ObjectiveTo explore the quantity-quality transfer process of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（Haliotis discus hannai） by analyzing the physical phase and compositional changes， so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha（H. discus hannai） from different habitats were collected and prepared into corresponding calcined products and standard decoction， and the content of CaCO₃ of the three samples were determined and the extract yield and transfer rate of CaCO₃ were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry（XRF）， X-ray diffraction（XRD） was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry（FTIR） was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram， while combining hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） to find the common and differential characteristics， in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha（H. discus hannai）. ResultsThe CaCO₃ contents of the 20 batches of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（H. discus hannai） were 93.87%-98.95%， 96.02%-99.97% and 38.29%-51.96%， respectively， and the extract yield of standard decoction was 1.71%-2.37%， and the CaCO₃ transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity， and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction， the difference in the relative contents was obvious， which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO₃ of aragonite and calcite， while calcined Haliotidis Concha only contained CaCO₃ of calcite， and standard decoction mainly contained CaCO₃ of calcite and Na₂CO₃ of natrite. FTIR results showed that there were internal vibrations of O-H， C-H， C=O， HCO₃^- and CO₃^2- groups in Haliotidis Concha， while O-H， HCO₃^- and CO₃^2- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO₃ content， the transformation of CaCO₃ aragonite crystal form to calcite crystal form and the absence of organic components after calcination， and the changes of calcined products and standard decoction are mainly the decrease of CaCO₃ content and the increase of Na₂CO₃ relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction， which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.

ObjectiveTo explore the quantity-quality transfer process of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（Haliotis discus hannai） by analyzing the physical phase and compositional changes， so as to provide references for the effective control of its quality. MethodsA total of 20 batches of Haliotidis Concha（H. discus hannai） from different habitats were collected and prepared into corresponding calcined products and standard decoction， and the content of CaCO₃ of the three samples were determined and the extract yield and transfer rate of CaCO₃ were calculated. The changes in elemental composition and their relative contents were investigated by X-ray fluorescence spectrometry（XRF）， X-ray diffraction（XRD） was used to study the changes in the phase compositions of the three samples and to establish their respective XRD specific chromatogram. Fourier transform infrared spectrometry（FTIR） was used to study the changes in the chemical composition and content changes of the three samples and to establish their respective FTIR specific chromatogram， while combining hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） to find the common and differential characteristics， in order to explore the quantity-quality transfer relationship in the preparation process of standard decoction of Haliotidis Concha（H. discus hannai）. ResultsThe CaCO₃ contents of the 20 batches of medicinal materials， decoction pieces and standard decoction of Haliotidis Concha（H. discus hannai） were 93.87%-98.95%， 96.02%-99.97% and 38.29%-51.96%， respectively， and the extract yield of standard decoction was 1.71%-2.37%， and the CaCO₃ transfer rate of decoction pieces-standard decoction was 0.68%-1.27%. XRF results showed that the elemental species and their relative contents contained in Haliotidis Concha and its calcined products had a high degree of similarity， and although there was no obvious difference in the elemental species contained in decoction pieces and standard decoction， the difference in the relative contents was obvious， which was mainly reflected in the decrease of the relative content of element Ca and the increase of the relative content of element Na. XRD results showed that Haliotidis Concha mainly contained CaCO₃ of aragonite and calcite， while calcined Haliotidis Concha only contained CaCO₃ of calcite， and standard decoction mainly contained CaCO₃ of calcite and Na₂CO₃ of natrite. FTIR results showed that there were internal vibrations of O-H， C-H， C=O， HCO₃^- and CO₃^2- groups in Haliotidis Concha， while O-H， HCO₃^- and CO₃^2- groups existed in the calcined products and standard decoction. ConclusionThe changes of Haliotidis Concha and calcined Haliotidis Concha are mainly the increase of CaCO₃ content， the transformation of CaCO₃ aragonite crystal form to calcite crystal form and the absence of organic components after calcination， and the changes of calcined products and standard decoction are mainly the decrease of CaCO₃ content and the increase of Na₂CO₃ relative content. The method established in the study is applicable to the quality control of the shellfish medicines-decoction pieces- standard decoction， which provides a new idea for the study of quality control of dispensing granules of shellfish medicines.

