Lnc-PSMA8-1 activated by GEFT promotes rhabdomyosarcoma progression via upregulation of mTOR expression by sponging miR-144-3p.

BACKGROUND: GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS. METHODS: GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT-PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT-PCR analysis, Western blot analysis, and cell functional experiments. RESULTS: The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P < 0.05). Silencing the 4 upregulated lncRNAs (lnc-CEACAM19-1, lnc-VWCE-2, lnc-GPX7-1, and lnc-PSMA8-1) and overexpressing the downregulated lnc-FAM59A-1 inhibited the proliferation, invasion, and migration and induced the apoptosis of RMS cells. Among the factors analyzed, the expression of lnc-PSMA8-1, miR-144-3p, and mTOR in RMS tissue samples and cells was consistent with the correlations among their expression indicated by the lncRNA-miRNA-mRNA regulatory network based on the ceRNA hypothesis. lnc-PSMA8-1 promoted RMS progression by competitively binding to miR-144-3p to regulate mTOR expression. CONCLUSION: Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.

The interval between staged bilateral total knee arthroplasties does not affect early complications of the second knee or long-term function of the first and second knees.

BACKGROUND: This study explored the optimal time interval between staged bilateral total knee arthroplasty (BTKA) to minimize early complications of the second TKA and maximise the long-term function of the first and second knees. METHODS: We retrospectively reviewed 266 patients who underwent staged BTKA between 2013 and 2018. Groups 1-4 had time intervals between BTKAs of 1-6, 6-12, 12-18, and 18-24 months, respectively. Demographics, postoperative complications within 90 days of the second TKA, Knee Society Score (KSS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) score were compared among the groups. RESULTS: In total, 54, 96, 75, and 41 patients were assigned to groups 1-4, respectively. Although group 1 had the highest overall complication rate (11.11%), there was no significant difference in the complication rate among the four groups. Also, no significant differences were found among the four groups in functional and patient-reported outcomes, in either the first or second knee at 5 years postoperatively, including KSS-knee, KSS-function, WOMAC-pain, WOMAC-stiffness, and WOMAC-physical function. The interval between BTKA did not influence complications or the function of the second knee. The TKA type (posterior-stabilised vs. medial-pivot) and age did not correlate significantly with any scores. CONCLUSIONS: There was no group difference in early complications of the second TKA, and postoperative function was equivalent between the two knees and did not vary by the interval between surgeries. The results of this study give surgeons and patients more choices. If patients cannot tolerate severe symptoms in the contralateral knee after the first TKA, the second TKA should be performed as early as possible. If knee joint function is not well recovered after the first TKA, and patients are anxious to undergo the second TKA, surgeons can advise patients to postpone the operation based on these results.

Isolation and neuronal apoptosis inhibitory property of bacoside-A3 via downregulation of ß-amyloid induced inflammatory response.

Alzheimer's disease is one of the neurodegenerative disorders caused by neuronal degeneration and apoptosis in brain. Bacoside A and B isolated from the Bacopa monniera plant are responsible for cognitive effects. These compounds repair damaged neurons by promoting activity of kinases, synaptic activity restoration, and improvement of nerve transmission. The present study explored the effect of bacoside-A3 on ß-amyloid-induced reduction of U87MG cell viability, generation of oxidative radicals, and activation of nuclear factor-κB. The U87MG cells were stimulated with ß-amyloid (10 µM) after 24 h of bacoside-A3 pretreatment or without pretreatment to induce characteristics of Alzheimer disease in vitro. Sulforhodamine B (SRB) assay was used to count viable cells and ELISA kit for analysis of PGE2 secretion. The pretreatment with bacoside-A3 prevented ß-amyloid-mediated suppression of U87MG cell proliferation. Pretreatment of U87MG cells with bacoside-A3 prior to ß-amyloid stimulation suppressed generation of ROS in a concentration-based manner. The ß-amyloid-mediated formation of iNOS in U87MG cells was suppressed by bacoside-A3 in a dose-based manner. The ß-amyloid-mediated PGE2 secretion was suppressed by bacoside-A3 pretreatment in U87MG cells in the dose-based manner. The overexpression of COX-2 by ß-amyloid stimulation was suppressed in bacoside-A pretreated cells in the dose-based manner. The bacoside-A3 pretreatment prevented nuclear translocation of NF-κB in U87MG cells in the dose-based manner. In summary, bacoside-A3 prevented ß-amyloid-mediated suppression of U87MG cell viability, inhibited generation of oxidative radicals, PGE2, and synthesis of iNOS. Therefore, bacoside-A3 has therapeutic potential for Alzheimer disease and further in vivo studies need to be performed.

