As a major global public health problem, pulmonary diseases threaten human life and health while causing a huge economic burden. The messenger RNA (mRNA)-based inhalation preparation, which effectively targets pulmonary cells can overcome the problems of traditional therapy, such as high side effects, low pulmonary bioavailability, and difficulty in synthesizing target proteins in vitro, thus providing new ideas for the treatment of pulmonary diseases. However, as the lung structure is complex and mRNA has trouble entering cells, researchers have been attempting to develop a suitable nano delivery system for higher delivery efficiency. This review introduces the barriers to pulmonary delivery, discusses the recent research development of the mRNA pulmonary delivery systems, including lipid nanoparticles, polymeric nanoparticles, polypeptides and exosomes, summarizes their limitations and looks forward to the application of mRNA inhalation preparations.

OBJECTIVE: To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD. METHODS: Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 ⁺), and DJ1-knockdown group (DJ1 ^-). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice. RESULTS: DJ1 ⁺ overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 ^- cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 ⁺ increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA). CONCLUSION DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1.
Animals ; Mice ; Alzheimer Disease/therapy* ; AMP-Activated Protein Kinases/metabolism* ; Amyloid beta-Protein Precursor/metabolism* ; Antioxidants/metabolism* ; Disease Models, Animal ; Hippocampus/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Mammals/metabolism* ; Mice, Inbred C57BL ; Mice, Transgenic ; NF-E2-Related Factor 2/metabolism* ; Presenilin-1/metabolism* ; TOR Serine-Threonine Kinases/metabolism*

Objective To design and validate a novel surgical guide for retrieval of foreign body in jaw. Methods Firstly, a surgical guide based on cone beam computed tomography and trephine technique was designed to remove broken dental instrument fragments. Its feasibility and accuracy were assessed by removing broken dental instrument in goat mandible, and then it was successfully applied in clinical cases. The linear and angular discrepancies between actual and planned columnar bone with imaginary fragment was analyzed. The euclidean distance was measured at the hex and apex of the columnar bone and the angle of axis deviation was also calculated. We obtained seven parameters (cdh, cda, hdh, hda, vdh, vda, and ad) to describe deviations. Results Mean central deviation at the hex and apex was (0.51 ± 0.14) mm and (0.62 ± 0.19) mm, respectively. Accompanying mean values were as follow: horizontal deviation at the hex was (0.48 ± 0.16) mm, horizontal deviation at the apex was (0.52 ± 0.22) mm, vertical deviation at the hex was (0.17 ± 0.09) mm, vertical deviation at the apex was (0.29 ± 0.13) mm, and angular deviation of (5.38 ± 3.43) degrees. In a clinical case, the guide successfully located and removed the fracture file. Conclusion This study reveals that this kind novel surgical guide could aid to locate and remove the foreign body in jaw.

The working principle and structural composition of the transcranial magnetic stimulator were introduced.The failures of the transcranial magnetic stimulator in some hospital were summarized from 2018 to 2022.The causes for common failures of the transcranial magnetic stimulator were analyzed with the fishbone diagram,and some suggestions were put forward on its daily utilization management.The maintenance thoughts for two common failures were described in detail including flow control alarm and no magnetic field output.References were provided for daily management and maintenance of the transcranial magnetic stimulator.[Chinese Medical Equipment Journal,2023,44(9):110-113]

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the K_D of which reached to 8.722×10^-10 g·mL^-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

Monoclonal antibody drugs that inhibit programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) have been widely used in esophageal cancer (EC) and yielded significant therapeutic responses. However, only a few patients obtain lasting clinical benefits due to primary or acquired drug resistance, and new treatment schemes are urgently needed. The tumor immune microenvironment is the main factor that affects patients' response to immunosuppressive agents. This article will discuss the role of immunosuppressive cells and non-cellular components in the immune process to provide ideas for the next research direction of EC.

Humans ; Fasciitis/pathology* ; Fibroma/pathology* ; Gene Rearrangement ; Proto-Oncogene Proteins/genetics* ; Ubiquitin Thiolesterase

Coronary heart disease (CHD) and stroke are the most well-known cardiovascular diseases, which share many common pathological basis. Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese patent medicine in the treatment of stroke and CHD. However, its action of mechanism of co-treatment for stroke and CHD is still unclear. The aim of this study was to explore the common mechanism of YDXNT in co-treatment of CHD and stroke using network pharmacology, experimental verification and molecular docking. An integrated literature mining and databases of IPA, ETCM, HERB, Swiss Target Prediction, OMIM and GeneCards were used to screen and predict active ingredients and potential targets of YDXNT in co-treatment of CHD and stroke. The protein-protein interaction network, GO analysis and pathway analysis were analyzed by IPA software. The effect of YDXNT on core targets was verified by immunofluorescence. UPLC-QTOF/MS and molecular docking were used to screen and predict the main active constituents of YDXNT and their interactions with core targets. A total of 151 potential targets are predicted for YDXNT in co-treatment of CHD and stroke. Hypoxia-inducible factor-1α (HIF1α)-matrix metalloproteinase-9 (MMP9)-mediated HIF1α signaling pathway serves as one of the common mechanisms. YDXNT could reduce the increase of mitochondrial fluorescence intensity and the protein expression of HIF1α and MMP9 in HL-1 and HA induced by oxygen and glucose deprivation/reperfusion (OGD/R) in a dose-dependent manner. Baicalin may be the material basis for treating stroke and CHD with YDXNT. In conclusion, the HIF1α signaling pathway is one of the common key mechanisms of YDXNT in the co-treatment of stroke and CHD. The study provides support and basis for the in-depth scientific connotation of the traditional Chinese medicine theory of "same treatment to different diseases".

As a natural drug delivery carrier with rough and porous surface and hollow core， yeast microcapsules have good safety， high targeting and high stability， and have excellent application prospects in oral drug delivery systems. Yeast cells can be treated and washed with acid-base and organic solvents to obtain loose and porous yeast microcapsules. Yeast microcapsules can encapsulate drugs through electrostatic interactions， passive diffusion， hydrophobic interaction and other methods. The surface of yeast microcapsules is mainly composed of β-glucan， which can maintain stability in the gastrointestinal environment； it can be recognized by the surface-related receptors of immune cells， thus activating the immune response， and can be transported to the lesion site with the movement of lymphocytes after being ingested. Yeast microcapsules are safe and very suitable for delivering vaccines， anti-inflammatory drugs， and anti-tumor drugs. They can not only achieve oral delivery of the aforementioned drugs， but also enhance drug efficacy and improve drug targeting. In the future， more research on systemic transport mechanisms or the development of more efficient combination drug delivery systems can be carried out to fully exhibit the clinical value of yeast microcapsules.

Serum and glucocorticoid-regulated kinase 1 (SGK1) plays an important role in the physiological processes of hormone release, neuronal excitation and cell proliferation. SGK1 also participates in the pathophysiological processes of inflammation and apoptosis in the central nervous system (CNS). Increasing evidence demonstrates that SGK1 may serve as a target of the intervention of neurodegenerative diseases. In this article, we summarize the recent progress on the role and molecular mechanisms of SGK1 in the regulation of the function of the CNS. We also discuss the potential of newly discovered SGK1 inhibitors in the treatment of CNS diseases.
Humans ; Cell Proliferation ; Central Nervous System Diseases/drug therapy* ; Inflammation ; Protein Serine-Threonine Kinases/physiology*