BACKGROUND:Stem cell therapy has broad prospects in improving cardiac remodeling after myocardial infarction;however,alteration in the myocardial microenvironment affects the therapeutic efficacy of stem cells.Exercise preconditioning is similar to ischemic preconditioning and can have a protective effect on the myocardium.However,little attention has been paid to the effects and mechanisms of the combined effects of exercise preconditioning and stem cell transplantation. OBJECTIVE:To observe the effect of exercise preconditioning on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction and to explore the mechanism of local inflammatory microenvironment. METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group,and combination group,with 20 rats in each group.The rat model of myocardial infarction was made by ligating the left anterior descending branch of coronary artery.The sham operation group was only threaded without ligature.The transplantation and combination groups were injected with bone marrow mesenchymal stem cells of male rats into the myocardium after modeling.In addition,the combination group also required 8 weeks of treadmill exercise(i.e.,exercise preconditioning)before modeling.Four weeks after stem cell transplantation,exercise performance was measured by incremental exercise exhaustion test;cardiac structure and function were measured by echocardiography;left ventricular hemodynamics was measured by pressure-volume catheterization,and myocardial histopathology was observed by in situ staining and myocardial collagen volume fraction was obtained.Quantitative reverse transcription polymerase chain reaction was used to detect left ventricular pro-inflammatory factor(interleukin-1β,interleukin-6,tumor necrosis factor-α),anti-inflammatory factor(interleukin-10),sex-determining region of Y chromosome,and fetal genes(atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain)mRNA expression level at 1,7 days and 4 weeks after stem cell transplantation. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:compared with sham operation group,exercise performance,and left ventricular ejection fraction were reduced(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were increased(P<0.05);the mRNA expression of fetal genes and pro-inflammatory factors were up-regulated(P<0.05),and the mRNA expression of interleukin-10 was down-regulated(P<0.05)in the model group.Compared with the model group,exercise performance and left ventricular ejection fraction were increased(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were decreased(P<0.05);mRNA expression of fetal genes and pro-inflammatory factors was down-regulated(P<0.05),and that of interleukin-10 had no significant change(P>0.05)in the transplantation group.Compared with the transplantation group,all the above indicators in the combination group were further improved(P<0.05).(2)One day and 7 days after stem cell transplantation,compared with the transplantation group,the mRNA expression of sex-determining region of Y chromosome in the combination group increased(P<0.05).(3)Correlation analysis showed that interleukin-1β,interleukin-6(except on the 1st day after transplantation),and tumor necrosis factor-α were negatively correlated with the mRNA expression of sex-determining region of Y chromosome(P<0.05),while interleukin-10 was positively correlated with that of sex-determining region of Y chromosome(P<0.05).These findings suggest that exercise preconditioning can enhance the effect of bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction,which is characterized by suppression of cardiac remodeling and further amelioration of cardiac function.The mechanism is related to the improvement of the myocardial inflammatory microenvironment to promote bone marrow mesenchymal stem cell retention and survival.

