A simple and successful treatment for rupture and defect of the posterior third superior sagittal sinus caused by open depressed skull fracture: A case report.

It is extremely dangerous to treat the posterior third of the superior sagittal sinus (PTSSS) surgically, since it is usually not completely ligated. In this report, the authors described the case of a 27-year-old man with a ruptured and defective PTSSS caused by an open depressed skull fracture, which was treated by ligation of the PTSSS and the patient achieved a positive recovery. The patient's occiput was hit by a height-limiting rod and was in a mild coma. A CT scan showed an open depressed skull fracture overlying the PTSSS and a diffuse brain swelling. He underwent emergency surgery. When the skull fragments were removed, a 4 cm segment of the superior sagittal sinus (SSS) and the adjacent dura mater were removed together with bone fragments. Haemorrhage occurred and blood pressure dropped. We completed the operation by ligating the severed ends of the fractured sagittal sinus. One month after the operation, apart from visual field defects, he recovered well. In our opinion, in primary hospitals, when patients with severely injured PTSSS cannot sustain a long-time and complicated operation, e.g., the bypass using venous graft, and face life-threatening conditions, ligation of the PTSSS is another option, which may unexpectedly achieve good results.

Traumatic pseudoaneurysms of external carotid artery branch: Case series and treatment considerations.

PURPOSE: To explore the diagnosis and treatment of traumatic external carotid branch pseudoaneurysms. METHODS: Eleven cases of traumatic external carotid artery branch pseudoaneurysms were admitted in our hospital. Digital subtraction angiography was performed in all patients. It revealed that the pseudoaneurysms originated from the internal maxillary artery in 5 cases, superficial temporal artery in 5 cases and occipital artery in 1 case. Five cases of internal maxillary artery pseudoaneurysms and 2 cases of superficial temporal artery pseudoaneurysms were treated by embolization; the other 3 cases were surgically resected. RESULTS: Complete cessation of nasal bleeding was achieved in all the 5 pseudoaneurysms of internal maxillary artery after the endovascular therapies. Scalp bleeding stopped and scalp defect healed up in 2 patients with superficial temporal artery pseudoaneurysms treated by interventional therapy. All patients were followed up for 0.5-2.0 years without recurrence of nosebleed and scalp lump. CONCLUSION: For patients with repeated severe epistaxis after craniocerebral injury, digital subtraction angiography should be performed as soon as possible to confirm traumatic pseudoaneurysm. Endovascular therapy is an effective method for traumatic internal maxillary artery pseudoaneurysms. For patients with scalp injuries and pulsatile lumps, further examinations including digital subtraction angiography should be performed to confirm the diagnosis. Surgical treatment or endovascular therapy for scalp traumatic pseudoaneurysm is effective.

Au Nanoparticles Attenuate RANKL-Induced Osteoclastogenesis by Suppressing Pre-Osteoclast Fusion.

Osteoclasts are multinucleated terminal cells that originate from a hematopoietic monocyte/macrophage lineage. Excessive osteoclast formation in vivo can lead to bone metabolic diseases such as postmenopausal osteoporosis, multiple myeloma, rheumatoid arthritis, and lytic bone metastases of cancer cells. Au nanoparticles (AuNPs) are inorganic nanoparticles with outstanding biocompatibility. We assessed their effect on osteoclastogenesis and found that pre-osteoclast fusion induced by receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colonystimulating factor (M-CSF) was suppressed by AuNPs. Cell migration and actin ring formation were also significantly inhibited. Finally, AuNPs reduced osteoclast bone absorption function. Interestingly, we observed altered fusogenic gene expression in treated pre-osteoclasts. Our results suggest that AuNPs have potential as a therapeutic agent for osteoclast-related bone metabolism diseases.

Highly Dispersed Fullerenols Hamper Osteoclast Ruffled Border Formation by Perturbing Ca2+ Bundles.

