Publications by authors named "Shi Cheng"

192 Publications

Correction to: The factors associated with nosocomial infection in elderly hip fracture patients: gender, age, and comorbidity.

Int Orthop 2021 Oct 13. Epub 2021 Oct 13.

Department of Orthopedics, Fourth Medical Center, General Hospital of Chinese PLA, Beijing, 100000, China.

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http://dx.doi.org/10.1007/s00264-021-05190-3DOI Listing
October 2021

Pure Mg-Al Layered Double Hydroxide Film on Magnesium Alloys for Orthopedic Applications.

ACS Omega 2021 Sep 16;6(38):24575-24584. Epub 2021 Sep 16.

Department of Orthopedics, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.

Mg alloys are promising biodegradable orthopedic implants in the future. However, poor corrosion resistance and biocompatibility limit their wide applications. In this study, a pure Mg-Al layered double hydroxide (Mg-Al LDH) film on AZ31 was prepared through combining hydrofluoric acid pretreatment and hydrothermal treatment. Electrochemical analysis and the immersion test suggested that the as-prepared Mg-Al LDH-coated sample exhibited significantly enhanced corrosion resistance. The cell culture revealed that the Mg-Al LDH film was favorable for the alkaline phosphatase activity, collagen secretion, and osteogenesis-related gene expression of MC3T3-E1. Furthermore, the LDH-coated sample was beneficial for the migration, vascular endothelial growth factor secretion, and angiogenesis-related gene expression of human umbilical vein endothelial cells. The subcutaneous implantation test demonstrated that the Mg-Al LDH film could protect the substrate from corrosion and induce milder inflammation. The femur implantation demonstrated that the Mg-Al LDH sample showed better bone regeneration and osseointegration than bare AZ31. In summary, the as-prepared pure Mg-Al LDH film is able to enhance the and performances of AZ31, indicating a promising application in the orthopedic field.
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http://dx.doi.org/10.1021/acsomega.1c03169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482458PMC
September 2021

Longitudinal analysis of the patient pathways to diagnosis of psoriatic arthritis.

Arthritis Res Ther 2021 Oct 1;23(1):252. Epub 2021 Oct 1.

Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Background: The occurrence of health events preceding a psoriatic arthritis (PsA) diagnosis may serve as predictors of diagnosis. We sought to assess patients' real-world experiences in obtaining a PsA diagnosis.

Methods: This retrospective cohort study analyzed MarketScan claims data from January 2006 to April 2019. Included were adult patients with ≥ 2 PsA diagnoses (ICD-9-CM/ICD-10-CM) ≥ 30 days apart with ≥ 6 years of continuous enrolment before PsA diagnosis. Controls were matched 2:1 to patients with PsA. Health events (diagnoses and provider types) were analyzed before PsA diagnosis and additionally stratified by presence of psoriasis.

Results: Of 13,661 patients, those with PsA had an increased history of coding for arthritis and dermatologic issues (osteoarthritis [48% vs 22%], rheumatoid arthritis [18% vs 2%], and psoriasis [61% vs 2%]) vs those without PsA. Diagnoses of arthritis, axial symptoms, and tendonitis/enthesitis increased over time preceding PsA diagnosis; notably, a sharp rise in psoriasis diagnoses was observed 6 months before PsA diagnosis. Rheumatology consults were more common immediately preceding a PsA diagnosis. Dermatologists were unlikely to code for arthritis and musculoskeletal issues, while rheumatologists were unlikely to code for psoriasis; general practitioners focused on axial and musculoskeletal symptoms. PsA was most commonly diagnosed by rheumatologists (40%), general practitioners (22%), and dermatologists (7%).

Conclusions: Rheumatologists, general practitioners, and dermatologists diagnosed two thirds of patients with PsA. Musculoskeletal symptoms were common preceding a PsA diagnosis. Greater awareness of patterns of health events may alert healthcare providers to suspect a diagnosis of PsA.
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http://dx.doi.org/10.1186/s13075-021-02628-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485539PMC
October 2021

Endoplasmic reticulum stress-related secretory proteins as biomarkers of early myocardial ischemia-induced sudden cardiac deaths.

Int J Legal Med 2021 Sep 27. Epub 2021 Sep 27.

Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, 131 Dongan Road, Shanghai, 200032, People's Republic of China.

Early myocardial ischemia-induced sudden cardiac deaths (EMI-SCD) remain a great diagnostic challenge for forensic pathologists due to no gross or non-specific histological pathology. The goal of this study was to assess whether three secretory proteins, related with cellular endoplasmic reticulum stress, can be applied in forensic diagnosis of EMI-SCD. These markers included LMAN2, CAPN-1, and VCP and were compared with two clinically used markers (CK-MB and cTnI). A total of 21 EMI-SCD cases with a mean age of 53.0 (± 10.5) years and a mean ischemia interval of < 2.77 (± 2.56) hours were collected. Another 23 cases (mean 44.6 ± 15.0 year old) that died from non-cardiac causes served as control. Enzyme-linked immunosorbent assay (ELISA) was performed to detect target proteins' serum concentrations in the EMI-SCD and control groups. We found that LMAN2, CAPN-1, and VCP were all significantly increased in the EMI-SCD group as compared with control serum, with the fold changes ranging from 1.48 (p = 0.0022, LMAN2), 1.33 (p = 0.041, CAPN-1), to 1.26 (p = 0.021, VCP), respectively. The concentrations of these proteins remained highly stable within 6 h and were not affected by death time, postmortem interval (< 4 h), age, and month at death. Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUC) were 0.8178 (LMAN2), 0.6988 (CAPN-1), and 0.7267 (VCP), all of which were higher than CK-MB (AUC 0.5590) and cTn-I (AUC 0.5911). The diagnostic specificity (all above 60%) was obviously higher than CK-MB (43.48%) and cTnI (34.78%). In conclusion, LMAN-2, CAPN-1, and VCP could be stable serological biomarkers for diagnosis of EMI-SCD cases.
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http://dx.doi.org/10.1007/s00414-021-02702-zDOI Listing
September 2021

A pH-response chemotherapy synergistic photothermal therapy for tumor suppression and bone regeneration by mussel-inspired Mg implant.

Regen Biomater 2021 Oct 10;8(6):rbab053. Epub 2021 Sep 10.

Department of Orthopedics, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong 510080, China.

Primary malignant bone tumors can be life-threatening. Surgical resection of tumor plus chemotherapy is the standard clinical treatment. However, postoperative recovery is hindered due to tumor recurrence caused by residual tumor cells and bone defect caused by resection of tumor tissue. Herein, a multifunctional mussel-inspired film was fabricated on Mg alloy, that is, an inner hydrothermal-treated layer, a middle layer of polydopamine, and an outer layer of doxorubicin. The modified Mg alloy showed excellent photothermal effect and thermal/pH-controlled release of doxorubicin. The synergistic effect of chemotherapy and photothermal therapy enabled the modified Mg alloy to kill bone tumor and inhibit tumor growth in nude mice. Moreover, because of the controlled release of Mg ions and biocompatibility of polydopamine, the modified Mg alloy supported extracellular matrix mineralization, alkaline phosphatase activity, and bone-related gene expression in C3H10T1/2. Bone implantation model in rats verified that the modified Mg showed excellent osteointegration. These findings prove that the use of mussel-inspired multifunction film on Mg alloy offers a promising strategy for the therapy of primary malignant bone tumor.
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http://dx.doi.org/10.1093/rb/rbab053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455343PMC
October 2021

Optimized pharmacological control over the AAV-Gene-Switch vector for regulable gene therapy.