Inhibition of O-glycosylation aggravates GalN/LPS-induced liver injury through activation of ER stress.

OBJECTIVE: O-glycosylation is the most common post-translational modification of proteins, which is involved in many pathophysiological processes including inflammation. Acute liver injury is characterized by an excessive, uncontrolled inflammatory response, but the effects of aberrant O-glycosylation on acute liver injury are yet to explore. Here we aimed to investigate the role of defective O-glycosylation in D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced acute liver damage in mice. MATERIAL AND METHODS: Experimental mice were administrated with an O-glycosylation inhibitor (benzyl-a-GalNac, 5 mg/kg) at 24 h before administration of GalN/LPS. At 12 h after GalN/LPS administration, mice were sacrificed to collect blood and liver samples for further analysis. RESULTS: We found that benzyl-a-GalNac treatment-induced abundant expression of Tn antigen, which is an immature O-glycan representing abnormal O-glycosylation. Benzyl-a-GalNac pretreatment exacerbated considerably GalN/LPS-induced liver damage in mice, evidenced by significantly reduced survival rates, more severe histological alterations, and notable elevation of multiple inflammatory cytokines and chemokines. Mechanistically, benzyl-a-GalNac could trigger endoplasmic reticulum (ER) stress in the liver of mice, demonstrated by the elevated expression of glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP), both of which are hallmarks for ER stress. Inhibition of ER stress by 4-phenylbutyric acid (4-PBA) markedly abrogated benzyl-a-GalNac-mediated enhanced hepatotoxicity and systemic inflammation in GalN/LPS-treated mice. CONCLUSIONS: This study demonstrated that inhibition of O-glycosylation caused by benzyl-a-GalNac aggravated GalN/LPS-induced liver damage and systemic inflammation, which may be due to activation of ER stress.

Recombinant Tissue-Type Plasminogen Activator Study of Wake-Up Ischemic Strokes Guided by Rapid MRI.

BACKGROUND: rt-PA intravenous thrombolytic therapy and its efficacy have been widely recognized and proved for strokes. However, for patients with wake-up ischemic stroke (WUIS), they lose the opportunity to receive rt-PA intravenous thrombolytic therapy because of the difficulty of determining the onset time window. AIM: This study is aimed at investigating the intravenous thrombolytic therapy of WUIS guided by rapid MRI. METHODS: Data were collected from patients with acute ischemic stroke within 4.5 h and from WUIS patients with uncertain onset time window, who received the treatment of rt-PA intravenous thrombolytic therapy in our hospital from November 2006 to April 2018. The improved Rankin scale was used to evaluate neurological function recovery. According to the Rankin scale score, patients were divided into two groups: those with good prognosis (modified Rankin scale [mRS] score 0-1) and those with poor prognosis (mRS score 2-6). RESULTS: A total of 253 patients received rt-PA intravenous thrombolysis after head MRI evaluation; this included 177 cases of acute ischemic stroke and 76 cases of WUIS (which contains 2 death cases, 0.8% mortality; 3 cases of symptomatic bleeding, 1.2% bleeding rate; and 5 cases of aggravation, 2.0% aggravation rate). There was no statistical difference between the baseline data from the acute ischemic stroke patients with 4.5 h onset time window and the baseline data from the WUIS patients with undetermined onset time window, when the treatment was guided by rapid MRI. There were also no significant statistical differences in National Institutes of Health Stroke Scale score, Rankin scale score, symptomatic bleeding, death and aggravation of the disease between the 2 groups at 24 h, 3 days, and 7 days after admission (p < 0.05). CONCLUSION: According to the characteristic of undetermined onset time window of WUIS, more WUIS patients would be benefited from the rt-PA intravenous thrombolytic treatment when it is conducted under the guidance of rapid MRI.

