Objective
To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA).
Methods
In this multicenter, randomized, sham‐controlled ...trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent‐to‐treat population, which included all randomized participants who had ≥1 post‐baseline measurement.
Results
Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between‐group differences were 13.0% (97.5% confidence interval 97.5% CI 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI −1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26.
Conclusion
Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow‐up.
Azathioprine is used as a first-line treatment to prevent relapses of neuromyelitis optica spectrum disorder (NMOSD). Tocilizumab has been reported to reduce NMOSD disease activity in retrospective ...case reports. We aimed to compare the safety and efficacy of tocilizumab and azathioprine in patients with highly relapsing NMOSD.
We did an open-label, multicentre, randomised, phase 2 trial at six hospitals in China. We recruited adult patients (aged ≥18 years) with highly relapsing NMOSD diagnosed according to 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, who had an Expanded Disability Status Scale (EDSS) score of 7·5 or lower, and had a history of at least two clinical relapses during the previous 12 months or three relapses during the previous 24 months with at least one relapse within the previous 12 months. Patients were randomly assigned (1:1) to intravenous tocilizumab (8 mg/kg every 4 weeks) or oral azathioprine (2–3 mg/kg per day) by an independent statistician using computer-generated randomisation software with permuted blocks of four. The central review committee, EDSS raters, laboratory personnel, and radiologists were masked to the treatment assignment, but investigators and patients were aware of treatment allocation. The minimum planned duration of treatment was 60 weeks following randomisation. The primary outcome was time to first relapse in the full analysis set, which included all randomly assigned patients who received at least one dose of study drug, and the per-protocol population, which included all patients who used azathioprine or tocilizumab as monotherapy. For the analyses of the primary outcome, the patients were prespecified into two subgroups according to concomitant autoimmune disease status. Safety was assessed in the full analysis set. This study is registered with ClinicalTrials.gov, NCT03350633.
Between Nov 1, 2017, and Aug 3, 2018, we enrolled 118 patients, of whom 59 were randomly assigned to tocilizumab and 59 were randomly assigned to azathioprine. All 118 patients received one dose of study drug and were included in the full analysis set. 108 participants were included in the per-protocol analysis (56 in the tocilizumab group and 52 in the azathioprine group). In the full analysis set, median time to the first relapse was longer in the tocilizumab group than the azathioprine group (78·9 weeks IQR 58·3–90·6 vs 56·7 32·9–81·7 weeks; p=0·0026). Eight (14%) of 59 patients in the tocilizumab group and 28 (47%) of 59 patients in the azathioprine group had a relapse at the end of the study (hazard ratio HR 0·236 95% CI 0·107–0·518; p<0·0001). In the per-protocol analysis, 50 (89%) of 56 patients in the tocilizumab group were relapse-free compared with 29 (56%) of 52 patients in the azathioprine group at the end of the study (HR 0·188 95% CI 0·076–0·463; p<0·0001); the median time to first relapse was also longer in the tocilizumab group than the azathioprine group (67·2 weeks IQR 47·9–77·9 vs 38·0 23·6–64·9; p<0·0001). In the prespecified subgroup analysis of the full analysis set stratified by concomitant autoimmune diseases, among patients without concomitant autoimmune diseases, three (9%) of 34 patients in the tocilizumab group and 13 (35%) of 37 patients in the azathioprine group had relapsed by the end of the study. Among patients with concomitant autoimmune diseases, a lower proportion of patients in the tocilizumab group had a relapse than in the azathioprine group (five 20% of 25 patients vs 15 68% of 22 patients; HR 0·192 95% CI 0·070–0·531; p=0·0004). 57 (97%) of 59 patients in the tocilizumab group and 56 (95%) of 59 patients in the azathioprine group had adverse events. Treatment-associated adverse events occurred in 36 (61%) of 59 tocilizumab-treated patients and 49 (83%) of 59 azathioprine-treated patients. One death (2%) occurred in the tocilizumab group and one (2%) in the azathioprine group, but neither of the deaths were treatment-related.
Tocilizumab significantly reduced the risk of a subsequent NMOSD relapse compared with azathioprine. Tocilizumab might therefore be another safe and effective treatment to prevent relapses in patients with NMOSD.
Tianjin Medical University, Advanced Innovation Center for Human Brain Protection, National Key Research and Development Program of China, National Science Foundation of China.
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•An explicit expression of the vibrational partition function for the improved Manning-Rosen potential model is presented.•Analytical expressions of four thermodynamic functions are ...given.•Behaviors of the thermodynamic functions for the 7Li2 molecule are discussed.
We present an explicit expression of the vibrational partition function for the improved Manning-Rosen potential energy model. We give analytical expressions for the vibrational mean energy, vibrational specific heat, vibrational free energy, and vibrational entropy for diatomic molecules. The properties of these thermodynamic functions for the a3Σu+ state of the 7Li2 molecule are discussed in detail.
We report an improved multiparameter exponential‐type potential (MPETP) energy model for diatomic molecules. It is found that this potential is identical to the Tietz potential in the realm of ...diatomic molecules. The efficiency of the improved MPETP is clarified by simulating the internuclear interaction potential curve for the A (3Π1) state of the chlorine monofluoride molecule.
In this work, the improved version of the multiparameter exponential‐type potential (MPETP) energy model is reported for diatomic molecules. The efficiency of the improved MPETP is clarified by simulating the internuclear interaction potential curves for the A (3Π1) state of the chlorine monofluoride molecule and for the X2∑+ state of the carbon monophosphide (CP) molecule.