Mol Ther Methods Clin Dev 2021 Dec 8;23:1-10. Epub 2021 Aug 8.

University Medical Center Göttingen, Department of Neurology, Waldweg 33, 37073 Göttingen, Germany.

Gene therapy in its current design is an irreversible process. It cannot be stopped in case of unwanted side effects, nor can expression levels of therapeutics be adjusted to individual patient's needs. Thus, the Gene-Switch (GS) system for pharmacologically regulable neurotrophic factor expression was established for treatment of parkinsonian patients. Mifepristone, the synthetic steroid used to control transgene expression of the GS vector, is an approved clinical drug. However, pharmacokinetics and -dynamics of mifepristone vary considerably between different experimental animal species and depend on age and gender. In humans, but not in any other species, mifepristone binds to a high-affinity plasma carrier protein. We now demonstrate that the formulation of mifepristone can have robust impact on its ability to activate the GS system. Furthermore, we show that a pharmacological booster, ritonavir (Rtv), robustly enhances the pharmacological effect of mifepristone, and allows it to overcome gender- and species-specific pharmacokinetic and -dynamic issues. Most importantly, we demonstrate that the GS vector can be efficiently controlled by mifepristone in the presence of its human plasma carrier protein, α1-acid glycoprotein, in a "humanized" rat model. Thus, we have substantially improved the applicability of the GS vector toward therapeutic use in patients.
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http://dx.doi.org/10.1016/j.omtm.2021.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426472PMC
December 2021

Mitochondria-related changes and metabolic dysfunction in low prognosis patients under the POSEIDON classification.

Hum Reprod 2021 Oct;36(11):2904-2915

Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing, China.

Study Question: What is the relationship between mitochondria of granulosa cells (GCs) and age and ovarian function in the patients under the POSEIDON classification?

Summary Answer: Our results revealed obvious abnormal mitochondrial-related changes in low prognosis IVF population, where age and the function of ovarian reserve exerted a divergent effect on mitochondrial content and function.

What Is Known Already: Mitochondria have an important role in the cross-talk between GCs and oocytes. However, factors affecting mitochondria of GCs and related mechanisms are still poorly understood.

Study Design, Size, Duration: GCs samples were obtained from 119 infertile women undergoing IVF from September 2020 to February 2021. Six groups were investigated by the POSEIDON stratification: young with normal prognosis (C1), aging with normal prognosis (C2), young and low prognosis group with normal ovarian reserve (NOR) (G1), aging and low prognosis group with NOR (G2), young and low prognosis group with diminished ovarian reserve (DOR) (G3), and aging and low prognosis group with DOR (G4).

Participants/materials, Setting, Methods: The morphology of GC mitochondria was observed by transmission electron microscopy. MtDNA copy number and mitochondrial replication-related genes were detected by real-time quantitative PCR (qPCR). Mitochondrial membrane potential (MMP) and cytosolic reactive oxygen species (ROS) were detected by confocal microscopy. Cellular glycolysis and aerobic respiratory capacity were analyzed by Seahorse XFe96 Analyzer, and related gene expression and protein levels were assessed by qPCR and Western blot.

Main Results And The Role Of Chance: Compared to the normal prognosis groups, mitochondrial morphology was impaired in the low prognosis groups, where the young groups (G1, G3) with low prognosis showed phenotypes undergoing oxidative stress (round, vacuolated, swollen with decreased matrix density) and the aging groups (G2, G4) revealed typical aging characteristics (an irregular shape with heterogeneous matrix density and cord-like cristae). Additionally, the degree of corresponding change and damage was more obvious in patients with DOR (G3, G4) regardless of age. For mitochondrial content, the mtDNA copy number in GCs was significantly negatively correlated with age in the low prognosis groups (β = -0.373, P = 0.005). Interestingly, the relationship between mtDNA copy number and anti-Mullerian hormone score differed between the two age groups with low prognosis, with a negative correlation in the young groups (β = -0.639, P = 0.049) and a positive correlation in the aging groups (β = 0.505, P = 0.039). In addition, significantly reduced mitochondrial activity (MMP, ROS) and cell metabolism (both glycolysis and OXPHOS) were observed in the low prognosis groups, with the most obvious decrease being observed in the DOR population. However, the metabolism of the GCs in normal prognosis aging women (C2) shifted from OXPHOS to anaerobic glycolysis.

Limitations, Reasons For Caution: Owing to the difficulties involved in primary GC collection and culture, the sample size was limited.

Wider Implications Of The Findings: Mitochondrial abnormality is closely linked to the low prognostic outcome in IVF patients. Supplementing the functional mitochondrial content or improving mitochondrial function by autologous mitochondrial transfer or mitochondrial-related regulating drugs may help improve the clinical outcomes in patients with a low prognosis, especially for those with DOR.

Study Funding/competing Interest(s): This work was supported by the National Natural Science Foundation of China (No. 21737001), the Peking University Clinical Medicine + X Youth Project (PKU2020LCXQ011), the Research and Development Program of Peking University People's Hospital (No. RDH2017-03; No. RDX2019-06) and the Application of Clinical Features of Capital Special Subject (Z171100001017130). There were no competing interests.

Trial Registration Number: This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR2100045531).
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http://dx.doi.org/10.1093/humrep/deab203DOI Listing
October 2021

Human Acellular Amniotic Matrix with Previously Seeded Umbilical Cord Mesenchymal Stem Cells Restores Endometrial Function in a Rat Model of Injury.

Mediators Inflamm 2021 3;2021:5573594. Epub 2021 Sep 3.

Peking University People's Hospital, Reproductive Medicine Center, Beijing 100044, China.

Background: Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Stem cell transplantation offers a potential alternative for some cases of severe Asherman's syndrome that cannot be treated with surgery or hormonal therapy. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. However, there is no report on the effects of UCMSCs previously seeded on human acellular amniotic matrix (AAM) on endometrial injury.

Methods: Absolute ethanol was injected into rat uteri to damage the endometrium. UCMSCs previously seeded on AAM were surgically transplanted. Using a variety of methods, the treatment response was assessed by endometrial thickness, endometrial biomarker expression, endometrial receptivity, cell proliferation, and inflammatory factors.

Results: Endometrial thickness was markedly improved after UCMSC-AAM transplantation. The expression of endometrial biomarkers, namely, vimentin, cytokeratin, and integrin 3, in treated rats increased compared with untreated rats. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. Moreover, in the AAM group, the MMP9 expression increased. The expression of proinflammatory factors (IL-2, TNF, and IFN-) in the UCMSC-AAM group decreased compared with the untreated group, whereas the expression of anti-inflammatory factors (IL-4, IL-10) increased significantly.