Background Vascular endothelial damage associated with endothelial progenitor cell dysfunction is considered as an initiating step of hypertension and target organ damage, in which oxidative stress plays a key role. High-intensity intermittent exercise is an effective prevention and treatment method of various chronic diseases; however, little attention has been paid to its effects and mechanisms on endothelial progenitor cells. Objective To observe the effect of high-intensity intermittent exercise on the function of endothelial progenitor cells in patients with hypertension and explore the mechanism of oxidative stress. Methods A total of 60 patients with essential hypertension were randomly divided into a control group and an exercise group. The control group received conventional drug treatment (including diuretics, calcium blockers, and beta-blockers), and the exercise group performed high-intensity intermittent exercise for 8 weeks (3 times·week⁻¹) in addition to the treatment plan of the control group. Before and after intervention, brachial artery flow-mediated vasodilation (FMD) was used to evaluate vascular endothelial function; venous blood was sampled to perfrom circulating endothelial progenitor cell counts; endothelial progenitor cells were cultured in vitro, and the modified Boyden chamber assay and Matrigel lumen formation assay were used to detect their migration and tube formation ability, superoxide fluorescent anion probe method to detect reactive oxygen species levels, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining method to detect cell apoptosis, Western blotting to determine protein expression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2, NADPH oxidase 4, and superoxide dismutase. Results Four patients (13.3%) in the control group and 2 patients (6.7%) in the exercise group dropped out; the completion rate of the exercise group's training plan was 94.9%. Compared with the before-intervention indicators, blood pressure decreased, brachial artery FMD increased, number of circulating endothelial progenitor cells increased, their migration and tube formation ability were enhanced, reactive oxygen species levels and cell apoptosis rate were reduced, NADPH oxidase 2 and NADPH oxidase 4 protein expressions were down-regulated, and superoxide dismutase protein expression was up-regulated in the after-intervention exercise group, and the differences were all statistically significant (P < 0.05). There was no significant difference in the above indicators in the control group between before and after intervention (P > 0.05). Conclusion High-intensity intermittent exercise regulates oxidative stress mediated by NADPH oxidase, improves endothelial progenitor cell function, and restores vascular endothelial disorders in patients with essential hypertension.

Objective: To identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma (KIRC) and verify their expression levels in clinical samples. Methods: Stage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA).Principal component analysis (PCA) was used for dimensionality reduction to screen differentially expressed genes (DEGs)，which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis (WGCNA) was used to screen genes significantly related to KIRC，and a protein-protein interaction (PPI) network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic (ROC) curve，and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included，and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR)，Western blotting，and enzyme-linked immunosorbent assay (ELISA). Results: A total of 8223 DEGs were screened out，including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion，plasma membrane composition，and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules，cytokine-cytokine receptor interactions，and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene，lymphocyte cytosolic protein 2 (LCP2)，screened out by the PPI network，was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues (P<0.000 1). Conclusion: LCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

Objective To analyze the composition of the aqueous extract of Polygonatum Cyrtonema Hua(PCHE)and evaluate its antitumor activity in vitro and in vivo.Our aim is to provide a theoretical basis for the further development and utilization of Polygonatum Cyrtonema Hua.Methods(1)PCHE was prepared by aqueous extraction,and the chemical composition of PCHE was analyzed by UPLC-Q-TOF/MS and phenol-sulfuric acid method.The inhibitory activity on tumor cells proliferation of PCHE was detected by CCK-8 assay.Cell cycle and apoptosis were detected by flow cytometry,and the expression of apoptosis-related proteins Bcl-2 and Bax was detected by Western Blot.The inhibitory activity of PCHE-containing serum on cell proliferation was detected.(2)A B16 tumor-bearing mice model was constructed and model mice were randomly divided into the model group(saline),the positive drug group(CTX:50 mg·kg-1),and PCHE low-,medium-,and high-dose groups(55.9,111.8,223.6 mg·kg-1),and treated by gavage for 7 days.Changes in body weight and tumor volume of mice were observed during the treatment period.The mice were executed after the treatment,and the histopathological changes of heart,liver,spleen,lung,kidney and tumor were observed by hematoxylin-eosin(HE)staining.The protein expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemistry(IHC).Results The polysaccharide content of PCHE reached(10.07±1.3)%,and the flavonoid content was(0.044±0.004)%,and thirty-nine components were detected by UPLC-Q-TOF/MS,which contained antitumor components such as flavonoids(baicalein,quercetin,luteolin and rutin),organic acids(ferulic acid)and polyphenols(gallic acid),etc.PCHE exhibited the inhibitory effects on Hela,A549,4T1,B16,MFC and HepG2 cells,among which the inhibitory effect on B16 cells was the most significant(P＜0.001),and PCHE induced cell cycle arrest at G0/G1 phase in B16 cells(P＜0.001).The results of double-staining flow cytometry and Western Blot showed that PCHE significantly promoted apoptosis of B16 cells,decreased the expression of Bcl-2,and promoted the expression of Bax(P＜0.01,P＜0.001).and PCHE constituents absorbed into blood also had an inhibitory effect on B16 cells(P＜0.001).In addition,the results of in vivo activity assay showed that different doses of PCHE could inhibit tumor growth,induce tumor cell necrosis,reduce Bcl-2 expression,and increase Bax expression compared with the model group.Conclusion The ingredients in PCHE are abundant.It contains a variety of antitumor active ingredients,which can inhibit tumor growth,induce tumor cell apoptosis,show strong anti-tumor effects and be worthy of in-depth study.

