Publications by authors named "Jianghui Dong"

35 Publications

Injectable gelatin microspheres loaded with platelet rich plasma improve wound healing by regulating early inflammation.

Int J Med Sci 2021 3;18(9):1910-1920. Epub 2021 Mar 3.

UniSA Clinical & Health Sciences, University of South Australia, Adelaide, SA 5001, Australia.

We investigated the potential of gelatin microspheres (GMs) loaded with platelet-rich plasma (PRP) to enhance their wound healing effect. Platelets from the PRP were immobilized onto GMs to form biomimetic bioreactor GM+PRP. The therapeutic effect of this agent was further investigated on a wound-healing model in rats. Wounds were locally injected with phosphate buffered saline (PBS), GM, PRP, and GM+PRP. Wound healing rate, vessel density, and inflammation level were measured histologically, by RT-PCR, and by Western blotting at days 3, 7, 14, and 21. Platelets on GM caused a continuous high release in both interleukin-10 and metalloproteinase-3 compared with PRP alone. Both GM+PRP and PRP successfully accelerated the wound healing process, while GM alone did not improve the wound healing process compared with the untreated control. Wounds treated with GM+PRP resulted in shorter healing period and improved dermal structure. GM+PRP improved angiogenesis in the wound by increasing expression of angiogenic factors. GM+PRP prolonged and enhanced the cytokine release profile compared with PRP. By promoting the inflammatory and angiogenic responses, GM+PRP has the potential to improve wound healing. Our findings demonstrate that GMs are an injectable carrier that enhanced the therapeutic effects of PRP.
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http://dx.doi.org/10.7150/ijms.51060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040391PMC
March 2021

Neuroprotective effect of magnesium supplementation on cerebral ischemic diseases.

Life Sci 2021 May 22;272:119257. Epub 2021 Feb 22.

College of Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, China. Electronic address:

Ischemic encephalopathy is associated with a high mortality and rate of disability. The most common type of ischemic encephalopathy, ischemic stroke, is the second leading cause of death in the world. At present, the main treatment for ischemic stroke is to reopen blocked blood vessels. However, despite revascularization, many patients are not able to achieve good functional results. At the same time, the strict time window (<4.5 h) of thrombolytic therapy limits clinical application. Therefore, it is important to explore effective neuroprotective drugs for the treatment of ischemic stroke. Magnesium is a natural calcium antagonist, which exerts neuroprotective effects through various mechanisms. However, while most basic studies have shown that magnesium supplementation can help treat cerebral ischemia, intravenous magnesium supplementation in large clinical trials has failed to improve prognosis of ischemic patients. Therefore, we review the basic and clinical studies of magnesium supplementation for cerebral ischemia. According to the route of administration, treatment can be divided into intraperitoneal magnesium supplementation, intravenous magnesium supplementation, arterial magnesium supplementation and intracranial magnesium supplementation. We also summarized the potential influencing factors of magnesium ion intervention in cerebral ischemia injury. Finally, in combination with influencing factors derived from basic research, this article proposes three future research directions, including magnesium supplementation into the circulatory system combined with magnesium supplementation in the lateral ventricle, magnesium supplementation in the lateral ventricle combined with hypothermia therapy, and lateral ventricle magnesium supplementation combined with intracarotid magnesium supplementation combined with selective hypothermia.
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http://dx.doi.org/10.1016/j.lfs.2021.119257DOI Listing
May 2021

Insights into protease sequence similarities by comparing substrate sequences and phylogenetic dynamics.

Math Biosci Eng 2020 12;18(1):837-850

College of Biotechnology, Guilin Medical University, Guilin 541004, China.

Based on substrate sequences, we proposed a novel method for comparing sequence similarities among 68 proteases compiled from the MEROPS online database. The rank vector was defined based on the frequencies of amino acids at each site of the substrate, aiming to eliminate the different order variances of magnitude between proteases. Without any assumption on homology, a protease specificity tree is constructed with a striking clustering of proteases from different evolutionary origins and catalytic types. Compared with other methods, almost all the homologous proteases are clustered in small branches in our phylogenetic tree, and the proteases belonging to the same catalytic type are also clustered together, which may reflect the genetic relationship among the proteases. Meanwhile, certain proteases clustered together may play a similar role in key pathways categorized using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Consequently, this method can provide new insights into the shared similarities among proteases. This may inspire the design and development of targeted drugs that can specifically regulate protease activity.
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http://dx.doi.org/10.3934/mbe.2021044DOI Listing
December 2020

Thoracic aorta stent grafts design in terms of biomechanical investigations into flexibility.

Math Biosci Eng 2020 12;18(1):800-816

School of Civil and Transportation Engineering, Guangdong University of Technology, Guangzhou 510006, China.

The present study aimed to design and optimize thoracic aorta stent grafts (SGs) based on the influence of geometric parameters on flexibility and durability. Five geometric parameters were selected, including strut height, strut number, strut radius, wire diameter, and graft thickness. Subsequently, 16 finite element (FE) models were established with an orthogonal design consisting of five factors and four levels. The influences of a single factor and all the geometric parameters' influence magnitude on the device flexibility were then determined. The results showed that all the other parameters had an opposite effect on global and local flexibility except for the wire diameter. The graft thickness exhibited the most remarkable impact on the global flexibility of SGs, while the strut radius influenced flexibility slightly. However, for the local flexibility analysis, the graft thickness became the least significant factor, and the wire diameter exerted the most significant influence. The SG with better global flexibility can be guided easily in the tortuous vessels, and better local flexibility improves the sealing effect between the graft and aortic arch. In conclusion, this study's results indicated that these geometric parameters exerted different influences on flexibility and durability, providing a strategy for designing thoracic aorta SGs, especially for the thoracic aortic arch diseases.
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http://dx.doi.org/10.3934/mbe.2021042DOI Listing
December 2020

Transanal and transabdominal combined endoscopic resection of rectal stenosis and anal reconstruction based on transanal endoscopic technique.

Surg Endosc 2021 Jan 4. Epub 2021 Jan 4.

Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.

