This article systematically reviews the current research status as well as diagnosis and treatment strategies of traditional Chinese medicine （TCM） for gastroesophageal reflux disease （GERD）. Studies demonstrate that TCM， based on the "disease-syndrome combination" approach， exhibits multi-target advantages in alleviating symptoms of various GERD subtypes， promoting mucosal repair， regulating emotions， and facilitating the reduction of western medication. To address clinical challenges such as symptom overlap and limited therapeutic efficacy， strategies have been proposed including "treating different diseases with the same method" and integrated regulation based on viscera correlation. Future efforts should focus on elucidating the mechanisms of compound prescriptions， promoting TCM drug development under the "three-combination" evaluation framework that integrates TCM theory， human experience and clinical trial evidence， and optimizing integrated traditional and western medicine models to enhance GERD management.

To investigate the current status of sleep quality among nurses in tertiary hospitals in China, analyze the correlations of work stress and perceived organizational support with the risk of sleep problems, and further examine the mediating effect of perceived organizational support between work stress and sleep problems in nurses.

Objective To summarize the best evidences of thirst management in the patients with tra-cheal intubation to provide the evidence-based evidence for clinical practice.Methods According to the"6S"evidence pyramid model,the literatures on thirst management of the patients with tracheal intubation were systematically retrieved from the relevant guide websites,evidence-based databases,association websites and original literature databases at home and abroad.The databases included BMJ Best Practice,Up To Date,JBI Evidence-Based Health Care Center Database,Guidelines International Network(GIN),National Institute for Health and Clinical Excellence,National Institute for Health and Clinical Excellence(NICE),Scottish Inter-collegiate Guidelines Network(SIGN),Registered Nurses'Association of Ontario,Canada(RNAO),National Guideline Clearing House(NGC),Cochrane Library,American Society of Critical Care Medicine(SCCM),A-merican Association of Critical Care(AACN),European Society of Intensive Medicine(ESIM),Chinese Socie-ty of Critical Care Medicine,PubMed,Embase,CNKI,Wanfang Medical Network,VIP Database and Chinese Biomedical Literature Database(SinoMed).The retrieval limit was from the database establishment to August 31,2023.Two researchers trained by evidence-based nursing independently completed the literature quality e-valuation,and the literatures meeting the quality standards conducted the evidence extracted and summary.Results A total of 23 literatures were included,including 1 clinical decision,1 evidence summary,12 random-ized controlled trials,3 quasi-experimental studies,and 6 cross-sectional studies.Eighteen pieces of best evi-dence were formed,including six aspects:definition of thirst,classification of thirst degree,risk factors,assess-ment methods,intervention strategies and quality management.Conclusion Nurses should conduct the clini-cal transform and application of the best evidences by combining the clinical situation and specific department policies to alleviate the thirst symptoms in the patients with tracheal intubation.

ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease （GERD） based on literature， providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis （RE）， nonerosive reflux disease （NERD） and Barrett's esophagus （BE） model construction from January 1， 2014 to January 27， 2024， were retrieved from databases such as CNKI， Wanfang， VIP， Web of Science， and Pubmed. Information on animal strains， genders， modeling methods including disease-syndrome combination models， modeling cycles were extracted； for studies with model evaluation， the methods of model evaluation were also extracted； then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE （88/148， 59.46%） and NERD （9/14， 64.29%）. For BE， C57BL/6 mice were most commonly used （11/20， 55.00%）. Male animals （RE： 111/135， 82.22%； NERD： 11/14， 78.57%； BE： 10/12， 83.33%） were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer， gastric content reflux， or mixed reflux， among which forestomach ligation + incomplete pylorus ligation （42/158， 26.58%） was the most common modeling method； the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa， visceral hypersensitivity， and emotional problems， and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus （8/14， 57.14%） was the most common modeling method； the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux， and constructing interleukin 2-interleukin 1β transgenic mice （7/25， 28.00%） was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE， NERD， and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics （e.g.， RE focusing on structural damage， NERD emphasizing visceral hypersensitivity）. Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches （e.g.， composite etiology simulation） and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.

