Achilles tendon thickening does not affect elasticity and functional outcome after surgical repair of Achilles rupture: A retrospective study.

PURPOSE: Previous studies have confirmed that Achilles tendon occurs Achilles thickening after repair surgery of the rupture. Although this mechanism has been elucidated in the laboratory, there are few reports on its impact on clinical function. We designed a retrospective study to investigate the Achilles thickening after Achilles tendon rupture repair and its correlation between the elasticity and postoperative function. METHODS: In this retrospective analysis, patients who underwent surgical treatment for acute Achilles tendon rupture from April 2016 to April 2020 were included. All the patients were regularly followed up at 3 months, 1 year, and 2 years after surgery. American Orthopaedic Foot Ankle Surgeon (AOFAS) scale and Leppilahti score were used to evaluate functional outcomes. Achilles elasticity was measured by ultrasound shear wave of elasticity. Achilles thickening was calculated as maximal transverse and longitudinal diameter in cross-sectional plane of magnetic resonance scan. Sample t-tests was used for different follow-up periods. Correlation between Achilles thickening and other factors were analyzed using Pearson's method. p < 0.05 indicates a statistically significant difference. RESULTS: AOFAS scale and Leppilahti score at 1 year were significantly higher than at 3 months postoperatively (both p < 0.001). These functional scales were also improved at 2-year follow-up significantly (both p < 0.001). The dorsiflexion difference showed gradually recovery in each follow-up period (t = -17.907, p < 0.001). The elasticity of the Achilles appeared to continuously decreases during the postoperative follow-up period in all position sets (p < 0.001). In thickening evaluation, the cross-sectional area of the thickest plane of Achilles was significantly higher at 1 year postoperatively (310.5 ± 25.2) mm2 than that at 3 months postoperatively ((278.0 ± 26.2) mm2, t = -8.219, p < 0.001) and became thinner in 2-year magnetic resonance scan ((256.1 ± 15.1) mm2, t = 16.769, p < 0.001). The correlations between Achilles thickening, elasticity, and functional outcome did not show statistical significance (p > 0.05) in every follow-up period. CONCLUSION: Achilles tendon thickens after surgery in the 1st year, but begins to gradually return to thinning about 2 years after surgery. There was no significant correlation between the increase and decrease of thickening and the patients' clinical function scores, Achilles elasticity, and bilateral ankle dorsiflexion difference.

Two new degrade triterpenoids from Buxus bodinieri Levl.

Two new degrade cycloartane triterpenoids, named buboditones A, B (1, 2), together with ten known alkaloids, cyclobuxoviridine (3), N-dimethylcycloxobuxovircine (4), cyclovirobuxine C (5), cyclovirobuxine A (6), cycloprotobuxine C (7), cycloprotobuxine A (8), cyclobuxoxazine (9), cyclobuxoxazine A (10), buxruguline B (11), irehine (12), were isolated from the leaves and stems of Buxus bodinieri Levl., The structures of compounds 1-2 were elucidated by 1 D and 2 D NMR spectroscopic methods including HSQC, HMBC, 1H-1H COSY, NOESY, as well as HRESIMS spectroscopic analysis.

[To explore mechanism of Scabiosa comosa against liver fibrosis based on pharmacodynamics and network pharmacology].