Prognostic Value of Diffusion-Weighted Imaging (DWI) Apparent Diffusion Coefficient (ADC) in Patients with Hyperacute Cerebral Infarction Receiving rt-PA Intravenous Thrombolytic Therapy.

BACKGROUND The aim of this study was to investigate the potential value of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) in the prognosis of patients with hyperacute cerebral infarction (HCI) receiving intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). MATERIAL AND METHODS From June 2012 to June 2015, 58 cases of HCI (<6 h) undergoing rt-PA intravenous thrombolytic therapy (thrombolysis group) and 70 cases of HCI (<6 h) undergoing conventional antiplatelet and anticoagulant therapy (control group) in the same period were collected. DWI was conducted on all the subjects, and ADC maps were generated with Functool software to quantify ADC value. The clinical outcomes of HCI patients were observed for 3 months, and prognostic factors were analyzed. RESULTS Before thrombolysis treatment, the lesion area presented high signal intensity on DWI map and low signal intensity on ADC map, and gradually weakened signal intensity on DWI map and gradually enhanced signal intensity on ADC map were observed after thrombolysis. The ADC values of the thrombolysis group were significantly higher than those of the control group after treatment (24 h, 7 d, 30 d, and 90 d) (all P<0.05), and the ADC and rADC values in the thrombolysis group gradually increased over time (all P<0.05). Multiple logistic regression analysis showed that baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline rADC value, and stroke history were the independent factors for the prognosis of HIC patients with thrombolysis (all P<0.05). CONCLUSIONS The values of ADC and rADC may provide guidance in the prognosis of HCI patients receiving rt-PA, and the baseline rADC value is the protective factor for the prognosis of HCI patients receiving rt-PA.

Perforator Propeller Flap for Oncologic Reconstruction of Soft Tissue Defects in Trunk and Extremities.

BACKGROUND: Defects after soft tissue sarcoma resection are usually managed by myocutaneous flaps or free flaps. However, harvesting muscle will cause functional morbidities, and some regions lack reliable recipient vessel. Our purpose is to use various perforator propeller flaps for oncologic reconstruction. METHODS: Between 2008 and 2014, 33 perforator propeller flaps were performed in 24 patients to reconstruct the defects after tumor resection in trunk and extremities. Fifteen patients underwent tumor resection previously. Thirteen patients underwent adjuvant radiotherapy or chemotherapy. Flaps based on perforators adjacent to the lesions were raised and rotated in propeller fashion to repair the defects. RESULTS: Twenty-seven flaps were based on perforators of known source vessels, and 6 were harvested in freestyle fashion. The defects were repaired with 2 flaps in 4 patients and 3 flaps in 2 patients. The mean skin paddle dimension was 8.36 cm in width and 20.42 cm in length. The mean degree of flap rotation was 158.79°. Complications include partial necrosis of 6 flaps in 5 cases and venous congestion of 1 flap. In these 6 patients, 3 underwent adjuvant radiotherapy. The donor sites were primarily closed in 21 patients and skin grafted in 3 patients. No functional loss related to flap harvesting was recognized. CONCLUSIONS: The perforator propeller flaps can be used to manage the medium defects in extremities and large defects in torso after soft tissue sarcoma resection. They avoid the sacrifice of the underlying muscle and eliminate the concerns of the unavailability of recipient vessels. The perforator propeller flaps provide flexible options for versatile oncologic reconstruction in trunk and extremities. However, the impact of radiotherapy on the viability of the flaps for local reconstruction needs further investigation.

