Research progress on pharmacological effects and bioavailability of berberine.

Berberine (BBR), a benzylisoquinoline alkaloid obtained from natural medicines such as coptidis rhizoma, has a wide range of pharmacological activities such as protecting the nervous system, protecting the cardiovascular system, anti-inflammatory, antidiabetic, antihyperlipidemic, antitumor, antibacterial, and antidiarrheal. However, factors such as poor solubility, low permeability, P-glycoprotein (P-gp) efflux, and hepatic-intestinal metabolism result in BBR having a low bioavailability (< 1%), which restricts its application in clinical settings. Therefore, improving its bioavailability is a prerequisite for its clinical applications. This review summarizes the various pharmacological effects of BBR and analyzes the main reasons for its poor bioavailability. It introduces methods to improve the bioavailability of BBR through the use of absorption enhancers and P-gp inhibitors, structural modification of BBR, and preparation of BBR salts and cocrystals as well as the development of new formulations and focuses on the bioavailability study of the new formulations of BBR. The research of BBR was also prospected in order to provide reference for the further research of BBR.

2.3-µm single-frequency Tm: ZBLAN fiber amplifier with output power of 1.41 W.

We present here the first watt-level single-frequency thulium-doped ZBLAN fiber amplifier system operating at a wavelength of 2.3 µm. Continuous-wave output of up to 1.41 W was generated from a two-stage Tm: ZBLAN fiber amplifier with direct ground-state pumping at 793 nm. Seeded by a single-frequency distributed feedback diode laser at 2332 nm, the thulium-doped ZBLAN fiber amplifier emitted a laser with linewidth no more than 10 MHz at maximal output power. This study examines the impact of a 2.3-µm seed on the competitive laser transition of 2 µm. The findings indicate that direct pumping of a Tm fiber amplifier holds the potential for achieving higher power output within the 2.3-µm band.

High power mid-infrared fiber amplifier at 3.1†µm by acetylene-filled hollow-core fibers.

We characterized high-power continuous-wave (CW) and pulsed mid-infrared (mid-IR) fiber amplifiers at a wavelength of 3.1 µm in acetylene-filled hollow-core fibers (HCFs) with a homemade seed laser. A maximum CW power of 7.9 W was achieved in a 4.2-m HCF filled with 4-mbar acetylene, which was 11% higher than the power without the seed. The maximum average power of the pulsed laser was 8.6 W (pulse energy of 0.86 µJ) at 7-mbar acetylene pressure, a 16% increase over the power without the seed. To the best of our knowledge, backward characteristics are reported for the first time for fiber gas lasers, and the backward power accounted for less than 5% of the forward power. The optimum acetylene pressure and HCF length for the highest mid-IR output are discussed based on theoretical simulations. This study provides significant guidance for high-power mid-infrared (mid-IR) output in gas-filled HCFs.

The effect of opioid-free anaesthesia on the quality of recovery after endoscopic sinus surgery: A multicentre randomised controlled trial.

