Objective To investigate whether Danshen injection (DSI) can protect human brain organoids from oxidative stress damage by regulating the Nrf2 signaling pathway and its mechanism. Methods A Nrf2 plasmid was constructed, lentivirus was packaged and transfected into human induced pluripotent stem cell (hiPSC) to form a stable cell line. Brain organoids with Nrf2 overexpression (LV-Nrf2 group) and knockdown (sh-Nrf2 group) were constructed using kit. The transfection efficiency was verified by real-time fluorescence quantitative polymerase chain reaction. An oxidative stress injury model was established by inducing hydrogen peroxide (H₂O₂). Intervention was performed either in combination or without DSI pre-treatment. Cell viability was detected by Cell Counting Kit-8 (CCK-8), and the expression levels of Nrf2, malondialdehyde (MDA), interleukin (IL)-1β, sex-determining region Y-box protein 2 (SOX2) and neuronal-specific nuclear protein (NeuN) were detected by Western blot and immunofluorescence staining. Total RNA from human brain organoids was extracted for transcriptome sequencing and analysis. Results LV-Nrf2 group and sh-Nrf2 group brain organoid models were successfully constructed. The CCK-8 results determined that the oxidative stress model was established with 32 mmol/L H₂O₂ intervention conditions. The fluorescence expression of Nrf2 in LV-Nrf2 group was higher than that in control group, and the fluorescence expressions of MDA and IL-1β were lower than those in control group; sh-Nrf2 group showed a damage phenotype of low Nrf2 expression, high MDA and IL-1β expression (all P < 0.05). Compared with H₂O₂ group, the Nrf2 signal in DSI + H₂O₂ group was stronger, and the levels of MDA and IL-1β were lower. Among them, the protective effect of LV-Nrf2 was the most significant. H₂O₂ treatment could down-regulate the protein levels of Nrf2, SOX2 and NeuN, and DSI intervention could effectively reverse the downward trend of these indicators. Sh-Nrf2 could weaken the recovery effect of DSI on SOX2 and NeuN, while LV-Nrf2 could synergistically enhance the regulatory effect of DSI. Conclusions DSI may antagonize oxidative stress damage in human brain organoids through the Nrf2 signaling pathway, and maintaining the stability of the neural cell lineage is its core therapeutic characteristic.

Objective:To evaluate the safety and necessity of vasopressor infusion through midline catheter.Methods:A convenient sampling method was used for a controlled study. A total of 88 adult patients who used vasopressors admitted to respiratory intensive care unit (RICU) of Fenyang Hospital in Shanxi Province from June 2022 to June 2023 were enrolled as the research subjects. A total of 44 patients who were infused with vasopressors through peripherally inserted central venous catheter (PICC) from June to December 2022 were enrolled as the PICC group, and 44 patients who were infused with vasopressors through midline catheter from January to June 2023 were enrolled as the midline catheter group. Both groups of patients used the modified Sedinger technique under the guidance of B-ultrasound for puncture and catheter placement. The middle 1/3 site between the cubital fossa and the axilla was selected. The catheters were 5 Fr double lumen. After catheter placement, the patients were followed until catheter removal, death, or 30 days (whichever came first). Based on the Infusion therapy standards of practice revised by American Infusion Nurses Society (INS), and combined with the results of previous preliminary tests, the safety evaluation was conducted on incomplete catheter obstruction, catheter-related bloodstream infection (CRBSI), phlebitis, thrombus within the catheter during extubation, redness of the puncture site (but no infection), and exudation of the puncture site in the two groups of patients.Results:There were no statistical differences in gender, age, catheter indwelling time, and primary disease between the two groups, indicating that the baseline data of the two groups were balanced and comparable. No CRBSI or phlebitis occurred in both groups during the observation period after catheterization. One patient in both groups had exudation at the puncture site [both were 2.27% (1/44)]. Compared with the PICC group, the incidence of incomplete catheter obstruction, thrombus within the catheter during extubation, redness of the puncture site (but no infection) in the midline catheter group were lowered [incomplete catheter obstruction: 4.55% (2/44) vs. 6.82% (3/44), thrombus within the catheter during extubation: 0% (0/44) vs. 2.27% (1/44), redness of the puncture site (but no infection): 0% (0/44) vs. 4.55% (2/44)], the overall incidence was significantly decreased [6.82% (3/44) vs. 15.91% (7/44), P < 0.01]. Conclusion:Administering vasopressor through a midline catheter can reduce the incidence of catheter-related complications, decrease the rate of central venous catheterization, and reduce the financial burden on patients.

Objective:To explore the clinical application effects of early pulmonary rehabilitation training based on bundle airway management in patients with tracheostomy and non-mechanical ventilation.Methods:Used convenience sampling, adult patients who underwent tracheostomy and non-mechanical ventilation admitted to Fenyang Hospital of Shanxi Province from January 2022 to May 2023 were enrolled. Patients were divided into control group and observation group based on their admission dates. The control group implemented bundle airway management based on the Airway care for patients with tracheostomy and non- mechanical ventilation. The observation group received additional pulmonary rehabilitation training implemented by a specialized respiratory rehabilitation team. The primary outcomes included hospital stay duration, improvement rate of muscle strength, diaphragmatic mobility, and successful extubation rate. Secondary outcomes included the incidence of pulmonary infection, improvement rate of self-care ability, and the duration of tracheal tube placement in extubated patients. Results:A total of 41 patients were included in the control group and 39 patients in the observation group. There were no significantly differences in gender, age, first diagnosis of disease, and activities of daily living (ADL) score at admission between the two groups, indicating balanced baseline data and comparability. Compared with the control group, the observation group had a significantly shorter hospital stay (days: 38.33±17.58 vs. 51.34±27.06), a higher improvement rate of muscle strength (76.92% vs. 39.02%), greater diaphragmatic mobility (cm: 1.86±0.64 vs. 1.44±0.57), and a higher success rate of tracheostomy tube extubation (38.46% vs. 17.07%), the duration of tracheal tube placement in successfully extubated patients was significantly reduced (days: 33.26±17.87 vs. 50.60±21.98), with all differences being statistically significant (all P < 0.05). Although the improvement rate of ADL score (56.41% vs. 36.59%) and the incidence of pulmonary infection (5.13% vs. 7.32%) in the observation group were better than those in the control group, but there were no differences (both P > 0.05). Conclusion:The addition of pulmonary rehabilitation training in bundle airway management can enhance exercise tolerance, improve respiratory function, promote sputum clearance, increase successful extubation rates, shorten hospital stays, and facilitate early recovery in patients with tracheostomy and non-mechanical ventilation.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

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