Exosomal miR-9-5p derived from iPSC-MSCs ameliorates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence.

Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-ß-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment.

Prognostic value of inflammatory cytokine detection for sepsis patients in ICU: a meta-analysis.

OBJECTIVE: To explore the prognostic effect of cytokine levels such as IL-6 (interleukin), IL-8 and TNF (tumor necrosis factor)-α on patients with sepsis in intensive care units (ICUs) by Meta-analysis. METHODS: We systematically searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and other databases up to May 2023 to retrieve clinical research articles on cytokine testing for predicting sepsis prognosis in ICU settings. Relevant indicators were extracted and recorded in Excel. Meta-analyses were performed using RevMan 5.3. RESULTS: A total of 25 studies were finally included in this Meta-analysis: 21 investigated IL-6, 6 examined IL-8, 11 addressed IL-10, 12 reviewed TNF-α, and 6 focused on IL-1ß. Meta-analysis results demonstrated that cytokine levels (IL-6, IL-8, IL-10, TNF-α and IL-1ß) in survival groups were substantially lower than those in non-survival groups (ALL P < 0.00001). Specific findings include significant differences in IL-6 [SMD = -25.32, 95% CI (-27.14, -23.49), P < 0.00001], IL-8 [SMD = -140.48, 95% CI (-154.32, -126.64), P < 0.00001], IL-10 [SMD = -54.10, 95% CI (-56.74, -51.47), P < 0.00001], TNF-α [SMD = -8.67, 95% CI (-9.82, -7.52), P < 0.00001], and IL-1ß [SMD = -3.71, 95% CI (-4.11, -3.30), P < 0.00001]. The funnel plots for IL-6, IL-8, IL-10, TNF-α, and IL-1ß displayed roughly symmetrical distributions, suggesting minimal bias and high reliability of the findings. CONCLUSION: Cytokine levels such as IL-6, IL-8, and TNF-α are valuable prognostic indicators for patients with sepsis in the ICUs. Early testing of these cytokines can guide clinical interventions and enable targeted treatments for high-risk patients to reduce the likelihood of adverse outcomes.

Detection of near-surface defects in viscoelastic material based on focused ultrasound thermal effects.

Viscoelastic materials will absorb and dissipate energy under stress, resulting in energy loss and heat generation. The conventional non-destructive testing methods have certain limitations when it comes to detecting near-surface defects in viscoelastic materials. In this paper, a detection method of near-surface defects based on focused ultrasonic thermal effect is proposed. Firstly, the difference in thermal effects caused by defective and non-defective regions of the material under ultrasound is analyzed according to the stress response equation of viscoelastic materials, and the detection principle is elucidated. Secondly, the feasibility of this method is verified through finite element simulation with an example of plexiglass material Subsequently, the variations in the surface temperature distribution of defective specimens with varying diameters and depths are analyzed. Finally, experimental validation reveals that ultrasonic waves operating at 1.12 MHz successfully detect artificial defects with a diameter of 1 mm. With the increase of the equivalent diameter of the defect, the width of the low-temperature depression area in the surface temperature field exhibits a linear increase relationship. With the increase of the defect depth, the surface temperature difference between the corresponding position of the defective and the surrounding non-defective area gradually decreases. This method effectively overcomes the half-wavelength limitation and introduces a novel detection approach for near-surface defect identification in viscoelastic materials such as plexiglass.

Flow regimes identification of air water counter current flow in vertical annulus using differential pressure signals and machine learning.