Objective:To understand the prevalence of frailty and the importance of its influencing factors in adult population in Shaanxi Province.Methods:The data were from Shaanxi baseline survey of natural population cohort study in northwest China during 2018-2019. The frailty index (FI) was constructed to evaluate the frailty status of the population, and XGboost model combined with Shapley method was used to analyze the importance of the sociodemographic and life behavior factors affecting the prevalence of frailty by gender and age.Results:A total of 25 079 subjects were included, in whom 964 (3.8%) had frailty, and there was no significant difference in the overall prevalence of frailty between women (3.9%) and men (3.8%) ( P=0.629), but there was a gender specific difference in the distribution of FI ( P<0.001), and the proportion of the pre-frailty in men was higher than that in women. The prevalence of frailty increased with age ( P<0.001), the prevalence of frailty were 1.3%, 2.5% and 7.8% in young, middle-aged and elderly women, respectively, and 1.9%, 2.7% and 5.5% in young, middle-aged and elderly men, respectively. Sociodemographic characteristics and lifestyle patterns were both influencing factors for the prevalence of frailty, but their importance varied with gender and age. The top five contributing factors were education level, staying up late, annual family income level, sedentary time and marital status in young women, and staying up late, smoking, annual family income level, sedentary time and drinking in young men. The top five contributing factors were education level, annual family income level, passive exposure to smoking, staying up late, and sedentary time in middle-aged women, and annual family income level, education level, sedentary time, staying up late and drinking in middle-aged men. The top five contributing factors were annual family income level, passive exposure to smoking, sedentary time, marital status, and smartphone use in elderly women, and education level, annual family income level, smoking, smartphone use and sedentary time in elderly men. Conclusions:There are gender specific differences in the distribution of FI in Shaanxi. The prevalence of frailty increased with age, but young and middle-aged people also have frailty risk. The prevalence of frailty in young men was mainly related to unhealthy life behaviors, such as staying up late, smoking, sedentary behavior and drinking, while the prevalence of frailty in middle-aged and elderly men and women were more affected by sociodemographic factors, such as education level, economic status and marital status.

Objective:To investigate the regulatory effect of leptin via the JAK2/STAT3 pathway on the core-binding factor β-subunit (CBFβ) and its molecular mechanism in promoting chondrocyte apoptosis.Methods:A total of five patients undergoing total knee arthroplasty due to knee osteoarthritis (OA group) and five patients undergoing amputation due to trauma (amputation group) were enrolled, and knee cartilage samples were obtained intraoperatively. Western blotting was used to detect the protein expression levels of leptin, CBFβ, matrix metalloproteinase-1 (MMP1), and MMP13. Flow cytometry was performed to determine the optimal treatment duration and concentration of leptin. Chondrocytes were divided into the following groups based on treatment conditions: control group (untreated chondrocytes), leptin group (chondrocytes treated with 50 ng/ml leptin), negative leptin group (chondrocytes transfected with a non-targeting sequence as a control), and leptin+shCBFβ group (chondrocytes transfected with shCBFβ to inhibit CBFβ expression). Apoptosis and the expression levels of MMP1 and MMP13 were analyzed in the four groups. Additionally, chondrocytes were categorized into the following groups for further analysis: control group (untreated cells), leptin group (cells stimulated with 50 ng/ml leptin for 48 h), AG490 group (cells treated with the JAK2/STAT3 inhibitor AG490), and leptin+AG490 group (cells pretreated with AG490 for 2 h followed by 50 ng/ml leptin stimulation for 48 h). The protein expression levels of CBFβ, MMP1, and MMP13, as well as the apoptosis rate, were examined in the four groups.Results:The relative expression levels of leptin, CBFβ, MMP1, and MMP13 in the amputation group were 0.66±0.06, 0.69±0.06, 0.74±0.05, and 0.41±0.03, respectively, which were significantly lower than those in the OA group (1.04±0.10, 1.06±0.09, 0.95±0.04, and 0.99±0.09, respectively) ( P<0.05). The optimal treatment duration and concentration of leptin were determined to be 48 h and 50 ng/ml, respectively. The expression levels of MMP1 and MMP13 significantly differed among the control, leptin, negative leptin, and leptin+shCBFβ groups ( P<0.05). Specifically, the leptin group showed higher expression levels compared to the control group, while the leptin+shCBFβ group exhibited lower expression levels than the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the four groups were 4.55%±1.30%, 22.52%±2.03%, 22.03%±2.01%, and 5.15%±0.91%, respectively, with significant differences ( F=114.066, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+shCBFβ group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Similarly, significant differences were observed in the expression levels of CBFβ, MMP1, and MMP13 among the control, leptin, AG490, and leptin+AG490 groups ( P<0.05). The expression levels in the leptin group were higher than those in the control group, while the leptin+AG490 group exhibited lower expression levels compared to the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the control, leptin, AG490, and leptin+AG490 groups were 5.19±0.94%, 31.52±2.63%, 5.51±1.41%, and 10.47±0.85%, respectively, with significant differences ( F=117.104, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+AG490 group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Conclusion:Leptin promotes CBFβ expression via the JAK2/STAT3 pathway, leading to chondrocyte apoptosis and extracellular matrix degradation.