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•We present an explicit representation of molar Gibbs free energy for gaseous substances.•The molar Gibbs free energy calculation model is only related to three molecular ...constants.•Gibbs free energies of gaseous phosphorus dimer are excellently predicted.
We establish an analytical representation for the prediction of the molar Gibbs free energies of gaseous diatomic molecule substances. By comparing the predicted values to the experimental data for the gaseous phosphorus dimer, the availability of the Gibbs free energy calculation model is verified. The present model is related to three molecular constants and away from the need of lots of experimental spectroscopy data.
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•We present vibrational partition function for the improved Manning-Rosen potential.•Analytical expressions of four thermodynamic functions are given.•Behaviors of the thermodynamic ...functions for the Na2 molecule are discussed.
We present a closed-form expression of the classical vibrational partition function for the improved Rosen-Morse potential energy model. We give explicit expressions for the vibrational mean energy, vibrational specific heat, vibrational free energy, and vibrational entropy for diatomic molecule systems. The properties of these thermodynamic functions for the Na2 dimer are discussed in detail. We find that the improved Rosen-Morse potential model is superior to the harmonic oscillator in calculating the heat capacity for the Na2 molecules.
By employing the dissociation energy and the equilibrium internuclear distance for a diatomic molecule as explicit parameters, we construct an improved Pöschl–Teller potential energy model. We ...analyze the average absolute deviations of the improved Pöschl–Teller and Morse potentials from the experimental Rydberg–Klein–Rees (RKR) potentials for six diatomic molecules. It is found that the improved Pöschl–Teller potential is more accurate than the Morse potential in fitting experimental RKR potential curves over a large range of internuclear distances for six molecules examined.
This article presents an improved Pöschl–Teller potential energy model, and gives the comparison of the improved Pöschl–Teller potential and Morse potential. Initially proposed in the 30s, the Pöschl–Teller potential energy model in an analytical potential to model diatomic interactions. By employing the dissociation energy and the equilibrium internuclear distance for a diatomic molecule as explicit parameters, an improved Pöschl–Teller potential energy model is now proposed. It is found that this improved potential is more accurate than the Morse potential in fitting experimental RKR potential curves over a large range of internuclear distances for six molecules examined.
MiR-221 and miR-222 (miR-221/222) are frequently up-regulated in various types of human malignancy including glioblastoma. Recent studies have reported that miR-221/222 regulate cell growth and cell ...cycle progression by targeting p27 and p57. However the underlying mechanism involved in cell survival modulation of miR-221/222 remains elusive.
Here we showed that miR-221/222 inhibited cell apoptosis by targeting pro-apoptotic gene PUMA in human glioma cells. Enforced expression of miR-22/222 induced cell survival whereas knockdown of miR-221/222 rendered cells to apoptosis. Further, miR-221/222 reduced PUMA protein levels by targeting PUMA-3'UTR. Introducing PUMA cDNA without 3'UTR abrogated miR-221/222-induced cell survival. Notably, knockdown of miR-221/222 induces PUMA expression and cell apoptosis and considerably decreases tumor growth in xenograft model. Finally, there was an inverse relationship between PUMA and miR-221/222 expression in glioma tissues.
To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
By employing the improved Greene–Aldrich approximation scheme to deal with the centrifugal term, we solve approximately the Klein–Gordon equation with the improved expression of the Manning–Rosen ...empirical potential energy model. The bound state energy equation and the unnormalized radial wave functions have been approximately obtained by using the supersymmetric WKB approach and the function analysis method. The relativistic vibrational transition frequencies for the a3Σu+ state of 7Li2 molecule have been computed by using the Manning–Rosen potential model. The relativistic vibrational transition frequencies are in good agreement with the observed data.
► Bound state solutions of the Klein–Gordon equation with the improved expression of the Manning–Rosen potential energy model are explored. ► Relativistic vibrational transition frequencies for the a3Σu+ state of 7Li2 molecule are presented. ► Relativistic vibrational transition frequencies are in good agreement with the observed data.
The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer ...cells and the molecular mediators involved in these processes.
MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines. Chromatin immunoprecipitation and luciferase reporter assay were performed to explore the transactivation of target LncRNA by CAFs. A series of in vitro assays was performed with RNAi-mediated knockdown to elucidate the function of LncRNA. An orthotopic mouse model of MDA-MB-231 was conducted to confirm the mechanism in vivo.
Here we reported that TGF-β1 was top one highest level of cytokine secreted by CAFs as revealed by cytokine antibody array. Paracrine TGF-β1 was essential for CAFs induced EMT and metastasis in breast cancer cells, which is a crucial mediator of the interaction between stromal and cancer cells. CAF-CM significantly enhanced the HOTAIR expression to promote EMT, whereas treatment with small-molecule inhibitors of TGF-β1 attenuated the activation of HOTAIR. Most importantly, SMAD2/3/4 directly bound the promoter site of HOTAIR, located between nucleotides -386 and -398, -440 and -452, suggesting that HOTAIR was a directly transcriptional target of SMAD2/3/4. Additionally, CAFs mediated EMT by targeting CDK5 signaling through H3K27 tri-methylation. Depletion of HOTAIR inhibited CAFs-induced tumor growth and lung metastasis in MDA-MB-231 orthotopic animal model.
Our findings demonstrated that CAFs promoted the metastatic activity of breast cancer cells by activating the transcription of HOTAIR via TGF-β1 secretion, supporting the pursuit of the TGF-β1/HOTAIR axis as a target in breast cancer treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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