Conclusions: UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The successful preparation of lyophilized AAM provides the possibility of secondary infectious disease screening and amniotic matrix quality detection, followed by retrospective analysis. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium.
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http://dx.doi.org/10.1155/2021/5573594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438588PMC
September 2021

Protective action of ultrasound-guided intraparenchymal transplantation of BMSCs in adriamycin nephropathy rats through the RIPK3/MLKL and NLRP3 pathways.

Acta Histochem 2021 Sep 10;123(7):151773. Epub 2021 Sep 10.

Department of Radiology, the Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China. Electronic address:

Background: Bone marrow stromal cells (BMSCs) are an effective new strategy for the treatment of kidney diseases. At present, noninvasive and efficient transplantation approaches to homing BMSCs to the renal parenchyma is still a serious challenge. The aim of this study was to investigate the feasibility and potential mechanism of ultrasound-guided intraparenchymal transplantation of BMSCs for the treatment of adriamycin nephropathy (AN) in rats.

Materials And Methods: A rat AN model was induced by 2 injections of doxorubicin. The rats were randomly divided into 4 groups (n = 10 animals in each group) : normal group (N group, no treatment), control medium group (CM group, transplant medium 1.0 mL), adriamycin nephropathy group (ADR group, phosphate buffered saline 1.0 mL), or BMSCs group (BMSCs fluid 1.0 mL). Intraparenchymal injection was completed under ultrasound guidance. After 4 weeks of treatment, blood samples were collected for serum biochemical measurements and ELISAs. The kidneys were removed for histopathological examination, electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), and western blot analysis.

Results: No deaths occurred in any group after BMSCs transplantation through the renal parenchyma under ultrasound guidance. Compared with the N and CM groups, in the ADR group, blood serum creatinine (SCr), blood urea nitrogen (BUN) and urine albumin (ALb) were higher, glomerular and tubular dilatation was observed, the number of apoptotic cells was higher, and the protein levels of receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL) and nucleotide leukin-rich polypeptide 3 (NLRP3), key components of pathways in rat kidney, were significantly higher. Compared with those in the ADR group, the levels of SCr, BUN, ALb and serum proinflammatory cytokines in the BMSCs group were lower, the pathological structure of the kidney was improved, the number of apoptotic cells was lower, and the levels of RIPK3/MLKL and NLRP3 were significantly lower.

Conclusion: Ultrasound-guided intraparenchymal transplantation of BMSCs regulated the RIPK3/MLKL and NLRP3 pathways in a minimally invasive and safe manner, thereby inhibiting renal necrosis and inflammation and playing a protective role in rat AN.
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http://dx.doi.org/10.1016/j.acthis.2021.151773DOI Listing
September 2021

Immobilization of Phospholipase A1 Using a Protein-Inorganic Hybrid System.

Polymers (Basel) 2021 Aug 26;13(17). Epub 2021 Aug 26.

National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.

In this study, four kinds of phospholipase A1-metal (Al/Co/Cu/Mn) hybrid nanostructures were prepared for enhancing the stability of the free PLA1. The formed hybrid complexes were characterized by scanning electron microscope (SEM), Fourier infrared spectroscopy (FTIR), and -ray diffraction (XRD). The stability and substrate specificity of immobilized enzymes were subsequently determined. After immobilization, the temperature tolerance of PLA1-metal hybrid nanostructures was enhanced. The relative activity of PLA1-Al/Co/Cu hybrid nanostructures remained above 60% at 50 °C, while that of free enzyme was below 5%. The thermal transition temperature measured by differential scanning calorimetry (DSC) was found to increase from 65.59 °C (free enzyme) to 173.14 °C, 123.67 °C, 96.31 °C, and 114.79 °C, referring to PLA1-Cu/Co/Al/Mn hybrid nanostructures, respectively. Additionally, after a storage for fourteen days at 4 °C, the immobilized enzymes could exhibit approximately 60% of the initial activity, while the free PLA1 was inactivated after four days of storage. In brief, using Co, Cu, Al, and Mn as the hybridization materials for immobilization could improve the catalytic properties and stability of the free PLA1, suggesting a promising method for a wider application of PLA1 in many fields such as food, cosmetics, and the pharmaceutical industry.
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http://dx.doi.org/10.3390/polym13172865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433775PMC
August 2021

Ultrasound-Guided Transplantation of Mesenchymal Stem Cells Improves Adriamycin Nephropathy in Rats through the RIPK3/MLKL and TLR-4/NF-κB signaling.

Stem Cells Dev 2021 Sep 5. Epub 2021 Sep 5.

Kunming Medical University Second Hospital, 66472, Radiology, Kunming, Yunnan, China.

Bone marrow stromal cell (BMSC) treatment has been shown to be beneficial for adriamycin nephropathy (AN).However, the low transplantation rate is still the key factor that affects this strategy. This study is the first to investigate the efficacy and potential mechanism of ultrasound-guided transrenal arterial transfer of BMSCs for the treatment of AN in rats. The AN rat model was established by two injections of doxorubicin. In addition, the rats were randomly divided into four groups (10 rats per group): the normal group (no treatment), the medium control group (treated with medium), the adriamycin group (treated with phosphate buffer), and the BMSC group (treated with BMSCs). After 4 weeks, the levels of serum creatinine (SCr), blood urea nitrogen (BUN) and urine albumin (ALb) were measured. In addition, pathological changes in kidney tissue were evaluated by pathological sectioning and electron microscopy. Western blotting was used to determine the levels of proteins in rat kidneys. Ultrasound-guided renal artery transplantation of BMSCs reduced the levels of SCr, BUN and ALb and improved the pathological structure of rat kidneys compared with those in the adriamycin group. This treatment inhibited renal cell necrosis by reducing the expression of receptor-interacting Serine/theronine Kinase 3 (RIPK3) and Mixed lineage kinase domain-like pseudokinase (MLKL) and inhibited renal inflammation and fibrosis by reducing the expression of Toll Like receptor 4 (TLR4) and Nuclear factor κB (NF-κB). Our study shows that ultrasound-guided transrenal artery transplantation of BMSCs can improve AN-induced renal injury in rats by regulating the RIPK3/MLKL and TLR-4/NF-κB pathways and inhibiting renal necrosis, inflammation and fibrosis.
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http://dx.doi.org/10.1089/scd.2021.0087DOI Listing
September 2021

Plasma metabolites associated with physiological and biochemical indexes indicate the effect of caging stress on mallard ducks (Anas platyrhynchos).

Anim Biosci 2021 Aug 25. Epub 2021 Aug 25.

Institute of Animal Husbandry and Veterinary Science, Hubei Academy of Agricultural Sciences/Hubei Key Laboratory of Animal Embryo Engineering and Molecular Breeding, Wuhan, 430064, China.

