (≤3 mm) posterior polar cataracts (PPC) and posterior lenticonus who had cataract extraction surgery with the visual outcomes of those who were managed conservatively.

Methods: Children who initially had small PPC and posterior lenticonus who were followed up over 1-year period were retrospective reviewed in the study. Patients receiving surgery were compared with those receiving conservative therapy. The axial length, keratometry, refraction, best-corrected visual acuity (BCVA), and strabismus measurements were recorded. Lens morphology, , the location, size, and depth of the cataract lesion, was measured with a Scheimpflug imaging system. To help control for baseline differences in the groups, patients were matched with controls by propensity score methodology.

Results: The study evaluated 60 patients (30 in the surgery group and 30 in the conservative therapy group) after matching by propensity score. Patients who underwent cataract surgery showed greater BCVA improvements (0.36±0.24 logMAR) than patients who were treated without surgery (0.22±0.26 logMAR; =0.036). Surgery was effective in patients with a rear projection length (RPL) less than 1.0 mm and a pretreatment BCVA worse than 0.52 logMAR.

Conclusion: Children with small PPC and posterior lenticonus who undergo cataract surgery experience greater BCVA improvements than those managed conservatively. Certain patients presenting with a RPL less than 1.0 mm and a pretreatment BCVA of 0.52 logMAR or worse may benefit from surgery.
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http://dx.doi.org/10.18240/ijo.2021.01.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790670PMC
January 2021

RNAi gene knockdown in the poultry red mite, Dermanyssus gallinae (De Geer 1778), a tool for functional genomics.

Parasit Vectors 2021 Jan 18;14(1):57. Epub 2021 Jan 18.

Moredun Research Institute, Pentland Science Park, Bush Loan, Penicuik, Midlothian, EH26 0PZ, UK.

Background: The avian haematophagous ectoparasite Dermanyssus gallinae, commonly known as the poultry red mite, causes significant economic losses to the egg-laying industry worldwide and also represents a significant welfare threat. Current acaricide-based controls are unsustainable due to the mite's ability to rapidly develop resistance, thus developing a novel sustainable means of control for D. gallinae is a priority. RNA interference (RNAi)-mediated gene silencing is a valuable tool for studying gene function in non-model organisms, but is also emerging as a novel tool for parasite control.

Methods: Here we use an in silico approach to identify core RNAi pathway genes in the recently sequenced D. gallinae genome. In addition we utilise an in vitro feeding device to deliver double-stranded (ds) RNA to D. gallinae targeting the D. gallinae vATPase subunit A (Dg vATPase A) gene and monitor gene knockdown using quantitative PCR (qPCR).

Results: Core components of the small interfering RNA (siRNA) and microRNA (miRNA) pathways were identified in D. gallinae, which indicates that these gene silencing pathways are likely functional. Strikingly, the P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway was absent in D. gallinae. In addition, feeding Dg vATPase A dsRNA to adult female D. gallinae resulted in silencing of the targeted gene compared to control mites fed non-specific lacZ dsRNA. In D. gallinae, dsRNA-mediated gene knockdown was rapid, being detectable 24 h after oral delivery of the dsRNA, and persisted for at least 120 h.

Conclusions: This study shows the presence of core RNAi machinery components in the D. gallinae genome. In addition, we have developed a robust RNAi methodology for targeting genes in D. gallinae that will be of value for studying genes of unknown function and validating potential control targets in D. gallinae.
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http://dx.doi.org/10.1186/s13071-020-04562-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813172PMC
January 2021

The O6-methyguanine-DNA methyltransferase inhibitor O6-benzylguanine enhanced activity of temozolomide + irinotecan against models of high-risk neuroblastoma.

Anticancer Drugs 2021 03;32(3):233-247

Cancer Center, School of Medicine, Texas Tech University Health Sciences Center.