BACKGROUND: It remains to be determined whether opioid-free anaesthesia (OFA) is consistently effective for different types of surgery. OBJECTIVES: The current study hypothesised that OFA could effectively inhibit intraoperative nociceptive responses, reduce side effects associated with opioid use, and improve the quality of recovery (QoR) in endoscopic sinus surgery (ESS). DESIGN: A multicentre randomised controlled study. SETTING: Seven hospitals participated in this multicentre trial from May 2021 to December 2021. PATIENTS: Of the 978 screened patients who were scheduled for elective ESS, 800 patients underwent randomisation, and 773 patients were included in the analysis; 388 patients in the OFA group and 385 patients in the opioid anaesthesia group. INTERVENTIONS: The OFA group received balanced anaesthesia with dexmedetomidine, lidocaine, propofol and sevoflurane; the opioid anaesthesia group received opioid-based balanced anaesthesia using sufentanil, remifentanil, propofol and sevoflurane. OUTCOME MEASURES: The primary outcome was 24-h postoperative QoR as evaluated by the Quality of Recovery-40 questionnaire. The key secondary outcomes were episodes of postoperative pain and postoperative nausea and vomiting (PONV). RESULTS: A significant difference ( P  = 0.0014) in the total score of 24-h postoperative Quality of Recovery-40 was found between the OFA group, median [interquartile range], 191 [185 to 196] and the opioid anaesthesia group (194 [187 to 197]). There were significant differences between the opioid anaesthesia group and the OFA group in the numerical rating scale score for pain after surgery at 30 min ( P   =  0.0017), 1 h ( P   =  0.0052), 2 h ( P   =  0.0079) and 24 h ( P  = 0.0303). The difference in the area under the curve of pain scale scores between the OFA group (24.2 [3.0 to 47.5]) and the opioid anaesthesia group (11.5 [1.0 to 39.0]) was significant ( P  = 0.0042). PONV occurred in 58 of 385 patients (15.1%) in the opioid anaesthesia group compared with 27 of 388 patients (7.0%) in the OFA group, suggesting the incidence of PONV in the OFA group was significantly lower than in the opioid anaesthesia group ( P   =  0.0021). CONCLUSION: OFA can provide good intraoperative analgesia and postoperative recovery quality as effectively as conventional opioid anaesthesia in patients undergoing ESS. OFA can be an alternative option in the pain management of ESS. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100046158; registry URL: http://www.chictr.org.cn/enIndex.aspx .).

Stimulated Raman scattering of H2 in hollow-core photonics crystal fibers pumped by high-power narrow-linewidth fiber oscillators.

The stimulated Raman scattering (SRS) process in gas-filled hollow-core fiber is mostly used to realize the wavelength conversion, which has the potential to produce narrow-linewidth and high-power fiber laser output. However, limited by the coupling technology, the current research is still at a few watts power level. Here, through the fusion splicing between the end-cap and the hollow-core photonics crystal fiber, several hundred watts pump power can be coupled into the hollow core. Homemade narrow-linewidth continuous wave (CW) fiber oscillators with different 3 dB linewidths are used as the pump sources, then the influences of the pump linewidth and the hollow-core fiber length are studied experimentally and theoretically. As the hollow-core fiber length is 5 m the H2 pressure is 30 bar, 109 W 1st Raman power is obtained with a Raman conversion efficiency 48.5%. This study is significant for the development of high-power gas SRS in hollow-core fibers.

Numerical simulation and observed rotational relaxation in CW and pulsed HBr-filled hollow-core fiber lasers.

Gas-filled hollow-core fiber (HCF) lasers have emerged as a promising technology for generating mid-infrared lasers. A four-energy level system laser model is presented to predict the performance of optically pumped HBr-filled HCF lasers under continuous wave (CW) and pulsed excitations. The steady state condition is considered in CW pumping and the characteristics of simulated population density and power distribution along HCF are investigated. The finite-difference time-domain method is employed in pulsed pumping and the simulated evolutions of pump pulse and laser pulse at different positions along the HCF are studied. In addition, the phenomena of rotational relaxation in HBr-filled HCF lasers are investigated experimentally for the first time, to the best of our knowledge, showing that using the absorption lines away from the strongest absorption lines and tuning the pump wavelength deviating from the center of the absorption line makes the rotational relaxation occur easily. The demonstration is conductive to reveal the underlying mechanism of such gas-filled HCF lasers.

High-gain single-frequency Tm3+-doped ZBLAN fiber amplifier at 2.33 µm.

We report here, to the best of our knowledge, the first high-gain, single-frequency Tm3+-doped fiber amplifier operating at the 2.3-µm band with conventional ground-state pumping transition (3H6→3H4) at 793 nm. The gain fiber is an 8.5-m-long ZBLAN fiber with a Tm3+ doping concentration of 3 mol.%, and the seed is a single-frequency distributed feedback diode laser operated at 2331.9 nm. A gain up to 24.1 dB is generated for ∼14 W of launched pump power with the maximum output power of 246 mW. The competitive 3F4 →3H6 laser transition at ∼2 µm is also investigated, and the prospects for further power scaling are discussed.

