[Network Meta-analysis of different Chinese medicine injections combined with conventional western medicine in treatment of acute heart failure].

This study aims to evaluate the efficacy and safety of Chinese medicine injection in the treatment of acute heart failure. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, Wanfang, and SinoMed were searched for the randomized controlled trial(RCT) of Chinese medicine injection combined with conventional western medicines in the treatment of acute heart failure with the time interval from the inception to July 10, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 15.1 was used to perform network Meta-analysis. A total of 117 RCTs were included, involving 10 529 patients and 7 Chinese medicine injections: Shenfu Injection, Shenmai Injection, Danhong Injection, Puera-rin Injection, Xinmailong Injection, Shengmai Injection, and Yiqi Fumai Injection. Network Meta-analysis yielded the following results.(1) In terms of improving the total response rate, the surface under the cumulative ranking curve(SUCRA) ranking was Shengmai Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shenmai Injection + conventio-nal western medicine > Shenfu Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > conventional western medicine.(2)In terms of reducing brain natriuretic peptide(BNP), the SUCRA ranking was Danhong Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Puerarin Injection + conventional wes-tern medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(3)In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the SUCRA ranking was Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > conventional western medicine.(4) In terms of improving the left ventricular ejection fraction(LVEF), the SUCRA ranking was Shenmai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(5) In terms of decreasing the left ventricular end-diastolic diameter(LVEDD), the SUCRA ranking was Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine=Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine > Puerarin Injection + conventional western medicine.(6) In terms of increasing the 6-min walk trail(6MWT), the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine.(7) In terms of reducing the Minnesota heart failure quality of life scale(MLHFQ) scores, the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > conventional western medicine.(8)In terms of safety, the group of Chinese medicine injection combined with conventional western medicine had lower incidence of adverse reactions than the control group. The current evidence shows that combining Chinese medicine injection with conventional western medicine treatment can improve the therapeutic effect on acute heart failure, with high safety. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

302 W single-mode power from an Er/Yb fiber MOPA: publisher's note.

This publisher's note contains corrections to Opt. Lett.45, 2910 (2020).OPLEDP0146-959210.1364/OL.392786.

302 W single-mode power from an Er/Yb fiber MOPA.

There has been very little progress in the power scaling of Er/Yb fiber lasers in over a decade, reflecting the difficulties involved. Here we report, to the best of our knowledge, a new record of 302 W single-mode power from an Er/Yb fiber master oscillator power amplifier (MOPA) with a record optical efficiency of 56%, near the quantum limit. This is made possible by new fiber development from Nufern and off-resonant pumping of the Er/Yb fiber. We also show that further power scaling is no longer limited by ytterbium parasitic lasing but by fiber fuse in the Er/Yb fiber.

Efficient 240W single-mode 1018nm laser from an Ytterbium-doped 50/400µm all-solid photonic bandgap fiber.

Lowering the quantum defect by tandem pumping with fiber lasers at 1018nm was critical for achieving the record 10kW single-mode ytterbium fiber laser. Here we report the demonstration of an efficient directly-diode-pumped single-mode ytterbium fiber laser with 240W at 1018nm. The key for the combination of high efficiency, high power and single-mode at 1018nm is an ytterbium-doped 50µm/400µm all-solid photonic bandgap fiber, which has a practical all-solid design and a pump cladding much larger than those used in previous demonstrations of single-mode 1018nm ytterbium fiber lasers, enabling higher pump powers. Efficient high-power single-mode 1018nm fiber laser is critical for further power scaling of fiber lasers and the all-solid photonic bandgap fiber can potentially be a significant enabling technology.

Large-mode-area fibers operating near single-mode regime.

Lower NA in large-mode-area fibers enables better single-mode operation and larger core diameters. Fiber NA has traditionally been limited to 0.06, mostly due to the control tolerance in the fabrication process. It has been recognized recently that transverse mode instability is a major limit to average power scaling in fiber lasers. One effective method to mitigate this limit is to operate nearer to the single-mode regime. Lower fiber NA is critical in this since it allows relatively larger core diameters which is the key to mitigate the limits imposed by nonlinear effects. We have developed a fabrication process of ytterbium-doped silica glass which is capable of highly accurate refractive index control and sufficient uniformity for LMA fibers. This process is also capable of large-volume production. It is based on a significant amount of post-processing once the fiber preforms are made. We have demonstrated 30/400 and 40/400 LMA fibers with a NA of ~0.028 operating very close to the single-mode regime. The second-order mode cuts off at ~1.2µm and ~1.55µm respectively. We have also studied issues related to bend losses due to the low NA and further optimization of LMA fibers.

