ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective To investigate the expression of YWHAQ protein in gastric adenocarcinoma tissues and its correlation with clinical pathological features and prognosis. Methods A total of 127 patients with gastric cancer who underwent radical surgery were enrolled. Clinical data and postoperative cancer tissue samples were collected from the patients. Immunohistochemistry was used to detect the protein expression of YWHAQ in gastric adenocarcinoma tissues. The relationship between YWHAQ expression and clinical pathological features and prognosis was analyzed. Bioinformatics prediction was performed to identify potential pathways regulated by YWHAQ in gastric adenocarcinoma. A protein-protein interaction network for YWHAQ was constructed using the STRING database. Results YWHAQ gene expression was significantly higher in gastric adenocarcinoma tissues than in normal tissues (P<0.05). The expression level of the YWHAQ protein was significantly correlated with age, tumor invasion depth, lymph node metastasis, and tumor stage (P<0.05). Kaplan-Meier survival analysis showed that patients with high YWHAQ expression had significantly poorer long-term survival than those with low expression (P<0.0001). Cox regression analysis revealed that high YWHAQ expression and distant metastasis were independent risk factors for gastric cancer (HR>1, P<0.05). Enrichment analysis indicated that YWHAQ positively regulated processes such as cell cycle, angiogenesis, and DNA damage repair. Conclusion YWHAQ is highly expressed in gastric adenocarcinoma tissues and may be associated with the occurrence, invasion, and metastasis of gastric adenocarcinoma. High YWHAQ expression and distant metastasis are independent risk factors for the prognosis of gastric adenocarcinoma patients.

Senecavirus A (SVA) is a major viral pathogen causing disease in pigs, and effective monitoring of SVA infection is critical for disease control. In this study, we aimed to develop a reliable ELISA method for rapidly detecting neutralizing antibodies against SVA. We used HEK293F cells to express an SVA-specific porcine Fab antibody and verified the biological activity of the Fab antibody by indirect ELISA, immunofluorescence assay, virus neutralization test, and Western blotting. The Fab antibody was biotinylated and used as a competitive antibody to establish a competitive ELISA (C-ELISA) for detecting neutralizing antibodies against SVA. We then evaluated the C-ELISA in terms of sensitivity, specificity, repeatability, and result agreement rate with the VNT. The results showed that we successfully prepared an SVA-specific porcine Fab antibody, which showed high affinity for SVA. We named this antibody 1M33Fab and designated it as Bio-1M33Fab after biotin labeling. The assay conditions were optimized as follows: the coating concentration of SVA particles being 1 μg/mL, the working concentration of Bio-1M33Fab being 0.5 μg/mL, the optimal serum dilution of 1:10, and the optimal dilution of enzyme-labeled avidin being 1:30 000. At a percent inhibition (PI) of 47%, the assay demonstrated the highest sensitivity (96.88%) and specificity (100%), with no cross-reactivity observed with the positive sera of major porcine viral diseases. The intra-assay coefficient of variation ranged from 1.12% to 7.34%, while the inter-assay coefficient of variation ranged from 1.10% to 8.97%, indicating good repeatability. In the detection of 224 clinical pig serum samples, C-ELISA and VNT showed a result agreement rate of 93.75%. In conclusion, we successfully develop a C-ELISA method for detecting neutralizing antibodies against SVA by using a porcine-derived Fab antibody, which lays a foundation for the development of detection kits.
Animals ; Swine ; Antibodies, Neutralizing/immunology* ; Enzyme-Linked Immunosorbent Assay/methods* ; Immunoglobulin Fab Fragments/immunology* ; Antibodies, Viral/immunology* ; Picornaviridae/immunology* ; Humans ; HEK293 Cells ; Swine Diseases/diagnosis* ; Picornaviridae Infections/diagnosis*

Hepatic fibrosis is a chronic pathological condition characterized by hepatic stellate cell activation and excessive deposition of extracellular matrix， which would progress to liver cirrhosis and even hepatocellular carcinoma. Therefore， reversal of hepatic fibrosis is of great importance for improving quality of life and prolonging survival time. Currently， various therapeutic drugs for hepatic fibrosis have entered the stage of clinical trial. This article reviews the research advances in therapeutic drugs for hepatic fibrosis in the recent years， in order to provide insights into the treatment of hepatic fibrosis and future research directions for drugs.

Objective:To investigate the effects of Shenfu Xiongze Prescription on myocardial fibrosis induced by isoproterenol (ISO) in rats.Methods:SD rats were divided into blank control group, model group, and Shenfu Xiongze Prescription low-, medium-, and high-dosage groups according to random number table method. with 7 rats in each group. Except for the blank control group, the other groups were induced to form myocardial fibrosis in rats by intraperitoneal injection of isoprenaline. Shenfu Xiongze Prescription low-, medium-, and high-dosage groups were administered Shenfu Xiongze Prescription solution at dosages of 8.4, 16.8, and 33.6 g/kg, respectively, while the blank control group and the model group were given the same volume of normal saline for gavage, once a day, for consecutive 3 weeks. The heart structure and function were observed by echocardiography, the levels of BNP and IL-6 in serum were detected by ELISA, the pathological changes of myocardial tissue were observed by HE and Masson staining, and the expressions of TGF-β1 and α-SMA proteins in myocardial tissue were detected by Western blot.Results:Compared with the model group, the EF and FS values of Shenfu Xiongze Prescription in all dosage groups decreased ( P<0.01), the LVIDd and LVIDs increased ( P<0.05 or P<0.01), and the expressions of TGF-β1 and α-SMA proteins in myocardial tissue decreased ( P<0.01 or P<0.05); the levels of BNP and IL-6 in serum of the Shenfu Xiongze Prescription medium and high-dosage groups decreased ( P<0.05 or P<0.01), while the level of IL-6 in the low-dosage group decreased ( P<0.01). Conclusion:Shenfu Xiongze Prescription can inhibit rat myocardial fibrosis induced by isoprenaline, improve rat cardiac function, and its mechanism may be related to reducing inflammation in the heart and down-regulating the expressions of TGF-β1 and α-SMA proteins.