Ginsenoside Represses Symptomatic Intracerebral Hemorrhage after Recombinant Tissue Plasminogen Activator Therapy by Promoting Transforming Growth Factor-ß1.

BACKGROUND: Currently, the most effective treatment for brain ischemic stroke is recombinant tissue plasminogen activator (rt-PA); however, increased incidence of symptomatic intracerebral hemorrhage severely reduced its favorable treatment outcome. METHODS: We aimed to investigate the effect of ginsenoside (Gs) on symptomatic intracerebral hemorrhage after rt-PA treatment. Stroke patients were randomly divided into 2 treatment groups, one receiving rt-PA + placebo (Pc) and the other rt-PA + Gs. Twenty-four hours after the treatment, outcomes were assessed with transcranial Doppler (TCD) ultrasonography and National Institutes of Health Stroke Scale (NIHSS), and plasma levels of transforming growth factor-ß1 (TGF-ß1), matrix metalloproteinase (MMP)-2, and MMP-9 were also measured. After initial cotreatment, the patients were continuously administered with either Pc or Gs, and the treatment outcomes at 7 days were assessed with TCD, NIHSS, modified Rankin scale (MRS), and Glasgow outcome scale (GOS). RESULTS: Cotreatment of rt-PA with Gs significantly improved outcomes in patients compared to the Pc group, as indicated by improved TCD and NIHSS scores and reduced incidence of symptomatic intracerebral hemorrhage, which could be attributed to a Gs-induced increase in TGF-ß1 and a decrease in both MMP-2 and MMP-9 serum levels. Seven days of Gs treatment also significantly improved outcomes in patients compared to the Pc group, assessed by TCD, NIHSS, MRS, and GOS. CONCLUSION: Our study supports the clinical use of Gs as a potential supplement with rt-PA treatment, which reduces symptomatic intracerebral hemorrhage, therefore improving the treatment outcome of stroke patients.

MicroRNA profile of tumorigenic cells during carcinogenesis of lung adenocarcinoma.

To obtain microRNA (miRNA) profile and clarify their biological function in tumorigenic Sca-1(+) CD34(+) cells during carcinogenesis of lung adenocarcinoma. After intranasal infection with recombinant Adeno-Cre viruses (AdV-Cre), lung adenocarcinoma was identified pathologically in Lox-stop-lox Kras (LSL-Kras) G12D mice. Sca-1(+) CD34(+) cells were sorted by flow cytometry and tested for tumor-initiating ability, self-renewal and tumorigenicity. MiRNA profiles were obtained using microarray and further confirmed by real-time RT-PCR (qRT-PCR). MiRNA functions were predicted bioinformatically, and miR-294 function was verified to explore its role in tumor migration and invasion. Lung adenocarcinoma was induced in LSL-Kras G12D mice within 30 days. In vivo, the tumorigenicity of Sca-1(+) CD34(+) cells was 25 times stronger than Sca-1(-) CD34(-) cells. During tumorigenesis of lung adenocarcinoma, the expression of 145 miRNAs in Sca-1(+) CD34(+) cells increased and 72 miRNAs decreased (P < 0.01). Four successively up-regulated miRNAs (miR-15a*, miR-203, miR-294 and miR-295*) and three successively down-regulated ones (miR-19b, miR-483 and miR-615-5p) were identified. Among them, miR-294 could constitutively bind to 3'-UTR of matrix metalloproteinase 3 (MMP3), and down-regulate MMP3 protein expression. MiR-294 also significantly inhibited migration and invasion of Lewis lung cancer cells. MiRNAs are characteristically expressed in tumor-initiating Sca-1(+) CD34(+) cells of lung adenocarcinoma, and may play important roles during the carcinogenesis of lung adenocarcinoma.

Acute Effects of Haloperidol, Amisulpride, and Quetiapine on Bone Turnover Markers in Patients With Schizophrenia.