Objective: To propose a method for the resection of the rectal anastomotic stenosis and anal reconstruction based on the transanal endoscopic technique through a transanal and transabdominal combined endoscopic resection, and to verify its clinical effectiveness.

Methods: Thirty-eight patients with anastomotic stenosis were admitted to the Sixth Affiliated Hospital, Sun Yat-sen University, China, from January 2016 to September 2019. Patients were divided into an experimental group (17 patients) and a control group (21 patients) subjected to the removal of the intestinal stenosis followed by anal reconstruction, they underwent transanal and transabdominal endoscopic surgery and traditional transabdominal surgery, respectively. Data on intraoperative blood loss, operation time, postoperative recovery, and prognosis were collected.

Results: (1) The median intraoperative blood loss was approximately 100 ml, without conversion to laparotomy during the surgery and intraoperative complications. The safety of the surgical operation was improved. (2) The operation time was shortened compared to previous reports, and the median operative time was 193 min. The average time of transanal endoscopic dissociation to the retroperitoneal fold was 76 min. (3) Laparoscopic assistance was carried out on 14 of the17 patients, and the incision was reduced. (4) The short-term curative effect was quite satisfactory, without permanent stoma. The average time to recover food intake after the surgery was 1.5 days. The average ambulation time was 3 days. Within 30 days after the surgery, one case suffered anastomotic leakage and then underwent refunctioning stoma through a second surgery. One patient suffered from intestinal obstruction, and the condition was improved through a conservative treatment. One case experienced delayed abdominal wound healing.

Conclusion: The transanal and transabdominal endoscopic resection of the rectal anastomotic stenosis and anal reconstruction reduced the difficulty of the surgery, improved its safety, shortened the operation time, decreased the operative complications, and enabled patients to recover well after surgery.
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http://dx.doi.org/10.1007/s00464-020-08188-xDOI Listing
January 2021

The immuno-reactivity of polypseudorotaxane functionalized magnetic CDMNP-PEG-CD nanoparticles.

J Cell Mol Med 2021 Jan 19;25(1):561-574. Epub 2020 Nov 19.

Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Guangdong Provincial Key Laboratory of Medical Biomechanics, Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

pH-magnetic dual-responsive nanocomposites have been widely used in drug delivery and gene therapy. Recently, a polypseudorotaxane functionalized magnetic nanoparticle (MNP) was developed by synthesizing the magnetic nanoparticles with cyclodextrin (CD) molecules (CDMNP) via polyethylene glycol (PEG) (CDMNP-PEG-CD). The purpose of this study was to explore the antigenicity and immunogenicity of the nanoparticles in vivo prior to their further application explorations. Here, nanoparticles were assessed in vivo for retention, bio-distribution and immuno-reactivity. The results showed that, once administered intravenously, CDMNP-PEG-CD induced a temporary blood monocyte response and was cleared effectively from the body through the urine system in mice. The introduction of β-CD and PEG/β-CD polypseudorotaxane on SiO magnetic nanoparticles (SOMNP) limited particle intramuscular dispersion after being injected into mouse gastrocnemius muscle (GN), which led to the prolonged local inflammation and muscle toxicity by CDMNP and CDMNP-PEG-CD. In addition, T cells were found to be more susceptible for β-CD-modified CDMNP; however, polypseudorotaxane modification partially attenuated β-CD-induced T cell response in the implanted muscle. Our results suggested that CDMNP-PEG-CD nanoparticles or the decomposition components have potential to prime antigen-presenting cells and to break the muscle autoimmune tolerance.
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http://dx.doi.org/10.1111/jcmm.16109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810964PMC
January 2021

Scoparone alleviates hepatic fibrosis by inhibiting the TLR-4/NF-κB pathway.

J Cell Physiol 2020 Oct 8. Epub 2020 Oct 8.

College of Pharmacy, Guilin Medical University, Guilin, Guangxi, China.

The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB; TLR-4/NF-κB) signals by inhibiting TLR-4, which in turn downregulates the expression of MyD88, promotes NF-κB inhibitor-α, NF-κB inhibitor-β, and NF-κB inhibitor-ε activation, while inhibiting NF-κB inhibitor-ζ. Subsequently, the decrease of phosphorylation of nuclear factor-κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR-4/NF-κB signals.
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http://dx.doi.org/10.1002/jcp.30083DOI Listing
October 2020

The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model.

Mol Med Rep 2020 Nov 21;22(5):3723-3734. Epub 2020 Aug 21.

Department of Respiratory and Critical Care Medicine, Chronic Airway Disease Laboratory, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510000, P.R. China.

The cellular and molecular mechanisms via which MK2206, an AKT inhibitor, prevents the activation of AKT in toluene diisocyanate (TDI)‑induced asthma remain unclear. Thus, the present study aimed to evaluate the potential effects of MK2206 on airway AKT activation, inflammation and remodeling in a TDI‑induced mouse model of asthma. A total of 24 BALB/c mice were selected and randomly divided into untreated (AOO), asthma (TDI), MK2206 (TDI + MK2206), and dexamethasone (TDI + DEX) groups. Phosphorylated AKT (p‑AKT), total AKT, airway remodeling indices, α‑smooth muscle actin (α‑SMA) and collagen I levels in pulmonary tissue were measured using western blotting. Airway inflammation factors, including interleukin (IL)‑4, ‑5, ‑6, and ‑13 in bronchoalveolar lavage fluid (BALF) and IgE in serum, were determined using ELISA. Additionally, the airway hyperresponsiveness (AHR) and pulmonary pathology of all groups were evaluated. The results of the present study demonstrated that p‑AKT levels in lung protein lysate were upregulated, and neutrophil, eosinophil and lymphocyte counts were increased in the lungs obtained from the asthma group compared with the AOO group. Both MK2206 and DEX treatment in TDI‑induced mice resulted not only in the attenuation of AKT phosphorylation, but also reductions in neutrophil, eosinophil and lymphocyte counts in the lungs of mice in the asthma group. Consistently, increases in the levels of the inflammatory cytokines IL‑4, ‑5, ‑6 and ‑13 analyzed in BALF, and serum IgE in the TDI group were demonstrated to be attenuated in the TDI + MK2206 and TDI + DEX groups. Furthermore, α‑SMA and AHR were significantly attenuated in the TDI + MK2206 group compared with the TDI group. These results revealed that MK2206 not only inhibited AKT activation, but also served a role in downregulating airway inflammation and airway remodeling in chemical‑induced asthma. Therefore, the findings of the present study may provide important insight into further combination therapy.
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http://dx.doi.org/10.3892/mmr.2020.11450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533517PMC
November 2020

Systemic inflammatory indices predict tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Oncol Lett 2020 Sep 3;20(3):2763-2770. Epub 2020 Jul 3.

Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China.

Systemic inflammatory responses are associated with the prognosis of patients with colorectal cancer. However, the value in predicting tumor responses to neoadjuvant chemoradiotherapy (nCRT) remains to be elucidated. The current study aimed to investigate the association between systemic inflammatory indices and pathological complete response (pCR). The training and validation cohorts included 225 and 96 patients with locally advanced rectal cancer. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio were recorded prior to nCRT and radical surgery. Univariate and multivariate analysis were used to investigate the association between systemic inflammatory indices and pCR. Systemic inflammatory indices prior to or following treatment had no significant association with pCR; however, the percentage change in NLR from pre-nCRT to post-nCRT was associated with a poor response, and a percentage change of >21.5% NLR (P=0.006; OR=0.413; 95% CI=0.22-0.773) was a predictor of poor pCR. Therefore, in rectal cancer, the percentage change in NLR from pre- to post-nCRT was found to be a predictor of poor pCR.
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http://dx.doi.org/10.3892/ol.2020.11812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400706PMC
September 2020

Photothermal therapy technology of metastatic colorectal cancer.

Am J Transl Res 2020 15;12(7):3089-3115. Epub 2020 Jul 15.

Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University Guangzhou 510655, Guangdong, China.

Colorectal cancer (CRC) is one of the most common malignancies. The current treatments of metastatic colorectal cancer (mCRC) are ineffective and the bottleneck problem. It is of significance to explore effective new therapeutic strategies to eradicate mCRC. Photothermal therapy (PTT) is an emerging technology for tumor therapy, with the potential in the treatment of mCRC. In this review, the current treatment approaches to mCRC including surgery, radiotherapy, chemotherapy interventional therapy, biotherapy, and photothermal therapy are reviewed. In addition, we will focus on the various kinds of nanomaterials used in PTT for the treatment of CRC both in vitro and in vivo models. In conclusion, we will summarize the combined application of PTT with other theranostic methods, and propose future research directions of PTT in the treatment of CRC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407689PMC
July 2020

Three-dimensional printing of patient-specific plates for the treatment of acetabular fractures involving quadrilateral plate disruption.

BMC Musculoskelet Disord 2020 Jul 10;21(1):451. Epub 2020 Jul 10.

Department of Hand Surgery, and Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Ningbo, 315040, China.

Background: Complicated acetabular fractures comprise the most challenging field for orthopedists. The purpose of this study was to develop three-dimensional printed patient-specific (3DPPS) Ti-6Al-4 V plates to treat complicated acetabular fractures involving quadrilateral plate (QLP) disruption and to evaluate their efficacy.

Methods: Fifty patients with acetabular fractures involving QLP disruption were selected between January 2016 and June 2017. Patients were divided into a control group (Group A, 35 patients) and an experimental group (Group B, 15 patients), and were treated by the conventional method of shaping reconstruction plates or with 3DPPS Ti-6AL-4 V plates, respectively. The efficacy of Ti-6AL-4 V plates was evaluated by blood loss, operative time, reduction quality, postoperative residual displacement, and complications.

Results: The operative time and blood loss in Group B were reduced compared to Group A, and the difference was statistically significant (P < 0.05). There was no significant difference in reduction quality between the two groups (P > 0.05). Reduction quality in Group B was anatomic in 10 (66.7%), satisfactory in four (26.7%), and poor in one (6.7%). In Group A, they were anatomic in 18 (51.4%), satisfactory in 13 (37.1%), and poor in four (11.4%). Residual displacement in Group B was less than that in Group A, and the difference was statistically significant (P < 0.05). In Group B, one case exhibited loosening of the pubic screw postoperatively. In Group A, there was one case of wound infection, one of deep vein thrombosis (DVT) in the ipsilateral lower limb, one case of traumatic arthritis and two obturator nerve injuries.

Conclusions: The 3DPPS Ti-6AL-4 V plate is a feasible, accurate and effective implant for acetabular fracture treatment.
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http://dx.doi.org/10.1186/s12891-020-03370-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350601PMC
July 2020

Bmi deficiency causes oxidative stress and intervertebral disc degeneration which can be alleviated by antioxidant treatment.

J Cell Mol Med 2020 08 24;24(16):8950-8961. Epub 2020 Jun 24.

Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

The transcriptional repressor Bmi-1 is involved in cell-cycle regulation and cell senescence, the deficiency of which has been shown to cause oxidative stress. This study investigated whether Bmi-1 deficiency plays a role in promoting disc degeneration and the effect of treatment with antioxidant N-acetylcysteine (NAC) on intervertebral disc degeneration. Bmi-1 mice were treated with the antioxidant NAC, supplied in drinking water (Bmi-1 +NAC). For in vitro experiments, mouse intervertebral discs were cultured under low oxygen tension and serum-limiting conditions in the presence of tumour necrosis factor α and interleukin 1β in order to mimic degenerative insult. Disc metabolism parameters in these in vitro and in vivo studies were evaluated by histopathological, immunohistochemical and molecular methods. Bmi-1 mice showed lower collagen Ⅱ and aggrecan levels and higher collagen Ⅹ levels than wild-type and Bmi-1 +NAC mice. Bmi-1 mice showed significantly lower superoxide dismutase (SOD)-1, SOD-2, glutathione peroxidase (GPX)-1 and GPX-3 levels than their wild-type littermates and Bmi-1 + NAC mice. Relative to Bmi-1 mice, the control and Bmi-1 +NAC mice showed significantly lower p16, p21, and p53 levels. These results demonstrate that Bmi-1 plays an important role in attenuating intervertebral disc degeneration in mice by inhibiting oxidative stress and cell apoptosis.
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http://dx.doi.org/10.1111/jcmm.15528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417700PMC
August 2020

Targeting and imaging colorectal cancer by activatable cell-penetrating peptides.