This study aims to systematically elucidate the pharmacodynamics and network pharmacological mechanism of Mongolian medicinal plants Scabiosa comosa, explore their key targets and related pathways, and further clarify the mechanism of the plants in treating liver fibrosis. Wistar rats were assigned into the blank group, carbon tetrachloride-induced liver fibrosis model group, and low-, medium-, and high-dose S. comosa groups. HE staining and Masson staining were performed for the observation of liver tissue under a microscope. Further, Wistar rats were assigned into a control group and a S. comosa group for administration. Seven days later, blood was collected from the abdominal aorta, and different doses of drug-containing serum samples were used to treat hepatic stellate cell-T6(HSC-T6). Flow cytometry was adopted to detect the apoptosis of HSC-T6 cells. Ultra-high performance liquid chromatography-time of flight-mass spectrometry(UHPLC-TOF-MS) was employed to determine the components in Scabiosa comosa. The target of S. comosa and liver fibrosis were obtained from SwissTargetPrediction and GeneCards, respectively, and the common targets were selected as the anti-liver fibrosis targets. Protein-protein interaction was analyzed via STRING. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out via Metascape. Phosphatidylinosital 3-kinase(PI3 K), protein kinase B(AKT), p-AKT, p38, and p-p38 targets which are involved in the top-ranked PI3 K/AKT and mitogen activated kinase-like protein(MAPK) signaling pathways were selected for validation via Western blot. The HE and Masson staining results showed that Scabiosa alleviated the hyperplasia of connective tissue and the fibrosis. The serum containing Scabiosa significantly promoted the apoptosis of HSC-T6 in a concentration-dependent manner. A total of 76 chemical components were identified by UHPLC-TOF-MS, among which flavonoids, alkaloids, terpenoids, phenols, and fatty acids were the main components. According to the prediction, there were 63 anti-liver fibrosis targets in Scabiosa comosa, the annotated GO terms of which involved biological processes, cell components, and molecular functions. The KEGG pathway enrichment showed that the targets were mainly involved in PI3 K/AKT, epidermal growth factor receptor(EGFR), RAS-associated protein 1(Rap1), hypoxia-inducible factor 1(HIF-1), resistance to audiogenic seizures(Ras), and MAPK signaling pathways. Western blot results showed that compared with the model group, S. comosa down-regulated the protein levels of α-smooth muscle actin(α-SMA), collagen Ⅰ, PI3 K, AKT, p-AKT, p38, and p-p38 in liver tissue. Compared with the control group, the low-, medium-, and high-dose S. comosa significantly down-regulated the protein levels of α-SMA, collagen Ⅰ, PI3 K, AKT, p-AKT, p38, and p-p38 in HSC-T6. The evidence of pharmacodynamics, network pharmacology, and molecular biology indicated that the plants of S. comosa had significant activity against liver fibrosis, the mechanism of which may involve the regulation of the key targets PI3 K, AKT, and MAPK14 p38 in the PI3 K/AKT and MAPK signaling pathways.

CSCAHHO: Chaotic hybridization algorithm of the Sine Cosine with Harris Hawk optimization algorithms for solving global optimization problems.

Because of the No Free Lunch (NFL) rule, we are still under the way developing new algorithms and improving the capabilities of the existed algorithms. Under consideration of the simple and steady convergence capability of the sine cosine algorithm (SCA) and the fast convergence rate of the Harris Hawk optimization (HHO) algorithms, we hereby propose a new hybridization algorithm of the SCA and HHO algorithm in this paper, called the CSCAHHO algorithm henceforth. The energy parameter is introduced to balance the exploration and exploitation procedure for individuals in the new swarm, and chaos is introduced to improve the randomness. Updating equations is redefined and combined of the equations in the SCA and HHO algorithms. Simulation experiments on 27 benchmark functions and CEC 2014 competitive functions, together with 3 engineering problems are carried out. Comparisons have been made with the original SCA, HHO, Archimedes optimization algorithm (AOA), Seagull optimization algorithm (SOA), Sooty Tern optimization algorithm (STOA), Arithmetic optimizer (AO) and Chimp optimization algorithm (ChOA). Simulation experiments on either unimodal or multimodal, benchmark or CEC2014 functions, or real engineering problems all verified the better performance of the proposed CSAHHO, such as faster convergence rate, low residual errors, and steadier capability. Matlab code of this algorithm is shared in Gitee with the following address: https://gitee.com/yuj-zhang/cscahho.

[Comparison of fracture strength of two chairside CAD/CAM ceramic blocs with different thickness].

