Tumorigenesis， invasion， and metastasis occur in the context of a persistent inflammatory microenvironment， and a variety of inflammatory factors can lead to the development of various tumors. Guided by the thought of "preventive treatment of disease" in TCM and the concept of tertiary prevention in modern medicine， it is of great significance to effectively intervene in the inflammatory stage of the disease， interrupt disease progression， prevent the occurrence of malignant tumors， and reverse the process of "inflammation-to-cancer transformation". Sinisan， a commonly used prescription in the Treatise on Febrile Diseases， has been widely applied in the treatment of precancerous lesions of the digestive system， demonstrating considerable advantages. This article reviewed literature from the past 20 years， summarizing the application of Sinisan in precancerous lesions of the digestive system from three aspects： the exploration of its prescription-syndrome relationship， clinical application， and mechanistic study. It is found that basic syndrome indications of Sinisan include harmonizing the Earth element to promote spleen-stomach transportation and transformation， soothing the liver and nourishing the Wood element to restore the smooth flow of Qi， and regulating Yin and Yang to relieve stagnation within the system. In clinical application， Sinisan has shown significant efficacy in atrophic gastritis and precancerous conditions such as intestinal metaplasia， gastric ulcer， ulcerative colitis， esophagitis， and pancreatitis. Mechanistic studies have revealed that Sinisan can inhibit inflammatory factors and improve the inflammatory microenvironment， inhibit cell proliferation and regulate apoptosis， exhibit anti-angiogenic and antitumorigenic effects， modulate immune function， and exert antioxidant effects. These mechanisms can be achieved by regulating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， farnesoid X receptor （FXR）/Nrf2， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A （TGR5/cAMP/PKA）， interleukin-4/signal transducer and activator of transcription 6 （IL-4/STAT6）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， RhoA/Rho-associated protein kinase （RhoA/ROCK）， and transforming growth factor-β/Smad proteins （TGF-β/Smads）， confirming Sinisan's role in reversing the inflammation-to-cancer transformation. The current research status of Sinisan in precancerous lesions of the digestive system was thoroughly examined through the above three aspects， along with the identification of limitations and areas for improvement in current research. The aim is to provide a basis and support for future in-depth research on Sinisan， promote the development of new integrated treatment models combining TCM and Western medicine for precancerous lesions， and aid in the research and development of drugs related to precancerous lesions.

Plants of the Isodon genus are an important source of terpenoids， with their constituents exhibiting rich structural diversity and remarkable biological activities （such as anticancer， antimicrobial， and anti-inflammatory properties）， demonstrating significant potential in the field of immunomodulation. This review summarizes recent advances in the immunomodulatory mechanisms， development and application of terpenoid compounds from the Isodon genus. It has been found that these compounds can modulate key inflammatory signaling pathways， such as nuclear factor-kappa B （NF-κB） and mitogen-activated protein kinases （MAPKs）， thereby blocking the cascade amplification of inflammatory factors， alleviating chronic inflammatory responses， and correcting immune dysregulation. Additionally， they can influence the polarization direction of macrophages and dynamically regulate the balance among different functional subsets of T cells， restoring immune homeostasis. Their clinical translation faces multiple challenges， including poor druggability， a lack of systematic safety data， the absence of precise pharmacodynamic biomarkers， complexities in clinical trial design， and unclear industrialization pathways.

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX₃CR1⁺CCR2^-Ly6C^-MHCII^- (MP1), CX₃CR1^lowCCR2^lowLy6C^-MHCII^- (MP2), CX₃CR1^-CCR2⁺Ly6C⁺MHCII^- (MP3), and CX₃CR1⁺CCR2^-Ly6C^-MHCII⁺ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.

Epithelial-mesenchymal transition (EMT ) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

Up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.
Activating Transcription Factor 4/genetics* ; Adenocarcinoma of Lung ; Amino Acids ; Cell Proliferation ; Eukaryotic Initiation Factor-2 ; Humans ; Lung Neoplasms ; RNA Helicases/metabolism* ; RNA, Messenger/metabolism* ; Trans-Activators/metabolism*

Objective:Through histological analysis, immunofluorescence staining, electrophysiological detection and Sensory and motor function evaluation to investigate the effects of 3D printed hydrogel scaffold combined with bone marrow mesenchymal stem cells (BMSCs) in promoting functional recovery of spinal cord injury.Methods:10% GelMA hydrogel and 10 6 U stem cell suspension were prepared into bioink of appropriate concentration to construct the biomimetic spinal cord scaffold through 3D printing platform. The scaffold was placed in the medium and cultured in an environment of 37 ℃ CO 2 incubator. The microstructure of the scaffolds and the distribution of BMSC in the scaffolds was observed by scanning electron microscope. CAM/PI staining and confocal microscopy were used to observe the survival of stem cells in the scaffolds and determine the biocompatibility of the scaffolds. The scaffolds were implanted into the subcutaneous tissues of the back of rats, and the subcutaneous tissues were determined by HE staining to detect the immunogenicity of the scaffolds. After the rat model of hemicytoma defect was made, stents were transplanted for treatment, and confocal microscopy was used to evaluate the regeneration of neurons and axons in local area of spinal cord injury. At the same time, BBB score was used to evaluate motor function, mechanical pain score was used to evaluate sensory function, and surface electrode detection method was used to evaluate electrophysiological recovery weekly. Results:The long spindle shaped BSMC were uniformly distributed in the scaffold with a loose reticular structure. The scaffolds had good biocompatibility, and the cell survival rate of the prepared scaffolds reached 96% after 24 hours of printing. After 28 days of subcutaneous transplantation, the immune rejection was mild and immunogenicity was low. It was shown that the regenerated spinal cord tissue in the treatment group was significantly increased compared with the control group, which was widely distributed with cells after 28 days by HE staining. It was confirmed that part of the regenerated spinal cord tissue was neurons by immunohistochemical staining.Compared with the injured group, the regeneration of neurons and axons in the treatment group were significantly increased by immunofluorescence staining and confocal microscopy. In the treatment group, the BBB score recovered to 10 points, while the control group only recovered to about 1 point in the first week, which was statistically significant. And it recovered to 17 in the fourth week, while the control group only recovered to about 4 point in the four week, which was statistically significant. The Angle of inclined plate support of the treatment group was restored to 40 degrees, while it was only restored to 22 degrees in the control group. The pain threshold of the treatment group decreased to 18.5 points, which was not statistically different from that of the control group. The latent recovery effect of electrophysiology in the treatment group was the same as that in the sham operation group and better than that in the control group.Conclusion:3D printing hydrogel scaffold with loose network structure is suitable for cell proliferation. It has well biological survival, low cytotoxicity and low immunogenicity, which promoted neurons and axons to recovery and extend so as to effectively promote the recovery of motor function, sensory function and neural signal transmission rate after spinal cord injury.