Am J Transl Res 2020 15;12(5):1754-1766. Epub 2020 May 15.

Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University Guangzhou 510655, Guangdong, China.

While it has been a great challenge to determine the positive status of metastasis lesions, intraoperative tumor imaging, which can show tumor localization and facilitate intraoperative staging of nodal metastases, have enabled surgeons to quickly and accurately perform radical resections. However, to date, there is no accurate method for evaluating nodal status intraoperatively. In this study, we synthesized activatable cell-penetrating peptides (ACPPs) that can specifically recognize colorectal cancer and their nodal status. ACPPs were labeled with Cy5 dye at the C-terminal, and named ACPP-Cy5. Laser scanning confocal microscopy and flow cytometry were used to measure the change in intracellular fluorescence intensity between cancer cells and normal cells. The results showed while the intracellular Cy5 fluorescent intensity can be visualized in both cancer and normal cells by 8 h after adding ACPP-Cy5, the relative fluorescence intensity of colorectal cancer cells was significantly higher than the normal cells. In addition, IVIS spectrum imaging system was used to observe the fluorescence intensity of ACPP-Cy5 after tail vein injection of mice with subcutaneous tumor or orthotopic colorectal cancer and liver metastasis. We found in mice with colorectal cancer and liver metastasis the Cy5 fluorescence intensity of cancer was significantly increased compared to the organs including liver, colorectum, lung, spleen, and heart. It is demonstrated here, this ACPPs can target colorectal cancer and liver metastasis, therefore ACPP-Cy5 may be a promising tool used for the diagnoses of colorectal cancer and to assist in tumor localization during surgery.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270030PMC
May 2020

Pure perforator free sensory proximal ulnar artery perforator flap for resurfacing hand defects.

J Int Med Res 2020 May;48(5):300060520922396

Department of Hand Surgery, Ningbo No. 6 Hospital, Ningbo, China.

Objective: This prospective study was performed to investigate the distribution of proximal ulnar artery perforating vessels through three-dimensional blood vessel reconstruction and examine the presence and consistency of the perforating vessels intraoperatively.

Methods: For anatomical guidance, three-dimensional blood vessel reconstruction was performed to determine the consistent presence of perforating vessels in the proximal ulnar artery. A free proximal ulnar artery perforator flap was then transferred in 17 patients to resurface skin defects on the hands. Color Doppler ultrasound was used to identify and mark the perforating vessels. Intraoperative evaluation was conducted to check for anastomosis of the perforating vessels at the marked sites and assess the vessel anastomosis conditions.

Results: No vascular crisis, flap necrosis, or wound infection occurred after surgery in 15 patients. Postoperative follow-up was conducted for 6 to 36 months. The appearance of the flap was satisfactory, the texture of the flap was soft, sensation was well restored, and hand function was not limited. The mean two-point discrimination of the flap was 7.6 ± 2.2 mm.

Conclusions: Free sensory proximal ulnar artery perforator flap transfer is a safe and reliable surgical technique with respect to restoration of both the appearance and sensory function of the hand.
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http://dx.doi.org/10.1177/0300060520922396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278109PMC
May 2020

Comparative biomechanical testing of customized three-dimensional printing acetabular-wing plates for complex acetabular fractures.

Adv Clin Exp Med 2020 Apr;29(4):459-468

The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.

Background: Three-dimensional (3D) printing of an acetabular wing-plate is a new minimally invasive surgical technique for complex acetabular fractures.

Objectives: To investigate the biomechanical stability of 3D printing acetabular wing-plates. The results were compared with 2 conventional fixation systems.

Material And Methods: Eighteen fresh frozen cadaveric pelvises with both column fractures were randomly divided to 3 groups: A - iliosciatic plates fixation system; B - 3D printing plates; C - 2 parallel reconstruction plates fixation system. These constructions were loaded onto a biomechanical testing machine. Longitudinal displacement and stiffness values of the constructs were measured to estimate their stability.

Results: When the load force reached 700 N, Group A was superior to Group B in the longitudinal displacement of point 1 (p > 0.05). The longitudinal displacement of point 2 showed no significant differences among Groups A, B and C, and the displacement of the fracture line over point 3 showed no significant differences between Groups A and B (p > 0.05). The axial stiffness of Groups A, B and C were 122.4800 ±8.8480 N/mm, 168.4830 ±14.8091 N/mm and 83.1300 ±3.8091 N/mm, respectively. Group B was significantly stiffer than A and C (p < 0.05). Loads at failure of internal fixation were 1378.83 ±34.383 N, 1516.83 ±30.896 N and 1351.00 ±26.046 N for Groups A, B and C, respectively. Group B was significantly superior to Groups A and C (p > 0.05).

Conclusions: Customized 3D printing acetabular-wing plates provide stability for acetabular fractures compared to intraspecific buttressing fixation.
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http://dx.doi.org/10.17219/acem/116749DOI Listing
April 2020

Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR-4/NF-κB and AMPK/Nrf2 signalling pathways.

J Cell Mol Med 2020 06 26;24(11):6397-6409. Epub 2020 Apr 26.

College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China.