Objective: Cage rearing has critical implications for the laying duck industry because it is convenient for feeding and management. However, caging stress is a type of chronic stress that induces maladaptation. Environmental stress responses have been extensively studied, but no detailed information is available about the comprehensive changes in plasma metabolites at different stages of caging stress in ducks. We designed this experiment to analyze the effects of caging stress on performance parameters and oxidative stress indexes in ducks.

Methods: Furthermore, liquid chromatography tandem mass spectrometry (LC/MS-MS) was used to determine the changes in metabolites in duck plasma at 5 (CR5), 10 (CR10), and 15 (CR15) days after cage rearing and traditional breeding (TB). The associated pathways of differentially altered metabolites were analyzed using KEGG database.

Results: The results of this study indicate that caging stress decreased performance parameters, and the plasma T-SOD levels were increased in the CR10 group compared with the other groups. In addition, 1431 metabolites were detected. Compared with the TB group, 134, 381 and 190 differentially produced metabolites were identified in the CR5, CR10 and CR15 groups, respectively. The results of principal component analysis (PCA) show that the selected components sufficiently distinguish the TB group and CR10 group. KEGG analysis results revealed that the differentially altered metabolites in duck plasma from the CR5 and TB groups were mainly associated with ovarian steroidogenesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism.

Conclusions: In this study, the production performance, blood indexes, number of metabolites and PCA were compared to determine effect of the caging stress stage on ducks. We inferred from the aforementioned experimental results that caging-stressed ducks were in the sensitive phase in the first 5 days after caging, caging for approximately 10 days was an important transition phase, and then the duck continually adapted.
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http://dx.doi.org/10.5713/ab.21.0241DOI Listing
August 2021

Effectiveness of interventions for people living with dementia and their carers in Chinese communities: protocol for a systematic review and meta-analysis of randomised controlled trials.

BMJ Open 2021 08 17;11(8):e047560. Epub 2021 Aug 17.

Department of Social Work and Social Administration, The University of Hong Kong, Hong Kong SAR, China

Introduction: As the largest and most rapidly ageing population, Chinese people are now the major driver of the continued growth in dementia prevalence globally. The need for evidence-based interventions in Chinese communities is urgent. Although a wide range of pharmacological and non-pharmacological interventions for dementia have been trialled in Chinese populations, the evidence has not been systematically synthesised. This systematic review and meta-analysis aims to map out the interventions for people living with dementia and their carers in Chinese communities worldwide and compare the effectiveness of these interventions.

Methods And Analysis: This protocol followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. We will search Chinese (China National Knowledge Infrastructure, WanFang DATA) and English bibliographical databases (MEDLINE, EMBASE, PsycINFO, CINAHL Plus, Global Health, WHO Global Index Medicus, Virtual Health Library, Cochrane CENTRAL, Social Care Online, BASE, MODelling Outcome and cost impacts of interventions for DEMentia (MODEM) Toolkit, Cochrane Database of Systematic Reviews), complemented by hand searching of reference lists. We will include studies evaluating the effectiveness of interventions for dementia or mild cognitive impairment in Chinese populations, using a randomised controlled trial design, and published between January 2008 and June 2020. We will use a standardised form to extract data and Version 2 of the Cochrane risk-of-bias tool for randomised trials to assess the risk of bias of the included studies. Collected data will be fully interpreted with narrative synthesis and analysed using pairwise and network meta-analyses to pool intervention effects where sufficient information is available. We will perform subgroup analysis and meta-regression to explore potential reasons for heterogeneity.

Ethics And Dissemination: No formal ethics approval is required for this protocol. The findings will facilitate the development of studies on interventions for dementia and timely inform dementia policymaking and practice. Planned dissemination channels include peer-reviewed publications, conference presentations, public events and websites.

Prospero Registration Number: CRD42019134135.
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http://dx.doi.org/10.1136/bmjopen-2020-047560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372806PMC
August 2021

Synthesis and Biological Evaluation of Novel Triazine Derivatives as Positive Allosteric Modulators of α7 Nicotinic Acetylcholine Receptors.

J Med Chem 2021 Aug 10;64(16):12379-12396. Epub 2021 Aug 10.

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

Enhancing neuronal α7 nicotinic acetylcholine receptor (α7 nAChR) function can alleviate cognitive deficits. Here, we report the design, synthesis, and evaluation of -(4-(trifluoromethoxy)phenyl)-1,3,5-triazin-2-amine derivatives - as a series of novel α7 nAChR positive allosteric modulators (PAMs). The representative compound functions as a type I PAM with an EC of 3.0 μM and approximately 38-fold enhancement of α7 current in the presence of agonist acetylcholine (100 μM). It specifically enhances α7 current with high selectivity. Compound shows good pharmacokinetic property in mice. Intraperitoneal injection of (3 mg/kg) exhibits sufficient blood-brain barrier penetration in mice. Furthermore, can also rescue the auditory gating deficit in mice with schizophrenia-like behavior. Molecular docking of with homopentameric α7 nAChR reveals a new mode of action. These results support the potential of for treatment for schizophrenia and Alzheimer's disease.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01058DOI Listing
August 2021

The factors associated with nosocomial infection in elderly hip fracture patients: gender, age, and comorbidity.

Int Orthop 2021 Aug 5. Epub 2021 Aug 5.

Department of Orthopedics, Fourth Medical Center, General Hospital of Chinese PLA, Beijing, 100000, China.

Purpose: This is a retrospective case-control study to ascertain the factors influencing nosocomial infection (NI) in elderly patients with hip fractures.

Methods: A total of 80,174 patients (≥ 60 years) who suffered hip fractures between 2006 and 2017 were identified through a national inquiry of 94 hospitals. The patients were divided into an NI group and control group according to the occurrence or lack of occurrence of NI within 48 hours after surgery, respectively. Age, gender, hip fracture pattern, whether to operate, surgical treatments, and comorbidities were recorded as variables.

Results: A total of 9806 elderly hip fracture patients (60 years) were included, 1977 of whom were patients diagnosed with NI. The control group consisted of randomly drawn cases from the 9806 patients from different hospitals with a rate of one NI patient: four patients without NI. Patient gender, age, and in particular the number of comorbidities were associated with occurrence of NI. Using regression models to predict infection outcomes based on the number of comorbidities had an area under the curve (AUC) of 0.714, while using the Charlson comorbidity index (CCI) yielded a smaller value of 0.694. The most common comorbidities of this elderly cohort were chronic respiratory disease, hypertension, diabetes mellitus, cerebrovascular disease, and coronary heart disease.

Conclusions: Older age, male gender, and greater number of comorbidities were found to be associated with the occurrence of NI. In particular, the number of comorbidities was the most accurate predictor of NI occurrence, and when used to build a regression model, it had greater predictive capability than CCI to predict NI in elderly hip fracture patients. Additionally, the common diseases of the elderly should be primarily considered when investigating the relationship between comorbidities and NI in older patients.
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http://dx.doi.org/10.1007/s00264-021-05104-3DOI Listing
August 2021

Impact of surgical margin width on long-term outcomes for intrahepatic cholangiocarcinoma: a multicenter study.