Risk factors of perioperative acute kidney injury in elderly patients: a single-center retrospective study.

PURPOSE: The elderly are vulnerable to perioperative acute kidney injury. The aim of this study was to determine the risk factors that associated with acute kidney injury among elderly patients. METHODS: Clinical data of elderly patients (> 65 years) who underwent noncardiac, nonrenal surgery between Dec 1 2009 and July 1 2016 were collected for this single-centered historical cohort study. Univariate and multivariate analyses were conducted to explore the risk factors that contribute to acute kidney injury, which was defined as a serum creatinine increase >0.3 mg/dL within 48 h or 1.5 times increase in serum creatinine within 7 days after surgery. RESULTS: 7775 patients were eligible for the final analysis, among which 511 (6.57%) patients developed acute kidney injury. We observed 21 risk factors being associated with perioperative acute kidney injury, with the most important disposing factors being history of kidney disease (adjusted OR = 2.94, 95% CI 2.25-3.84), operation time > 180 min (aOR = 2.93, 95% CI 2.04-4.24), preoperative eGFR [15, 30) (aOR = 2.43, 95% CI 1.29-4.45), and protective factor being intraoperative use of sufentanil (aOR = 0.35, 95% CI 0.23-0.54). CONCLUSION: This study determined risk factors for perioperative acute kidney injury among the elderly in the Second Xiangya Hospital and visualized the risk factors using nomogram and Excel calculator, which may provide some clues to further investigations. Overall, the prevalence of AKI among this large cohort is 6.57%. CLINICAL TRIALS REGISTRATION: http://www.chictr.org.cn ; ChiCTR1900027007; October 28, 2019.

Effect of Ice Slush on Reducing the Oculocardiac Reflex During Strabismus Surgery.

BACKGROUND: The aim of this study was to explore whether ice slush (IS) causing local hypothermia can effectively inhibit the oculocardiac reflex (OCR) during strabismus surgery. METHODS: This prospective, randomized, double-blind study included 58 patients with concomitant strabismus scheduled for lateral rectus (LR) recession under general anesthesia. Patients were randomly allocated to receive IS (IS group) or standard treatment (control group) with sterile saline at room temperature before surgery. OCR was defined as a sudden decrease in heart rate (HR) of >15% from baseline. If one incidence of the OCR was found in 1 patient in any stage (0/I/II/III), the patient was defined as an OCR responder, and the incidence of overall OCR was the incidence of OCR responders. The primary outcome was the incidence of overall OCR during all stages of the surgery, which was analyzed by the Z test and computed based on the absolute risk difference with 2-sided 95% confidence intervals (CIs) using the Newcombe method. RESULTS: The overall OCR occurred in 19 of 29 patients (62.5% [95% CI, 45.7-82.1]) in the IS group and 28 of 29 patients (96.6% [95% CI, 82.2-99.9]) in the control group (absolute risk difference, -31.0% [95% CI, -49.4 to -11.0]; Z test, P < .001), which demonstrated that the incidence of overall OCR in IS group was significantly lower than that in the control group. CONCLUSIONS: IS on the ocular surface causing local hypothermia is a promising and easily accessible method to reduce the overall OCR, which can improve the safety of strabismus surgery.

Mid-infrared fiber gas amplifier in acetylene-filled hollow-core fiber.

We report here the first, to the best of our knowledge, demonstration of a mid-infrared (mid-IR) fiber gas amplifier based on acetylene-filled hollow-core fibers. A quasi-all-fiber structure fiber acetylene laser in a single-pass configuration is used as a seed. The injection of the seed removes the threshold and increases the laser efficiency, which are more pronounced at high pressure. In a 3.1-m HCF filled with 2.5 mbar of acetylene, the fiber gas amplifier shows a conversion efficiency (relative to the coupled pump power) of 22.2% at 3.1 µm, which is increased by 35% compared with that without the seed. Both the seed laser and the amplifier laser have good beam quality with M2 < 1.1. It is predictable that such a fiber gas amplifier can achieve a more efficient and higher power mid-IR output for other selected molecular species compared with the single-pass structure, which is beneficial to the development of high-power mid-IR fiber gas lasers.