The purpose of this study was to alleviate liver disturbance by applying polysaccharides from Dicliptera chinensis (DCP) to act on the adenosine monophosphate-activated protein kinase/ nuclear factor erythroid 2-related factor 2 (AMPK/ Nrf2) oxidative stress pathway and the Toll-like receptor 4 (TLR-4)/ nuclear factor kappa-B (NF-κB) inflammatory pathway and to establish an in vivo liver disturbance model using male C57BL/6J and TLR-4 knockout ( ) mice. For this, we evaluated the expression levels of SREBP-1 and Nrf2 after silencing the expression of AMPK using siRNA technology. Our results show that with regard to the TLR-4/ NF-κB inflammatory pathway, DCP inhibits TLR-4, up-regulates the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduces the expression of phospho(p)-NF-κB and leads to the reduction of downstream inflammatory factors, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β, thereby inhibiting the inflammatory response. Regarding the AMPK/ Nrf2 oxidative stress pathway, DCP up-regulates the expression of p-AMPK and Nrf2, in addition to regulating glucose and lipid metabolism, oxidative stress and ameliorating liver disturbance symptoms. In summary, our study shows that DCP alleviates liver disturbances by inhibiting mechanisms used during liver inflammation and oxidative stress depression, which provides a new strategy for the clinical treatment of liver disturbance.
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http://dx.doi.org/10.1111/jcmm.15286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294158PMC
June 2020

The Expression of GLAST and GLT1 in a Transient Cerebral Ischemia Mongolian Gerbil Model.

Neuropsychiatr Dis Treat 2020 23;16:789-800. Epub 2020 Mar 23.

Department of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin, Guangxi 541004, People's Republic of China.

Purpose: Excitatory amino acid transporters (EAATs) have an indispensable function in the reuptake of extracellular glutamate. To investigate the relationship and the expression of neuronal and astrocytic markers after brain ischemia, the temporal profile of glial EAATs in both peripheral and core regions of the cortex was examined.

Methods: Transient common carotid artery occlusion was used to induce unilateral transient forebrain ischemia of Mongolian gerbils, and post-ischemic brains (6 h to 2 w) were collected and prepared for immunohistochemical and Western blotting analysis of glutamine synthetase (GS), GLT-1, GLAST, S100β, and NeuN, and for Alizarin red staining of calcium deposits.

Results: The expression of GLAST and GLT-1 were significantly escalated at 6 h both in the core and periphery regions, while reduced from 12 h to 2 w in the core region post-ischemia. GS-positive cells increased at 6 h both in the core and periphery regions, while the density of Alizarin red-positive cells increased and peaked at 12 h in the ischemic cortex. The density of S100β-positive cells decreased in the ischemic core and increased in the periphery region. Immunofluorescence staining showed that S100β and TUNEL double-positive cells increased at 12 h in the core region.

Conclusion: The results of GLT-1 and GLAST expression in the cortex indicate that their up-regulation was time-dependent and occurred in the acute post-ischemia period, whereas their down-regulation was region-dependent and it is involved in the pathological progress of nerve cell and glial cell death, and has a series of cascade reactions.
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http://dx.doi.org/10.2147/NDT.S238455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125407PMC
March 2020

Repair Method for Complete High Ulnar Nerve Injury Based on Nerve Magnified Regeneration.

Ther Clin Risk Manag 2020 3;16:155-168. Epub 2020 Mar 3.

Department of Hand Surgery, Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Ningbo 315040, People's Republic of China.

Purpose: Complete high ulnar nerve injury can cause serious sequelae, including residual sensation and loss of movement and especially dysfunction of the intrinsic muscles of the hand. As a solution to treat complete high ulnar nerve injury, we proposed a new repair method for ulnar nerve injury based on nerve-magnified regeneration.

Methods: Twenty-two patients with complete division of the ulnar nerve at a high level who were treated from May 2013 to December 2016 were divided into two groups. The proposed repair method for complete high ulnar nerve injury was performed in group I (11 patients), while the traditional repair method, ie, repair of the original injury site of the ulnar nerve, was used in group II (11 patients).

Results: The results showed no significant difference in the mean sensory scores assigned by the Highet-Zachary scheme (the Highet Scale) between the two groups. The mean Highet Scale score of muscle strength for the first dorsal interosseus muscle was significantly better in group I than that in group II (p=0.010). In group I, 10 of 11 patients were graded as M4 or M5. Grip strength, pinch strength, and the Disabilities of the Arm, Shoulder, and Hand (DASH) score were significantly better in group I than those in group II (p<0.01).

Conclusion: Therefore, this method for complete high ulnar nerve injury based on nerve-magnified regeneration can shorten the path of motor nerve regeneration, effectively reduce atrophy of the intrinsic muscles of the hand, and provide better hand function.
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http://dx.doi.org/10.2147/TCRM.S237851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060778PMC
March 2020

Phosphorylation of Tau and α-Synuclein Induced Neurodegeneration in MPTP Mouse Model of Parkinson's Disease.

Neuropsychiatr Dis Treat 2020 4;16:651-663. Epub 2020 Mar 4.

Department of Hand Surgery, Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Ningbo 315040, People's Republic of China.

Purpose: Parkinson's disease (PD) is the second most common neurodegenerative disease. The α-Synuclein is a major component of Lewy bodies and Lewy neurites, the pathologic hallmark of PD. It is known that α-Synuclein is phosphorylated (p-α-Synuclein) in PD and tau-hyperphosphorylation (p-Tau) is also a pathologic feature of PD. However, the relationship between p-Synuclein and p-Tau in PD is not clear, in particular in the MPTP model of PD. The purpose of this study was to reveal their relationship in the mouse MPTP model.

Methods: Firstly, the p-α-Synuclein, α-Synuclein, p-Tau and Tau protein levels were analyzed. Then, GSK3β activation was determined using immunoblot and immunohistochemical staining. Finally, the dopaminergic neurodegeneration was assessed using Tyrosine Hydroxylase (TH) staining and retrograde labeling and microglial marker were labeled. Microglial activation and nigrostriatal pathway degeneration were observed.

Results: The results showed that p-α-Synuclein, α-Synuclein, p-Tau and Tau were upregulated in both hippocampus and substantia nigra of the PD mouse model. Furthermore, p-α-Synuclein and p-Tau were localized in the same regions of substantial nigra (SN) and dentate gyrus (DG) of hippocampus (Hippo). The activated form of GSK3β (phosphor GSK3β Y216) was increased in multiple brain areas. The GSK3β inhibitor AZD1080 injected in MPTP mice suppressed the expression of p-Tau and p-GSK3β and improved motor functions.