BMC Cancer 2021 Jul 20;21(1):840. Epub 2021 Jul 20.

Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian, People's Republic of China.

Background: The objective of this study was to investigate the survival outcomes of surgical margin width in intrahepatic cholangiocarcinoma (ICC).

Methods: Between November 2011 and August 2017, patients who underwent hepatectomy for ICC were collected from 13 major hepatopancreatobiliary centers in China. The survival outcomes for patients who underwent wide margin hepatectomy (WMH) were compared with those who underwent narrow margin hepatectomy (NMH) using the 1:1 propensity score matching (PSM).

Results: Among 478 included patients, 195 (40.8%) underwent WMH whereas 283 (59.2%) underwent NMH. PSM yielded 79 matched patients with similar baseline characteristics. Patients underwent WMH had a significant better OS and DFS compared with those underwent NMH (before PSM: median OS 27 vs 17 months, P < 0.05; median DFS 15 vs 8 months, P = 0.001, after PSM: median OS 41 vs 22 months, p < 0.05; median DFS 16 vs 10 months, p < 0.05). However, subgroup analysis based on the AJCC staging system, WMH could only improve the survival outcomes in AJCC I ICC patients (Stage I: OS, DFS, P<0.05).

Conclusions: Surgeons should strive to achieve a wide surgical margin for patients with AJCC I ICC to optimize the long-term outcome.
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http://dx.doi.org/10.1186/s12885-021-08560-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293518PMC
July 2021

Oleic Acid Protects Mothers From Mating-Induced Death and the Cost of Reproduction.

Front Cell Dev Biol 2021 11;9:690373. Epub 2021 Jun 11.

Department of Molecular Biology, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, United States.

Reproduction comes at a cost, including accelerated death. Previous studies of the interconnections between reproduction, lifespan, and fat metabolism in were predominantly performed in low-reproduction conditions. To understand how increased reproduction affects lifespan and fat metabolism, we examined mated worms; we find that a Δ9 desaturase, FAT-7, is significantly up-regulated. Dietary supplementation of oleic acid (OA), the immediate downstream product of FAT-7 activity, restores fat storage and completely rescues mating-induced death, while other fatty acids cannot. OA-mediated lifespan restoration is also observed in mutants suffering increased death from short-term mating, and in mated females, indicating a conserved role of oleic acid in post-mating lifespan regulation. Our results suggest that increased reproduction can be uncoupled from the costs of reproduction from somatic longevity regulation if provided with the limiting lipid, oleic acid.
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http://dx.doi.org/10.3389/fcell.2021.690373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226236PMC
June 2021

Sex and death.

Curr Top Dev Biol 2021 29;144:353-375. Epub 2020 Sep 29.

Lewis-Sigler Institute for Integrative Genomics and Department of Molecular Biology, Princeton University, Princeton, NJ, United States. Electronic address:

Sexual interactions negatively impact health and longevity in many species across the animal kingdom. C. elegans has been established as a good model to study how mating and intense sexual interactions influence longevity of the individuals. In this chapter, we review the most recent discoveries in this field. We first describe the phenotypes caused by intense mating, including shrinking, fat loss, and glycogen loss. We then describe three major mechanisms underlying mating-induced killing: germline activation, seminal fluid transfer, and male pheromone-mediated toxicity. Next, we summarize the current knowledge of genetic pathways involved in regulating mating-induced death, including DAF-9/DAF-12 steroid signaling, Insulin/IGF-1 signaling (IIS), and TOR signaling. Finally, we discuss the possible fitness benefits of mating-induced death. Throughout this review, we compare and contrast mating-induced death between the sexes and among different species in an effort to discuss this phenomenon and underlying mechanisms from the evolutionary perspective. Further investigation using mated C. elegans will improve our understanding of sexual antagonism, as well as the coordination between reproduction and somatic longevity in response to various external signals. Due to the evolutionary conservation in many aspects of mating-induced death, what we learn from a short-lived mated worm could provide new strategies to improve our own fitness and longevity.
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http://dx.doi.org/10.1016/bs.ctdb.2020.08.004DOI Listing
September 2020

Evaluation of automated segmentation algorithms for neurons in macaque cerebral microscopic images.

Microsc Res Tech 2021 Oct 27;84(10):2311-2324. Epub 2021 Apr 27.

CEA-CNRS-UMR 9199, Laboratoire des Maladies Neurodégénératives, MIRCen, Fontenay-aux-Roses, Université Paris-Saclay, Gif-sur-Yvette, France.

Accurate cerebral neuron segmentation is required before neuron counting and neuron morphological analysis. Numerous algorithms for neuron segmentation have been published, but they are mainly evaluated using limited subsets from a specific anatomical region, targeting neurons of clear contrast and/or neurons with similar staining intensity. It is thus unclear how these algorithms perform on cerebral neurons in diverse anatomical regions. In this article, we introduce and reliably evaluate existing machine learning algorithms using a data set of microscopy images of macaque brain. This data set highlights various anatomical regions (e.g., cortex, caudate, thalamus, claustrum, putamen, hippocampus, subiculum, lateral geniculate, globus pallidus, etc.), poor contrast, and staining intensity differences of neurons. The evaluation was performed using 10 architectures of six classic machine learning algorithms in terms of typical Recall, Precision, F-score, aggregated Jaccard index (AJI), as well as a performance ranking of algorithms. F-score of most of the algorithms is superior to 0.7. Deep learning algorithms facilitate generally higher F-scores. U-net with suitable layer depth has been evaluated to be excellent classifiers with F-score of 0.846 and 0.837 when performing cross validation. The evaluation and analysis indicate the performance gap among algorithms in various anatomical regions and the strengths and limitations of each algorithm. The comparative result highlights at the same time the importance and difficulty of neuron segmentation and provides clues for future improvement. To the best of our knowledge, this work is the first comprehensive study for neuron segmentation in such large-scale anatomical regions. Neuron segmentation plays a critical role in extracting cerebral information, such as neuron counting and neuron morphological analysis. Accurate automated cerebral neuron segmentation is a challenging task due to different kinds, poor contrast, staining intensity differences, and fuzzy boundaries of neurons. The comprehensive evaluation and analysis of performance among existing machine learning algorithms in diverse anatomical regions allows to make clear of the strengths and limitations of state-of-the-art algorithm. The comprehensive study provides clues for future improvement and creation of automated methods.
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http://dx.doi.org/10.1002/jemt.23786DOI Listing
October 2021

Study of the effect of light on follicular development in laying hens.

Anim Biosci 2021 Apr 13. Epub 2021 Apr 13.

Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Science, Wuhan, 430064, P. R. China.

Objective: The oxidative stress status and changes of chicken ovary tissue after shading were studied, to determine the mechanism of the effect of shading on follicular development.

Methods: Twenty healthy laying hens (40 weeks old) with uniform body weight and the same laying rate were randomly divided into two groups (the shading group and normal light group). In the shading group, the cage was covered to reduce the light intensity inside the cage to 0 without affecting ventilation or food intake. The normal lighting group received no additional treatment. After 7 days of shading, oxidative stress related indicators and gene expression were detected.