OBJECTIVE: This prospective study sought to compare the acute effects of haloperidol, amisulpride, and quetiapine on serum markers of bone formation and resorption in relatively young patients with minimal previous exposure to antipsychotic drugs. METHODS: Patients included in the study were randomly assigned to receive haloperidol, amisulpride, or quetiapine monotherapy in an open-label manner. Serum osteocalcin (OC, a marker of bone formation), C-terminal peptide of type I collagen (CTX, a marker of bone resorption), prolactin (PRL), estradiol, and testosterone were measured in 70 patients at baseline and after 4 weeks of antipsychotic treatment. RESULTS: A repeated-measures analysis of variance revealed a significant difference in CTX levels and in the OC to CTX ratio between treatment groups (F = 4.481, P < 0.05; F = 8.114, P < 0.01). After 4 weeks of treatment, only the amisulpride group had significantly increased CTX levels and decreased OC/CTX. In addition, an obvious increase in PRL level and a reduction of sex hormone secretion after amisulpride treatment were found. No significant changes in bone turnover were observed in the haloperidol or quetiapine groups. Notably, a positive correlation between the CTX change to the change in PRL after treatment (r = 0.255, P < 0.05) was observed. CONCLUSIONS: The PRL-raising antipsychotic drug amisulpride influenced bone turnover balance very early in the course of treatment, which may require long-term monitoring of bone metabolism. Bone resorption marker changes induced by acute antipsychotic drug treatment are likely related to increased PRL levels.

Freestyle perforator-based propeller flap of medial arm for medial elbow reconstruction.

Elbow reconstruction is challenging for reconstructive surgeons. The purpose of this report is to present the results of the use of freestyle perforator-based propeller flap designed from the medial arm region for elbow reconstruction. The defects following soft tissue sarcoma resection at the medial and posterior elbow were repaired in two patients. The dimensions of the defects were 11 × 7 cm(2) and 10 × 7 cm(2). Two perforators were identified in each case using Doppler ultrasound probe in the medial arm, adjacent to the defect. The perforator with visible pulsation was chosen as the pedicle vessel, which was 12-cm and 7-cm proximal to the medial epicondyle. An elliptical flap, extending almost the full length of arm, was raised and rotated 180° to repair medial elbow defects. The sizes of the flaps were 17 × 8 cm(2) and 11 × 7 cm(2). The donor sites were closed directly. Both flaps survived; temporary venous congestion occurred in one case. There were no other postoperative complications. These cases illustrated that the medial arm flap might be used for reconstruction of medial elbow defects with this freestyle perforator-based propeller flap design.

KIAA0101 mRNA overexpression in peripheral blood mononuclear cells acts as predictive marker for hepatic cancer.

KIAA0101 always overexpresses in tumor tissues, which is also a marker of tumor recurrence. This study aims to explore whether overexpression of KIAA0101 mRNA in peripheral blood mononuclear cells (PBMCs) could act as a noninvasive and predictive biomarker of hepatic cancer. Real-time polymerase chain reaction (RT-PCR) was employed to detect KIAA0101 mRNA expression in PBMCs isolated from 93 hepatic cancer patients and 55 healthy individuals. The diagnostic sensitivity and specificity of KIAA0101 mRNA, CEA, and CD44V were analyzed and compared. A multivariate logistic regression analysis was utilized to analyze risk factors for overall survival of hepatic cancer patients. A concordance analysis was employed to compare the overexpression of KIAA0101 mRNA with clinicopathological diagnosis. All of the 93 hepatic cancer patients were followed up routinely at least 36 months or until death to analyze the 3-year overall survival rate. The results indicated that KIAA0101 mRNA expression was increased significantly in hepatic patients' PBMCs, when compared with that of healthy individuals (P < 0.05). Both the sensitivity and specificity of KIAA0101 mRNA in PBMCs were enhanced significantly compared with those of the CEA and CD44V biomarkers. The multivariate logistic regression analysis indicated that the KIAA0101 mRNA level and pTNM stage were significantly related with the overall survival of the hepatic patients. There was a better concordance between KIAA0101 mRNA overexpression and clinicopathological diagnosis for hepatic cancer (kappa = 0.914, P < 0.001). KIAA0101 mRNA overexpression in PBMCs decreased the 3-year survival rate significantly. In conclusion, overexpression of KIAA0101 mRNA in PBMCs could act as a predictive biomarker for hepatic cancer and has a better sensitivity and specificity.