Conclusion: These findings revealed that p-α-Synuclein and p-Tau proteins are key pathological events leading to neurodegeneration and motor dysfunctions in the mouse MPTP model of PD. Our data suggest that the interference with the GSK3β activity may be an effective approach for the treatment of PD.
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http://dx.doi.org/10.2147/NDT.S235562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061418PMC
March 2020

p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle.

Elife 2020 03 3;9. Epub 2020 Mar 3.

Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

The cell cycle regulator p16 is known as a biomarker and an effector of aging. However, its function in intervertebral disc degeneration (IVDD) is unclear. In this study, p16 expression levels were found to be positively correlated with the severity of human IVDD. In a mouse tail suspension (TS)-induced IVDD model, lumbar intervertebral disc height index and matrix protein expression levels were reduced significantly were largely rescued by p16 deletion. In TS mouse discs, reactive oxygen species levels, proportions of senescent cells, and the senescence-associated secretory phenotype (SASP) were all increased, cell cycling was delayed, and expression was downregulated for Sirt1, superoxide dismutase 1/2, cyclin-dependent kinases 4/6, phosphorylated retinoblastoma protein, and transcription factor E2F1/2. However, these effects were rescued by p16 deletion. Our results demonstrate that p16 plays an important role in IVDD pathogenesis and that its deletion attenuates IVDD by promoting cell cycle and inhibiting SASP, cell senescence, and oxidative stress.
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http://dx.doi.org/10.7554/eLife.52570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065909PMC
March 2020

Cannulated iliac screw fixation combined with reconstruction plate fixation for Day type II crescent pelvic fractures.

J Int Med Res 2020 Jan;48(1):300060519896120

Department of Hand Surgery, Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Ningbo, China.

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http://dx.doi.org/10.1177/0300060519896120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114278PMC
January 2020

Propeller perforator flaps from the dorsal digital artery perforator chain for repairing soft tissue defects of the finger.

BMC Surg 2019 Dec 11;19(1):188. Epub 2019 Dec 11.

Department of Hand Surgery, Ningbo No. 6 Hospital, Ningbo, 315040, China.

Background: When restoring the appearance and function of the fingers, hand surgeons face a challenge in choosing a suitable surgical method to repair finger skin defects.

Methods: In this study, we designed a long elliptical flap based on a propeller perforator flap and located slightly toward the dorsal lateral aspect of the finger. The flap with a pedicle consisting of the dorsal perforator of the distal digital artery and dorsal digital artery perforator chain is rotated to cover a large wound on the distal end. From December 2014 to December 2017, 10 patients with finger soft tissue defects were treated with the propeller perforator flap described in this study.

Results: All flaps survived after surgery, and 2 had a transient venous congestion. After a follow-up period of 3 to 12 months, the static two-point discrimination of the flap was 8.06 ± 1.75 mm, and the range of motion was 149.4 ± 12.9°. This designed flap can span several angiosomes supplied by the perforators. Due to the inclusion of a vessel chain between the dorsal digital artery perforators, the length-to-width ratio of the flap can be up to 3:1.

Conclusions: This technique increases the size of flap that can be harvested safely while retaining a reliable blood supply. The present study describes a new method for repairing soft tissue defects of the finger by using the technique of propeller perforator flaps based on dorsal digital artery perforator chains.

Trial Registration: The registration number of this study is ChiCTR1800014588; it has been retrospectively registered with Chinese Clinical Trial Registry (chictr.org.cn), 18/11/2019.
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http://dx.doi.org/10.1186/s12893-019-0649-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907148PMC
December 2019

Hydrocortisone Suppresses Early Paraneoplastic Inflammation And Angiogenesis To Attenuate Early Hepatocellular Carcinoma Progression In Rats.

Onco Targets Ther 2019 8;12:9481-9493. Epub 2019 Nov 8.

School of Pharmacy and Medical Sciences, and UniSA Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia.

Background: Inflammation is implicated in both hepatic cirrhosis development and hepatocellular carcinogenesis, and treatment with long-acting glucocorticoid dexamethasone prevented liver carcinogenesis in mice. However, it is unclear whether glucocorticoids have anti-inflammatory effect on hepatocellular carcinoma (HCC) and if short-acting glucocorticoids (with fewer adverse effects) inhibit paraneoplastic inflammation and HCC progression.

Methods: To investigate whether different types of anti-inflammatory agents attenuate HCC progression, the current study compared effects of treatments with hydrocortisone (a short-acting glucocorticoid) or aspirin on HCC progression. HCC was induced in diethylnitrosamine-treated rats which were randomly divided into 4 groups (n=8), respectively receiving orally once daily vehicle, glucuronolactone, glucuronolactone+hydrocortisone, and glucuronolactone+aspirin. Diethylnitrosamine (DEN) was given to rats in drinking water (100mg/L) to induce HCC. At weeks 12 and 16 post-induction, effects were compared on HCC nodule formation, microvessel density, and macrophage infiltration, and levels of paraneoplastic protein expression of tumor necrosis factor (TNF)-α, p38 mitogen-activated protein kinase (p38), phosphorylated p38 (p-p38), nuclear factor (NF)-κB, interleukin (IL)-10, hepatocyte growth factor (HGF), transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF).

Results: Compared to the model and glucuronolactone alone groups, HCC nodule number and microvessel density in the glucuronolactone+hydrocortisone group were significantly lower at week 12. At week 12 but not week 16, significantly lower levels of macrophages, TNF-α, p-p38, NF-κB, IL-10, HGF, TGF-β1 and VEGF were observed in the paraneoplastic tissue of the glucuronolactone+hydrocortisone group when compared with the control and glucuronolactone groups.

Conclusion: The results suggest that hydrocortisone treatment reduces macrophage polarization, expression of inflammatory and anti-inflammatory cytokines, and angiogenesis in paraneoplastic tissue, and attenuates early HCC progression. Although hydrocortisone did not have attenuation effect on advanced solid tumor, the current study shows the potential benefits and supports potential clinical use of hydrocortisone in attenuating early progression of HCC, which is through suppressing paraneoplastic inflammation and angiogenesis.
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http://dx.doi.org/10.2147/OTT.S224618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850701PMC
November 2019

Treatment Of Magnesium-L-Threonate Elevates The Magnesium Level In The Cerebrospinal Fluid And Attenuates Motor Deficits And Dopamine Neuron Loss In A Mouse Model Of Parkinson's disease.