DNA-damaging chemotherapy is a major component of therapy for high-risk neuroblastoma, and patients often relapse with treatment-refractory disease. We hypothesized that DNA repair genes with increased expression in alkylating agent resistant models would provide therapeutic targets for enhancing chemotherapy. In-vitro cytotoxicity of alkylating agents for 12 patient-derived neuroblastoma cell lines was assayed using DIMSCAN, and mRNA expression of 57 DNA repair, three transporter, and two glutathione synthesis genes was assessed by TaqMan low-density array (TLDA) with further validation by qRT-PCR in 26 cell lines. O6-methylguanine-DNA methyltransferase (MGMT) mRNA was upregulated in cell lines with greater melphalan and temozolomide (TMZ) resistance. MGMT expression also correlated significantly with resistance to TMZ+irinotecan (IRN) (in-vitro as the SN38 active metabolite). Forced overexpression of MGMT (lentiviral transduction) in MGMT non-expressing cell lines significantly increased TMZ+SN38 resistance. The MGMT inhibitor O6-benzylguanine (O6BG) enhanced TMZ+SN38 in-vitro cytotoxicity, H2AX phosphorylation, caspase-3 cleavage, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling. TMZ+IRN+O6BG delayed tumor growth and increased survival relative to TMZ+IRN in two of seven patient-derived xenografts established at time of death from progressive neuroblastoma. We demonstrated that high MGMT expression was associated with resistance to alkylating agents and TMZ+IRN in preclinical neuroblastoma models. The MGMT inhibitor O6BG enhanced the anticancer effect of TMZ+IRN in vitro and in vivo. These results support further preclinical studies exploring MGMT as a therapeutic target and biomarker of TMZ+IRN resistance in high-risk neuroblastoma.
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http://dx.doi.org/10.1097/CAD.0000000000001020DOI Listing
March 2021

Activatable Polymeric Nanoprobe for Near-Infrared Fluorescence and Photoacoustic Imaging of T Lymphocytes.

Angew Chem Int Ed Engl 2021 03 1;60(11):5921-5927. Epub 2021 Feb 1.

School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.

Development of real-time non-invasive imaging probes to assess infiltration and activation of cytotoxic T cells (CTLs) is critical to predict the efficacy of cancer immunotherapy, which however remains challenging. Reported here is an activatable semiconducting polymer nanoprobe (SPNP) for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of a biomarker (granzyme B) associated with activation of CTLs. SPNP comprises a semiconducting polymer (SP) conjugated with a granzyme B cleavable and dye-labeled peptide as the side chain, both of which emit NIRF and PA signals. After systemic administration, SPNP passively targets the tumor and in situ reacts with granzyme B to release the dye-labeled peptide, leading to decreased NIRF and PA signals from the dye but unchanged signals from the polymer. Such ratiometric NIRF and PA signals of SPNP correlate well with the expression level of granzyme B and intratumoral population of CTLs. Thus, this study not only presents the first PA probes for in vivo imaging of immune activation but also provides a molecular design strategy that can be generalized for molecular imaging of other immune-related biomarkers.
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http://dx.doi.org/10.1002/anie.202015116DOI Listing
March 2021

[Functional analysis of CG8005 gene in Drosophila testis].

Yi Chuan 2020 Nov;42(11):1122-1132

Department of Gynecology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.