Highly efficient ytterbium-doped phosphosilicate fiber lasers operating below 1020 nm.

Highly-efficient high-power fiber lasers operating at wavelength below 1020 nm are critical for tandem-pumping in >10 kW fiber lasers to provide high pump brightness and low thermal loading. Using an ytterbium-doped-phosphosilicate double-clad leakage-channel fiber with ~50 µm core and ~420 µm cladding, we have achieved ~70% optical-to-optical efficiency at 1018 nm. The much larger cladding than those in previous reports demonstrates the much lower required pump brightness, a key for efficient kW operation. The demonstrated 1018 nm fiber laser has ASE suppression of ~41 dB. This is higher than previous reports and further demonstrates the advantages of the fiber used. Limiting factors to efficiency are also systematically studied.

Extending mode areas of single-mode all-solid photonic bandgap fibers.

Mode area scaling of optical fiber is highly desirable for high power fiber laser applications. It is well known that incorporation of additional smaller cores in the cladding can be used to resonantly out-couple higher-order modes from a main core to suppress higher-order-mode propagation in the main core. Using a novel design with multiple coupled smaller cores in the cladding, we have successfully demonstrated a single-mode photonic bandgap fiber with record effective mode area of ~2650µm(2). Detailed numeric studies have been conducted for multiple cladding designs. For the optimal designs, the simulated minimum higher-order-mode losses are well over two orders of magnitudes higher than that of fundamental mode when expressed in dBs. To our knowledge, this is the best higher-order-mode suppression ever found in fibers with this large effective mode areas. We have also experimentally validated one of the designs. M(2)<1.08 across the transmission band was demonstrated.

Polarizing ytterbium-doped all-solid photonic bandgap fiber with ~1150µm(2) effective mode area.

We demonstrate an Yb-doped polarizing all-solid photonic bandgap fiber for single-polarization and single-mode operation with an effective mode area of ~1150µm(2), a record for all-solid photonic bandgap fibers. The differential polarization mode loss is measured to be >5dB/m over the entire transmission band with a 160nm bandwidth and >15dB/m on the short wavelength edge of the band. A 2.6m long fiber was tested in a laser configuration producing a linearly polarized laser output with a PER value of 21dB without any polarizer, the highest for any fiber lasers based on polarizing fibers.

400-W near diffraction-limited single-frequency all-solid photonic bandgap fiber amplifier.

An ytterbium-doped large-mode area photonic bandgap fiber is used to demonstrate 400 W of single-frequency output at 1064 nm with excellent beam quality and minimal stimulated Brillouin scattering. The fiber possesses all-solid microstructures embedded in the cladding and a core composed of phosphosilicate with a diameter of ∼50 µm. As the signal power is pushed beyond 450 W, there is degradation in the beam quality due to the modal instability. We briefly discuss techniques to alleviate this problem in future designs. To the best of our knowledge, the 400-W single-frequency near diffraction-limited output far exceeds the current state-of-the-art from such type of fiber amplifier.

Quantitative mode quality characterization of fibers with extremely large mode areas by matched white-light interferometry.

Quantitative mode characterization of fibers with cores much beyond 50µm is difficult with existing techniques due to the combined effects of smaller intermodal group delays and dispersions. We demonstrate, for the first time, a new method using a matched white-light interferometry (MWI) to cancel fiber dispersion and achieve finer temporal resolution, demonstrating ~20fs temporal resolution in intermodal delays, i.e. 6µm path-length resolution. A 1m-long straight resonantly-enhanced leakage-channel fiber with 100µm core was characterized, showing ~55fs/m relative group delay and a ~29dB mode discrimination between the fundamental and second-order modes.

Ytterbium-doped large-mode-area all-solid photonic bandgap fiber lasers.