Results: Analysis of paraffin and ultrathin sections showed that apoptosis of ovarian granulosa cells increased significantly after light shading. ELISA (enzyme linked immunosorbent assay) results revealed that the levels of T-AOC (total antioxidant capacity), MDA (malondialdehyde), SOD (superoxide dismutase), GSH (glutathione), CAT (catalase) and other substances in the sera, livers, ovaries, and follicular granulosa cells of laying hens increased significantly after shading for 7 days; and ROS (reactive oxygen species) levels in the livers of laying hens also increased significantly. ROS in the serum, ovarian and granulosa cell (GCs)also increased. After shading for 7 days, the levels of 8-OHdG (8-hydroxy-2 deoxyguanosine) in the sera and ovarian tissues of laying hens increased significantly. CCK-8 (cell counting kit-8) detection showed that the proliferation activity of GCs in layer follicles decreased after shading for 7 days; the expression level of the anti-apoptotic gene BCL2 (B-cell lymphoma-2) in ovarian tissue and follicular GCs was significantly reduced, and the expression levels of pro-apoptotic casp3 (caspase 3) and SOD, GPX2 (glutathione peroxidase 2) and CAT were all significantly increased.

Conclusion: Oxidative stress induced by shading light has a serious inhibitory effect on follicular development during reproduction in laying hens.
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http://dx.doi.org/10.5713/ab.20.0791DOI Listing
April 2021

The Role of Unfolded Protein Response in Human Intervertebral Disc Degeneration: Perk and IRE1- as Two Potential Therapeutic Targets.

Oxid Med Cell Longev 2021 24;2021:6492879. Epub 2021 Mar 24.

Department of Orthopedic Surgery, Sixth Medical Center, Chinese PLA General Hospital, Beijing, China.

Inflammation plays a key role in intervertebral disc degeneration (IDD). The association between inflammation and endoplasmic reticulum (ER) stress has been observed in many diseases. However, whether ER stress plays an important role in IDD remains unclear. Therefore, this study is aimed at investigating the expression of ER stress in IDD and at exploring the underlying mechanisms of IDD, ER stress, and inflammation. The expression of ER stress was activated in nucleus pulposus cells from patients who had IDD (D-NPCs) compared with patients without IDD (N-NPCs); and both the proliferation and synthesis capacity were decreased by inducer tunicamycin (Tm) and proinflammatory cytokines. Pretreatment of NPCs with 4-phenyl butyric acid (4-PBA) prevented the inflammatory cytokine-induced upregulation of unfolded protein response- (UPR-) related proteins and recovered cell synthetic ability. Furthermore, proinflammatory cytokine treatment significantly upregulated the expression of inositol-requiring protein 1 (IRE1-) and protein kinase RNA-like ER kinase (PERK), but not activating transcription factor 6 (ATF6). Finally, knockdown of IRE1- and PERK also restored the biological activity of NPCs. Our findings identified that IRE1- and PERK might be the potential targets for IDD treatment, which may help illustrate the underlying mechanism of ER stress in IDD.
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http://dx.doi.org/10.1155/2021/6492879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016586PMC
May 2021

Biomimetic Ti-6Al-4V alloy/gelatin methacrylate hybrid scaffold with enhanced osteogenic and angiogenic capabilities for large bone defect restoration.

Bioact Mater 2021 Oct 21;6(10):3437-3448. Epub 2021 Mar 21.

Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.

Titanium-based scaffolds are widely used implant materials for bone defect treatment. However, the unmatched biomechanics and poor bioactivities of conventional titanium-based implants usually lead to insufficient bone integration. To tackle these challenges, it is critical to develop novel titanium-based scaffolds that meet the bioadaptive requirements for load-bearing critical bone defects. Herein, inspired by the microstructure and mechanical properties of natural bone tissue, we developed a Ti-6Al-4V alloy (TC4)/gelatin methacrylate (GelMA) hybrid scaffold with dual bionic features (GMPT) for bone defect repair. GMPT is composed of a hard 3D-printed porous TC4 metal scaffold (PT) backbone, which mimics the microstructure and mechanical properties of natural cancellous bone, and a soft GelMA hydrogel matrix infiltrated into the pores of PT that mimics the microenvironment of the extracellular matrix. Ascribed to the unique dual bionic design, the resultant GMPT demonstrates better osteogenic and angiogenic capabilities than PT, as confirmed by the and rabbit radius bone defect experimental results. Moreover, controlling the concentration of GelMA (10%) in GMPT can further improve the osteogenesis and angiogenesis of GMPT. The fundamental mechanisms were revealed by RNA-Seq analysis, which showed that the concentration of GelMA significantly influenced the expression of osteogenesis- and angiogenesis-related genes via the Pi3K/Akt/mTOR pathway. The results of this work indicate that our dual bionic implant design represents a promising strategy for the restoration of large bone defects.
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http://dx.doi.org/10.1016/j.bioactmat.2021.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988351PMC
October 2021

Prognostic Value of Lymph Node Dissection for Intrahepatic Cholangiocarcinoma Patients With Clinically Negative Lymph Node Metastasis: A Multi-Center Study From China.

Front Oncol 2021 11;11:585808. Epub 2021 Mar 11.

Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.

Background: The clinical value of lymph-node dissection (LND) for intrahepatic carcinoma (ICC) patients with clinically negative lymph node metastasis (LNM) remains unclear; hence we conducted a multi-center study to explore it.

Methods: Patients who were diagnosed ICC with clinically negative LNM and underwent hepatectomy with or without LND from December 2012 to December 2015 were retrospectively collected from 12 hepatobiliary centers in China. Overall survival (OS) was analyzed using the Kaplan-Meier method, and then subgroup analysis was conducted stratified by variables related to the prognosis.

Results: A total of 380 patients were eligible including 106 (27.9%) in the LND group and 274 (72.1%) in the non-LND group. Median OS in the LND group was slightly longer than that in the non-LND group (24.0 18.0 months, = 0.30), but a significant difference was observed between the two groups (24.0 14.0 months, = 0.02) after a well-designed 1:1 propensity score matching without increased severe complications. And, LND was identified to be one of the independent risk factors of OS (HR = 0.66, 95%CI = 0.46-0.95, = 0.025). Subgroup analysis in the matched cohort showed that patients could benefit more from LND if they were male, age <60 years, had no HBV infection, with ECOG score <2, CEA ≤5 ug/L, blood loss ≤400 ml, transfusion, major hepatectomy, resection margin ≥1 cm, tumor size >5 cm, single tumor, mass-forming, no satellite, no MVI, and no perineural invasion (all < 0.05). Furthermore, only patients with pathologically confirmed positive LNM were found to benefit from postoperative adjuvant therapy ( < 0.001).

Conclusion: With the current data, we concluded that LND would benefit the selected ICC patients with clinically negative LNM and might guide the postoperative management.
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http://dx.doi.org/10.3389/fonc.2021.585808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991319PMC
March 2021

Risk factors for cholesterol polyp formation in the gallbladder are closely related to lipid metabolism.

