SGLT2 inhibitors as a potential therapeutic option for pulmonary hypertension: mechanisms and clinical perspectives.

Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.

208 W single-frequency 1064 nm laser based on a single-crystal fiber master-oscillator power amplifier.

High-power all-solid-state continuous-wave (CW) single-frequency laser with high linear polarization is a significant source for quantum optics and precision measurement. In this Letter, a high-power linearly polarized CW single-frequency laser based on the single-crystal fiber (SCF) master-oscillator power amplifier (MOPA) is presented, in which a homemade 140 W low-noise CW single-frequency laser and a Nd:YAG SCF are firstly employed as the seed laser and the medium of the MOPA, respectively. The mode-matching between the pump laser propagated with waveguide form and the freely propagated seed laser is optimized by considering the influence of the degradations of the polarization and the beam quality. Finally, when the incident powers of the pump and seed lasers are 262.6 W and 126.3 W, respectively, the seed waist radius is optimized to 200 µm. In this case, the output power of the linearly polarized laser reaches up to 208 W, which is the highest output power, to the best of our knowledge. The presented results provide a good reference for implementing a high power and high degree of the polarization and good beam quality laser based on the SCF MOPA.

Self-mode-matching compact low-noise all-solid-state continuous wave single-frequency laser with output power of 140 W.

The high power all-solid-state continuous wave single-frequency laser is a significant source for science and application due to good beam quality and low noise. However, the output power of the laser is usually restricted by the harmful thermal lens effect of the solid gain medium. To address this issue, we develop a self-mode-matching compact all-solid-state laser with a symmetrical ring resonator in which four end-pumped Nd:YVO4 laser crystals are used for both laser gain media and mode-matching elements. With this ingenious design, the thermal lens effect of every laser crystal can be controlled and the dynamic of the designed laser including the stability range and the beam waist sizes at crystals can be manipulated only by adjusting the pump power used on each laser gain medium. Under an appropriate combination of pump powers on four crystals, self-mode-matching in a resonator is realized. A stable CW single-frequency at 1064 nm with 140-W power, 102-kHz linewidth, and low intensity noise is obtained. The presented design paves an effective way to further scale-up the output power of a compact laser by employing more pieces of gain media.

Self-injection locked CW single-frequency tunable Ti:sapphire laser.

A self-injection locked continuous-wave (CW) single-frequency tunable Ti:sapphire laser is demonstrated in this paper. Unidirectional operation of the presented Ti:sapphire laser is achieved by using a retro-reflecting device which can retro-reflect a seed laser beam from one direction back into the counter-propagating field. On the basis, the influence of the transmission of output coupler on the unidirectional operation is investigated and it is found that stable unidirectional and single-frequency operation of the Ti:sapphire laser is achieved when the loss difference between both output directions is larger than a certain value, which is easy to be realized by choosing the transmission of output coupler. When the output coupler with transmission of 6.5% is utilized, the maximal 5 W CW single-frequency Ti:sapphire laser with stable unidirectional operation is obtained with the pump power of 18 W. The measured power stability and M2 are better than ±0.9% and 1.1, respectively. The maximal tuning range and continuous frequency-tuning ability are 120 nm and 40.75 GHz, respectively.

Single-frequency CW Ti:sapphire laser with intensity noise manipulation and continuous frequency-tuning.

We present a tunable single-frequency CW Ti:sapphire laser with intensity noise manipulation. The manipulation of the laser intensity noise is realized by varying the frequency of the modulation signal loaded on the electrodes of an intracavity electro-optic etalon. A lithium niobate (LiNbO3) crystal is used to act as the electro-optic etalon, and its electro-optic effect is utilized to modulate the intracavity laser intensity for locking itself to the oscillating wavelength of the laser to implement continuous frequency-tuning. When the electro-optic etalon is locked to the oscillating mode of the Ti:sapphire laser with arbitrarily selected modulation frequency, the maximal continuous frequency-tuning range can reach to 20 GHz, and the laser intensity noise is successfully manipulated simultaneously.