Osteoporosis, a common and serious bone disorder affecting aged people and postmenopausal women, is characterized by osteoclast overactivity. One therapeutic strategy is suppressing the bone resorption function of hyperactive osteoclasts, but there is no effective drug in clinical practice so far. Herein, it is demonstrated that fullerenols suppress the bone resorption of osteoclasts by inhibiting ruffled borders (RBs) formation. The RBs formation, which is supported by well-aligned actin bundles (B-actins), is a critical event for osteoclast bone resorption. To facilitate this function, osteoclast RBs dynamics is regulated by variable microenvironments to bundle F-actins, protrude cell membrane, and so on. B-actin perturbation by fullerenols is determined here, offering an opportunity to regulate osteoclast function by destroying RBs. In vivo, the therapeutic effect of fullerenols on overactive osteoclasts is confirmed in a mouse model of lipopolysaccharide-induced bone erosion. Collectively, the findings suggest that fullerenols adhere to F-actin surfaces and inhibit RBs formation in osteoclasts, mainly through hampering Ca2+ from bundling F-actins, and this is likely due to the stereo-hindrance effect caused by adherent fullerenols.

[Non-leaching, broad-spectrum antibacterial poly (ε-caprolactone)/gelatin-QAS nanofiberous membranes for wound dressing].

5-20 wt% trimethoxysilylpropyl octadecyldimethyl ammonium chloride (QAS) was used to modify Poly (ε-caprolactone) (PCL)-gelatin hybrid to fabricate non-leaching antibacterial nanofiber membranes (PG-Q) by electrospinning. The results from scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that the QAS leaded to phase separation between the QAS and PCL. Hydrophilic test demonstrated that the PG-Q nanofiber membranes had hydrophobic surface, which was help for peeling off the dressing from the wound. Additionally, the physical and chemical cross-linking between the QAS/PCL and QAS/gelatin were confirmed by Fourier transform infrared (FTIR), which were good for long lasting antibacterial effect. The PG-Q membranes also showed excellent cell-biocompatibility. Furthermore, compared with pure PCL nanofiber membrane, the PG-Q nanofiber membranes, especially PG-Q15 (QAS: 15 wt%) and PG-Q20 (QAS: 20 wt%), showed a considerable increase in the bacteriostatic rate of S. aureus and P. aeruginosa (more than 99% after 12 h). Therefore, electrospinning non-leaching antibacterial nanofiber membranes could be an optimal choice for antibacterial wound dressing.

Metabolizer in vivo of fullerenes and metallofullerenes by positron emission tomography.

Fullerenes (C60) and metallofullerenes (Gd@C82) have similar chemical structure, but the bio-effects of both fullerene-based materials are distinct in vivo. Tracking organic carbon-based materials such as C60 and Gd@C82 is difficult in vivo due to the high content of carbon element in the living tissues themselves. In this study, the biodistribution and metabolism of fullerenes (C60 and Gd@C82) radiolabeled with (64)Cu were observed by positron emission tomography (PET). (64)Cu-C60 and (64)Cu-Gd@C82 were prepared using 1, 4, 7, 10-tetrakis (carbamoylmethyl)-1, 4, 7, 10-tetra-azacyclodo-decanes grafted on carbon cages as a chelator for (64)Cu, and were obtained rapidly with high radiochemical yield (≥90%). The new radio-conjugates were evaluated in vivo in the normal mouse model and tissue distribution by small animal PET/CT imaging and histology was carried out. The PET imaging, the biodistribution and the excretion of C60 and Gd@C82 indicated that C60 samples have higher blood retention and lower renal clearance than the Gd@C82 samples in vivo and suggested that the differences in metabolism and distribution in vivo were caused by the structural differences of the groups on the fullerene cages though there is chemical similarity between C60 and Gd@C82.

The physiological metabolite α-ketoglutarate ameliorates osteoarthritis by regulating mitophagy and oxidative stress.