Hepatitis E virus(HEV)is one of the most common pathogens in acute viral hepatitis.There are at least eight distinct genotypes of HEV.Only humans can contract HEV genotypes 1 and 2,but zoonotic viruses like genotypes 3 and 4 are mostly spread by eating undercooked or in-fected pork in some affluent nations.As a result,boars,both domestic and wild,are typically regar-ded as primary hosts of HEV.Nevertheless,during the past few years,a growing body of research has demonstrated that a number of other wild ruminant animals,such as wild deer and goats,are also susceptible to HEV infection.Determining their participation in the epidemiological cycle of hepatitis E thus requires an understanding of the risk variables that influence the transmission be-tween wild ruminants and humans.With an emphasis on published serological and molecular re-search,this review offers a broad summary of the body of knowledge currently available on the epi-demiology of HEV in wild ruminants.It addresses potential risk factors that could impact the spread of HEV among animals as well as their potential to serve as a source of infectious zoonotic illnesses.It presents an overview of the most recent developments in the epidemiology of HEV in wild ruminants and offers a framework for HEV prevention and management based on science.

Objective:To investigate the efficacy of different types of neoadjuvant therapy for esophageal cancer.Methods:The clinical data of 542 patients with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant therapy in Anyang Tumor Hospital of Science and Technology from January 2015 to May 2022 were retrospectively analyzed. These patients, consisting of 198 females and 344 males, with 289 cases aging ≤ 65 and 253 cases aging >65, were divided into a neoadjuvant chemoradiotherapy (NCRT) group (137 cases), a neoadjuvant chemotherapy (NCT) group (241 cases), and a neoadjuvant immunotherapy plus chemotherapy (NICT) group (164 cases). In this study, primary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, and secondary endpoints comprised overall survival (OS), progression-free survival (PFS), and safety. Survival analysis was performed using the Kaplan-Meier method, and inter-group comparisons were made using the Log-rank test. Furthermore, prognostic factors were analyzed based on the Cox proportional hazards regression model.Results:The NCRT, NCT, and NICT groups exhibited MPR and pCR rates of 66.4% (91/137) and 35.3% (85/241), 63.4% (104/164) and 35.8% (49/137), and 6.6% (16/241) and 31.1% (51/164), respectively ( χ2=1.67, P < 0.001). These groups displayed 1-, 2-, and 3-year OS rates of 89.8%, 85.9%, and 91.9%; 82.3%, 71.4%, and 81.5%; and 72.3%, 61.4%, and 77.8%, respectively, with significant differences ( χ2=9.20, P < 0.01). Furthermore, they exhibited 1-, 2-, and 3-year PFS rates of 81.5%, 75.9%, and 80.1%; 67.9%, 61.0%, and 65.5%; and 66.6%, 53.5%, and 65.3%, respectively, with significant differences ( χ2=4.62, P < 0.05). Multivariate analysis showed that therapeutic modality, T stage, and N stage were independent prognostic factors for OS ( P < 0.05). Additionally, there was no difference in adverse reactions and postoperative complications among the three groups. Conclusions:Compared to NCT, NICT and NCRT feature higher pCR and MPR rates, along with more survival benefits. Therefore, neoadjuvant immunotherapy has the potential to serve as a preoperative therapeutic modality for esophageal cancer, yet large-scale randomized controlled trials are still required for confirmation.