On the security of a novel probabilistic signature based on bilinear square Diffie-Hellman problem and its extension.

Probabilistic signature scheme has been widely used in modern electronic commerce since it could provide integrity, authenticity, and nonrepudiation. Recently, Wu and Lin proposed a novel probabilistic signature (PS) scheme using the bilinear square Diffie-Hellman (BSDH) problem. They also extended it to a universal designated verifier signature (UDVS) scheme. In this paper, we analyze the security of Wu et al.'s PS scheme and UDVS scheme. Through concrete attacks, we demonstrate both of their schemes are not unforgeable. The security analysis shows that their schemes are not suitable for practical applications.

Comparison of fast MRI-based individual thrombolysis therapy for patients with superacute infarction.

BACKGROUND: The aim of this study is to investigate the outcomes of magnetic resonance imaging (MRI)-based individual thrombolysis therapy using recombinant tissue plasminogen activator (rt-PA) in patients with superacute infarction, comparing the outcome in 1 group of patients treated within 4.5 hours compared with 4.5- to 12-hour window treatment group. METHODS: We studied 135 patients stratified to 2 different groups based on whether they presented with stroke symptoms within 4.5 hours (4.5-hour group, 72 patients) or between 4.5 and 12 hours (4.5- to 12-h group, 63 patients). All patients were treated with rt-PA after MRI confirmed superacute ischemic stroke (hyperintense in diffusion-weighted imaging but no hypointense change in T2-weighted image (T2WI) or fluid-attenuated inversion recovery). Clinical neurologic deficit was evaluated using the National Institutes of Health Stroke Scale on admission, at 24 hours, and 7 days later. A 90-day clinical outcome was assessed using the modified Rankin Scale (mRS). RESULTS: There was no significant difference in the clinical outcome between the patients treated with thrombolysis within the first 4.5 hours and those treated between 4.5 and 12 hours. The 2 groups both had recanalization, mRS, and favorable outcome at 90 days (P > .05). CONCLUSIONS: Our study suggested that fast MR-based thrombolysis using rt-PA was safe and reliable in superacute infarction within 4.5 hours and 4.5-12 hours poststroke.

A secure RFID authentication protocol for healthcare environments using elliptic curve cryptosystem.

With the fast advancement of the wireless communication technology and the widespread use of medical systems, the radio frequency identification (RFID) technology has been widely used in healthcare environments. As the first important protocol for ensuring secure communication in healthcare environment, the RFID authentication protocols derive more and more attentions. Most of RFID authentication protocols are based on hash function or symmetric cryptography. To get more security properties, elliptic curve cryptosystem (ECC) has been used in the design of RFID authentication protocol. Recently, Liao and Hsiao proposed a new RFID authentication protocol using ECC and claimed their protocol could withstand various attacks. In this paper, we will show that their protocol suffers from the key compromise problem, i.e. an adversary could get the private key stored in the tag. To enhance the security, we propose a new RFID authentication protocol using ECC. Detailed analysis shows the proposed protocol not only could overcome weaknesses in Liao and Hsiao's protocol but also has the same performance. Therefore, it is more suitable for healthcare environments.

An efficient anonymous authentication scheme for wireless body area networks using elliptic curve cryptosystem.

With the development of wireless networks and medical sensors, wireless body area networks are playing more and more important role in the field of healthcare service. The data transmitted in WBANs is very sensitive since it will be used in clinical diagnoses or measurements. Therefore, security and privacy of communication in WBANs derive increasing attentions from the academia and industry. In this paper, we propose an identity (ID)-based efficient anonymous authentication scheme for WBANs using elliptic curve cryptosystem (ECC). Due to the ID-based concept, there is no certificate is needed in the proposed scheme. Moreover, the proposed scheme not only provides mutual authentication between the client and the application provider but also provides client anonymity. Performance analysis shows that improvements of 50.58% and 3.87% in the client side and the application provider side separately. Then the proposed scheme is more suitable for WBANs.