Single-mode operation in a large-mode-area fiber laser is highly desired for power scaling. We have, for the first time, demonstrated a 50µm-core-diameter Yb-doped all-solid photonic bandgap fiber laser with a mode area over 4 times that of the previous demonstration. 75W output power has been generated with a diffraction-limited beam and an efficiency of 70% relative to the launched pump power. We have also experimentally confirmed that a robust single-mode regime exists near the high frequency edge of the bandgap. These fibers only guide light within the bandgap over a narrow spectral range, which is essential for lasing far from the gain peak and suppression of stimulated Raman scattering. This work demonstrates the strong potential for mode area scaling of in single-mode all-solid photonic bandgap fibers.

Bioinformatic analysis reveals an association between Metadherin with breast cancer prognosis and tumor immune infiltration.

Breast cancer metastasis and invasion are both promoted by the oncoprotein Metadherin (MTDH). However, the the role of Metadherin in breast cancer progression and its role in the immune microenvironment. Are not clear. A bioinformatic analysis was performed to demonstrate the prognostic value of Metadherin in BC. In the present study, we found that Metadherin is overexpressed in BC and is significantly correlated with individual cancer stage, age, subclasses, menopause and nodal metastasis status. Metadherin overexpression was associated with a significant decrease in OS and DSS. Cox multivariate analysis indicated that Metadherin was an independent negative prognostic indicator for OS and DSS. Moreover, Metadherin hypomethylation status was associated with poor prognosis. A negative correlation was also noted between Metadherin overexpression and the number of plasmacytoid dendritic cells, cluster of differentiation 8+ T cells, and natural killer cells. Association patterns varied with different subtypes. Various associations between Metadherin levels and immune cell surface markers were revealed. A total of 40 groups of BC and adjacent normal breast tissue samples were collected. Metadherin mRNA was detected by PCR, and its expression levels in BC tissues were significantly increased compared with those noted in normal tissues. The expression levels of Metadherin were also measured in normal and BC cell lines, respectively, and similar conclusions were obtained. The Metadherin mRNA levels were knocked down in SK-BR3 and MDA-MB-231 cell lines and the cell proliferative and migratory activities were determined using Cell Counting Kit-8 and scratch assays, respectively. The results indicated that the cell proliferative and migratory abilities were reduced following knockdown of Metadherin expression. Therefore, Metadherin may be considered as a novel prognostic biomarker in BC.

Association of ADP­ribosylation factor family genes with prognosis and immune infiltration of breast cancer.

Breast cancer (BC) is the most common type of cancer found in women. ADP-ribosylation factors (ARFs) are a group of small proteins that bind to GTP and are involved in controlling different cellular functions. The function and evolution of multiple ARFs in BC have remained to be fully elucidated, despite existing studies on this protein family in Homo sapiens and other species. In the present study, a systematic analysis of ARF expression levels in BC tissues compared to normal breast tissues was performed using data from The Cancer Genome Atlas database. The analysis revealed significantly higher expression of ARFs in BC tissues. In addition, the prognostic significance of ARF1 and ARF3-6 expression levels was assessed in patients with BC. Of note, elevated ARF1 expression was associated with reduced rates of distant metastasis-free survival (DMFS), overall survival (OS) and recurrence-free survival (RFS) in affected individuals. Similarly, patients with high expression levels of ARF3 had lower post-progression survival (PPS) rates. In addition, patients with higher ARF4 expression had worse PPS and patients with high ARF5 expression exhibited lower DMFS. Patients with high ARF6 expression had worse DMFS, OS, RFS and predictive power score values. Furthermore, the expression of ARF was found to be strongly linked to the infiltration of various immune cell types, namely dendritic cells, macrophages, neutrophils, CD8+ T cells and B cells. These significant associations offer a solid foundation for the potential utilization of new therapeutic targets and predictive markers for the treatment of BC.

Comprehensive pan­cancer analysis of MTDH for human tumor prognosis and as an immunological biomarker including breast and kidney cancer.