Fiber laser source of 8 W at 3.1 µm based on acetylene-filled hollow-core silica fibers.

We report here the characteristics of a nanosecond high-power mid-infrared (mid-IR) light source based on an anti-resonant hollow-core fiber (AR-HCF) filled with acetylene gas. It is a single-pass configuration with 9.3-m HCFs, pumped by a modulated and amplified diode laser. A maximum average power of approximately 8 W (pulse energy of ∼0.8 µJ and peak power of ∼40 W) at 3.1 µm is achieved with a laser slope efficiency of ∼22.8% at 6 mbar of acetylene, which is, to the best of our knowledge, a record output power for such mid-IR HCF lasers. This work demonstrates the great potential of fiber gas lasers for high-power output in the mid-IR.

Combined Programmed Intermittent Bolus Infusion With Continuous Infusion for the Thoracic Paravertebral Block in Patients Undergoing Thoracoscopic Surgery: A Prospective, Randomized, and Double-blinded Study.

BACKGROUND: Continuous thoracic paravertebral block (TPVB) connected with patient-controlled analgesia (PCA) pump is an effective modality to reduce postoperative pain following thoracic surgery. For the PCA settings, the programmed intermittent bolus infusion (PIBI) and continuous infusion (CI) are commonly practiced. However, the comparative effectiveness between the 2 approaches has been inconsistent. Thus, the aim of this study was to explore the optimal PCA settings to treat postthoracotomy pain by combing PIBI and CI together. METHODS: All enrolled patients undergoing thoracoscopic surgery accepted ultrasound-guided TPVB catheterization before the surgery and then were randomly allocated in to 3 groups depending on different settings of the PCA pump connecting to the TPVB catheter: the PIBI+CI, PIBI, and CI groups. Numerical Rating Scales were evaluated for each patient at T1 (1 h after extubation), T2 (12 h after the surgery), T3 (24 h after the surgery), T4 (36 h after the surgery), and T5 (48 h after the surgery). Besides, the consumptions of PCA ropivacaine, the number of blocked dermatomes at T3, and the requirement for extra dezocine for pain relief among the 3 groups were also compared. RESULTS: First, the Numerical Rating Scale scores in the PIBI+CI group were lower than the CI group at T2 and T3 (P<0.05) when patients were at rest and were also lower than the CI group at T2, T3, and T4 (P<0.01) and the PIBI group at T3 when patients were coughing (P<0.01). Second, the 2-day cumulative dosage of PCA in the PIBI+CI group was lower than both the CI and PIBI groups (P<0.01). Third, the number of blocked dermatomes in the PIBI and PIBI+CI groups were comparable and were both wider than the CI group at T3 (P<0.01). Finally, a smaller proportion (not statistically significant) of patients in the PIBI+CI group (5.26%, 2/38) had required dezocine for pain relief when compared with the PIBI group (19.44%, 7/36) and the CI group (15.79%, 6/38). CONCLUSIONS: The combination of PIBI and CI provides superior analgesic modality to either PIBI or CI alone in patients undergoing thoracoscopic surgery. Therefore, it should be advocated to improve the management of postoperative pain, clinical outcomes, and ultimately patient satisfaction.

NLRP3 inflammasome of microglia promotes A1 astrocyte transformation, neo-neuron decline and cognition impairment in endotoxemia.