Lipids Health Dis 2021 Mar 22;20(1):26. Epub 2021 Mar 22.

Department of General Surgery, Xuanwu Hospital, The First Clinical Medical College, Capital Medical University, No.45 Changchun Street, Beijing, China.

Background: The purpose of this study was to assess the risk factors for cholesterol polyp formation in the gallbladder.

Methods: This was a multicenter retrospective study based on pathology. From January 2016 to December 2019, patients who underwent cholecystectomy and non-polyp participants confirmed by continuous ultrasound follow-ups were reviewed. Patients in the cholesterol polyp group were recruited from three high-volume centers with a diagnosis of pathologically confirmed cholesterol polyps larger than 10 mm. Population characteristics and medical data were collected within 24 h of admission before surgery. The non-polyp group included participants from the hospital physical examination center database. They had at least two ultrasound examinations with an interval longer than 180 days. Data from the final follow-up of the non-polyp group were analyzed. The risk factors for cholesterol polyp formation were analyzed by comparing the two groups.

Results: A total of 4714 participants were recruited, including 376 cholesterol polyp patients and 4338 non-polyp participants. In univariate analysis, clinical risk factors for cholesterol polyps were age, male sex, higher body mass index (BMI), higher low-density lipoprotein (LDL), lower high-density lipoprotein (HDL), and higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. In multivariate logistic analysis, independent risk factors were age > 50 years (odds ratio [OR] = 3.02, 95% confidence interval [CI] 2.33-3.91, P < 0.001], LDL > 2.89 mmol/L (OR = 1.38, 95% CI 1.08-1.78, P = 0.011), lower HDL (OR = 1.78 95% CI 1.32-2.44, P < 0.001), AST > 40 IU/L (OR = 3.55, 95% CI 2.07-6.07, P < 0.001), and BMI > 25 kg/m (OR = 1.32, 95% CI 1.01-1.72, P = 0.037).

Conclusions: Age, LDL, HDL, AST, and BMI are strong risk factors for cholesterol polyp formation. Older overweight patients with polyps, accompanied by abnormal lipid levels, are at high risk for cholesterol polyps.
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http://dx.doi.org/10.1186/s12944-021-01452-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983281PMC
March 2021

Zn-contained mussel-inspired film on Mg alloy for inhibiting bacterial infection and promoting bone regeneration.

Regen Biomater 2021 Feb 30;8(1):rbaa044. Epub 2020 Sep 30.

Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.

Infection and insufficient osteointegration are the main causes of orthopedic implant failure. Furthermore, activating favorable inflammation response is vital to the fast osteointegration of implants. Therefore, endowing the implants with multifunctions (antibacterial, anti-inflammation, and pro-osteointegration) is a promising strategy to improve the performance of orthopedic implants. In this study, a Zn-contained polydopamine (PDA) film was fabricated on AZ31 alloy. The film possessed a stable Zn ion release in 14 days. The results of electrochemical analysis implied the favorable corrosion protection of the film, and thus, leading to a suitable hemolysis ratio (below 1%). The antibacterial assessment revealed that the film exhibited excellent resistance against (nearly 100%), which can be ascribed to the release of Zn ions. The cell-culture evaluation revealed that the extract of Zn-contained PDA-coated sample can activate RAW264.7 polarization to an anti-inflammatory phenotype, as well as enhance the osteogenic differentiation ability of MC3T3-E1. Additionally, the femoral osteomyelitis model indicated that the as-prepared film had a high antibacterial capability at early stage of the implantation, and showed better osteogenesis and osteointegration after 8 weeks of implantation. With favorable antibacterial, anti-inflammation, and pro-osteogenesis abilities, the novel designed Zn-contained PDA film is promising to be used in Mg-based orthopedic implants.
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http://dx.doi.org/10.1093/rb/rbaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947588PMC
February 2021

Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue.

Acta Neuropathol Commun 2021 03 12;9(1):41. Epub 2021 Mar 12.

Department of Clinical Neurosciences, UK Dementia Research Institute at the University of Cambridge, Cambridge, UK.

A fundamental property of infectious agents is their particulate nature: infectivity arises from independently-acting particles rather than as a result of collective action. Assemblies of the protein tau can exhibit seeding behaviour, potentially underlying the apparent spread of tau aggregation in many neurodegenerative diseases. Here we ask whether tau assemblies share with classical pathogens the characteristic of particulate behaviour. We used organotypic hippocampal slice cultures from P301S tau transgenic mice in order to precisely control the concentration of extracellular tau assemblies in neural tissue. Whilst untreated slices displayed no overt signs of pathology, exposure to recombinant tau assemblies could result in the formation of intraneuronal, hyperphosphorylated tau structures. However, seeding ability of tau assemblies did not titrate in a one-hit manner in neural tissue. The results suggest that seeding behaviour of tau arises at high concentrations, with implications for the interpretation of high-dose intracranial challenge experiments and the possible contribution of seeded aggregation to human disease.
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http://dx.doi.org/10.1186/s40478-021-01141-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953780PMC
March 2021

Enhanced osteogenesis of titanium with nano-Mg(OH) film and a mechanism study via whole genome expression analysis.

Bioact Mater 2021 Sep 13;6(9):2729-2741. Epub 2021 Feb 13.

Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.

Titanium (Ti) has been the most widely used orthopedic implant in the past decades. However, their inert surface often leads to insufficient osteointegration of Ti implant. To solve this issue, two bioactive Mg(OH) films were developed on Ti surfaces using hydrothermal treatment (Ti-M1# and Ti-M2#). The Mg(OH) films showed nano-flake structures: sheets on Ti-M1# with a thickness of 14.7 ± 0.7 nm and a length of 131.5 ± 2.9 nm, and on Ti-M2# with a thickness of 13.4 ± 2.2 nm and a length of 56.9 ± 5.6 nm. Both films worked as Mg ions releasing platforms. With the gradual degradation of Mg(OH) films, weakly alkaline microenvironments will be established surrounding the modified implants. Benefiting from the sustained release of Mg ions, nanostructures, and weakly alkaline microenvironments, the as-prepared nano-Mg(OH) coated Ti showed better and osteogenesis. Notably, Ti-M2# showed better osteogenesis than Ti-M1#, which can be ascribed to its smaller nanostructure. Moreover, whole genome expression analysis was applied to study the osteogenic mechanism of nano-Mg(OH) films. For both coated samples, most of the genes related to ECM-receptor interaction, focal adhesion, and TGF-β pathways were upregulated, indicating that these signaling pathways were activated, leading to better osteogenesis. Furthermore, cells cultured on Ti-M2# showed markedly upregulated BMP-4 gene expression, suggesting that the nanostructure with Mg ion release ability can better activate BMP-4 related signaling pathways, resulting in better osteogenesis. Nano-Mg(OH) films demonstrated a superior osteogenesis and are promising surface modification strategy for orthopedic applications.
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http://dx.doi.org/10.1016/j.bioactmat.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895731PMC
September 2021

Novel Strategy of Curettage and Adjuvant Microwave Therapy for the Treatment of Giant Cell Tumor of Bone in Extremities: A Preliminary Study.