Osteoarthritis (OA) is an age-related metabolic disease. Low-grade inflammation and oxidative stress are the last common pathway of OA. α-ketoglutarate (α-KG) is an essential physiological metabolite from the mitochondrial tricarboxylic acid (TCA) cycle, with multiple functions, including anti-inflammation and antioxidation, and exhibits decreased serum levels with age. Herein, we aimed to investigate the effect and mechanism of α-KG on OA. We first quantified the α-KG levels in human cartilage tissue and osteoarthritic chondrocytes induced by IL-1ß. Besides, IL-1ß-induced osteoarthritic chondrocytes were treated with different concentrations of α-KG. Chondrocyte proliferation and apoptosis, synthesis and degradation of extracellular matrix, and inflammation mediators were analyzed. RNA sequencing was used to explore the mechanism of α-KG, and mitophagy and oxidative stress levels were further detected. These results were verified in an anterior cruciate ligament transection (ACLT) induced age-related OA rat model. We found that α-KG content decreased by 31.32% in damaged medial cartilage than in normal lateral cartilage and by 36.85% in IL-1ß-induced human osteoarthritic chondrocytes compared to control. α-KG supplementation reversed IL-1ß-induced chondrocyte proliferation inhibition and apoptosis, increased the transcriptomic and proteinic expression of ACAN and COL2A1 in vivo and in vitro, but inhibited the expression of MMP13, ADAMTS5, IL-6, and TNF-α. In mechanism, α-KG promoted mitophagy and inhibited ROS generation, and these effects could be prevented by Mdivi-1 (a mitophagy inhibitor). Overall, α-KG content decreased in human OA cartilage and IL-1ß-induced osteoarthritic chondrocytes. Moreover, α-KG supplementation could alleviate osteoarthritic phenotype by regulating mitophagy and oxidative stress, suggesting its potential as a therapeutic target to ameliorate OA.

The Clinical Characteristics of Electrolyte Disturbance in Patients with Moderate and Severe Traumatic Brain Injury Who Underwent Craniotomy and Its Influence on Prognosis.

OBJECTIVE: The present study aimed to investigate the clinical characteristics of electrolyte imbalance in patients with moderate to severe traumatic brain injury (TBI) who underwent craniotomy and its influence on prognosis. METHODS: A total of 156 patients with moderate to severe TBI were prospectively collected from June 2019 to June 2021. All patients underwent craniotomy and intracranial pressure (ICP) monitoring. We aimed to explore the clinical characteristics of electrolyte disturbance and to analyze the influence of electrolyte disturbance on prognosis. RESULTS: A total of 156 patients with moderate and severe TBI were included. There were 57 cases of hypernatremia, accounting for 36.538%, with the average level of 155.788±7.686 mmol/L, which occurred 2.2±0.3 days after injury. There were 25 cases of hyponatremia, accounting for 16.026%, with the average level of 131.204±3.708 mmol/L, which occurred 10.2±3.3 days after injury. There were three cases of hyperkalemia, accounting for 1.923%, with the average level of 7.140±1.297 mmol/L, which occurred 5.3±0.2 days after injury. There were 75 cases of hypokalemia, accounting for 48.077%, with the average level of 3.071±0.302 mmol/L, which occurred 1.8±0.6 days after injury. There were 105 cases of hypocalcemia, accounting for 67.308%, with the average level of 1.846±0.104 mmol/L, which occurred 1.6±0.2 days after injury. There were 17 cases of hypermagnesemia, accounting for 10.897%, with the average level of 1.213±0.426 mmol/L, which occurred 1.8±0.5 days after injury. There were 99 cases of hypomagnesemia, accounting for 63.462%, with the average level of 0.652±0.061 mmol/L, which occurred 1.3±0.4 days after injury. Univariate regression analysis revealed that age, Glasgow coma scale (GCS) score at admission, pupil changes, ICP, hypernatremia, hypocalcemia, hypernatremia combined with hypocalcemia, epilepsy, cerebral infarction, severe hypoproteinemia were statistically abnormal (p<0.05), while gender, hyponatremia, potassium, magnesium, intracranial infection, pneumonia, allogeneic blood transfusion, hypertension, diabetes, abnormal liver function, and abnormal renal function were not statistically significant (p>0.05). After adjusting gender, age, GCS, pupil changes, ICP, epilepsy, cerebral infarction, severe hypoproteinemia, multivariate logistic regression analysis revealed that hypernatremia or hypocalcemia was not statistically significant, while hypernatremia combined with hypocalcemia was statistically significant (p<0.05). CONCLUSION: The incidence of hypocalcemia was the highest, followed by hypomagnesemia, hypokalemia, hypernatremia, hyponatremia and hypermagnesemia. Hypocalcemia, hypomagnesemia, and hypokalemia generally occurred in the early post-TBI period, hypernatremia occurred in the peak period of ICP, and hyponatremia mostly occurred in the late period after decreased ICP. Hypernatremia combined with hypocalcemia was associated with prognosis.

Exosomes derived from the blood of patients with sepsis regulate apoptosis and aerobic glycolysis in human myocardial cells via the hsa­miR­1262/SLC2A1 signaling pathway.