The processes of self-renewal and differentiation of germ cells are crucial to the development of male infertility and germ cell tumors. CG8005 gene is one of the regulatory factors of the testicular germ stem cells in Drosophila melanogaster, and its functional mechanism is still unknown. To explore the biological function(s) of CG8005 gene in the germ cell niche of Drosophila testis, first, the UAS-gal4 system was used to drive the expression of UAS-CG8005 RNAi in Drosophila testicular germ cells and cyst cells. Fertility tests were then performed to determine the fertility rate of male flies. Second, the expression patterns of Vasa, IBI, Zn finger homeodomain 1 (Zfh1), eyes absent (Eya), DE-cad, FasIII and Phospho-Histone H3(PH3), and TUNEL were analyzed by immunofluorescence staining in both control and CG8005 RNAi testes. Lastly, small interfering RNA (siRNA) was used to silence the CG8005 gene expression in Drosophila S2 cells; and PH3 was used to detect the proliferation ability of Drosophila S2 cells in the control group and CG8005 siRNA group. Apoptosis of Drosophila S2 cells was analyzed with TUNEL and flow cytometry. To observe the relative expression of the spliceosome, the mRNA levels of the spliceosome subunits were detected by fluorescence quantitative RT-PCR. As compared with the control group, the results showed that deletion of the CG8005 gene in the germ cells and cyst cells of the testis reduced or even completely abolished the fertility of male fruit flies. In addition, nos-gal4 driven UAS-CG8005 RNAi led to loss of fusomes and reduce the proliferative ability of germ cells. Noticeably, tj-gal4-directed UAS-CG8005 RNAi knockdown of CG8005 gene in the testis led to germ cell tumor development. Knockdown of CG8005 gene in Drosophila S2 cells resulted in increase in apoptosis and inhibition of proliferation. Further, the silencing of the CG8005 gene in Drosophila S2 cells caused increases in the mRNA levels of the spliceosome subunits. Hence, CG8005 gene is essential for the self-renewal and differentiation of germ cells in Drosophila testis. Its deletion may lead to restricted germ cell survival and the formation of germ cell-like tumors. CG8005 gene can participate in the regulation of proliferation and apoptosis of Drosophila S2 cells, which is essential for the maintenance of cell life, and might competitively regulate the mRNA levels of spliceosome subunits.
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http://dx.doi.org/10.16288/j.yczz.20-163DOI Listing
November 2020

Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus.

Hum Brain Mapp 2021 02 13;42(2):485-494. Epub 2020 Oct 13.

Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou City, Guangdong Province, China.

The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty-four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High-density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy subjects, acute tinnitus patients had a significant reduction in superior frontal cortex activity across all frequency bands, whereas chronic tinnitus patients had a significant reduction in the superior frontal cortex at beta 3 and gamma frequency bands as well as a significant increase in the inferior frontal cortex at delta-band and superior temporal cortex at alpha 1 frequency band. When compared to the chronic tinnitus group, the acute tinnitus group activity was significantly increased in the middle frontal and parietal gyrus at the gamma-band. Functional connectivity analysis showed that the chronic tinnitus group had increased connections between the parahippocampus gyrus, posterior cingulate cortex, and precuneus when compared with the healthy group. Alterations of local brain activity and connections between the parahippocampus gyrus and other nonauditory areas appeared in the transition from acute to chronic tinnitus. This indicates that the appearance and development of tinnitus is a dynamic process involving aberrant local neural activity and abnormal connectivity in multifunctional brain networks.
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http://dx.doi.org/10.1002/hbm.25238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776005PMC
February 2021

An Efficient Lens Structures Segmentation Method on AS-OCT Images.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1646-1649

Lens structures segmentation on anterior segment optical coherence tomography (AS-OCT) images is a fundamental task for cataract grading analysis. In this paper, in order to reduce the computational cost while keeping the segmentation accuracy, we propose an efficient segmentation method for lens structures segmentation. At first, we adopt an efficient semantic segmentation network in the work, and used it to extract the lens area image instead of the conventional object detection method, and then used it once again to segment the lens structures. Finally, we introduce the curve fitting processing (CFP) on the segmentation results. Experiment results show that our method has good performance on accuracy and processing speed, and could be applied to CASIA II device for practical applications.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175944DOI Listing
July 2020

Clinical significance of lymph node micrometastasis in T1N0 early gastric cancer.

Math Biosci Eng 2020 04;17(4):3252-3259

Departments of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310004, Zhejiang Province, China.

To investigate the significance of lymph node micrometastasis in T1N0 early gastric cancer. Lymph node micrometastasis may be a key mechanism in the recurrent T1N0 EGC patients after surgical treatment. It's unknow whether it is safe to leave the lymph nodes with micrometastasis untreated after ESD. A total of 106 T1N0 EGC patients were enrolled in this study. Immunohistochemical technique with CAM5.2 was employed to detect lymph node micrometastasis, and Immunohistochemical with D2-40 was used to detect the lymphatic vessels. Prognostic significance of lymph node micrometastasis and the relationship of lymph nodes micrometastasis with Clinicopathological features were analyzed. Twenty-two of the 106 T1N0 EGC cases were detected with lymph nodes micrometastasis, with the detection rate of 20.8%. The median survival time of the group with positive lymph nodes micrometastasis was lower than that of the group with negative micrometastasis, 48 vs 60 months. The incidence of lymph nodes micrometastasis in submucosal T1N0 EGC was 23.9%, while no micrometastasis was found in the mucosal T1N0 EGC. Of all the 30 cases according with the expanded ESD indications, six patients were found with lymph nodes micrometastasis. The occurrence of lymph node micrometastasis was common in T1N0 EGC. The cases with positive lymph nodes micrometastasis showed a lower median survival time than those with negative micrometastasis. lymph nodes micrometastasis incidence was higher in the submucosal ECG than in the mucosal ECG. lymph nodes micrometastasis was also found in the cases according to the expanded ESD indications.
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http://dx.doi.org/10.3934/mbe.2020185DOI Listing
April 2020