Hidden blood loss and its influencing factors after cement augmentation for vertebral metastasis.

Introduction: Few studies have focused on the risk factors for hidden blood loss (HBL) during cement augmentation surgery for pathologic vertebral compression fraction (PVCFs). Method: From January 2014 to December 2020, the clinical data of 169 PVCF patients (283 levels) who underwent cement augmentation were retrospectively analysed. HBL was calculated according to the linear Gross formula using the patient's average Hct during the perioperative course and PBV. Multivariate linear regression analysis was performed to evaluate the independent factors associated with HBL. Results: The mean HBL was 448.2 ± 267.2 ml, corresponding to 10.8% ± 6.2% of the patient blood volume (PBV). There were significant differences between pre- and postoperative haematocrit (Hct) (P < 0.001) and Hb (P < 0.001), and 132 patients developed anaemia postoperatively, while 79 patients had anaemia preoperatively (P < 0.001). Multivariate linear regression revealed that bone lesion quality (p = 0.028), number of PVCFs (p = 0.002), amount of bone cement (p = 0.027), bone cement leakage (p = 0.001), and percentage of vertebral height loss (VHL) (p = 0.011) were independent risk factors for HBL. Conclusion: In conclusion, patients with lytic vertebral destruction, larger amounts of bone cement, greater amounts of bone cement leakage, more PVCF(s), and greater percentages of VHL may be more prone to HBL.

Synthesis, structure analysis, antitumor evaluation and 3D-QSAR studies of 3,6-disubstituted-dihydro-1,2,4,5-tetrazine derivatives.

3,6-Diaryl-dihydro-1,2,4,5-tetrazine derivatives were synthesized and their structures were confirmed by single-crystal X-ray diffraction. Monosubstituted dihydrotetrazines are the 1,4-dihydro structure, but disubstituted dihydrotetrazines are the 1,2-dihydro structure. The results of further research indicated there may be a rearrangement during the synthesis process of disubstituted dihydrotetrazines. Their antitumor activities were evaluated against A-549 and P388 cells in vitro. The results showed several compounds to be endowed with cytotoxicity in the low micromolar range. Two compounds were highly effective against A-549 cell and IC50 values were 0.575 and 2.08 µM, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 37 1,2,4,5-tetrazine derivatives with antitumor activity against A-549 cell. Models with good predictive abilities were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.744 and 0.757, respectively. Conventional r(2) values were 0.978 and 0.988, respectively, the predicted R(2) values were 0.916 and 0.898, respectively. The results provide the tool for guiding the design and synthesis of novel and more potent tetrazine derivatives.

Anti-tumor effects of atractylenolide I isolated from Atractylodes macrocephala in human lung carcinoma cell lines.

Atractylenolide I (ATL-1) is the major sesquiterpenoid of Atractylodes macrocephala. This study was designed to investigate whether ATL-1 induced apoptosis in A549 and HCC827 cells in vitro and in vivo. In our results, ATL-1 significantly decreased the percentage of in vitro viability, in a dose-dependent manner. In addition, DAPI staining and flow cytometry tests demonstrated the induction of apoptosis by ATL-I. Western blot analysis indicated that the protein levels of caspase-3, caspase-9 and Bax were increased in A549 and HCC827 cells after ATL-I exposure; to the contrary, the expressions of Bcl-2, Bcl-XL were decreased after treatment with ATL-1. In the in vivo study, ATL-I effectively suppressed tumor growth (A549) in transplanted tumor nude mice with up-regulation of caspase-3, caspase-9, and Bax and down-regulation of Bcl-2 and Bcl-XL. In conclusion, our results demonstrated that ATL-I has significant antitumor activity in lung carcinoma cells, and the possible mechanism of action may be related to apoptosis induced by ATL-I via a mitochondria-mediated apoptosis pathway.