Myocardial injury occurs in the majority of patients with sepsis and is associated with early mortality. MicroRNAs (miRs) transported by exosomes have been implicated in numerous diseases, such as tumors, acute myocardial infarction and cardiovascular disease. Human serum albumin (hsa)­miR­1262 has been shown to serve a role in sepsis; however, its role in exosomes isolated from patients with sepsis and septic myocardial injury remains unclear. In the present study, serum exosomes were isolated via ultracentrifugation. Solute carrier family 2 member 1 (SLC2A1), an essential mediator in energy metabolism, was silenced and overexpressed in the human myocardial AC16 cell line using lentiviral plasmids containing either SLC2A1­targeting short interfering RNAs or SLC2A1 cDNA, respectively. Cell apoptosis was analyzed using flow cytometry, and the extracellular acidification rate and oxygen consumption rate of AC16 cells were determined using an XFe24 Extracellular Flux Analyzer. Furthermore, the dual­luciferase reporter assay was used to evaluate the interaction between hsa­miR­1262 and SLC2A1. Finally, reverse transcription­quantitative PCR and western blotting were used to evaluate gene and protein expression levels, respectively. Exosomes isolated from the blood of patients with sepsis (Sepsis­exo) markedly reduced aerobic glycolysis activity, but significantly promoted the apoptosis of human AC16 cells in a time­dependent manner. Moreover, Sepsis­exo significantly increased hsa­miR­1262 expression levels, but significantly decreased SLC2A1 mRNA expression levels in a time­dependent manner. Bioinformatics analysis indicated that hsa­miR­1262 bound to the 3' untranslated region of SLC2A1 to negatively regulate its expression. The silencing of SLC2A1 promoted apoptosis and suppressed glycolysis in AC16 cells, whereas SLC2A1 overexpression resulted in the opposite effects. Therefore, the present study demonstrated that exosomes derived from patients with sepsis may inhibit glycolysis and promote the apoptosis of human myocardial cells through exosomal hsa­miR­1262 via its target SLC2A1. These findings highlighted the importance of the hsa­miR­1262/SLC2A1 signaling pathway in septic myocardial injury and provided novel insights into therapeutic strategies for septic myocardial depression.

Rhein Protects Against Severe Acute Pancreatitis In vitro and In vivo by Regulating the JAK2/STAT3 Pathway.

Rhein is widely used in inflammation treatment in China, but its effects on severe acute pancreatitis (SAP) have not been studied closely. This study investigated rhein's protective effects against SAP using in vitro and in vivo models to determine whether its protective mechanism regulated the Janus kinase two and signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway. Thirty-six male Sprague-Dawley rats were randomised into sham operation, SAP and rhein groups. The SAP model was induced by retrograde pancreatic bile duct injection of sodium taurocholate. Serum TNF-α and interleukin (IL)-6 levels were determined by ELISA, whereas serum amylase and lipase concentrations were measured using test kits. Western blot and/or immunohistochemistry quantified JAK2 and STAT3 expression. Furthermore, histopathological pancreatic changes were detected by haematoxylin and eosin staining. AR42J cells were randomly divided into the control, cerulein and rhein groups. Amylase activity was assessed using an amylase test kit; the tumour necrosis factor-α (TNF-α) expression was determined by enzyme-linked immunosorbent assay (ELISA). JAK2 and STAT3 protein expression were evaluated by western blot. SAP was concomitant with increased JAK2 and STAT3 expressions in vivo. Pre-treatment with rhein attenuated serum TNF-α and IL-6 levels effectively, and notably reduced p-JAK2, p-STAT3, JAK2 and STAT3 protein expression. Rhein significantly alleviated pancreatic histopathology. Compared to untreated groups, rhein significantly reduced amylase activity in supernatants of AR42J cells induced by cerulein in vitro. Furthermore, rhein altered JAK2 and STAT3 protein levels in AR42J cells after cerulein induction. Overall, rhein exerted protective effect on SAP in vitro and in vivo, possibly through the JAK2/STAT3 signalling pathway.

WITHDRAWN: Hydroxysafflor Yellow A Ameliorates Toll-like Receptor 4-Mediated Septic Cardiomyopathy

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Zoledronic Acid Enhanced the Antitumor Effect of Cisplatin on Orthotopic Osteosarcoma by ROS-PI3K/AKT Signaling and Attenuated Osteolysis.

