Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

Protein phosphorylation modification is one of the key regulatory mechanisms in cellular signaling transduction and metabolic processes. The phosphorylation state of target proteins is regulated by specific protein kinases and phosphatases, which add or remove phosphate groups. Histidine phosphorylation (pHis) plays a crucial role in both prokaryotes and eukaryotes life activities and is linked to various pathological processes. Unlike the stable phosphorylation of proteins via phosphate ester bonds, histidine phosphorylation is linked through phosphoramide bonds, making it highly sensitive to high temperatures and low pH. This sensitivity has historically impeded progress in identifying and studying histidine phosphorylation. In recent years, the development of new techniques in phosphoproteomics and the emergence of pHis-specific antibodies have promoted the identification and functional research of pHis-modified substrates. For the first time, more than 700 pHis-modified proteins have been identified in mammalian cells, and pHis-modified substrates such as focal adhesion kinase (FAK) and phosphoglycerate mutase 1 (PGAM1) have been found to promote tumor development. This article mainly reviewed the key mechanisms and functions of histidine kinases and histidine phosphatases in regulating the histidine phosphorylation of specific substrates, and highlights their significant roles in human physiological and pathological processes, aiming to provide guidance for further research into the biological functions of histidine phosphorylation.

The conventional oral drug delivery frequently results in the drug elimination before its complete release due to rapid gastric emptying and short gastrointestinal transport time, thus reducing the bioavailability of drug. In order to maintain an effective concentration of drug in the body and maximize its optimal efficacy, the frequency of administrations often needs to be increased. By contrast, gastric retention drug delivery system (GRDDS), as an innovative method of drug delivery, prolongs the retention time of the drug in the stomach and reduces irritation to the gastrointestinal tract. Consequently, it enhances the bioavailability of drug, reduces dosing frequency for patients and improves treatment adherence. In recent years, domestic and foreign studies have been conducted on gastric retention drug delivery systems. Here, we provide a comprehensive overview of the relevant literature published in recent years, examining their current marketing status, various types, as well as in vivo and in vitro evaluation methods.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

ObjectiveThis study aimed to observe the impact of sinomenine hydrochloride on the proliferation of fibroblasts and the mRNA expression of related genes in knee joint adhesion and contracture in rabbits. Additionally, we sought to explore its potential mechanisms in combating knee joint adhesion and contracture. MethodsFibroblasts were cultured in vitro, and experimental groups with varying concentrations of sinomenine hydrochloride were established alongside a control group. Cell proliferation was assessed using the CCK-8 assay. Changes in the mRNA expression of fibroblast-related genes following sinomenine hydrochloride treatment were evaluated using RT-qPCR. The impact of the drug on serum levels of inflammatory cytokines was determined using the ELISA method, and the expression of related proteins was assessed using Western blot. ResultsSinomenine hydrochloride was found to inhibit fibroblast viability, with viability decreasing as the concentration of sinomenine hydrochloride increased. The effects of sinomenine hydrochloride in all experimental groups were highly significant (P<0.05). At the mRNA expression level, compared to the control group, sinomenine hydrochloride led to a significant downregulation of inflammatory cytokines in all groups (P<0.05). Additionally, the expression levels of apoptosis-related proteins significantly increased, while Bcl-2 mRNA expression decreased (P<0.05). The mRNA expression levels of the PI3K/mTOR/AKT3 signaling pathway also decreased (P<0.05). At the protein expression level, in comparison to the control group, the levels of inflammatory cytokines IL-6, IL-8, IL-1β, and TGF-β were significantly downregulated in the middle and high-dose sinomenine hydrochloride groups (P<0.05). The expression levels of cleaved-PARP, cleaved caspase-3/7, and Bax increased and were positively correlated with the dose, while the expression levels of the anti-apoptotic protein Bcl-2 and the PI3K/AKT3/mTOR signaling pathway were negatively correlated with the dose. Sinomenine hydrochloride exhibited a significant inhibitory effect on the viability of rabbit knee joint fibroblasts, which may be associated with the downregulation of inflammatory cytokines IL-6, IL-8, and IL-1β, promotion of apoptosis-related proteins cleaved-PARP, cleaved caspase-3/7, and Bax, suppression of Bcl-2 expression, and inhibition of gene expression in the downstream PI3K/AKT3/mTOR signaling pathway. ConclusionSinomenine hydrochloride can inhibit the inflammatory response of fibroblasts in adhesive knee joints and accelerate fibroblast apoptosis. This mechanism may offer a novel approach to improving and treating knee joint adhesion.

BACKGROUND:Osteonecrosis of the femoral head is a common orthopedic disease,and hip preservation surgery with bone grafting is commonly used in the early stage,in which autologous bone and allograft bone are commonly used as bone grafting materials.However,autologous bone transplantation is highly traumatic and bone supply is limited,and allograft bone is rich in sources,but there are serious risks of immune rejection and absorption.In recent years,the tissue engineering technique based on mesenchymal stem cells is a new method for the treatment of femoral head necrosis,which is gradually widely used after basic experiments and clinical application. OBJECTIVE:To review the application and prospect of tissue engineering in the treatment of osteonecrosis of the femoral head to provide a new choice for the clinical treatment of osteonecrosis of the femoral head. METHODS:The PubMed database and CNKI database from 2013 to 2023 were searched by the first author with Chinese and English search terms"tissue engineering,mesenchymal stem cells,biological scaffolds,cytokines,osteonecrosis of the femoral head,bone graft,hip preservation".The articles on the treatment of osteonecrosis of the femoral head with tissue engineering technology were selected,and 55 representative articles were included for review after the initial screening of all articles according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)With the continuous development of biotechnology and materials science,great progress has been made in the treatment of osteonecrosis of the femoral head by bone tissue engineering,such as the application of gene-modified mesenchymal stem cells to repair osteonecrosis,the combination of gene recombination technology and surface modification technology with bone tissue engineering in the treatment of osteonecrosis of the femoral head.(2)When applied to the necrotic femoral head,tissue engineering technology can promote the regeneration of necrotic bone tissue and the repair of the vascular system,provide biomechanical stability for the necrotic area,and use bioactive factors to accelerate the repair of seed cells to complete the regeneration of new bone in necrotic area.(3)However,most of these studies are still in the animal experiment stage,and there are still many unsolved problems and challenges in bone tissue engineering research.With the rapid development of nanotechnology,tissue engineering and clinical medicine,biomimetic replacement bone grafting materials with perfect performance are expected to come into being.(4)In the future,bone tissue engineering for osteonecrosis of the femoral head is expected to be a satisfactory treatment for patients with hip preservation.

