This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all p < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all p < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.

Background: Aspiration pneumonia (AP), which can be caused by gastric content inhalation into the lower airways, causes acute lung injury (ALI) through complex mechanisms, including inflammation, oxidative stress, and apoptosis. Here, we evaluated the efficacy of exosomes derived from human placental mesenchymal stem cells (hpMSCs) in mitigating ALI in a murine model of AP. We also investigated the role of hsa-let-7i-5p, the most abundant miRNA in hpMSC-derived exosomes, in this respect.Methods: Adult male C57BL/6 mouse AP models were administered hpMSC-derived exosomes (APExo group) or phosphate-buffered saline (AP group) intra-tracheally. After 48 h, the mice were euthanized and evaluated. The effects of hsa-let-7i-5p were assessed by specific inhibition or overexpression.Results: Compared with the APExo group, the AP group exhibited significantly greater ALI, as evidenced by histological damage, increased lung injury scores, impaired lung function, increased leukocyte infiltration, and elevated tissue edema (all P < 0.05). The untreated AP group also showed more inflammation, characterized by nuclear factor-κB upregulation, macrophage M1 polarization, and cytokine level elevation (tumor necrosis factor-α, interleukin-1β, and interleukin-6), as well as increased oxidation and activation of the apoptosis pathway (all P < 0.05). Notably, the therapeutic effects of hpMSC-derived exosomes were compromised by specific inhibition of hsa-let-7i-5p. Furthermore, engineered exosomes derived from genetically modified RAW264.7 overexpressing hsa-let-7i-5p demonstrated therapeutic effects against AP similar to those obtained with hpMSC-derived exosomes.Conclusions: In a murine AP model, intra-tracheal administration of hpMSC-derived exosomes has ALI-mitigating effects, involving inflammation, oxidation, and apoptosis modulation, with hsa-let-7i-5p playing a pivotal mediating role.

The iliopsoas plane (IP) is a fascial plane deep to the iliopsoas complex and is the target of several novel ultrasound-guided analgesic interventions for hip. Currently, limited information is known about its parameters. From the pelvic magnetic resonance (MR) images of an adult Eastern Asian population (n = 49), the IP width, depth, and needle-beam angle in the axial plane immediately caudal to the level of indirect tendon of rectus femoris (RF) were found to be 10.7 ± 1.6 mm, 48.5 ± 15.5 mm, and 84.2 ± 8.2 degrees, respectively. There was a statistically significant difference in the age categories for IP width, and older patients seemed to have wider IP. Our data may provide applications for the technical modification of ultrasound-guided iliopsoas plane block (IPB) in acute hip pain management and the future development of ultrasound-guided single-needle-entry radiofrequency neuroablation in chronic hip pain management.

Background: Disruption of the gut microbiota has been increasingly recognized in respiratory infections, contributing to impaired intestinal barrier function, systemic inflammation, and worse clinical outcomes. Microbiome-based therapeutic interventions (MBTIs), including probiotics and synbiotics, may modulate host immune responses through the gut-lung axis; however, their clinical efficacy in acute COVID-19 remains uncertain.Methods: We conducted a systematic review and meta-analysis of 14 randomized controlled trials involving 1,644 participants (812 intervention; 832 control). Eleven studies evaluated probiotics and three evaluated synbiotics, with sample sizes ranging from 39 to 300. Random-effects models calculated risk ratios (RRs) and mean differences (MDs), with subgroup analyses by MBTI type; heterogeneity was assessed using the I² statistic.Results: MBTIs were associated with reductions in all-cause mortality (RR = 0.51, 95% CI 0.28–0.90; I² = 0%; p = 0.02), disease progression (RR = 0.55, 95% CI 0.39–0.77; I² = 0%; p = 0.0005), hospital stay (MD = –1.00 days, 95% CI –1.94 to –0.05; I² = 74%; p = 0.040), and C-reactive protein (MD = –0.61 mg/L, 95% CI –1.01 to –0.21; I² = 91%; p = 0.003) versus standard care. Probiotics showed the most consistent benefits compared with synbiotics.Conclusions: Microbiome-based therapeutic interventions, particularly probiotics, may improve clinically relevant outcomes in COVID-19, likely through immunomodulation and modulation of the gut-lung axis. These findings support the potential role of microbiome-targeted therapies as adjunctive strategies in respiratory infections, although further well-designed trials are required.