Osteoclasts can interact with osteosarcoma to promote the growth of osteosarcoma. Cisplatin is common in adjuvant chemotherapy of osteosarcoma. However, due to chemoresistance, the efficacy is profoundly limited. Previous studies have found that zoledronic acid (ZA) has osteoclast activation inhibition and antitumor effect. However, the combined effect of ZA and cisplatin on osteosarcoma remains unclear. In vitro, the effects of ZA and cisplatin alone or in combination on 143B cell activity, proliferation, apoptosis, and ROS-PI3K/AKT signaling were detected. At the same time, the effect of ZA and cisplatin on osteoclast formation, survival, and activity was detected by TRAP staining and bone plate absorption test. These were further verified in mice. The results showed that in vitro, compared with the single treatment and control, the combination of ZA and cisplatin could significantly inhibit the activity and proliferation of 143B cells and induced their apoptosis and further promoted the generation of ROS and inhibited the phosphorylation of PI3K and AKT. ROS scavenger and the agonist of the PI3K/AKT pathway could reverse these results. In addition, cisplatin in synergy with ZA could significantly inhibit osteoclast formation and survival to reduce bone plate absorption. In vivo, compared with the single group, the tumor volume and cell proliferation were significantly reduced, apoptosis and necrosis of tumor cells increased, and TRAP+ osteoclasts and osteolysis destruction decreased in the combined group. In conclusion, ZA enhanced the antitumor effect of cisplatin on osteosarcoma by ROS-PI3K/AKT signaling, reducing the chemoresistance and osteoclast activation to enhance chemotherapy and inhibit osteolysis. And this present study raised the possibility that combining ZA and cisplatin may represent a novel strategy against osteosarcoma.

Salidroside protects endothelial cells against LPS-induced inflammatory injury by inhibiting NLRP3 and enhancing autophagy.

BACKGROUND: Salidroside (SAL) is a bioactive compound extracted from Rhodiola rosea with various biological properties. This study was designed to explore the functions of SAL on the endothelial damage induced by lipopolysaccharide (LPS) and its related mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were pretreated with SAL (0, 10, 25, 50, 100 µM), and then incubated with LPS (10 µg/mL). Cell viability was evaluated by MTT assay, cell injury by lactate dehydrogenase (LDH) release, and inflammatory cytokines release by ELISA assay. Oxidative stress was evaluated by malondialdehyde (MDA) and superoxide dismutase (SOD) in cell lysate. Apoptosis was detected by flow cytometry and caspase-3 activity. Western blot were performed to determine expression levels of autophagy and NOD-like receptor protein 3 (NLRP3) related proteins. RESULTS: SAL at 50 µM concentration showed no toxicity on HUVECs, but attenuated LPS-induced injury, as evidenced by increased cell viability, reduction in LDH level and inflammatory cytokines in culture media. SAL also reduced MDA level and increased SOD activity in HUVECs, and inhibited apoptosis rate and caspase-3 activity. (P < 0.05). Moreover, LPS enhanced HUVECs autophagy, and SAL pretreatment further enhanced autophagy, with increased Beclin-1 protein and decreased P62 protein. SAL also attenuated LPS-induced activation of NLRP3 inflammasome, reduced the protein expression of NLRP3-related proteins, including ASC and caspase-1. Autophagy inhibition by 3-MA markedly reversed SAL-modulated changes in cell viability and NLRP3 expression in LPS-stimulated HUVECs. CONCLUSION: SAL protects endothelial cells against LPS-induced injury through inhibition of NLRP3 pathways and enhancing autophagy.

The comparison analysis of polyphyllin I and its analogues induced apoptosis of colon and lung cancer cells via mitochondrial dysfunction.