Objective To analyze the management and countermeasures of adverse nursing events in a municipal tertiary hospital in Guangxi Zhuang Autonomous Region.Methods The adverse nursing events in 2023 in a municipal tertiary hospital in Guangxi were retrospectively analyzed.Logistic regression analysis was utilized to identify the causes of these adverse events and propose suitable countermeasures.Results In 2023,a total of 121 adverse nursing events were recorded,with falls being the most prominent(42 cases,accounting for 34.71％),followed by drug extravasation,drug safety incidents and unplanned ex-tubation,accounting for 13.22％,9.92％,and 7.44％respectively.Logistic regression analysis revealed that factors such as age ≥70 years,coexisting diseases,Basel Index score ≤40,pain score ≥4,tube slip risk assessment ≥10,RASS sedation score ≥3,NGASR score ≥9,lost risk assessment score ≥ 7,GCS Coma Scale score ≤8,Stress Injury Assessment Scale score ≤10,and Morse score ≥45 were associated with the risk of adverse nursing events.In addition,inadequate awareness of nursing risks among nursing staff,ineffective patient health education methods,and non-compliance to nursing protocols were identified as primary causes of adverse nursing events.Conclusion Advanced age,combined with other diseases,and hospitali-zation scale assessment results are critical factors for adverse nursing events.Lack of nursing responsibility and risk awareness among nursing staff,inadequate system implementation,and irregular operations can increase the risk.Hospitals should optimize management systems and work processes,enhance nursing staff training,and develop targeted preventive measures for adverse nursing events to improve the quality of nursing management and reduce the risk of adverse nursing events.

Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide.For lung adenocarcinoma,identifying specific gene mutations,fusions,and giving corresponding targeted drugs can greatly improve the survival time of the patients.Among them,anaplastic lymphoma kinase(ALK)fusion occurs in 3％-7％of non-small cell lung cancer(NSCLC).In clinical practice,a variety of detection methods can be used to determine the ALK fusion status,but false negative test results are possible.This paper retrospectively analyzed the diagnosis and treatment of a patient with lung adeno-carcinoma,judged the ALK fusion status by various detection methods.Among them,immunohistochemistry(IHC)(Ventana D5F3),RNA based next-generation sequencing(RNA-based NGS)confirmed positive echinoderm microtubule associated protein like 4(EML4)-ALK fusion,while DNA-based NGS was negative.This paper analyzed the detection methods of ALK fusion,in order to clarify which detection method is the most accurate and simple to choose in different clinical cases and guide the subsequent treatment.

Objective To explore the Helicobacter pylori (Hp) infection rate and antibody typing of 1111 physical examination people in plateau area, and to analyze the risk factors of Hp infection by logistics regression analysis. Methods 1111 healthy people with physical examination in plateau area from January 2022 to December 2022 were selected as the research subjects. The Hp infection rate and antibody typing were calculated, and the risk factors of Hp infection were analyzed by logistics regression analysis. Results The Hp infection rate of physical examination people in plateau area was 62.47% (694/1 111). The infection rate of type I HP in infected patients was higher than that of type Ⅱ HP(75.50% vs 24.50%) (χ²=361.141, P<0.001). The AUC of CagA in the diagnosis of Hp infection was higher than that of antibody VacA or Ure positive diagnosis alone (Z=6.740, 7.608, P<0.001). The proportions of people with male gender, often eating pickled or barbecued foods, history of chronic gastric disease and family members living together≥4 in infected group were higher than those in uninfected group (χ²=4.418, 8.708, 16.565, 32.583, P=0.036, 0.003, <0.001, <0.001) while the proportion of people with regular garlic consumption was lower than that in uninfected group (χ²=5.153, P=0.023). Often eating pickled or barbecued foods [OR (95%CI)=2.038 (1.049-3.961)], history of chronic gastric disease [OR(95%CI)=1.706 (1.132-2.569)] and family members living together≥4 [OR (95%CI)=1.857 (1.135-3.037)] were risk factors of Hp infection, and regular garlic consumption [OR (95%CI)=0.559 (0.346-0.903)] was a protective factor (P=0.036, 0.011, 0.014, 0.018). Conclusion The Hp infection rate and antibody Ure positive rate are higher in physical examination people in plateau area, and chronic gastric disease history and often eating pickled or barbecued foods are risk factors of Hp infection.

In order to improve the poor photostability of nifedipine, this study designed a cocrystal based on the principles of crystal engineering and prepared nifedipine-imidazole cocrystal by suspension method. The new cocrystal was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and infrared spectroscopy (IR) to confirm the formation of the cocrystal. The photostability of nifedipine and its cocrystal was measured by powder X-ray diffraction and high-performance liquid chromatography (HPLC). The results showed that the nifedipine-imidazole cocrystal improved the photostability of nifedipine to a certain extent. This study provides guidance for the development of nifedipine cocrystals and the improvement of its druggability.