Neuropsychiatr Dis Treat 2019 11;15:3143-3153. Epub 2019 Nov 11.

Department of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541004, Guangxi, People's Republic of China.

Purpose: Epidemiology research has demonstrated that magnesium (Mg) deficiency is associated with a high incidence of Parkinson's disease (PD). It is known that the systemic administration of MgSO is not able to elevate the Mg concentration in cerebrospinal fluid (CSF). This study aims to verify the protective effect of magnesium-L-threonate (MgT) in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model.

Methods: C57BL/6J mice were orally administered MgT or MgSO for 4 weeks, and received MPTP in the third week. After analysis of open-field and rotarod tests on the last day, tyrosine hydroxylase (TH) immunopositive cells and protein levels were quantified in the substantia nigra pars compacta (SNpc) and striatum. The expression of inducible nitric oxide synthase (iNOS) level was evaluated. Mg concentration in serum and CSF was measured after oral administration of MgSO or MgT in normal mice. Mg concentration in the CSF was increased in the mice treated with MgT but not MgSO.

Results: The total distance and mean speed in open-field tests, and the time spent on rotarod in the MgT group were increased, compared with MPTP group. The MgT treatment but not MgSO dose-dependently attenuated the loss of TH-positive neurons, and the reduction of the TH expression in the SNpc. The MgT treatment also inhibited the expression of iNOS as measured by immunohistochemistry and Western blots. Double-immunofluorescence staining of TH and iNOS showed iNOS-positive cells were collocalized for TH-positive cells.

Conclusion: The treatment with MgT is associated with an increase of Mg in the CSF. MgT, rather than MgSO4, can significantly attenuate MPTP-induced motor deficits and dopamine (DA) neuron loss.
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http://dx.doi.org/10.2147/NDT.S230688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857673PMC
November 2019

Calmodulin-dependent signalling pathways are activated and mediate the acute inflammatory response of injured skeletal muscle.

J Physiol 2019 11 10;597(21):5161-5177. Epub 2019 Oct 10.

Guangdong Provincial Key Laboratory of Medical Biomechanics, Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.

Key Points: There is a close relationship between skeletal muscle physiology and Ca /calmodulin (CaM) signalling. Despite the effects of Ca /CaM signalling on immune and inflammatory responses having been extensively explored, few studies have investigated the role of CaM pathway activation on the post-injury muscle inflammatory response. In this study, we investigated the role of CaM-dependent signalling in muscle inflammation in cardiotoxin induced myoinjuries in mice. The Ca /calmodulin-dependent protein kinase II (CaMII), Ca /calmodulin-dependent protein kinase IV (CaMKIV), and nuclear factor of activated T cells (NFAT) pathways are likely to be simultaneously activated in muscle cells and in infiltrating lymphocytes and to regulate the immune behaviours of myofibres in an inflammatory environment, and these pathways ultimately affect the outcome of muscle inflammation.

Abstract: Calcium/calmodulin (Ca /CaM) signalling is essential for immune and inflammatory responses in tissues. However, it is unclear if Ca /CaM signalling interferes with muscle inflammation. Here we investigated the roles of CaM-dependent signalling in muscle inflammation in mice that had acute myoinjuries in the tibialis anterior muscle induced by intramuscular cardiotoxin (CTX) injections and received intraperitoneal injections of either the CaM inhibitor calmidazolium chloride (CCL) or CaM agonist calcium-like peptide 1 (CALP1). Multiple inflammatory parameters, including muscle autoantigens and toll-like receptors, mononuclear cell infiltration, cytokines and chemokines associated with peripheral muscle inflammation, were examined after the injury and treatment. CALP1 treatment enhanced intramuscular infiltration of monocytes/macrophages into the damaged tibialis anterior muscle and up-regulated mRNA and protein levels of muscle autoantigens (Mi-2, HARS and Ku70) and Toll-like receptor 3 (TLR3), and mRNA levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), Monocyte chemoattractant protein-1 (MCP1), Monocyte chemoattractant protein-3 (MCP3) and Macrophage inflammatory protein-1(MIP-1α) in damaged muscle. In contrast, CCL treatment decreased the intramuscular cell infiltration and mRNA levels of the inflammatory mediators. After CALP1 treatment, a substantial up-regulation in Ca /calmodulin-dependent protein kinase II (CaMKII), Ca /calmodulin-dependent protein kinase IV (CaMKIV) and nuclear factor of activated T cells (NFAT) activity was detected in CD45 cells isolated from the damaged muscle. More pro-inflammatory F4/80 Ly-6C cells were detected in CD45-gated cells after CALP1 treatment than in those after CCL treatment or no treatment. Consistently, in interferon-γ-stimulated cultured myoblasts and myotubes, CALP1 treatment up-regulated the activities of CaMKII, CaMKIV and NFAT, and levels of class I/II major histocompatibility complexes (MHC-I/II) and TLR3. Our findings demonstrated that CaM-dependent signalling pathways mediate the injury-induced acute muscle inflammatory response.
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http://dx.doi.org/10.1113/JP278478DOI Listing
November 2019

An enhanced staining method K-B-2R staining for three-dimensional nerve reconstruction.

BMC Neurosci 2019 07 8;20(1):32. Epub 2019 Jul 8.

Department of Hand Surgery, Ningbo No. 6 Hospital, Ningbo, 315040, China.

Background: Three-dimensional (3D) reconstruction of human peripheral nerves, as a useful tool to understand the nerve internal information and functional basis, has become an important area of research in the peripheral nerve field.

Methods: In this study, we proposed a two-dimensional (2D) Karnovsky-Roots toluidine blue ponceau 2R (K-B-2R) staining method based upon conventional Karnovsky-Roots staining. It significantly improved the ability to display nerve fascicles, motor and sensory nerve fiber textures. In this method, Karnovsky-Roots staining was carried out, followed by toluidine blue counterstain and ponceau 2R counterstain.