Background: Multimodal analgesia, combining adductor canal block (ACB) and local infiltration analgesia (LIA), is commonly used for pain control after total knee arthroplasty (TKA). However, ACB alone may not fully cover the anteromedial knee, a region extensively disrupted by TKA. Recent studies suggest that blocking branches of the anterior femoral cutaneous nerve (AFCN) could enhance analgesia, but targeted AFCN blocks are technically challenging. We evaluated supra-sartorial subcutaneous infiltration (SSSI) at the femoral triangle apex as a simpler alternative to AFCN blocks. Methods: We retrospectively reviewed 19 patients undergoing TKA with a standardized multimodal analgesic protocol, including intraoperative LIA limited to posterior capsule (PC-LIA), postoperative SSSI, and delayed intermittent ACB via catheter. SSSI involved infiltrating 20 mL of 0.3% ropivacaine into the subcutaneous plane above the sartorius muscle at the level of femoral triangle apex. Pain was assessed using Numerical Rating Scale (NRS) scores at rest and during movement at 9:00 PM on postoperative day 0 (POD 0) and 9:00 AM on POD 1, with scheduled ACB doses administered at the time of NRS pain score assessments. Rescue ACB boluses were given for intolerable pain before the first scheduled dose. Results: Eleven patients (58%) required no rescue analgesia before the first scheduled ACB, maintaining NRS scores ≤ 4 at rest and with movement for a minimum of 575–785 min post-spinal anesthesia. Eight patients needed rescue ACB, with variable pain relief. Conclusions: SSSI, when combined with PC-LIA, provided clinically meaningful analgesia in 58% of our patient cohort following TKA, though the variability observed suggests limited consistency. As a practical alternative to targeted AFCN blocks, SSSI could potentially complement ACB in multimodal pain management, but its efficacy remains uncertain due to the retrospective, non-controlled study design without a comparator group. Further investigation through prospective randomized controlled trials is warranted to validate these preliminary findings.

Background: Aspiration pneumonia (AP) remains a major cause of morbidity and mortality, yet non-invasive tools for monitoring lung injury in preclinical models are limited. Lung ultrasound (LUS) is widely used clinically, but existing murine scoring systems lack anatomical resolution and have not been validated for aspiration-related injury. Methods: We developed the Modified Lung Edema Ultrasound Score (MLEUS), a region-structured adaptation of the Mouse Lung Ultrasound Score (MoLUS), designed to accommodate the heterogeneous and gravity-dependent injury patterns characteristic of murine AP. Male C57BL/6 mice were assigned to sham, 6 h, 24 h, or 48 h groups. Regional LUS findings were compared with histological injury scores and wet-to-dry (W/D) ratios. Inter-rater reliability was assessed using the intraclass correlation coefficient (ICC). Results: Global LUS–histology correlation was weak (ρ = 0.33, p = 0.114). In contrast, regional performance varied markedly. The right upper (RU) zone showed the strongest correspondence with histological injury (r = 0.55, p = 0.005), whereas right and left diaphragmatic regions demonstrated minimal association. LUS abnormalities were detectable as early as 6 h, preceding clear histological progression. Inter-rater reliability was good (ICC = 0.87). Conclusions: MLEUS provides a reproducible, region-specific framework for evaluating aspiration-induced lung injury in mice. Although global correlations with histology were limited, region-dependent analysis identified that the RU zone as a reliable acoustic window for concurrent injury assessment. Early ultrasound changes highlight the sensitivity of LUS to dynamic aeration and interstitial alterations rather than cumulative tissue damage. These findings support the use of LUS as a complementary, non-invasive physiological monitoring tool in small-animal respiratory research and clarify its methodological scope relative to existing scoring frameworks.