Polyphyllin I (PPI) and its analogues, including polyphyllin II (PPII), polyphyllin VI (PPVI) and polyphyllin VII (PPVII), are major bioactive compounds isolated from the Chinese herb Chonglou. However, the susceptibilities of PPI and its analogues towards the different cell lines are diversified and the mechanisms are not fully clarified. Thus, the present study aimed to investigate the cytotoxicity of PPI and its analogues on two different cell lines, as well as to explore the underlying mechanisms of these agents via inducing mitochondrial dysfunction. The results showed that PPI and its analogues were cytotoxic agents towards both A549 and HT-29 cells, with IC50 values ranged from 1.0 to 4.5 µmol/L. Further investigations demonstrated that they decreased the mitochondrial membrane potentials of both A549 and HT-29 cells in a dose-dependent manner. Among all tested compounds, PPVI and PPI induced the most obvious changes in Ca2+ haemostasis in these two cell lines. In addition, they could induce the accumulation of ROS in cells and down-regulated the Bcl-2 expression, up-regulated the Bax expression and induced the activity of cleaved caspase-3 in cells. Collectively, our findings clearly demonstrated the cytotoxic differences and mechanisms of PPI and its analogues induced cell apoptosis and could partially explain the anticancer effects of these natural constituents in Chonglou.

Adult rhabdomyosarcoma originating in the temporal muscle, invading the skull and meninges: A case report.

BACKGROUND: Rhabdomyosarcoma (RMS) is a rare malignant tumor of mesenchymal origin that mainly affects children. Spindle cell/sclerosing RMS (SSRMS) is even rarer. It is a new subtype that was added to the World Health Organization disease classification in 2013. To the best of our knowledge, this is the first reported case of adult SSRMS disease classification originating in the temporal muscle. CASE SUMMARY: SSRMS originating in the temporal muscle of a male adult enlarged rapidly, destroyed the skull, and invaded the meninges. The tumor was completely removed, and the postoperative pathological diagnosis was SSRMS. Postoperative recovery was good and chemotherapy and radiotherapy were given after the operation. Followed up for 3 mo, no tumor recurred. CONCLUSION: RMS is one of the differential diagnoses for head soft tissue tumors with short-term enlargement and skull infiltration. Preoperative computed tomography or magnetic resonance imaging is necessary for early detection of tumor invasion of the skull and brain tissue.

GSH attenuates RANKL-induced osteoclast formation in vitro and LPS-induced bone loss in vivo.

Osteoclasts are capable of adhering the bone matrix, then secrete acid and lytic enzymes to resorb it. Reactive oxygen species (ROS), as a signaling messenger, plays an important role in the receptor activator nuclear factor κB ligand (RANKL) signal pathway during osteoclast differentiation. Glutathione (GSH) is known to be a powerful antioxidant which can scavenge intracellular ROS. This study aimed to investigate whether GSH can as a protective agent against the RANKL-stimulated osteoclastogenesis by suppressing intracellular ROS. Here, we showed that GSH markedly restricted RNAKL-induced differentiation of bone marrow-derived macrophages (BMMs) to form osteoclasts. GSH suppressed RANKL-induced ROS generation and subsequent ROS-induced NF-κB signaling pathways within BMMs during osteoclastogenesis. Further, GSH acted to significantly downregulate the osteoclastogenic genes expression of nuclear factor in activated T cells, cytoplasmic1 (NFATc1), C-fos, the tartrate-resistant acid phosphatase (TRAP), and osteoclast-associated immunoglobulin-like receptor (OSCAR). Our results suggested that GSH inhibits intracellular ROS-mediated NF-κB signal pathway involved in osteoclast differentiation. These findings might form the basis of a new strategy for treating bone disease associated with excessive bone resorption.

Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for osteoporosis treatment.

Overactivation and excessive differentiation of osteoclasts (OCs) has been implicated in the course of bone metabolism-related diseases. Although fullerenol nanoparticles (fNPs) have been suggested to inhibit OC differentiation and OC function in our previous work, systemic studies on the effect of fNPs on bone diseases, e.g., osteoporosis (OP), in vivo remain elusive. Herein, it is demonstrated that fNPs significantly suppress the differentiation of OCs that derived from the murine bone marrow monocytes and inhibit the formation of the sealing zone by blocking the formation and patterning of podosomes in OCs spatiotemporally. In vivo, fNPs are supposed to be an efficient inhibitor of the overactivation of OCs in a LPS-induced bone erosion mouse model. The therapeutic effect of fNPs on osteoporosis is also investigated in an ovariectomy-induced osteoporosis rat model. The well-organized trabecular bone, the reduction in the number of TRAP positive cells, the improvement of bone-associated parameters, and the mechanical properties all demonstrate that fNPs, similar to diphosphonates, can be a promising candidate for the effective treatment of osteoporosis.

Correction: Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for osteoporosis treatment.