Results: Comparisons were conducted between the three methods in staining of median nerve sections, which showed similar distribution characters in acetylcholinesterase-positive sites. The additional counterstaining did not change the basis of Karnovsky-Roots staining. However, the resulting images from this new method significantly facilitated the subsequent 3D nerve reconstruction and 3D printing.

Conclusions: These results show that the new staining method significantly enhanced the display qualities of nerve fascicle edges and fiber textures of motor and sensory nerves and facilitated 3D nerve reconstruction.
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http://dx.doi.org/10.1186/s12868-019-0515-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615204PMC
July 2019

Computational Modeling of Bone Cells and Their Biomechanical Behaviors in Responses to Mechanical Stimuli.

Crit Rev Eukaryot Gene Expr 2019 ;29(1):51-67

Department of Hand surgery, Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Ningbo, 315040, China; School of Pharmacy and Medical Sciences, and UniSA Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia.

Bone cells, including osteoblasts, osteoclasts, and osteocytes, have the ability to develop and maintain bone architecture. Although improved experimental testing approaches are increasing our understanding of the complex structures and functions of bone cells and bone, computational models, particularly finite element analyses, are being used to extend this knowledge and to develop a more theoretical understanding of bone cell behaviors. There are many challenges to developing an accurate and validated computational model due to the complex structure and biomechanical behaviors of the bone cells and bone tissue. A better understanding of the geometry and material properties of bone cells and bone will improve our understanding of the bone's biomechanical behaviors. In this review, we summarize and discuss the different geometric representations and material properties that have been used to model the bone cells. The current status of computational models, a comprehensive overview of the modeling methods for the bone cells, and the challenges for validating the models are presented.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2019025150DOI Listing
December 2019

Preparation of adriamycin gelatin microsphere-loaded decellularized periosteum that is cytotoxic to human osteosarcoma cells.

J Cell Physiol 2019 07 27;234(7):10771-10781. Epub 2018 Nov 27.

Department of Hand Surgery, Ningbo No. 6 Hospital, Ningbo, China.

The purpose of this study was to develop a novel approach to treat bone osteosarcoma using a multipurpose scaffold aiming for local drug delivery. The slowly releasing microspheres was designed to deliver the chemotherapy drug adriamycin (ADM) and a decellularized (D) periosteum scaffold (which is known to be able to promote bone regeneration) was used to carry these microspheres. D-periosteum was obtained by physical and chemical decellularization. Histological results showed that the cellular components were effectively removed. The D-periosteum showed an excellent cytocompatibility and the ability to promote adhesion and growth of fibroblasts. Two kinds of slowly releasing microspheres, adriamycin gelatin microspheres (ADM-GMS) and adriamycin poly (dl-lactide-co-glycolide) gelatin microspheres (ADM-PLGA-GMS), were prepared and anchored to D-periosteum, resulting in two types of drug-releasing regenerative scaffolds. The effectiveness of these two scaffolds in killing human osteosarcoma cells was tested by evaluating cell viability overtime of the cancer cells cultured with the scaffolds. In summary, a gelatin/decellularized periosteum-based biologic scaffold material was designed aiming for local delivery of chemotherapy drugs for osteosarcoma, with the results showing ability of the scaffolds in sustaining release of the cancer drug and in suppressing growth of the cancer cells in vitro.
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http://dx.doi.org/10.1002/jcp.27753DOI Listing
July 2019

Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer.

J Cell Physiol 2019 05 14;234(5):7032-7039. Epub 2018 Oct 14.

Department of Hand Surgery, Department of Plastic Reconstructive Surgery, Ningbo No. 6 Hospital, Zhejiang, China.

Long noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value. Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT-PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc-small-nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set. Furthermore, in the expanded validation set, high expression of lnc-SNHG15 was significantly associated with lymph-node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA-SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003). Multivariate analyses demonstrated that lncRNA-SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Cox's regression: 2.731). Lnc-SNHG15 overexpression was significantly associated with CLM and high-expression of lnc-SNHG15 in CRC was an independent predictor of poor survival.
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http://dx.doi.org/10.1002/jcp.27456DOI Listing
May 2019

Associations between the cyclooxygenase-2 expression in circulating tumor cells and the clinicopathological features of patients with colorectal cancer.

J Cell Biochem 2019 04 27;120(4):4935-4941. Epub 2018 Sep 27.

UniSA Cancer Research Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.

While previous studies have shown that the number of circulating tumor cells (CTCs) alone is not sufficient to reflect tumor progression and that cyclooxygenase-2 (COX-2) expression is correlated with colorectal cancer (CRC) metastasis, COX-2 expression status and its potential functions in CTCs of CRC patients are unknown. Here, epithelial-mesenchymal transition (EMT) phenotype-based subsets of CTCs and the COX-2 expression status in CTCs were identified and their potential clinical values were assessed in 91 CRC patients. CTCs were enumerated in peripheral blood and subsets of CTCs (epithelial [eCTCs], mesenchymal [mCTCs], and biophenotypic [bCTCs]) and the COX-2 expression status were determined using the RNA in situ hybridization method. CTCs were detected in 80.2% (73 of 91) patients. Neither the total CTC nor eCTC numbers were found to significantly associate with any of the clinicopathological features. However, the number of mCTCs was significantly associated with distance metastasis (P = 0.035) and had a trend of being associated with lymph node metastasis ( P = 0.055). Among the 73 patients enrolled for evaluating COX-2 expression, 52.5% (38 of 73) were found to express COX-2 in CTCs, and COX-2 expression in CTCs was not found to associate with the clinicopathological factors. However, COX-2 expression in mCTCs tended to have a higher rate in patients with metastasis compared with those without metastasis (72.0% vs 42.8%; P = 0.072). Furthermore, COX-2 expression and mCTC marker expression correlated positively ( R = 0.287; P = 0.017). Further studies are required to investigate the clinical value of the expression of COX-2 in mCTCs, especially in CRC patients with the advanced tumor stage and distant metastasis.
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http://dx.doi.org/10.1002/jcb.27768DOI Listing
April 2019