PURPOSE: To provide theoretical basis for clinical CAD/CAM restorations with a comparison of the fracture strength between two chairside CAD/CAM immediate restorative materials (IPS e.max CAD and Vita Enamic) with different occlusal thickness in vitro. METHODS: IPS e.max CAD and Vita Enamic full-crowns with occlusal thicknesses 1.5/2.0/2.5 mm were fabricated with CEREC and adhesively seated to dies customized by manufacturer (n=42). All specimens were stored in distilled water at 37 ℃ for 24 h. Later, static fractural loading was performed. The fracture surface was observed through scanning electron microscope (SEM) and energy dispersive spectrum (EDS). The composites of two materials were detected by X-Ray diffraction (XRD) techniques. The results of fracture strength were analyzed by one-way ANOVA and t-test via SPSS 20.0 software package. RESULTS: With the increase of occlusal thickness, the fracture strength of IPS e.max CAD increased remarkably. However, the Vita Enamic's fracture strength remained the same with no significant difference. With the occlusal thickness increased from 1.5 to 2.0 mm, there was no significant difference in the fracture strength between IPS e.max CAD group and Vita Enamic group. As the thickness increased from 1.5 to 2.0 mm, the fracture strength of IPS e.max CAD group was significantly higher than that of Vita Enamic group. The results of SEM showed that the filler particles of IPS e.max CAD were smaller compared to that of Vita Enamic. Cone cracks were mainly found in the fracture surface of IPS e.max CAD, while radical cracks appeared in Vita Enamic. EDS showed the metal oxide and SiO2 in Vita Enmic was significantly higher than that in IPS e.max CAD. XRD showed that the primary crystal phase of IPS e.max CAD was lithium silicate, while Vita Enamic was amorphous. CONCLUSIONS: Both IPS e.max CAD and Vita Enamic can meet the standard of clinical application as the occlusal thickness reaches 1.5 mm. IPS e.max CAD showed better fracture resistance when the thickness was greater than 2.0 mm.

[Research progress on joint replacement for hemiplegic femoral neck fracture].

With China's aging society, the number of patients with hemiplegia caused by cerebrovascular accident is increasing gradually. The risk of hip fracture in the first year after the onset of this kind of patients is 4 times higher than that of ordinary people, and most of them occur in the side of hemiplegia. For senile femoral neck fracture, artificial joint replacement is almost the first choice of treatment, with mature operation technology and good curative effect. At present, it is considered that if the muscle strength of hemiplegic side can reach grade III after cerebral vascular accident, hip arthroplasty can be the first choice for hemiplegic patients with hemiplegic femoral neck fracture. However, the situation of hemiplegic patients is different from that of ordinary people. The hemiplegic limbs may have muscle atrophy, muscle strength imbalance, osteoporosis and other problems, which brings difficulties to the formulation of surgical plan. This paper mainly discusses the choice of surgical approach, the use of total hip arthroplasty or hemiarthroplasty, the use of cemented prosthesis or cementless prosthesis, and how to reduce the incidence of postoperative dislocation The purpose is to provide more reference evidence for orthopedic doctors in clinical decision-making.

Down-Regulation of Ribosomal Protein RPS21 Inhibits Invasive Behavior of Osteosarcoma Cells Through the Inactivation of MAPK Pathway.

OBJECTIVE: The goal of our present study was to explore the expression level, biological function, and underlying molecular mechanism of ribosomal protein s21 (RPS21) in human osteosarcoma (OS). METHODS: Firstly, we evaluated the expression of RPS21 in OS tissue samples based on the Gene Expression Omnibus (GEO) datasets and also measured the RPS21 expression of OS cell lines (MG63, and U2OS) by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA interference method was used to reduce the expression of RSP21 in the OS cells. Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, and transwell assays were conducted to measure the proliferation, migration, and invasion of OS cells. The mitogen-activated protein kinase (MAPK) pathway-related proteins levels were examined by Western blot. RESULTS: Our analyses showed that the expression of RPS21 was significantly increased in OS, compared with normal samples. Upregulation of RPS21 was associated with worse outcomes of OS patients. Knockdown of RPS21 suppressed OS cell proliferation, colony-forming ability, migration, and invasion capacities. Moreover, down-regulation of RPS21 inactivated the MAPK signaling pathway. CONCLUSION: RPS21 plays an oncogenic candidate in OS development via regulating the activity of MAPK pathway; therefore, it may serve as a novel therapeutic target for OS treatment.

Ganoderma atrum polysaccharide ameliorates anoxia/reoxygenation-mediated oxidative stress and apoptosis in human umbilical vein endothelial cells.