Generation of high-power single-frequency 397.5 nm laser with long lifetime and perfect beam quality in an external enhancement-cavity with MgO-doped PPSLT.

Continuous-wave single-frequency high power 397.5 nm laser with long lifetime and perfect beam quality is one of the essential resource to generate the squeezed and entanglement states of optical beams resonant with D1 line of Rubidium atoms at 795 nm. In this paper, We present the experimental generation of single-frequency high power 397.5 nm ultra-violet (UV) laser with long lifetime and perfect beam quality by using periodically poled MgO-doped stoichiometric lithium tantalate (MgO:PPSLT) crystal as the frequency doubler in an external enhancement ring cavity. When the transmission of the input coupler is 5.5%, the maximal output power of single-frequency 397.5 nm UV laser of 407 mW is obtained under the incident pump power of 1.9 W with the corresponding conversion efficiency of 22.8%. When the output power is 290 mW, the measured power stability and the beam quality are lower than 0.28% and 1.02, respectively. Moreover, any damage is not observed in our experiment which lasts about 1 year.

Direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension patients: A retrospective cohort study.

INTRODUCTION: Direct oral anticoagulants (DOACs) are increasingly prescribed for life-long anticoagulation in chronic thromboembolic pulmonary hypertension (CTEPH) patients, despite not being recommended in the guidelines. This study aims to evaluate the efficacy and safety of DOACs in CTEPH patients. METHODS: From May 2013 to December 2022, patients who were first diagnosed with CTEPH in Fuwai Hospital and started long-term anticoagulation treatment with warfarin or DOACs were retrospectively included and followed up until (1) death, (2) transition to other kinds of anticoagulants, or (3) discontinuation of anticoagulation. Propensity score matching was used to balance confounding bias of baseline characteristics. All-cause death, major bleeding, clinically relevant nonmajor bleeding and venous thromboembolism (VTE) recurrence were obtained and analysed. RESULTS: After propensity score matching, 115 patients taking warfarin and 206 patients taking DOACs were included in our study and followed up for 5.5 [3.4, 7.1] years. There was no significant difference of survival between the warfarin and the DOAC group (p = 0.77). The exposure adjusted event rate of major bleeding (0.3 %/person-year vs 0.4 %/person-year, p = 0.705) and clinically relevant nonmajor bleeding (3.1 %/person-year vs 3.2 %/person-year, p > 0.999) was similar between two groups. The exposure adjusted rate of VTE recurrence was significantly higher in the DOAC group (1.5 %/person-year vs 0.3 %/person-year, p = 0.030). CONCLUSION: In anticoagulation of CTEPH patients, DOACs have similar survival rate, similar risk of bleeding but higher risk of VTE recurrence than warfarin.

Functional follow-up after endoscopic calcaneoplasty for Haglund's deformity using the biodex isokinetic muscle testing system: A case series.

Isokinetic muscle strength test implemented by the Biodex system is a method used for evaluating muscle function that has been applied clinically in the field of sports and rehabilitation medicine. However, information on its application on Haglund's deformity remain insufficient. Therefore, the present study examined the effectiveness of the muscle strength test using the Biodex system in evaluating the recovery of athletic capacity in patients with Haglund's deformity following endoscopic surgery. In total, 34 patients treated by the authors from June 2012 to November 2018 at Peking University Third Hospital (Beijing, China) were included. To compare muscle strength before surgery, then 3 and 6 months after surgery, using the uninjured side as the control, the Biodex system test was conducted in parallel to the collection of the American Orthopaedic Foot and Ankle Score values and visual analog scale scores. The Biodex system test results showed that Haglund's deformity mainly hinders plantar flexion strength. Patients recovered daily living capacity within 3 months and athletic capacity within 6 months following surgery, which matched the AOFAS values, VAS scores and the self-assessments of the patients. These findings suggest that the Biodex system can dynamically reflect the degree of postoperative recovery in Haglund's deformity.