Cardiovascular safety of zoledronic acid in the treatment of primary osteoporosis: A meta-analysis and systematic review.

PURPOSE: Osteoporosis is intimately linked to cardiovascular disease and it has been uncertain that zoledronic acid is not correlated with cardiovascular disease. We intended to assess the cardiovascular safety of zoledronic acid in the treatment of primary osteoporosis. METHODS: We included only randomized controlled trials (RCTs) of patients with osteoporosis receiving zoledronic acid or a placebo. We systematically searched PubMed, Embase, Web of Science, Cochrane CENTRAL, Scopus, the Chinese National Knowledge Infrastructure, ClinicalTrials.gov, and ICTRP from the time of database creation to April 5, 2023. Two investigators extracted data independently on study characteristics, outcomes of interest, and risk of bias based on PRISMA guidelines. RESULTS: As of April 5, 2023, our search identified 32,361 records, and after excluding these records, 9 RCTs were included in the meta-analysis. The overall risk ratio for cardiovascular events with zoledronic acid for primary osteoporosis compared with placebo was 1.15 (95 % CI 1.05-1.26, I2=12 %, P = 0.002), while the risk of major adverse cardiovascular events with zoledronic acid (RR 1.03, 95 % CI 0. 89-1.18, I2=21 %, P = 0.71) was not significant, possibly due to atrial fibrillation (RR 1.21, 95 % CI 0.99-1.47, I2=0 %, P = 0.06) versus the increased relative risk of arrhythmia (RR 1.30, 95 % CI 1.11-1.52, I2=34 %, P = 0.001). Overall, the cardiovascular risk of zoledronic acid for the treatment of primary osteoporosis was not significant; however, the relative risk of elevated atrial fibrillation and arrhythmias remains to be further studied. CONCLUSIONS: In women with primary osteoporosis, zoledronic acid may increase the risk of atrial fibrillation (P = 0.06) and arrhythmias (P = 0.001) compared with placebo, independent of the risk of major adverse cardiovascular events, angina, and heart failure. However, the sample size of men with primary osteoporosis is small, and the cardiovascular risk of zoledronic acid in men with osteoporosis is uncertain.

Proposal for collinear integrated acousto-optic tunable filters featuring ultrawide tuning ranges and multi-band operations.

Integrated optical tunable filters are key components for a wide spectrum of applications, including optical communications and interconnects, spectral analysis, and tunable light sources, among others. Compared with their thermo-optic counterparts, integrated acousto-optic (AO) tunable filters provide a unique approach to achieve superior performance, including ultrawide continuous tuning ranges of hundreds of nm, low power consumption of sub-mW and fast tuning speed of sub-µs. Based on suspended one-dimensional (1D) AO waveguides in the collinear configuration, we propose and theoretically investigate an innovative family of integrated AO tunable filters (AOTFs) on thin-film lithium niobate. The AO waveguides perform as tunable wavelength-selective narrow-band polarization rotators, where highly efficient conversion between co-propagating TE0 and TM0 modes is enabled by the torsional acoustic A1 mode, which can be selectively excited by a novel antisymmetric wavefront interdigital transducer. Furthermore, we systematically and quantitatively explore the possibilities of exciting modulated acoustic waves, which contain multiple frequency components, along the AO waveguide to achieve independently reconfigurable multi-band operations, with tunable time-variant spectral shapes. By incorporating a complete set of ultrawide-band polarization-handling components, we have proposed and theoretically investigated several representative monolithic AOTF configurations, featuring different arrangements of single or cascaded identical AO waveguides. One of the present AOTF designs exhibits a theoretical linewidth of ∼8 nm (∼4 nm), a sidelobe suppression ratio of ∼75 dB, and theoretically no excess loss at the center wavelength of 1550 nm (1310 nm), with an ultrawide tuning range of 1.25-1.65 µm (from O-band to L-band), a fast tuning speed of 0.14 µs, and a low power consumption of a few mW.