Ganoderma atrum polysaccharide (PSG-1), a main polysaccharide from Ganoderma atrum, possesses potent antioxidant capacity and cardiovascular benefits. The aim of this study was to investigate the role of PSG-1 in oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs) under anoxia/reoxygenation (A/R) injury conditions. The results showed that exposure of HUVECs to A/R triggered cell death and apoptosis. Administration of PSG-1 significantly inhibited A/R-induced cell death and apoptosis in HUVECs. PSG-1-reduced A/R injury was mediated via mitochondrial apoptotic pathway, as evidenced by elevation of mitochondrial Bcl-2 protein and mitochondrial membrane potential, and attenuation of Bax translocation, cytochrome c release and caspases activation. Furthermore, PSG-1 enhanced the activities of superoxide dismutase, catalase and glutathione peroxidase and glutathione content, and concomitantly attenuated reactive oxygen species generation, lipid peroxidation and glutathione disulfide content. The antioxidant, N-acetyl-l-cysteine, significantly ameliorated all of these endothelial injuries caused by A/R, suggesting that antioxidant activities might play a key role in PSG-1-induced endothelial protection. Taken together, these findings suggested that PSG-1 could be as a promising adjuvant against endothelial dysfunction through ameliorating oxidative stress and apoptosis.

(-)-Epigallocatechin-3-gallate alleviates doxorubicin-induced cardiotoxicity in sarcoma 180 tumor-bearing mice.

AIMS: (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol compound, plays an important role in the prevention of cardiovascular disease and cancer. The present study aimed to investigate the effects of EGCG on doxorubicin (DOX)-induced cardiotoxicity in Sarcoma 180 (S180) tumor-bearing mice. MAIN METHODS: S180 tumor-bearing mice were established by subcutaneous inoculation of S180 cells attached to the axillary region. The extent of myocardial injury was accessed by the amount of lactate dehydrogenase (LDH) released in serum. Heart tissue was morphologically studied with transmission electron microscopy. Apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (ΔÑ°m) as well as calcium concentration were measured by flow cytometric analysis. Expression levels of manganese superoxide dismutase (MnSOD) were analyzed by Western blot. KEY FINDINGS: Results showed that the combination with EGCG and DOX significantly inhibited tumor growth and enhanced induction of apoptosis compared with DOX alone. Moreover, administration of EGCG could suppress DOX-induced cardiotoxicity as evidenced by alleviating LDH release and apoptosis in cardiomyocyte. EGCG-evoked cardioprotection was in association with the increase of ΔÑ°m and MnSOD expression. EGCG was also found to attenuate ROS generation and myocardial calcium overload in Sarcoma 180 tumor-bearing mice subjected to DOX. SIGNIFICANCE: EGCG alleviated DOX-induced cardiotoxicity possibly in part mediated by increasing of MnSOD and Ñ°m, reducing myocardial calcium overload and subsequently attenuating the apoptosis and LDH release. Our findings suggest that co-administration of EGCG and DOX have potential as a feasible strategy to mitigate cardiotoxicity of DOX without compromising its chemotherapeutic value.

Identification and antifeedant activities of limonoids from Azadirachta indica.

Four new limonoids, azadiraindins A-D (1-4, resp.), together with seven known analogs, were isolated from the MeOH extract of Azadirachta indica. The structures of 1-4 were elucidated by NMR and MS spectroscopic analyses, and the relative configuration of 1 was determined by single-crystal X-ray crystallography. The compounds isolated in comparatively large amount were evaluated for their antifeedant activities against Plutella xylostella; the antifeedant rate of 10 was 90.6% and the corrected mortality of 8 was 79.2%.

Three new limonoids from Azadirachta indica.

Three new limonoids, azadiraindins E-G (1-3, respectively), together with six known analogs, were isolated from the fresh fruit coats of Azadirachta indica. The structures of these compounds were elucidated by spectroscopic methods (IR, MS, HR-ESI-MS, 1D NMR, and 2D NMR).

Four new polycyclic meroterpenoids from Ganoderma cochlear.

Four pairs of new polycyclic-meroterpenoid enantiomers, ganocins A-C (1-3) possessing a spiro[4,5]decane ring system, along with ganocin D (4) with an eight-membered ring, were isolated from the fruiting bodies of Ganoderma cochlear. Their structures were determined by spectroscopic data and X-ray diffraction crystallography. Their anti-AChE activities were evaluated, and a possible biogenetic pathway was also proposed.

Cytotoxic steroids from Sarcococca saligna.

Two new C21-steroidal esters, sarsaligates A(1) and B(2), and two new steroidal alkaloids, sarsaligenines A(3) and B(4), together with four known compounds (sarcovagine, sarcorucinine, dimethylamino-3 ß-pregnane-20-one, and ß-sitosterol 5- 8, respectively), were isolated from the leaves and stems of Sarcococca saligna. The structures of compounds 1-4 were elucidated by NMR and MS spectroscopic analysis. Of the compounds tested, 5 and 6 were the most cytotoxic against the cell lines K562, SK-BR-3, and PANC-1, with IC50 values in the range of 2.25-5.00 µM, while 3 and 4 selectively inhibited HL-60 cells with IC50 values of 2.87 and 3.61 µM, respectively. Compounds 3-6 therefore deserve further evaluation of their cytotoxic potentials.

