Abstract: To study the protective effect of asiaticoside(AS) on Isoproterenol Hydrochloride(ISO)-induced myocardial injury in mice. Methods: Sixty male C57BL/6 mice were randomly divided into blank control(CON) group, model group [ISO,ISO 10/(kg·d)], Low dose group [ISO+AS-L,ISO 10 mg/(kg·d)+AS 5 mg/(kg·d)], Medium dose group [ISO+AS-M, ISO 10 mg/(kg·d)+AS 10 mg/(kg·d)], High dose group [ISO+AS-H, ISO 10 mg/(kg·d)+AS 20 mg/(kg·d)]. Heart mass ratio was counted; changes were observed in electrocardiogram; Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-1β and cardiac troponin T(cTn-T) in serum; Masson staining was used to observe the fibrosis of mouse myocardial tissue; Western blot was used to detect the ratio of Bax and Bcl-2 protein expression levels(Bax/Bcl-2) and the expression levels of Caspase-3 and NLRP3 proteins in myocardial tissue; real-time quantitative polymerase chain reaction(qPCR) was used to detect the mRNA expression levels ofANP,BNP,β-MHC,TNF-α, IL-6, Type Ⅰ collagen(COLⅠ), and Type Ⅲ collagen(COLⅢ). Results: Compared with the CON group, the ISO group had an elevated heart-to-mass ratio(P<0.01), a lower heart rate(P<0.05), a prolonged QT interval(P<0.05), elevated expression of myocardial injury markers cTn-T,ANP,BNP, andβ-MHC(P<0.01); increased expression of IL-1β in the serum(P<0.01), increased expression ofTNF-αin the cardiac tissue and increasedIL-6expression(P<0.001), and NLRP3 protein expression was elevated(P<0.05); myocardium showed a large number of collagen fibers bluish staining(P<0.001),COLⅠ,COLⅢmRNA expression levels increased(P<0.001), and Bax/Bcl-2 ratio(P<0.001) and Caspase-3 expression were significantly elevated(P<0.05). Compared with ISO group, heart-to-mass ratio of mice in ISO+AS-L and ISO+AS-M groups decreased(P<0.05), heart rate increased, QT interval was shortened, cTn-T, ANP, BNP and β-MHC decreased(P<0.001), myocardial collagen fiber blue-staining decreased(P<0.01). The mRNA expression levels ofCOLⅠandCOLⅢdecreased(P<0.05). The expression levels of IL-1β and TNF-α decreased(P<0.01). NLRP3, Caspase-3 protein expression and Bax/Bcl-2 ratio decreased(P<0.05). The expression level ofIL-6in ISO+AS-M group decreased(P<0.01). The expression levels ofANP,BNP, andTNF-αmRNA expression were reduced in the ISO+AS-H group(P<0.001); the degree of myocardial fibrosis was improved(P<0.05), and the expression levels ofCOLⅠandCOLⅢmRNA were reduced(P<0.05). Conclusion AS has a protective effect against ISO-induced myocardial injury in mice by ameliorating cardiac fibrosis, inhibiting cardiomyocyte apoptosis and attenuating myocardial tissue inflammatory response.

Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.

Paclitaxel， a highly effective natural antitumor drug， has been demonstrated to be efficacious in the treatment of a variety of cancers， including breast cancer， ovarian cancer， and lung cancer. The traditional paclitaxel injections have been observed to present certain issues， including overt adverse reactions and a decline in the quality of life of patients following treatment. This ultimately leads to an inability to meet the comprehensive needs of patients， thereby limiting the clinical applications of the drugs. Compared with injectable administration， the oral administration can avoid the risk of infection present in the invasive route， is conducive to improving patient compliance and quality of life， and reduces healthcare costs， and has a good application prospect. However， paclitaxel has low solubility， poor permeability， and is susceptible to the exocytosis of P-glycoprotein， which presents a significant challenge in the development of its oral preparations. Novel drug delivery technologies can enhance the solubility of paclitaxel and facilitate its controlled release， which is beneficial for the oral absorption and efficacy. The paper reviews the development history of oral preparations of paclitaxel， and summarizes the delivery technologies such as polymer micelles， nanoparticles， nanoemulsions and nanocrystals， and discusses the application mechanisms， advantages and limitations of these technologies and their adaptability in different cancer treatments. Finally， the challenges faced in the development of oral preparations of paclitaxel are summarized， and future research directions are proposed in order to provide new ideas for the development of oral delivery of paclitaxel.