Infection, predominantly induced by gram-negative bacteria, is a critical health problem and a leading cause of death worldwide. Advance of techniques, such as antibiotics and life-supporting modality, allows a decreasing death rate of patients with infection in recent decades. Nevertheless, infection-associated complications, in particular cognitive dysfunction, largely influence the mortality of patients and the life quality of survivors. However, the effective medicine is still scant due to the poor interpretion of underlying mechanisms. Herein, we determined multiple cytokines of cerebrospinal fluid in mice challenged with various doses of lipopolysaccharides (LPS)-a pathogenic component of gram-negative bacteria, and found that IL-1ß, the downstream of NLRP3 inflammasome, was boosted to a peak extent after a challenge of LPS in high dose. Genetically knockout of Nlrp3 or the downstreams, such as Asc and Gsdmd, dramatically restored LPS-induced cognitive impairment, which was attributed to inhibiting microglia-induced A1 astrocytes and so-caused neo-neuron decline. Taken together, NLRP3 inflammasome of microglia promotes transformation of A1 astrocytes and consequently exacerbates neo-neuron decline, resulting in cognitive impairment after a challenge of LPS. Our study thus discovers a novel understanding in the pathogenesis of LPS-induced cognitive dysfunction, and indicates that NLRP3 inflammasome would be a promising target in the treatment of the syndrome.

Intelligent Algorithm-Based Coronary Angiography Characteristics of Acute Non-ST-Segment Elevation Myocardial Infarction Patients with Different Genders.

OBJECTIVE: This study was aimed at comparing the characteristics of coronary angiography based on intelligent algorithm in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) of different genders. METHODS: Eighty patients were selected to segment the coronary angiogram using the convolutional neural network (CNN) algorithm, the input layer of the CNN was used to receive the image dataset, and three-dimensional data were input during semantic segmentation to achieve automatic segmentation of the target features. Segmentation results were quantitatively assessed by accuracy (Acc), sensitivity (Se), specificity (Sp), and Dice coefficient (Dice). The characteristics of coronary angiography were compared between the two groups. RESULTS: The CNN algorithm had good segmentation effect, complete vessel extraction, and little noise, and Acc, Se, Sp, and Dice were 90.32%, 93.39%, 91.25%, and 89.75%, respectively. The proportion of diabetes mellitus was higher in female patients with NSTEMI (68.8%) than that in male patients (46.3%); the proportion of the left main coronary artery (LM) and left anterior descending artery (LAD) was lower in the female group (7.5%, 41.3%) than that in the male group (13.8%, 81.3%), and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION: The CNN algorithm achieves accurate extraction of vessels from coronary angiographic images, and women with diabetes and hyperlipidemia are more likely to have NSTEMI than men, especially the elderly.

Towards high-power mid-IR light source tunable from 3.8 to 4.5 µm by HBr-filled hollow-core silica fibres.

Fibre lasers operating at the mid-IR have attracted enormous interest due to the plethora of applications in defence, security, medicine, and so on. However, no continuous-wave (CW) fibre lasers beyond 4 µm based on rare-earth-doped fibres have been demonstrated thus far. Here, we report efficient mid-IR laser emission from HBr-filled silica hollow-core fibres (HCFs) for the first time. By pumping with a self-developed thulium-doped fibre amplifier seeded by several diode lasers over the range of 1940-1983 nm, narrow linewidth mid-IR emission from 3810 to 4496 nm has been achieved with a maximum laser power of about 500 mW and a slope efficiency of approximately 18%. To the best of our knowledge, the wavelength of 4496 nm with strong absorption in silica-based fibres is the longest emission wavelength from a CW fibre laser, and the span of 686 nm is also the largest tuning range achieved to date for any CW fibre laser. By further reducing the HCF transmission loss, increasing the pump power, improving the coupling efficiency, and optimizing the fibre length together with the pressure, the laser efficiency and output power are expected to increase significantly. This work opens new opportunities for broadly tunable high-power mid-IR fibre lasers, especially beyond 4 µm.

3.1†W mid-infrared fiber laser at 4.16†µm based on HBr-filled hollow-core silica fibers.

We present the characteristics of a continuous-wave (CW) mid-infrared fiber laser source based on HBr-filled hollow-core fibers (HCFs) made of silica. The laser source delivers a maximum output power of 3.1 W at 4.16 µm, showing a record value for any reported fiber laser beyond 4 µm. Both ends of the HCF are supported and sealed by especially designed gas cells with water cooling and inclined optical windows, withstanding higher pump power accompanied by accumulated heat. The mid-infrared laser exhibits a near-diffraction-limited beam quality with a measured M2 of 1.16. This work paves the way for powerful mid-infrared fiber lasers beyond 4 µm.