Metadherin (MTDH), initially discovered in primary astrocytes of the human fetus through rapid subtraction hybridization and labeled as astrocyte elevated gene-1, represents a widely recognized oncogene present in multiple types of cancers. However, the role of MTDH in different types of cancer remains unclear. To address this, a comprehensive analysis of MTDH across various types of cancers was conducted by utilizing multiple databases such as The Cancer Genome Atlas. The present analysis discovered that MTDH exhibits differential expression in different types of cancer and is associated with important factors including tumor mutational burden and microsatellite instability. These findings highlighted the significance of MTDH in the tumor microenvironment and its involvement in the development of immune cells in specific cancers. Furthermore, the results of the present study indicated that the expression of MTDH is strongly correlated with clinical prognosis, mutations and immune cell infiltration. MTDH could serve as a potential indicator of patient prognosis and potentially play a role in modulating the immune system. Given its potential as a novel immunological checkpoint, MTDH may be a viable target for tumor immunotherapy.

Impact of fiber outer boundaries on leaky mode losses in leakage channel fibers.

In a leakage channel fiber, the desired fundamental mode (FM) has negligible waveguide loss. Higher-order modes (HOM) are designed to have much higher waveguide losses so that they are practically eliminated during propagation. Coherent reflection at the fiber outer boundary can lead to additional confinement especially for highly leaky HOM, leading to lower HOM losses than what are predicted by conventional FEM mode solver considering infinite cladding. In this work, we conducted, for the first time, careful measurements of HOM losses in two leakage channel fibers (LCF) with circular and rounded hexagonal boundary shapes respectively. Impact on HOM losses from coiling, fiber boundary shapes and coating indexes were studied in comparison to simulations. This work, for the first time, demonstrates the limit of the simulation method commonly used in the large-mode-area fiber designs and the need for an improved approach. More importantly, this work also demonstrates that a deviation from circular fiber outer shape may be an effective method to mitigate HOM loss reduction from coherent reflection from fiber outer boundary, even in double-clad fibers, with HOM losses in excess of 20 dB/m measured in the hexagonal LCF with ~50 µm core diameter while keeping FM loss negligible.

Flat-top mode from a 50 µm-core Yb-doped leakage channel fiber.

We demonstrate for the first time a flat-top mode from a 50 µm-core Yb-doped leakage channel fiber (LCF). The flat intensity distribution leads to an effective mode area of ~1880 µm(2) in the straight fiber, an over 50% increase comparing to that of regular LCF with the same core diameter. The flat-top mode was achieved by using a uniform Yb-doped silica glass in the core center with an index of ~2 × 10(-4) lower than that of the silica background. The fiber was also tested in a laser configuration, demonstrating an optical-to-optical efficiency of ~77% at 1026 nm with respect to the pump at 975 nm.

​Efficacy and safety of pyrotinib in combination with albumin­bound paclitaxel for the treatment of HER2­positive advanced breast cancer: A real­world study.

The present study aimed to determine the efficacy and safety of pyrotinib in combination with albumin-bound paclitaxel in patients with HER2-positive advanced breast cancer (ABC). A total of 48 patients diagnosed with HER2-positive ABC were included in the present study, and these patients were prescribed a combination of pyrotinib and albumin-bound paclitaxel in routine clinical practice. During a 21-day cycle, the standard dosage of pyrotinib was 400 mg single dose/day, which was administered orally, and 130 mg/m2/day albumin-bound paclitaxel on days 1, 8 and 15, which was administered by intravenous drip. The primary efficacy endpoint was progression-free survival (PFS) and the secondary efficacy endpoint was overall response rate (ORR), which was defined as the percentage of patients with complete remission or partial remission. Safety indicators were also observed in the present study. The results of the present study demonstrated that the median PFS (mPFS) was 8.1 months for all patients, ranging from 3.3-10.6 months. Patients receiving pyrotinib as second-line therapy exhibited a longer mPFS of 8.5 months compared with those receiving it as third- or higher-line therapy (mPFS, 5.9 months). In 17 patients with brain metastases, mPFS was 7.3 months, ranging from 4.8-10.1 months. The results of the present study also demonstrated that the ORR for the 48 patients was 33.3%. Notably, diarrhea was the most common grade 3-4 adverse event, occurring in 22.9% of patients, followed by neutropenia (6.3%), leukopenia (4.2%) and anemia (4.2%). Collectively, the results of the present study indicated that pyrotinib-based treatment is effective for patients with HER2+ ABC, including those who have previously been treated with trastuzumab. Thus, the combination of pyrotinib with albumin-bound paclitaxel is recommended due to high levels of efficacy, convenience and tolerability.