This study investigates the gas-liquid two-phase counter-current flow through a vertical annulus, a phenomenon prevalent across numerous industrial fields. The presence of an inner pipe and varying degrees of eccentricity between the inner and outer pipes often blur the clear demarcation of flow regime boundaries. To address this, we designed a vertical annulus with adjustable eccentricity (outer and inner diameters of 125 mm and 75 mm, respectively). We conducted gas-liquid counter-current flow experiments under specific conditions: gas superficial velocity ranging from 0.06 to 5.04 m/s, liquid superficial velocity from 0.01 to 0.25 m/s, and five levels of eccentricity (e = 0, 0.25, 0.5, 0.75, 1). We collected differential pressure data at two distinct height distances (DP1: 50 mm and DP2: 1000 mm). We used vectors, composed of both the probability density functions (PDFs) of the differential pressure signals and the power spectral density (PSD) reduced via Principal Component Analysis, as features. Using the CFDP clustering algorithm-based on local density-we clustered the flow regimes of the experimental data, thereby achieving an objective and consistent identification of the flow regime of gas-liquid two-phase counter-current flow in a vertical annulus. Our analysis reveals that for DP1, the main differences in the PSD of various flow regimes occur within the 0.5-1 Hz range. Among the three flow regimes involved, the slug flow exhibits the highest power intensity, followed by the bubbly flow, with the churn flow having the least. In terms of differential pressure distribution, the bubbly and churn flows have a concentrated distribution, while the slug flow is more dispersed. For DP2, the PSD differences primarily exist within the 0.5-2 Hz range. The churn flow has the highest power intensity, followed by the slug flow, with the bubbly flow being the weakest. Here, the bubbly flow's differential pressure distribution is concentrated, while the slug and churn flows are more dispersed. Based on the results of the flow regime classification, we generated a flow regime map and analyzed the influence of annulus eccentricity on the flow regime. We found that in most cases, pipe eccentricity does not significantly affect the flow regime. However, in the transition region-such as the bubbly to slug flow transition zone-flows with medium eccentricity values (e = 0.5, 0.75) are more likely to transition to slug flow. We compared the visual recognition results of flow regimes with the clustering results. 4.04% of the total samples showed different results from visual recognition and clustering, primarily located in the flow regime transition area. Since visually distinguishing flow regimes in these areas is typically challenging, our methodology offers an objective classification approach for gas-liquid two-phase counter-current flow in a vertical annulus.

Topical Use of Low-dose Tranexamic Acid Has no Effect on Drainage Volume after Medial Open Wedge High Tibial Osteotomy: A Case Control Study.

OBJECTIVE: Many studies reported that tranexamic acid (TXA) was effective in reducing surgical blood loss in the perioperative period of medial open wedge high tibial osteotomy (MOWHTO). However, few studies focused on the simple topical use of TXA in MOWHTO, and the modality and dosage of topical use of TXA varied. The purpose of this study was to observe the effect of topical use of low-dose TXA on drainage volume after MOWHTO, and to analyze the related influencing factors. METHODS: Data of patients who underwent MOWHTO combined with arthroscopic knee surgery in our department from January 2019 to September 2021 were retrospectively analyzed. A total of 105 patients (38 males and 67 females, aged 57.7 ± 7.5 years) were included in this study who received topical TXA or no TXA. The patients were divided into three groups: control group (39 cases), 0.5 g TXA group (40 cases), 1 g TXA group (26 cases). Postoperative drainage volume, wound healing, incidence of hematoma and deep venous thrombosis (DVT) were observed and analyzed in the three groups. The effects of gender, hypertension and diabetes on postoperative drainage volume were analyzed using a t-test. The correlation between age, body mass index (BMI), osteotomy gap and postoperative drainage volume were analyzed using the Pearson correlation coefficient. RESULTS: The average postoperative drainage volume of the control group was 259.54 ± 226.33 mL, that of the 0.5 g TXA group was 277.18 ± 177.68 mL, and that of the 1 g TXA group was 229.15 ± 219.93 mL. There was no statistically significant difference in postoperative drainage volume among the three groups (F = 0.423, p = 0.656). There was no local hematoma and wound infection in the three groups. The wound fat liquefaction was found in one patient of the control group. The incidence of DVT was 38.9% (7/18) and 57.1% (8/14) in the control group and 0.5 TXA group, respectively. There was no significant difference in the incidence of DVT between the above two groups (p = 0.476). The average postoperative drainage volume of male patients in the three groups was higher than that of female patients, and the differences were statistically significant (p < 0.05). There was no correlation between age, BMI, osteotomy gap and postoperative drainage volume in the three groups (p > 0.05). CONCLUSION: Topical use of low-dose TXA has no significant effect on drainage volume after MOWHTO. The drainage volume after MOWHTO in male patients was more than that in female patients. Topical administration of low-dose TXA does not increase postoperative complications, such as DVT and hematoma.