Associations between peak expiratory flow and frailty in olderly individuals: findings from the China health and retirement longitudinal study.

Purpose: Peak Expiratory Flow (PEF) is associated with a variety of adverse health outcomes in older adults; however, the relationship between PEF and frailty remains uncertain, and this study investigated the relationship between PEF and frailty within an olderly Asian demographic. Methods: Data were sourced from the Chinese Health and Retirement Longitudinal Study (CHARLS). Individuals in the study, all 60 years or older, underwent baseline PEF assessments quantified as standardized residual (SR) percentile values. The evaluation of frailty was conducted based on the criteria established by Fried. Participants without frailty at the outset were tracked over a four-year period, during which the relationships between PEF and frailty were examined through logistic regression and discrete-time Cox regression analyses. Results: Among 5,060 participants, cross-sectional analysis revealed that the prevalence of frailty was 2-3 times higher in the lower 10-49th and < 10th SR percentile groups compared to the 80-100th SR percentile group. The longitudinal study corroborated these results, showing an adjusted hazard ratio (HR) of 2.01 (95% CI, 1.15-3.51) for PEF SR percentiles below the 10th, in contrast to those between the 80th and 100th percentiles. Conclusion: PEF independently predicts and determines frailty in older adults. Declines in PEF greater than expected are associated with the development of frailty. Subsequent studies are encouraged to delve deeper into the connection between respiratory function and frailty in diverse contexts.

Comparison efficacy and safety of acupuncture and moxibustion therapies in breast cancer-related lymphedema: A systematic review and network meta-analysis.

OBJECTIVE: Although several acupuncture and moxibustion therapies have been tested in managing breast cancer-related lymphedema (BCRL), there is little consensus regarding the best options for treating this condition. This systematic review and network meta-analysis compared the efficacy of various acupuncture and/or moxibustion therapies for BCRL. METHODS: Seven databases and two clinical registration centers were searched from their inception to December 1st, 2023. The Cochrane Collaboration risk-of-bias assessment tool evaluated the quality of included RCTs. A pairwise meta-analysis was performed in STATA 16.0, while a network meta-analysis was performed in R 4.2.2. RESULTS: 18 studies were included in this analysis. Our results showed that acupuncture and moxibustion methods had great advantages in improving BCRL of patients with breast cancer. In particular, needle-warming moxibustion (NWM) could be the optimal acupuncture and moxibustion method for improving clinical effectiveness and reducing the degree of swelling of affected limbs. CONCLUSION: Our findings suggest that NWM has great potential in treating BCRL. It may reduce arm circumference, lower swelling levels, and improve clinical effectiveness. Nevertheless, more multi-center, high-quality, and large sample RCTs will be needed in the future.

In Vitro Antibacterial and Anti-Inflammatory Properties of Imidazolium Poly(ionic liquids) Microspheres Loaded in GelMA-PEG Hydrogels.

Repairing damaged tissue caused by bacterial infection poses a significant challenge. Traditional antibacterial hydrogels typically incorporate various components such as metal antimicrobials, inorganic antimicrobials, organic antimicrobials, and more. However, drawbacks such as the emergence of multi-drug resistance to antibiotics, the low antibacterial efficacy of natural agents, and the potential cytotoxicity associated with metal antibacterial nanoparticles in hydrogels hindered their broader clinical application. In this study, we successfully developed imidazolium poly(ionic liquids) (PILs) polymer microspheres (APMs) through emulsion polymerization. These APMs exhibited notable antibacterial effectiveness and demonstrated minimal cell toxicity. Subsequently, we integrated the APMs into a gelatin methacryloyl (GelMA)-polyethylene glycol (PEG) hydrogel. This composite hydrogel not only showcased strong antibacterial and anti-inflammatory properties but also facilitated the migration of human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) and promoted osteogenic differentiation in vitro.

The genetic basis and process of inbreeding depression in an elite hybrid rice.

Inbreeding depression refers to the reduced performance arising from increased homozygosity, a phenomenon that is the reverse of heterosis and exists among plants and animals. As a natural self-pollinated crop with strong heterosis, the mechanism of inbreeding depression in rice is largely unknown. To understand the genetic basis of inbreeding depression, we constructed a successive inbreeding population from the F2 to F4 generation and observed inbreeding depression of all heterotic traits in the progeny along with the decay of heterozygosity in each generation. The expected depression effect was largely explained by 13 QTLs showing dominant effects for spikelets per panicle, 11 for primary branches, and 12 for secondary branches, and these loci constitute the main correlation between heterosis and inbreeding depression. However, the genetic basis of inbreeding depression is also distinct from that of heterosis, such that a biased transmission ratio of alleles for QTLs with either dominant or additive effects in four segregation distortion regions would result in minor effects in expected depression. Noticeably, two-locus interactions may change the extent and direction of the depression effects of the target loci, and overall interactions would promote inbreeding depression among generations. Using an F2:3 variation population, the actual performance of the loci showing expected depression was evaluated considering the heterozygosity decay in the background after inbreeding. We found inconsistent or various degrees of background depression from the F2 to F3 generation assuming different genotypes of the target locus, which may affect the actual depression effect of the locus due to epistasis. The results suggest that the genetic architecture of inbreeding depression and heterosis is closely linked but also differs in their intrinsic mechanisms, which expand our understanding of the whole-genome architecture of inbreeding depression.

Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus.

BACKGROUND: Hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT) exhibit poor prognoses and treatment responses. AIM: To investigate efficacies and safety of the combination of PD-1 inhibitor, transcatheter arterial chemoembolization (TACE) and Lenvatinib in HCC subjects comorbid with PVTT. METHODS: From January 2019 to December 2020, HCC patients with PVTT types I-IV were retrospectively enrolled at Beijing Ditan Hospital. They were distributed to either the PTL or TACE/Lenvatinib (TL) group. The median progression-free survival (mPFS) was set as the primary endpoint, while parameters like median overall survival, objective response rate, disease control rate (DCR), and toxicity level served as secondary endpoints. RESULTS: Forty-one eligible patients were finally recruited for this study and divided into the PTL (n = 18) and TL (n = 23) groups. For a median follow-up of 21.8 months, the DCRs were 88.9% and 60.9% in the PTL and TL groups (P = 0.046), res-pectively. Moreover, mPFS indicated significant improvement (HR = 0.25; P < 0.001) in PTL-treated patients (5.4 months) compared to TL-treated (2.7 months) patients. There were no treatment-related deaths or differences in adverse events in either group. CONCLUSION: A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types I-IV.

In pursuit of feedback activation: New insights into redox-responsive hydropersulfide prodrug combating oxidative stress.

Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.

Comparative pharmacokinetic and intracerebral distribution of MDMB-4F-BICA in mice following inhalation ('vapor') and subcutaneous injection.

MDMB-4F-BICA, also known as 4F-MDMB-BICA, is a new psychoactive substance that emerged in 2020. It is often illegally added to electronic cigarette oil for inhalation abuse, leading to serious adverse symptoms and even death. There are significant differences in pharmacokinetics between inhalation administration and conventional drug delivery methods. Inhalation administration can pass through the blood-brain barrier to enter the brain directly. However, the specific distribution of the drug in the brain following inhalation has not been well investigated. In order to scientifically compare the absorption and distribution of MDMB-4F-BICA after two administration methods (inhalation and subcutaneous injection), this study analyzed the drug concentration in mice blood and brain by LC-MS/MS after systemic exposure inhalation in the form of electronic cigarettes. The aim was to conduct the pharmacokinetics study of MDMB-4F-BICA after inhalation('vapor') administration. Pharmacokinetics and distribution of the compound revealed that the maximum concentrations in blood of this compound were reached at 0.5 min and 15 min, respectively, and the concentration in the brain reached the maximum at the same time after two modes of administration. The drug concentration in the brain was higher than that of subcutaneous injection, and the drug remained at a low concentration in the brain for a long period (20 ng/g brain tissue) with a significant distribution in several olfactory primary cortex brain regions. Taken together, the pharmacokinetics of the synthetic cannabinoid MDMB-4F-BICA after single systemic exposure inhalation were investigated for the first time in this study. A basis for subsequent evaluation research of inhalation-related harmfulness is provided by comparing the distribution of drugs in the brain after the two administration modes.

Gut microbiota and liver metabolomics reveal the potential mechanism of Lactobacillus rhamnosus GG modulating the liver toxicity caused by polystyrene microplastics in mice.

Microplastics (MPs) are known to cause liver toxicity as they can spread through the food chain. Most researches on their toxicity have focused on individual organs, neglecting the crucial "gut-liver axis"-a bidirectional communication pathway between the gut and liver. Probiotics have shown promise in modulating the effects of environmental pollutants. In this study, we exposed mice to Lactobacillus rhamnosus GG (LGG, 100 mg/kg b.w./d) and/or polystyrene microplastics (PS-MPs, 5 mg/kg b.w./d) for 28 d via gavage to investigate how probiotics influence live toxicity through the gut-liver axis. Our results demonstrated that PS-MPs induced liver inflammation (increased IL-6 and TNF-α) and disrupted lipid metabolism. However, when combined with LGG, these effects were alleviated. LGG also improved colon health, rectifying ciliary defects and abnormal mucus secretion caused by PS-MPs. Furthermore, LGG improved gut microbiota dysbiosis induced by PS-MPs. Metabolomics and gene expression analysis (Cyp7a1 and Cyp7b1) indicated that LGG modulated bile acid metabolism. In summary, LGG appears to protect the liver by maintaining gut homeostasis, enhancing gut barrier integrity, and reducing the liver inflammation. These findings confirm the potential of LGG to modulate liver toxicity caused by PS-MPs through the gut-liver axis, offering insights into probiotics' application for environmental pollutant detoxification.