Design of easy-manufacturing superdirective antenna: a theoretical study.

Appl Opt 2020 Sep;59(27):8302-8309

An easy-fabricating superdirective antenna with needlelike radiation in the microwave band is proposed for the first time to the best of our knowledge. The electromagnetic field of the superdirective antenna excited by an electric line source is calculated. The parameters of the superdirective antenna are obtained by optimization algorithms. A two-step optimization method is carried out to reduce the difficulty of fabrication. The mechanism of superdirectivity in the microwave band is explained briefly by traditional multilayered dielectric resonances. A machinable 10-layered superdirective antenna, using this method, is proposed. Unlike traditional superdirective antennas, the proposed antenna, after two-step optimization in this paper, has all-positive integral permittivities, which reduce the fabrication difficulty significantly.
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http://dx.doi.org/10.1364/AO.395069DOI Listing
September 2020

[Three-dimensional printed Ti6Al4V-4Cu alloy promotes osteogenic gene expression through bone immune regulation].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Sep;34(9):1170-1176

Department of Orthopedics, the First Affiliated Hospital of Army Medical University of Chinese PLA, Chongqing, 400038, P.R.China.

Objective: To investigate the effects of three-dimensional (3D) printed Ti6Al4V-4Cu alloy on inflammation and osteogenic gene expression in mouse bone marrow mesenchymal stem cells (BMSCs) and mouse mononuclear macrophage line RAW264.7.

Methods: Ti6Al4V and Ti6Al4V-4Cu alloys were prepared by selective laser melting, and the extracts of the two materials were prepared according to the biological evaluation standard of medical devices. The effects of two kinds of extracts on the proliferation of mouse BMSCs and mouse RAW264.7 cells were detected by cell counting kit 8 method. After co-cultured with mouse BMSCs for 3 days, the expression of osteogenesis- related genes [collagen type Ⅰ (Col-Ⅰ), alkaline phosphatase (ALP), Runx family transcription factor 2 (Runx-2), osteoprotegerin (OPG), and osteopontin (OPN)] were detected by real-time fluorescence quantitative PCR. After co-cultured with mouse RAW264.7 cells for 1 day, the expressions of inflammation-related genes [interleukin 4 (IL-4) and nitric oxide synthase 2 (iNOS)] were detected by real-time fluorescence quantitative PCR, and the supernatants of the two groups were collected to detect the secretion of vascular endothelial growth factor a (VEGF-a) and bone morphogenetic protein 2 (BMP-2) by ELISA. The osteogenic conditioned medium were prepared with the supernatants of the two groups and co-cultured with BMSCs for 3 days. The expressions of osteogenesis-related genes (Col-Ⅰ, ALP, Runx-2, OPG, and OPN) were detected by real-time fluorescence quantitative PCR.

Results: Compared with Ti6Al4V alloy extract, Ti6Al4V-4Cu alloy extract had no obvious effect on the proliferation of BMSCs and RAW264.7 cells, but it could promote the expression of OPG mRNA in BMSCs, reduce the expression of iNOS mRNA in RAW264.7 cells, and promote the expression of IL-4 mRNA. It could also promote the secretions of VEGF-a and BMP-2 in RAW264.7 cells. Ti6Al4V-4Cu osteogenic conditioned medium could promote the expressions of Col-Ⅰ, ALP, Runx-2, OPG, and OPN mRNAs in BMSCs. The differences were all significant ( <0.05).