All-fiber gas Raman laser oscillator.

Here, we report the first, to the best of our knowledge, all-fiber gas Raman laser oscillator (AFGRLO), which is formed by fusion splicing solid-core fibers and a hydrogen-filled hollow-core photonic crystal fiber, and further introducing fiber Bragg gratings at a Stokes wavelength. Pumping with a homemade 1.54 µm fiber amplifier seeded by a narrow linewidth diode laser, we obtain the maximum output Stokes power of 1.8 W at 1693 nm by rotational stimulated Raman scattering of hydrogen molecules. Due to the involvement of the resonant cavity, the measured Raman threshold is as low as 0.98 W, which has been reduced nearly 20 times, compared with that of the single-pass structure. Moreover, a numerical model of an AFGRLO is established for the first time, to the best of our knowledge, and the simulations agree well with the experimental results. This Letter is significant for the development of fiber gas Raman lasers (FGRLs), particularly for achieving compact CW FGRLs towards the mid-infrared.

Narrow-Linewidth 2 µm All-Fiber Laser Amplifier with a Highly Stable and Precisely Tunable Wavelength for Gas Molecule Absorption in Photonic Crystal Hollow-Core Fibers.

In recent years, mid-infrared fiber lasers based on gas-filled photonic crystal hollow-core fibers (HCFs) have attracted enormous attention. They provide a potential method for the generation of high-power mid-infrared emissions, particularly beyond 4 µm. However, there are high requirements of the pump for wavelength stability, tunability, laser linewidth, etc., due to the narrow absorption linewidth of gases. Here, we present the use of a narrow-linewidth, high-power fiber laser with a highly stable and precisely tunable wavelength at 2 µm for gas absorption. It was a master oscillator power-amplifier (MOPA) structure, consisting of a narrow-linewidth fiber seed and two stages of Thulium-doped fiber amplifiers (TDFAs). The seed wavelength was very stable and was precisely tuned from 1971.4 to 1971.8 nm by temperature. Both stages of the amplifiers were forward-pumping, and a maximum output power of 24.8 W was obtained, with a slope efficiency of about 50.5%. The measured laser linewidth was much narrower than the gas absorption linewidth and the wavelength stability was validated by HBr gas absorption in HCFs. If the seed is replaced, this MOPA laser can provide a versatile pump source for mid-infrared fiber gas lasers.

Baicalein attenuates acute liver injury by blocking NLRP3 inflammasome.

Infection and/or drug-mediated acute liver injury, the leading cause of lethal liver failure, is a critical health problem worldwide and lacks effective treatment. Here, we used Lipopolysaccharides (LPS)/D-galactosamine (D-gal)-treated primary hepatocytes to screen a natural library that contains 1130 chemicals. Baicalein in the library showed highest inhibitory effects against LPS/D-Gal-induced liver injury. In-vivo study similarly validated the protection of baicalein against dampened liver function and increased lethality after a challenge of LPS/D-Gal. Using a cytometric bead array, we found that IL-1α and IL-1ß, the downstream of NLRP3, had highest reduction among the plasma inflammatory cytokines in LPS/D-Gal-challenged mice after a treatment of baicalein. To determine the target of baicalein and the underlying mechanism, Nlrp3-/-, Gsdmd-/- or WT mice were treated with or without baicalein, IL-1R antibody or recombinant mouse IL-1ß (rmIL-1ß) prior to a challenge of LPS/D-Gal. Deficiency of Nlrp3 or Gsdmd significantly restored LPS/D-Gal-induced acute liver injury and lethality, and further administration of baicalein did not have additive effects. In addition, the inhibition of the downstream by IL-1R antibody phenocopied the knockout of Nlrp3 or Gsdmd. Moreover, a challenge of rmIL-1ß reversed the improvement in Nlrp3-/- mice or the mice treated with baicalein. Taken together, NLRP3 functions as a pivotal promoter in acute liver injury and baicalein attenuates acute liver injury by inhibiting NLRP3 inflammasome.