Paclitaxel， a highly effective natural antitumor drug， has been demonstrated to be efficacious in the treatment of a variety of cancers， including breast cancer， ovarian cancer， and lung cancer. The traditional paclitaxel injections have been observed to present certain issues， including overt adverse reactions and a decline in the quality of life of patients following treatment. This ultimately leads to an inability to meet the comprehensive needs of patients， thereby limiting the clinical applications of the drugs. Compared with injectable administration， the oral administration can avoid the risk of infection present in the invasive route， is conducive to improving patient compliance and quality of life， and reduces healthcare costs， and has a good application prospect. However， paclitaxel has low solubility， poor permeability， and is susceptible to the exocytosis of P-glycoprotein， which presents a significant challenge in the development of its oral preparations. Novel drug delivery technologies can enhance the solubility of paclitaxel and facilitate its controlled release， which is beneficial for the oral absorption and efficacy. The paper reviews the development history of oral preparations of paclitaxel， and summarizes the delivery technologies such as polymer micelles， nanoparticles， nanoemulsions and nanocrystals， and discusses the application mechanisms， advantages and limitations of these technologies and their adaptability in different cancer treatments. Finally， the challenges faced in the development of oral preparations of paclitaxel are summarized， and future research directions are proposed in order to provide new ideas for the development of oral delivery of paclitaxel.

Energy metabolism reconstruction is the new target of the treatment of heart failure. By combing the researches of Chinese medicinals for energy metabolism reconstruction of heart failure， it was found that Chinese medicinal compound formula and single Chinese medicinal have a certain role in regulating energy metabolism， mainly through three aspects， including the optimization of substrate utilization， improvement of mitochondrial structure， function， and homeostasis， and improvement of mitochondrial energy transport， so as to make the energy metabolism of the cardiomyocyte adjusted in the direction of beneficial to the organism， increasing the supply of energy， and improving the cardiac function.

ObjectiveThis study aims to explore the mechanism and targets of Shenfu Injection in regulating glycolysis to intervene in myocardial fibrosis in chronic heart failure based on the hypoxia-inducible factor-1α （HIF-1α）/ 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3） signaling pathway. MethodsA rat model of chronic heart failure was established by subcutaneous injection of isoproterenol （ISO）. After successful modeling， the rats were randomly divided into the Sham group， Model group， Shenfu injection （SFI， 6 mL·kg^-1） group， and inhibitor （3PO， 35 mg·kg^-1） group， according to a random number table， and they were treated for 15 days. Cardiac function was evaluated by echocardiography， and serum N-terminal pro-brain natriuretic peptide （NT-proBNP） levels were detected by enzyme-linked immunosorbent assay （ELISA）. Fasting body weight and heart weight were measured， and the heart index （HI） was calculated. Pathological changes in myocardial tissue were observed by hematoxylin-eosin （HE） and Masson staining， and the fibrosis rate was calculated. Biochemical assays were used to determine serum levels of glucose （GLU）， lactic acid （LA）， and pyruvic acid （PA）. Western blot was used to analyze the expression of proteins related to the HIF-1α/PFKFB3 signaling pathway （HIF-1α and PFKFB3）， glycolysis-related proteins （HK1， HK2， PKM2， and LDHA）， and fibrosis-related proteins ［transforming growth factor （TGF）-β₁， α-smooth muscle actin （α-SMA）， and Collagen type Ⅰ α1 （ColⅠA1）］. Real-time PCR was used to detect the mRNA expression of HIF-1α and PFKFB3 in myocardial tissue. ResultsCompared with the Sham group， the Model group showed significantly decreased left ventricular ejection fraction （LVEF）， left ventricular shortening fraction （LVFS）， interventricular septal thickness （IVSd）， and interventricular septal strain （IVSs） （P<0.05）， while left ventricular internal dimension at end-diastole （LVDd） and end-systole （LVIDs） were increased （P<0.05）. Serum NT-proBNP levels were significantly increased （P<0.01）， and body weight was decreased. Heart weight was increased， and the HIT index was increased （P<0.05）. Myocardial tissue exhibited inflammatory cell infiltration and collagen fiber deposition， and the fibrosis rate was significantly increased （P<0.05）. Serum GLU was decreased （P<0.05）， while LA and PA levels were increased （P<0.05）. Protein expressions of HIF-1α， PFKFB3， HK1， HK2， PKM2， LDHA， TGF-β₁， α-SMA， and ColⅠA1， as well as the mRNA expression of HIF-1α and PFKFB3 were increased （P<0.05）. Compared with the Model group， both the SFI group and 3PO groups showed significant improvements in LVEF， LVFS， IVSd， and IVSs （P<0.05） and decreases in LVDd， LVIDs， and NT-proBNP levels （P<0.05）. Body weight was significantly increased. Heart weight was significantly decreased， and the HIT index was significantly decreased （P<0.05）. Inflammatory cell infiltration， collagen fiber deposition， and the fibrosis rate were significantly decreased （P<0.05）. Serum GLU levels were significantly increased （P<0.05）， while LA and PA levels were decreased （P<0.05）. Expressions of glycolysis-related proteins， fibrosis-related proteins， and HIF-1α/PFKFB3 pathway-related proteins and mRNAs were significantly suppressed （P<0.05）. ConclusionSFI improves cardiac function in chronic heart failure by downregulating the expression of HIF-1α/PFKFB3 signaling pathway-related proteins， regulating glycolysis， and inhibiting myocardial fibrosis.