Conclusion: 3D printed Ti6Al4V-4Cu alloy can promote RAW264.7 cells to secret VEGF-a and BMP-2 by releasing copper ions, thus promoting osteogenesis through bone immune regulation, which lays a theoretical foundation for the application of metal prosthesis.
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http://dx.doi.org/10.7507/1002-1892.201912139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171737PMC
September 2020

Hyperbaric oxygen protects against myocardial ischemia‑reperfusion injury through inhibiting mitochondria dysfunction and autophagy.

Mol Med Rep 2020 Nov 9;22(5):4254-4264. Epub 2020 Sep 9.

Department of Hyperbaric Oxygen, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.

Our previous study demonstrated that hyperbaric oxygen (HBO) improves heart function predominantly through reducing oxygen stress, modulating energy metabolism and inhibiting cell apoptosis. The present study aimed to investigate the protective effects of HBO on mitochondrial function and autophagy using rats with a ligated left anterior descending artery. The cardioprotective effects of HBO were mainly evaluated using ELISA, fluorescent probes, transmission electron microscopy and reverse transcription‑quantitative PCR (RT‑qPCR). HBO pretreatment for 14 days (once a day) using a 0.25 MPa chamber improved mitochondrial morphology and decreased the number of autophagic vesicles, as observed using a transmission electron microscope. HBO pretreatment significantly increased the levels of ATP, ADP, energy charge and the opening of the mitochondrial permeability transition pore, but decreased the levels of AMP, cytochrome c and reactive oxygen species. Moreover, HBO pretreatment significantly increased the gene or protein expression levels of eIF4E‑binding protein 1, mammalian target of rapamycin (mTOR), mitochondrial DNA, NADH dehydrogenase subunit 1, mitofusin 1 and mitofusin 2, whereas it decreased the gene or protein expression levels of autophagy‑related 5 (Atg5), cytochrome c, dynamin‑related protein 1 and p53, as determined using RT‑qPCR or immunohistochemistry. In conclusion, HBO treatment was observed to protect cardiomyocytes during myocardial ischemia‑reperfusion injury (MIRI) by preventing mitochondrial dysfunction and inhibiting autophagy. Thus, these results provide novel evidence to support the use of HBO as a potential agent for the mitigation of MIRI.
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http://dx.doi.org/10.3892/mmr.2020.11497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533464PMC
November 2020

Conjunctival microvascular responses to anti-inflammatory treatment in patients with dry eye.

Microvasc Res 2020 09 29;131:104033. Epub 2020 Jun 29.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address:

Purpose: This study characterized conjunctival microvascular morphological and haemodynamic responses after anti-inflammatory treatment in dry eye (DE).

Materials And Methods: Twenty-five patients with moderate DE (17 females and 8 males aged 48 ± 16 years) who underwent anti-inflammatory therapy (0.1% fluorometholone) and 25 healthy subjects (20 females and 5 males aged 48 ± 17 years) recruited as controls were enrolled. The conjunctival blood flow rate (BFR), blood flow velocity (BFV) and vessel diameter were measured by functional slit-lamp biomicroscopy (FSLB). DE symptoms and signs were assessed. All measurements were performed at baseline and at 30 and 60 days after commencement of treatment.

Results: At baseline, the conjunctival BFR, BFV, and vessel diameter were higher in the DE group than in the control group (p < 0.05). The BFR, BFV and corneal fluorescein staining (CFS) scores decreased at 60 days after therapy compared to at baseline and 30 days (all p < 0.05); Ocular surface diseases index (OSDI), the hyperaemia index (HI) and vessel diameters only showed significant decreases at 30 days. Moreover, significant increases in the noninvasive tear film break-up time (NI-BUT) and Schirmer I test score (ST) were observed. The CFS score correlated positively with BFV (r = 0.46), BFR (r = 0.58) and vessel diameter (r = 0.47).

Conclusion: This study characterized conjunctival microvascular responses to anti-inflammatory treatment in DE patients. The results suggest that conjunctival BFV and BFR can be used as dynamic markers for treatment efficacy in DE.
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http://dx.doi.org/10.1016/j.mvr.2020.104033DOI Listing
September 2020
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