During pandemic of corona virus disease 2019 (COVID-19), emergency orthopedic trauma is commonly seen. It is particularly important to ensure the emergency treatment quality of orthopedic trauma but avoid cross-infection between doctors and patients. The double-buffered diagnosis and treatment mode refers to the model of patients first undergoing medical observation in the comprehensive buffer ward and the inpatient buffer rooms of various disciplines after admission to confirm the exclusion of COVID-19 and then receiving specialist diagnosis and treatment. The authors summarize the experiences of using the double-buffered diagnosis and treatment model in the Department of Orthopedics, Renmin Hospital of Wuhan University during the prevention and control of COVID-19 pandemic so as to provide a reference for treatment of orthopedic patients.

Objective To investigate the correlation between the insertion depth of the left-sided double-lumen tube (DLT) and some specific body landmarks in order to guide left-sided DLT intubation. Methods Ninety-five adult patients who underwent thoracic surgery were chosen, and the age (A), sex (S), height (H), weight (W), distance between the cricothyroid membrane and upper notch of the sternum angle (L), size of the left-sided DLT (F), and predicted depth of intubation (y) were recorded. After anesthesia induction, the final corrected insertion depth of the left-sided DLT (Y) were recorded using fiberoptic bronchoscopy. The Y and y were compared.Linear regression and Pearson's correlation analysis were used to analyze the data. Results There was no difference between the Y and y (P＞ 0.05). The Y was significantly correlated with H, W, and L (P ＜ 0.01), and was not correlated with A (P＞ 0.05). Three linear regression equations for H, L, and Y were obtained. H and L were linearly dependent on Y, and the determination coefficients R2 were 0.43 (Y=7.285+0.128 H) and 0.41 (Y=19.305+0.866 L), respectively. Using both H and L as the independent variables, the determination coefficient R2 was 0.56 (Y=8.127+0.087 H+0.559 L). Conclusion The linear regression equation Y=8.127+0.559 H+0.087 L could be used as a rapid method to assess the insertion depth of the left-sided DLT. However, the ideal insertion depth of the left-sided DLT still needs to be confirmed using fiberoptic bronchoscopy.

Objective To investigate the application value of DFY-Ⅱ ultrasound imaging analysis software in evaluation of fetal lung maturity in different pregnancy.Methods Totally 315 cases of healthy single pregnancies (24-41 weeks) were collected.The sonographic views of fetal right side sagittal plane were obtained.The echo intensity of fetal lung and liver were analyzed and the ratio was canculated with DFY-Ⅱ ultrasound imaging analysis software.Results The ratio of echo intensity from fetal lung and liver had positive correlation with gestational weeks (r=0.94,P＜0.05),the linear regression equation was Y=0.60+0.07X (r2 =0.883).Conclusion The ratio of echo intensity by fetal lung and liver analyzed with DFY-Ⅱ ultrasound imaging analysis software can be an effective method to evaluate fetal lung maturity.

OBJECTIVEThe purpose of this study was to investigate the regulatory role of tyrosine kinase 2 with immunoglobulin-like and epidermal growth factor homology domains (Tie2) on apoptosis and proliferation in the endothelial cells.

METHODSRNA interference (RNAi) technique was used to silence Tie2 gene expression by transfecting an expression vector containing short hairpin RNA(shRNA) for Tie2 into human umbilical vein endothelial cells (HUVECs). Real time quantitation reverse transcriptase polymerase chain reaction (QRT-PCR) and Western blot were used to monitor Tie2 mRNA, as well as protein expression. The proliferation of HUVECs was examined by methyl thiazolyl tetrazolium (MTT), and the apoptosis was detected under microscope. HUVECs transfected with pGenesil-hk was negative control, and HUVECs transfected with nothing was empty control.

RESULTSTie2 mRNA expression was down-regulated 24 h and 48 h after transfection, and Tie2 protein expression was significantly down-regulated at 24 h and 48 h (P< 0.05), especially 48 h after transfection. The apoptosis rate was conspicuously higher in experimental group than in negative control and empty control group after 48 h (P<0.05). The growth monitoring showed that proliferation was also markedly inhibited in experimental group (P<0.05) compared with two control groups.

CONCLUSIONDown-regulated expression of Tie2 by RNAi can promotes apoptosis of HUVECs and has an anti-proliferation activity effect on them.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; EGF Family of Proteins ; Human Umbilical Vein Endothelial Cells ; Humans ; Immunoglobulins ; RNA Interference ; RNA, Messenger ; RNA, Small Interfering ; TYK2 Kinase ; Transfection