Objective:To explore the factors leading to communication disorders in ICU patients during mechanical ventilation from the perspective of both patients and medical staff, and to use the theoretical framework of acceptability to identify the barriers that can be improved by intervention.Methods:Using the method of descriptive phenomenology from July to August 2022, 11 patients with mechanical ventilation and 8 medical staff in the comprehensive ICU of a Yuhuangding Hospital in Yantai were selected for interviews by the purpose sampling method, combined with participatory observation. The interviews of patients were conducted off ventilator. With Nvivo12.0 Plus software, the seven-step analysis method of Colaizzi phenomenology was adopted to summarize the theme and the theoretical framework of acceptability was used to identify the obstacle factors that could be improved by intervention.Results:The age of 11 patients was 18-46 years old, the duration of mechanical ventilation was 9.5-312.3 h. The age of 8 medical staff was 26-54 years old, the length of service in ICU was 2-30 years. A total of 14 themes were extracted. For patients: defensive mood, difficulty in presenting information, introverted personality, communication tools are hard to use, emergency treatment conflict, deny the ability to communicate, thought slowness. For medical staff: defensive mood, cognitive load, high time cost, lack of humane communication strategies, poor training, other priorities, loss of confidence in effective communication, awareness of the importance of communication was not enough.Conclusions:There are many factors that can be improved for patients with mechanical ventilation in ICU. It is suggested to speed up the research and development of high-tech and personalized alternative communication tools in China, reduce negative communication between doctors and patients and nurses and patients, and implement evidence-based multi-mode and progressive communication intervention strategies.