Objective To investigate the effects of Aurora kinase A(AURKA)on the tumor microenvironment of colorectal cancer(CRC)and to predict the active compounds in Chinese herbs that can target AURKA.Methods Based on the transcriptomic data and clinical information from 380 CRC tissues and 51 paracancerous tissues in The Cancer Genome Atlas(TCGA)database,the infiltration of different cells in the tumor tissues was analyzed using xCell and the binding of active compounds of Chinese herbs with AURKA was predicted through molecular docking.Results The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues(P＜0.05),and CRC patients with high AURKA expression had shorter overall survival.Compared with the AURKA low-expression group,the abundance of macrophages,monocytes,and effector memory CD4+and CD8+T cells was significantly downregulated in the AURKA high-expression group(P＜0.05).In addition,the cytotoxicity of T cells was significantly reduced(P＜0.05).Further analysis revealed that AURKA expression was positively correlated with the abundance of myeloid-derived suppressor cells(MDSCs)and the expression levels of their chemokines CXCL2 and CXCL5(P＜0.05).Genes that were differentially expressed between the AURKA high-and low-expression groups were mainly enriched in monocyte migration,chemokine-induced cellular responses,and other related processes.Chinese herbal compounds,including hesperidin,aristololactam A Ⅱ a,anacardic acid,coumestrol,and 17β-estradiol,all showed binding energies to AURKA lower than-1.2 kcal/mol,indicating a certain level of binding stability.Among these Chinese herbal compounds,17β-estradiol exhibited the best binding stability to AURKA-3UOL.Conclusion The high expression of AURKA in CRC tissues suggests a poor clinical prognosis.AURKA can promote the development of a suppressive immune microenvironment in CRC,and 17β-estradiol,an active compound from Chinese herbs,is a potential therapeutic agent targeting AURKA.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Objective To investigate the compliance status of ankle pump movement(APM)in high-risk patients with deep venous thrombosis(DVT)of the lower limbs and analysis the related influencing factors.Methods From January 2019 to March 2023,a total of 302 patients with high-risk lower limb DVT who admitted to our hospital were selected as the research objects.The APM compliance scale,clinical data sheet,visual analog scale(VAS),family support scale,self-efficacy scale,self-rating anxiety scale,and self-rating depression scale were used to evaluate the research subjects,and the evaluation results were analyzed.Results Among the 302 patients with high-risk DVT,171 patients had APM compliance,with a compliance rate of 56.62％.The results of univariate analysis showed that there were statistically significant differences in APM compliance among patients of different age groups,gender,education level,marital status,family economic income,work status,family support,medical insurance type,place of residence,reason for hospitalization,comorbidities,pain level,APM prescription time,self-efficacy,and psychological status(all P＜0.05).The results of multivariate Logistic analysis showed that comorbidities(≥2 types),pain(moderate and above),and prescription time(≥7d)were risk factors for APM compliance in DVT high-risk patients(all P＜0.05),while education level(college or above),family support(moderate and above),and self-efficacy(moderate and above)were protective factors for APM compliance(all P＜0.05).Conclusion The comorbidities,degree of pain,APM prescription time,educational level,family support,and patient self-efficacy can affect ankle pump compliance in high-risk patients with lower limb deep vein thrombosis,and should be given attention and targeted intervention.

Alzheimer's disease(AD),the most common progressive neurodegenerative disease in dementia,is also a special lipid disease.From the perspective of modern medicine,cholesterol homeostasis is an important risk factor for AD.Amyloid-beta plaque deposition,neurofibrillary tangles,and large amount of lipid granule accumulation are typical pathological features of AD.From the perspective of TCM,turbidity is the key to the pathogenesis of AD.Phlegm turbid,stasis turbid and turbid toxin are the concrete derivation of turbidity,which are the standard of AD.Cholesterol is the greasy lipid which is produced from of the essence of water and food,the disturbance of cholesterol homeostasis is a typical embodiment of the pathogenesis mechanism of endogenous turbidity.Regulating cholesterol homeostasis by traditional Chinese medicine may be a new direction for the treatment of AD in the future.Focusing on the modern research of cholesterol homeostasis,taking the theory of turbidity as the starting point,this paper analyzed the correlation between the connotation of turbidity theory and the imbalance of cholesterol homeostasis as well as the pathogenesis mechanism,and further elucidated the clinical application results in the treatment of AD from the aspects of phlegm turbid,stasis turbid and turbid toxin,so as to better guide clinical practice and scientific research.

Literature related to children's adenoid hypertrophy was retrieved to form an expert questionnaire.According to the group standard writing rules of the China Association of Chinese Medicine,the peer consultation,quality evaluation and suitability eval-uation were completed through three rounds of Delphi expert questionnaire surveys and expert discussion meetings,and the Clinical Practice Guidelines for TCM in Children with Adenoidal Hypertrophy was finally formed.The guidelines have been formulated to clarify the scope of application of the guidelines,normative reference documents,terms and definitions,diagnosis,syndrome differentiation,treatment,prevention and care,and to provide an important reference for the clinical practice and diagnosis and treatment norms of tra-ditional Chinese medicine for children with adenoid hypertrophy.