Objective:To investigate the effects of Clostridium butyricum on ulcerative colitis（UC）in mice and its impact on gut microbiota and autophagy levels. Methods:Eighteen C57BL/6J mice were randomly divided into a control group，a model group，and a treatment group，with six mice in each group using simple random sampling. Mice in the model and treatment groups were freely given 2.5% dextran sulfate sodium salt（DSS）solution for 5 days to establish a UC model. After successful modeling，the control and model groups were gavaged with PBS，while the treatment group was gavaged with 5×10 8 CFU/ml of live Clostridium butyricum. After the intervention，changes in body weight，disease activity index（DAI），colonic length，and pathological conditions were compared among the groups. Fluorescence quantitative PCR was used to detect the expression levels of intestinal inflammatory cytokines IL-1β and TNF-α. Myeloperoxidase（MPO）levels were analyzed，and Western blot was employed to detect the expression levels of zonula occludens-1（ZO-1），Occludin，LC3Ⅱ/LC3I，p62，and AMP-activated protein kinase/mammalian target of rapamycin AMPK/mTOR proteins. High-throughput sequencing technology was utilized to analyze the intestinal microbiota of the mice. Results:Compared with mice in the control group，the mice in the model group exhibited significant weight loss，markedly increased DAI and inflammation levels（ P<0.01），destruction of colonic structure，decreased expression levels of intestinal tight junction proteins（ P<0.05），suppressed autophagy levels（ P<0.05），and dysbiosis of the intestinal microbiota. In contrast，mice in the treatment group had a slower weight decline compared to the model group（ P<0.000 1），reduced DAI（ P<0.01），down-regulated inflammation levels（ P<0.01），improved barrier function（ P<0.05），up-regulated autophagy levels（ P<0.01），and an improved intestinal microbiota composition. Conclusions:Clostridium butyricum may ameliorate UC by modulating the intestinal microbiota composition，and enhancing autophagy levels，thus improving intestinal barrier function and inhibiting inflammatory progression in UC mice.

Objective To investigate the role of the GPR120 gene in the progression of sepsis,explore the molecular mechanisms through which GPR120 gene regulates NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)inflammasome activation and macrophage polarization.Methods The blood and pleural fluid samples were collected from the sepsis patients and the control group.The expression of inflammatory factors and the associated proteins were detected by flow cytometry and ELISA.C57BL/6 mice and monocyte-macrophage cell line(Raw264.7)were treated with lipopolysaccharide(LPS)to construct the sepsis models.After the intervention of GPR120 agonist TUG891,the expression of GPR120 gene,NLRP3 inflammasome protein and macrophage polarization protein were detected between the control group and the sepsis group.Results The expression of inflammatory factors,such as IL-1β in the serum of septic patients,significantly increased compared with the control(P<0.001).And the expression of inflammasome proteins such as NLRP3,Caspase-1 and IL-1β in the pleural fluid also increased(all P<0.05).In vivo,LPS could induce severe inflammation in lung tissue,the GPR120 gene expression decreased in lung tissue,and inflammatory factors were up-regulated in mouse serum(P<0.01).The inflammasome-associated protein and M1 type polarization of macrophages were enhanced,the TUG891 could reduce the inflammatory response,inhibit the NLRP3 inflammasome activating,and promote the M2 polarization of macrophages(P<0.01).In vitro,LPS could inhibit the intracellular GPR120 expression.The inflammatory factors secreted more in LPS-induced sepsis cells.TUG891 could promote the up-regulation of GPR120 protein and alleviate the secretion of inflammatory factors(P<0.05).Conclusion In sepsis,GPR120 gene activation could inhibit the NLRP3 inflammasome activation,promote macrophage polarization,and reduce the inflammatory damage,thereby delay the rapid progression of sepsis.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.