High-performance lithium-niobate-on-insulator optical filter based on multimode waveguide gratings.

A high-performance optical filter is proposed and realized with multimode waveguide grating (MWG) and two-mode multiplexers on the x-cut lithium-niobate-on-insulator (LNOI) platform for the first time, to the best of our knowledge. The present optical filter is designed appropriately to avoid material anisotropy as well as mode hybridness, and has a low excess loss of 0.05 dB and a high sidelobe suppression ratio (SLSR) of 32 dB in theory with Gaussian apodization. The fabricated filters show a box-like response with 1-dB bandwidth of 6-23 nm, excess loss of ∼0.15 dB, sidelobe suppression ratio of >26 dB. The device performance is further improved with a sidelobe suppression ratio as high as 48 dB and a low excess loss of ∼0.25 dB by cascading two identical MWGs.

Demonstration of high-speed thin-film lithium-niobate-on-insulator optical modulators at the 2-µm wavelength.

Optical communication wavelength is being extended from the near-infrared band of 1.31/1.55 µm to the mid-infrared band of 2 µm or beyond for satisfying the increasing demands for high-capacity long-distance data transmissions. An efficient electro-optic (EO) modulator working at 2 µm is highly desired as one of the indispensable elements for optical systems. Lithium niobate (LiNbO3) with a large second-order nonlinear coefficient is widely used in various EO modulators. Here, we experimentally demonstrate the first Mach-Zehnder EO modulator working at 2 µm based on the emerging thin-film LiNbO3 platform. The demonstrated device exhibits a voltage-length product of 3.67 V·cm and a 3-dB-bandwidth of >22 GHz which is limited by the 18 GHz response bandwidth of the photodetector available in the lab. Open eye-diagrams of the 25 Gb/s on-off keying (OOK) signals modulated by the fabricated Mach-Zehnder EO modulator is also measured experimentally with a SNR of about 14 dB.

The pharmacokinetics and tissue distribution of coumaroylspinosin in rat: A novel flavone C-glycoside derived from Zizyphi Spinosi Semen.

Zizyphi Spinosi Semen (ZSS) has a long history of sedative-hypnotic use in China. As a novel flavone C-glycoside, coumaroylspinosin is a main flavonoid only found in ZSS. Up to now, its pharmacokinetic information and tissue distribution in vivo are not available yet. With a simple, rapid and sensitive HPLC-MS/MS method, the pharmacokinetics and tissue distribution of coumaroylspinosin were investigated in Sprague-Dawley (SD) rats after its intravenous administration. Puerarin was used as the internal standard (IS). The samples were extracted by a simple protein precipitation method with methanol. The MS analysis was performed with multiple reaction monitoring (MRM), and the transitions were set at m/z 753.3→427.0 for coumaroylspinosin and m/z 415.3→295.3 for IS, respectively. The method was successfully applied for investigating the pharmacokinetics and tissue distribution of coumaroylspinosin in Sprague Dawley (SD) rats after tail vein injection with 4.0mg/kg of the flavonoid. The calibration curves covered over the range of 0.02-10µg/mL in plasma and various tissues samples with good linearity(r≥0.9956). The lower limit of quantification (LLOQ) in all samples was less than 20ng/mL. The intra- and inter-day precisions were below 15% and accuracy was from -3.78% to 4.68%. No significant matrix effect was observed, and the average extraction recovery was acceptable. Coumaroylspinosin could be cleared quickly from the rat plasma with the half-life (t1/2) of 1.86±0.15h. It was distribute widely in vivo, and the main tissue depots of coumaroylspinosin in rats were found to be intestine, muscle and lung. With the method, the pharmacokinetic parameters and tissue distribution of coumaroylspinosin in SD rats were investigated for the first time. The results demonstrated that coumaroylspinosin was distributed widely and rapidly in various rat tissues after intravenous administration.