Correction for 'Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for osteoporosis treatment' by Kui Chen et al., Nanoscale, 2020, 12, 9359-9365, DOI: 10.1039/D0NR01625J.

Effect of Podophyllotoxin Conjugated Stearic Acid Grafted Chitosan Oligosaccharide Micelle on Human Glioma Cells.

OBJECTIVE: To study the physiochemical characteristics of podophyllotoxin (PPT) conjugated stearic acid grafted chitosan oligosaccharide micelle (PPT-CSO-SA), and evaluate the ability of the potential antineoplastic effects against glioma cells. METHODS: PPT-CSO-SA was prepared by a dialysis method. The quality of PPT-CSO-SA including micellar size, zeta potential, drug encapsulation efficiency and drug release profiles was evaluated. Glioma cells were cultured and treated with PPT and PPT-CSO-SA. The ability of glioma cells to uptake PPT-CSO-SA was observed. The proliferation of glioma cells was determined by 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The apoptosis and morphology of U251 cells were observed by 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) dye staining. Cell cycle analysis was performed by flow cytometry. The migration ability of U251 cells was determined by wound healing test. RESULTS: PPT-CSO-SA had nano-level particle size and sustained release property. The encapsulation efficiency of drug reached a high level. The cellular uptake percentage of PPT in glioma cells was lower than that of PPT-CSO-SA (p<0.05). The inhibitory effect of PPT-CSO-SA on glioma cells proliferation was significantly stronger than that of PPT (p<0.05). The morphologic change of apoptosis cell such as shrinkage, karyorrhexis and karyopyknosis were observed. The percentage of U251 cells in G2/M phase increased significantly in the PPT-CSO-SA group compared with PPT group (p<0.05). Compared with the PPT group, the cell migration ability of the PPT-CSO-SA group was significantly inhibited after 12 and 24 hours (p<0.05). CONCLUSION: PPT-CSO-SA can effectively enhance the glioma cellular uptake of drugs, inhibit glioma cells proliferation and migration, induce G2/M phase arrest of them, and promote their apoptosis. It may be a promising anti-glioma nano-drug.

The effect of extracorporeal shock wave therapy on the treatment of moderate to severe knee osteoarthritis and cartilage lesion.

BACKGROUND: Knee osteoarthritis (KOA) is a major cause leading to chronic bone and muscle pain. Extracorporeal shock wave therapy (ESWT) has been applied in treating KOA in recent years. METHODS: From April 2016 to April 2017, 82 patients were diagnosed with KOA that received ESWT were selected as the ESWT group. The treatment parameters were as follows, 2.0 bar, 0.25 mJ/mm, and 8 Hz/s for twice a week for 4 weeks continuously. In addition, 104 patients receiving oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) from April 2015 to April 2016 were also selected as the NSAIDs group. At 4, 8, 12, and 16 weeks upon the completion of treatment, the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were adopted to evaluate the changes in pain and function of patients in both groups. For the ESWT group, the 50-m quick walk time and gait analysis were applied to observe the functional recovery at 4, 8, 12, and 16 weeks upon the completion of treatment; meanwhile, patients were followed up by magnetic resonance imaging (MRI) at 24 weeks upon the completion of treatment, so as to observe the cartilage changes. RESULTS: Differences in VAS, 4, 8, and 12 weeks after treatment were statistically significant compared with that before treatment (4.59 ±â€Š0.5, P < .05; 2.55 ±â€Š0.5, P < .05; 4.39 ±â€Š0.49, P < .05). Differences in 4, 8, and 12 weeks after treatment were statistically significant compared with that before treatment (90.41 ±â€Š6.64, P < .05; 59.94 ±â€Š3.19, P < .05; 90.49 ±â€Š6.87, P < .05). Gait analysis suggested differences in 50 m walk time, walking speed, swing phase, and stance phase 8 weeks after treatment were statistically significant compared with that before treatment (36.23 ±â€Š4.08, P < .05; 1.25 ±â€Š0.09, P < .05; 58.56 ±â€Š0.87, P < .05; 41.44 ±â€Š0.87, P < .05). Differences in the VAS and WOMAC at 4 and 8 weeks after treatment between ESWT group and NASIDs group were not statistically significant. CONCLUSIONS: The ESWT has potential in reducing pain and improving knee function, and the therapeutic effects may peak at 8 weeks after the completion of treatment. Further research is needed to arrive at a definitive conclusion.