Human umbilical cord mesenchymal stem cells alleviated TNBS-induced colitis in mice by restoring the balance of intestinal microbes and immunoregulation.

AIMS: Human umbilical cord mesenchymal stem cells (HUMSCs) have been documented to be effective for several immune disorders including inflammatory bowel diseases (IBD). However, it remains unclear how HUMSCs function in regulating immune responses and intestinal flora in the trinitrobenzene sulfonic acid (TNBS)-induced IBD model. MATERIALS AND METHODS: We assessed the regulatory effects of HUMSCs on the gut microbiota, T lymphocyte subpopulations and related immune cytokines in the TNBS-induced IBD model. The mice were divided into the normal, TNBS, and HUMSC-treated groups. The effect of HUMSCs was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Metagenomics Illumina sequencing was conducted for fecal samples. KEY FINDINGS: We demonstrated that the disease symptoms and pathological changes in the colon tissues of TNBS-induced colitis mice were dramatically ameliorated by HUMSCs, which improved the gut microbiota and rebalanced the immune system, increasing the abundance of healthy bacteria (such as Lactobacillus murinus and Lactobacillus johnsonii), the Firmicutes/Bacteroidetes ratio, and the proportion of Tregs; the Th1/Th17 ratio was decreased. Consistently, the expression levels of IFN-γ and IL-17 were significantly decreased, and transforming growth factor-ß1 (TGF-ß1) levels were significantly increased in the plasma of colitis mice HUMSC injection. SIGNIFICANCE: Our experiment revealed that HUMSCs mitigate acute colitis by regulating the rebalance of Th1/Th17/Treg cells and related cytokines and remodeling the gut microbiota, providing potential future therapeutic targets in IBD.

Association between the triglyceride-glucose index and the risk of mortality among patients with chronic heart failure: results from a retrospective cohort study in China.

BACKGROUND: The triglyceride-glucose (TyG) index has been demonstrated to be a reliable surrogate marker of insulin resistance (IR) and an effective predictive index of cardiovascular (CV) disease risk. However, its long-term prognostic value in patients with chronic heart failure (CHF) remains uncertain. METHODS: A total of 6697 consecutive patients with CHF were enrolled in this study. Patients were divided into tertiles according to their TyG index. The incidence of primary outcomes, including all-cause death and CV death, was recorded. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. RESULTS: During a median follow-up of 3.9 years, a total of 2158 (32.2%) all-cause deaths and 1305 (19.5%) CV deaths were documented. The incidence of primary events from the lowest to the highest TyG index tertiles were 50.61, 64.64, and 92.25 per 1000 person-years for all-cause death and 29.05, 39.40, and 57.21 per 1000 person-years for CV death. The multivariate Cox hazards regression analysis revealed hazard ratios for all-cause and CV deaths of 1.84 (95% CI 1.61-2.10; P for trend < 0.001) and 1.94 (95% CI 1.63-2.30; P for trend < 0.001) when the highest and lowest TyG index tertiles were compared. In addition, the predictive ability of the TyG index against all-cause death was more prominent among patients with metabolic syndrome and those with heart failure with preserved ejection fraction phenotype (both P for interaction < 0.05). Furthermore, adding the TyG index to the established model for all-cause death improved the C­statistic value (0.710 for the established model vs. 0.723 for the established model + TyG index, P < 0.01), the integrated discrimination improvement value (0.011, P < 0.01), the net reclassification improvement value (0.273, P < 0.01), and the clinical net benefit (probability range, 0.07-0.36). CONCLUSIONS: The TyG index was significantly associated with the risk of mortality, suggesting that it may be a reliable and valuable predictor for risk stratification and an effective prognostic indicator in patients with CHF.

Efficacy and safety of pyrotinib and radiotherapy vs. pyrotinib-based therapy in patients with HER2+ breast cancer with brain metastasis: a retrospective cohort study.

Background: At present, local therapy, such as surgery and radiotherapy, is the mainstay treatment for brain metastasis and anti-human epidermal growth factor receptor type 2 (HER2)-targeted therapy has been shown to be efficacious for HER2+ breast cancer (BC) patients with brain metastasis. However, Clinical studies comparing the combined effects of the two treatments are lacking. This study sought to investigate the efficacy and safety of pyrotinib and radiotherapy versus pyrotinib-based therapy in treating HER2+ BC patients with brain metastasis. Methods: This retrospective, observational study collected data from 79 HER2+ BC patients with brain metastasis who received pyrotinib-based therapy from May 2018 to December 2021. Among these patients, 35 received pyrotinib-based therapy concurrently with, or within 3 months before or after, brain radiotherapy (Group A), and 44 received pyrotinib-based therapy as the primary regimen (with no restriction as to whether they had received brain radiotherapy previously or not, the interval between receiving radiotherapy and receiving pyrotinib was >3 months) (Group B). Patient information was collected by the Electronic Medical Records System. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the objective response rate (ORR), the clinical benefit rate (CBR), and safety. The assessment of adverse effects was based on CTCAE5.0. Results: The intracranial ORRs were 48.6% in Group A and 20.5% (9/44) in Group B (P=0.015). The intracranial CBRs were 80.0% in Group A and 65.9% in Group B. The median intracranial PFS times (IC-PFS) were 15.0 months and 9.0 months in Group A and Group B, respectively (P=0.385). There was no statistically significant difference in OS between the 2 groups (95.0 vs. 98.0 months, P=0.872). The subgroup analysis showed that patients with active brain metastasis who received pyrotinib and radiotherapy had a longer IC-PFS time than those who received pyrotinib-based therapy(P=0.056). No serious adverse reactions (e.g., acute brain edema, cognitive dysfunction, or treatment-related death events) were observed. Conclusions: Pyrotinib combined with radiotherapy is recommended for HER2+ breast cancer active brain metastasis patients who can tolerate radiotherapy and pyrotinib. Pyrotinib-based therapy may be considered for patients who cannot tolerate radiotherapy and pyrotinib.

Near quantum-noise limited and absolute frequency stabilized 1083 nm single-frequency fiber laser.

The Earth's magnetic field has significant effects that protect us from cosmic radiation and provide navigation for biological migration. However, slow temporal variations originating in the liquid outer core invariably exist. To understand the working mechanism of the geomagnetic field and improve accuracy of navigation systems, a high-precision magnetometer is essential to measure the absolute magnetic field. A helium optically pumping magnetometer is an advanced approach, but its sensitivity and accuracy are directly limited by the low-frequency relative intensity noise and frequency stability characteristics of a light source. Here, we demonstrate a near quantum-noise limited and absolute frequency stabilized 1083 nm single-frequency fiber laser. The relative intensity noise is only 5 dB higher than the quantum-noise limit, and the root mean square of frequency fluctuation is ∼17 kHz after locked. This fiber laser could suppress the fluctuation of magnetic resonant frequency and improve the signal-to-noise ratio of the magnetic resonance signal detection.

Frequency noise of distributed Bragg reflector single-frequency fiber laser.

We investigated the frequency noise in the distributed Bragg reflector single-frequency fiber laser (DBR-SFFL) theoretically and experimentally. A complete theoretical analysis is demonstrated by considering the energy-transfer upconversion (ETU) process and establishing linkages between the frequency noise and the relative intensity noise (RIN) of the DBR-SFFL. The experimental results of the diverse DBR-SFFLs in different working conditions are in good agreement with the theoretical analyses. These investigations are beneficial to optimizing frequency noise property to promote the wide application of the DBR-SFFLs. The proposed results can be generally applicable to the short-linear-cavity SFFL with centimeters order of the cavity length.