BACKGROUND:Calcium phosphate(CaP)coatings are widely used to improve the integration of titanium implants into bone but these coatings are associated with risks of infection.It is thus desirable to confer antibacterial properties to CaP coatings. OBJECTIVE:To prepare CaP-MgO composite coatings by impregnating magnesium oxide(MgO)sol into CaP coatings and assess the in vitro antibacterial activities and cytocompatibility. METHODS:An electrolyte was determined by titration and used for CaP coating electrodeposition on titanium(referred to as Ti-CaP).MgO was impregnated into the coating by immersing in an MgO sol with different mass fractions(15%,30%,50%)and subsequently calcined to form MgO-CaP composite coatings,which were recorded as Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg,respectively.Microstructure,tensile properties,critical load,and Mg2+ release of coatings in vitro were characterized.Antibacterial activity was assayed using spread plate method by culturing S.aureus on the pure titanium sheet surface and Ti-CaP,Ti-Cap-15mg,Ti-Cap-30mg and Ti-Cap-50mg surfaces for 24 and 48 hours.Mouse osteoblast suspension was inoculated on pure titanium sheets and Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg coated titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay,and cell survival rate was calculated.The morphology of composite coating soaked in DMEM was also observed. RESULTS AND CONCLUSION:(1)Homogeneous,microporous CaP coatings consisting of octacaclium phosphate crystal flakes were prepared on titanium by electrodeposition.After sol impregnation-calcination,MgO aggregates were filled into the inter-flake voids.The extent of MgO filling and Mg concentration in the coating increased with the number of sol impregnation procedures.When immersed in phosphate buffered saline,all composite coatings actively released Mg2+ within 1 day;subsequently,the Mg2+ release slowed down on day 3.A small amount of Mg2+ release was still detected on day 7.The yield strength,tensile strength and fracture growth rate of Ti-CaP-30Mg coated titanium were not significantly different from those of pure titanium(P>0.05).There was no significant difference in the critical load of Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups(P>0.05).(2)Except that pure titanium sheet and Ti-CaP had no antibacterial properties,the other samples had good antibacterial properties,and the antibacterial rate increased with the increase of MgO content in the coating.(3)After 1 and 3 days of co-culture,the cell survival rate of Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups was lower than that of pure titanium group and Ti-CaP group(P<0.05).After 5 and 7 days of culture,there was no significant difference in cell survival rate among five groups(P>0.05).The content of MgO in the coating decreased gradually with the time of immersion in the medium.(4)The MgO sol impregnation added antibacterial properties to the CaP coatings while retained their biocompatibility.

Objective:To construct prediction models of necrotizing enterocolitis (NEC) using machine learning (ML) methods.Methods:From January 2015 to October 2021, neonates with suspected NEC symptoms receiving abdominal ultrasound examinations in our hospital were retrospectively analyzed. The neonates were assigned into NEC group (modified Bell's staging≥Ⅱ) and non-NEC group for diagnostic prediction analysis (dataset 1). The NEC group was subgrouped into surgical NEC group (staging≥Ⅲ) and conservative NEC group for severity analysis (dataset 2). Feature selection algorithms including extremely randomized trees, elastic net and recursive feature elimination were used to screen all variables. The diagnostic and severity prediction models for NEC were established using logistic regression, support vector machine (SVM), random forest, light gradient boosting machine and other ML methods. The performances of different models were evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, negative predictive value and positive predictive value.Results:A total of 536 neonates were enrolled, including 234 in the NEC group and 302 in the non-NEC group (dataset 1).70 were in the surgical NEC group and 164 in the conservative NEC group (dataset 2). The variables selected by extremely randomized trees showed the best predictive performance in two datasets. For diagnostic prediction models, the SVM model had the best predictive performance, with AUC of 0.932 (95% CI 0.891-0.973) and accuracy of 0.844 (95% CI 0.793-0.895). A total of 11 predictive variables were determined, including portal venous gas, intestinal dilation, neutrophil percentage and absolute monocyte count at the onset of illness. For NEC severity prediction models, the SVM model showed the best predictive performance, with AUC of 0.835 (95% CI 0.737-0.933) and accuracy of 0.787 (95% CI 0.703-0.871). A total of 25 predictive variables were identified, including age of onset, C-reactive protein and absolute neutrophil count at clincial onset. Conclusions:NEC prediction model established using feature selection algorithm and SVM classification model in ML is helpful for the diagnosis of NEC and grading of disease severity.

Cannabinoid is a kind of special compound in Cannabis sativa L., with a variety of biological activities, which have been widely used in medicine, food, cosmetics, textile, and other industries. However, Cannabis sativa contains the addictive ingredient Δ9-tetrahydrocannabinol, which also makes the application of Cannabis sativa subject to legal constraints. To prevent the abuse of Cannabis sativa related products and ensure the safety and effectiveness of products, it is very important to establish convenient, efficient, environmentally friendly, and inexpensive analytical methods that can be applied to the cannabinoid components in various matrices. Because of the high structural similarity, the poor stability of cannabinoid structure and the matrix effect in different matrices, the analysis becomes more complicated. At present, there is no unified standard for the quality control of cannabinoids, and there are various analytical methods. Based on the above questions, this paper introduces the classification of cannabinoids, expounds on the analysis methods of cannabinoids in Cannabis sativa plants, biological samples, food, cosmetics, and textiles, and looks forward to the future development direction of cannabinoid analysis methods, to provide useful help for the further development and rational application of Cannabis sativa .