Orthop Surg 2021 Feb 13;13(1):185-195. Epub 2021 Jan 13.

Department of Orthopaedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Objectives: To evaluate whether curettage with adjuvant microwave therapy was successful in the treatment of giant cell tumor of the bone (GCTB) in extremities, especially for GCTB with pathological fractures and GCTB of the distal radius.

Methods: This was a retrospective study of 54 cases of GCTB of the extremities treated by curettage with adjuvant microwave therapy between 2007 and 2019. Five patients were lost to follow up and excluded from the study. A total of 33 male and 21 female patients were included in this study. Patients were aged 15-57 years (mean 29.72 ± 10.48 years). Among these patients, there were 10 cases of GCTB with pathological fractures and eight cases of GCTB of the distal radius; one of these cases was combined with a pathological fracture. Comprehensive imaging examinations (X-rays [including lesion site and chest], CT, MRI, emission computed tomography, and pathology examination) of all patients were reviewed. The clinical staging of these patients were evaluated radiologically using the Campanacci classification system based on the extent of spread of the tumor. All patients underwent curettage with adjuvant microwave therapy. Clinical and imaging evaluations were performed in all cases to check for recurrence or metastasis. Lower limb and upper limber function were assessed using the Musculoskeletal Tumor Society score (MSTS), and wrist function was assessed according to the disabilities of the arm, shoulder and hand (DASH) score. Data on surgical-related complications were recorded.

Results: All cases were followed up for 24-126 months (mean 60.69 ± 29.61 months). There were 24 patients with a Campanacci grade of 3 and 30 with a Campanacci grade of 2. The 52 patients were continuously disease-free. The local recurrence rate was 3.70% (2 patients). One patient had recurrence in the proximal femur, and the other developed in soft tissue of the calf muscle. No recurrence occurred for GCTB of the distal radius. One recurrence occurred in a GCTB with pathological fractures. The intervals were 9 and 28 months, respectively. The cases of recurrence all had a Campanacci grade of 3 (8.33%). The median MSTS among the 54 patients was 27.67 ± 3.81. The mean wrist function DASH score was 8.30 ± 2.53. The mean MSTS was 28.67 ± 1.63 and 26.71 ± 5.49 for patients with GCTB of the distal radius and for those with pathological fractures, respectively. In comparing patients with and without pathological fractures, there was no significant difference in the MSTS functional score. Five patients had complications after the surgery.

Conclusion: Curettage with adjuvant microwave ablation therapy provided favorable local control and satisfactory functional outcomes in the treatment of GCTB, especially for cases with pathological fractures and those with GCTB of the distal radius.
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http://dx.doi.org/10.1111/os.12865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862174PMC
February 2021

Similar Repair Effects of Human Placenta, Bone Marrow Mesenchymal Stem Cells, and Their Exosomes for Damaged SVOG Ovarian Granulosa Cells.

Stem Cells Int 2020 3;2020:8861557. Epub 2020 Dec 3.

Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing 100044, China.

Background: This study is aimed at investigating the repairing effect of mesenchymal stem cells and their exosomes from different sources on ovarian granulosa cells damaged by chemotherapy drugs-phosphoramide mustard (PM).

Methods: In this study, we choose bone marrow mesenchymal stem cells (BMSCs) and human placental mesenchymal stem cells (HPMSCs) for research. Then, they were cocultured with human ovarian granulosa cells (SVOG) injured by phosphoramide mustard (PM), respectively. -Galactosidase staining, flow cytometry, and Western blot were used to detect the changes in the senescence and apoptosis of SVOG cells before and after their coculture with the above two types of MSCs. Subsequently, exosomes from these two types of MSCs were extracted and added to the culture medium of SVOG cells after PM injury to test whether these two types of exosomes played a role similar to that of MSCs in repairing damaged SVOG cells.

Results: PM treatment-induced apoptotic SVOG cells were significantly decreased after HPMSCs and BMSCs as compared with control group. After coculturing with these two types of MSCs, PM-treated SVOG cells showed significantly reduced senescence and apoptosis proportions as well as cleaved-Caspase 3 expression, and HPMSCs played a slightly stronger role than BMSCs in repairing SVOG cells in terms of the above three indicators. In addition, the ratios of senescent and apoptotic SVOG cells were also significantly reduced by the two types of exosomes, which played a role similar to that of MSCs in repairing cell damages.

Conclusions: The results indicated that BMSCs, HPMSCs, and their exosomes all exerted a certain repair effect on SVOG cells damaged by PM, and consistent repair effect was observed between exosomes and MSCs. The repair effect of exosomes secreted from BMSCs and HPMSCs on the SVOG cells was studied for the first time, and the results fully demonstrated that exosomes are the key carriers for MSCs to play their role.
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http://dx.doi.org/10.1155/2020/8861557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738794PMC
December 2020

Feasibility of Controlling Metastatic Osseous Pain Using Three Kinds of Image-Guided Procedures for Thermal Microwave Ablation: A Retrospective Study.

Orthop Surg 2021 Feb 10;13(1):116-125. Epub 2020 Dec 10.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Objectives: To evaluate the feasibility and safety of treating painful osseous metastases using image-guided percutaneous thermal microwave ablation.

Methods: This is a retrospective study of patients treated from December 2016 to December 2019 in one institute. A total of 50 patients (35 men, 15 women; mean age 55.24 ± 11.03 years) with 56 osseous metastatic lesions underwent image-guided percutaneous microwave ablation. There were 7 patients with multiple and 43 patients with single metastases. The numbers of patients with primary cancer were as follows: lung, 13; liver, 17; kidney, 10; prostate, 1; breast, 3; osteosarcoma, 1; and thyroid, 5. Seventeen patients had cancer combined with soft tissue masses. The radiological images for the ablative procedures were obtained by CT, fluoroscopy with ultrasound, and fluoroscopy alone in 16, 11, and 23 patients, respectively. Pain severity was estimated using the visual analogue scale before and after treatment (1 week, 1 month, and 3 months after treatment). Radiological evaluations were performed at baseline and 3 months after the procedure.

Results: In all patients, pain reduction occurred from the first day after treatment. Pain did not recur during the 3 months of follow up. The mean total ablation time per microwave electrode was 3.99 ± 2.48 min (range, 1-15 min). The mean power of the microwave electrode was 66.40 ± 12.08 W. The average volume of bone (load-bearing bone, such as vertebra and acetabulum) cement after ablation was 2.82 ± 0.81 mL. There were no significant differences in visual analogue scale pain scores for different imaging techniques or ablation energies. No procedure-related complications occurred.

Conclusion: Image-guided percutaneous thermal microwave ablation of osseous metastases relieves pain and improves mobility. CT remains the first choice for percutaneous ablation. Fluoroscopy combined with ultrasound is effective for cases with soft tissue masses; fluoroscopy is also suitable for combination with vertebroplasty. However, further investigations are required.
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http://dx.doi.org/10.1111/os.12849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862186PMC
February 2021
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