Precise tailoring of acoustic velocity in optical fibers by hydrogenation and UV exposure.

Tailoring of acoustic properties in solids has many potential applications in both acoustics, i.e. acoustic gratings and waveguides, and photon-phonon interactions, i.e. stimulated Brillouin scattering (SBS). One immediate application is in the area of SBS suppression in optical fibers. We demonstrate, for the first time, a post-processing technique where hydrogen is diffused in to a fiber core and then locally and permanently bonded to core glass by a subsequent UV exposure. It is discovered that local acoustic velocity can be altered by as much as ~2% this way, with strong potential for much further improvements with an increased hydrogen pressure. It is also found that the large change in acoustic velocity is primarily due to a reduction in bulk modulus, possibly as a result of network bonds being broken up by the addition of OH bonds. It is possible to use this technique to precisely tailor acoustic velocity along a fiber for more optimized SBS suppression in a fiber amplifier. Change in Brillouin Stokes frequency of ~320MHz at 1.064µm was observed.

Mode area scaling with all-solid photonic bandgap fibers.

There are still very strong interests for power scaling in high power fiber lasers for a wide range of applications in medical, industry, defense and science. In many of these lasers, fiber nonlinearities are the main limits to further scaling. Although numerous specific techniques have studied for the suppression of a wide range of nonlinearities, the fundamental solution is to scale mode areas in fibers while maintaining sufficient single mode operation. Here the key problem is that more modes are supported once physical dimensions of waveguides are increased. The key to solve this problem is to look for fiber designs with significant higher order mode suppression. In conventional waveguides, all modes are increasingly guided in the center of the waveguides when waveguide dimensions are increased. It is hard to couple a mode out in order to suppress its propagation, which severely limits their scalability. In an all-solid photonic bandgap fiber, modes are only guided due to anti-resonance of cladding photonic crystal lattice. This provides strongly mode-dependent guidance, leading to very high differential mode losses. In addition, the all-solid nature of the fiber makes it easily spliced to other fibers. In this paper, we will show for the first time that all-solid photonic bandgap fibers with effective mode area of ~920?m2 can be made with excellent higher order mode suppression.

Effect of Probiotic-Assisted Eradication of cagA+/vacA s1m1 Helicobacter pylori on Intestinal Flora.

Objective: We attempted to evaluate the effects of probiotic-assisted eradication of cytotoxin-associated gene A (cagA)+/vacuolating cytotoxin A (vacA) s1m1 Helicobacter pylori (H. pylori) on the intestinal flora, inflammatory factors, and clinical outcomes. Methods: A total of 180 patients with cagA+/vacA s1m1 H. pylori were randomly divided into two groups. Group A was treated with bismuth quadruple therapy (BQT). Group B was treated with S. boulardii in addition to BQT. The distribution of intestinal flora, serum interleukin-8 (IL-8), IL-17, tumor necrosis factor-α (TNF-α) levels, recovery time of clinical symptoms, total effective rate of clinical symptoms, H. pylori eradication rate, and adverse reactions were observed. Results: 2 weeks after treatment, the contents of Bifidobacterium, Bacteroides, and Lactobacillus in the intestinal tract of Group A decreased, while the amounts of Enterococcus and Enterobacter increased. In Group B, the contents of Bifidobacterium, Bacteroides, and Lactobacillus increased, while the amounts of Enterococcus and Enterobacter did not change significantly. Moreover, the trend of this flora change was still present at 4 weeks after treatment. Compared with Group A, Group B had lower IL-8, IL-17, and TNF-α levels, shorter recovery time of clinical symptoms, higher overall efficiency of clinical symptoms, and lower occurrence of adverse reactions. The eradication rate did not differ significantly between the two groups. Conclusion: BQT can lead to intestinal flora disorders in cagA+/vacA s1m1 H. pylori patients. S. boulardii can improve the distribution of intestinal flora, downregulate immune-inflammatory mediators, and modify clinical symptoms in patients.