Triterpenoid alkaloids from Buxus microphylla.

Two new triterpenoid alkaloids, buxmicrophyllines J and K (1 and 2, resp.), together with four analogues, 3-6, were isolated from the leaves and stems of Buxus microphylla. The structures of the new compounds were elucidated by NMR and MS spectroscopic analyses. The partial assignments of the NMR spectra of 3 were also revised. Compounds 1 and 3-6 were evaluated for their growth inhibitory activity against human cell lines HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1. Compound 6 showed significant cytotoxicity against HL-60, SK-BR-3, and PANC-1 cell lines, with IC(50) values of 6.46, 19.61, and 28.57 microM, respectively.

Pregnane alkaloids from Pachysandra axillaris.

Nine new pregnane alkaloids, pachysamines J-R (1-9), together with seven known ones, were isolated from Pachysandra axillaris. The chemical structures of the new alkaloids were elucidated by spectroscopic methods. All the compounds were evaluated for their inhibitory activities against HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1 cell lines. Compound 15 possessed moderate activities against A-549, SK-BR-3, and PANC-1 cells, with the IC(50) values of 11.17, 4.17, and 10.76 microM, respectively. Besides, compound 11 showed cytotoxicities against A-549 cell, with the IC(50) values as 24.94 microM.

Three new triterpenoids containing four-membered ring from the fruiting body of Ganoderma sinense.

Methyl ganosinensate A (1), ganosinensic acid A (1a), and ganosinensic acid B (2), three new triterpenoids with an unusual four-membered ring skeleton produced by a bond across C-1 to C-11, were isolated from the fruiting body of Ganoderma sinense . Their structures were established on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques, and methyl ganosinensate A was confirmed by X-ray crystallographic analysis.

Cytotoxic triterpenoid alkaloids from Buxus microphylla.

Five new triterpenoid alkaloids, buxmicrophyllines E-I (1-5), and six known ones (6-11) were isolated from the leaves and stems of Buxus microphylla. The structures of compounds 1-5 were elucidated by NMR and MS spectroscopic analysis, and the relative stereochemistry of 5 was determined by single-crystal X-ray crystallography. Compounds 3 and 9 were cytotoxic against HepG2 cells, with IC(50) values of 0.89 and 0.78 microM, and compounds 2, 3, 7, 8, and 9 were cytotoxic against K562 cells, with IC(50) values of 2.95, 4.44, 1.70, 5.61, and 0.37 microM, respectively.

Cell-based high-throughput screening assay system for monitoring G protein-coupled receptor activation using beta-galactosidase enzyme complementation technology.

A novel cell-based functional assay to directly monitor G protein-coupled receptor (GPCR) activation in a high-throughput format, based on a common GPCR regulation mechanism, the interaction between beta-arrestin and ligand-activated GPCR, is described. A protein-protein interaction technology, the InteraX trade mark system, uses a pair of inactive beta-galactosidase (beta-gal) deletion mutants as fusion partners to the protein targets of interest. To monitor GPCR activation, stable cell lines expressing both GPCR- and beta-arrestin-beta-gal fusion proteins are generated. Following ligand stimulation, beta-arrestin binds to the activated GPCR, and this interaction drives functional complementation of the beta-gal mutant fragments. GPCR activation is measured directly by quantitating restored beta-gal activity. The authors have validated this assay system with two functionally divergent GPCRs: the beta2-adrenergic amine receptor and the CXCR2 chemokine-binding receptor. Both receptors are activated or blocked with known agonists and antagonists in a dose-dependent manner. The beta2-adrenergic receptor cell line was screened with the LOPAC trade mark compound library to identify both agonists and antagonists, validating this system for high-throughput screening performance in a 96-well microplate format. Hit specificity was confirmed by quantitating the level of cAMP. This assay system has also been performed in a high-density (384-well) microplate format. This system provides a specific, sensitive, and robust methodology for studying and screening GPCR-mediated signaling pathways.