Objective To explore the mechanism of lepirudine in inhibiting thrombin activation by regulating the Notch signaling pathway for the treatment of acute pulmonary embolism.Methods SD rats were randomly divided into sham group,model group and experimental group,with 10 rats in each group.Acute pulmonary embolism model was established by autologous thrombosis in model group and experimental group.Experimental group was intraperitoneally injected with lepiludine(2.0 mg·kg-1)at 24 h,0.5 h before and 24 h after modeling,respectively,while sham group and model group were intraperitoneally injected with 0.9％NaCl at the same time point.The contents of platelet P-selectin 62(CD62P),platelet granule membrane protein-140(GMP-140),N-terminal pro-brain natriuretic peptide(NT-proBNP)and cardiac troponin T(cTnT)in rat plasma were detected by enzyme-linked immunosorbent assay(ELISA).The contents of thromboxane B2(TXA2)and prostacyclin(PGI2)in rat plasma were detected by RIA.The protein expression levels of Notch receptor protein 1(Notch1)and Notch ligand protein 1(JAGGED1)in lung tissue of rats were detected by Western blot.Results The plasma CD62P content in sham group,model group and experimental group were(9.31±1.31),(25.03±2.66)and(11.42±2.21)ng·mL-1;the contents of GMP-140 were(43.23±5.61),(114.33±14.02)and(73.44±6.97)ng·mL-1;the contents of NT-proBNP were(14.71±1.93),(20.57±3.46)and(11.07±3.06)ng·mL-1;cTnT content were(81.07±9.77),(233.24±27.61)and(134.76±15.00)pg·mL-1;TXA2 content were(231.06±17.33),(378.69±29.10)and(268.61±24.15)pg·mL-1;PGI2 content were(147.25±16.44),(104.37±11.62)and(136.09±13.40)pg·mL-1;the relative expression levels of Notch1 protein in lung tissue were 1.24±0.21,0.51±0.06 and 0.87±0.09;the relative expression levels of JAGGED1 protein were 1.02±0.15,0.17±0.02 and 0.28±0.06.Compared with sham group and experimental group,there were statistically significant differences in the above indexes in model group(P＜0.01,P＜0.001).Conclusion Lepirudine can inhibit thrombin activation in the treatment of acute pulmonary embolism by activating the Notch signaling pathway.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

Objective:To identify the key genes involved in the development and progression of prostate cancer(PCa)and those associated with the prognosis of the malignancy.Methods:We obtained the single-cell sequencing data on 4 cases of PCa from the GSE156632 database.Using R language and the Seurat package,we performed cell clustering and annotation,selected the subpop-ulations of epithelial cells for differential analysis after quality control and cell type identification,and conducted enrichment analysis of the identified differential genes using the Hiplot website.Then we downloaded the single nucleotide polymorphism(SNP)loci corre-sponding to the expression quantitative trait loci(eQTL)of these genes from the UK Biobank(UKB)database,and the clinical data and corresponding gene expression data on PCa patients from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),followed by univariate COX regression analysis of the impact of the genes on the prognosis of the patients after Mendelian ran-domization.Results:A total of 1 566 genes were identified and subjected to enrichment analysis,which indicated that the differenti-al genes might be enriched in the Ras,apoptosis and oxidative phosphorylation signaling pathways.Subsequent Mendelian randomiza-tion revealed 74 potential causal genes among the 1 566 genes,and univariate COX regression analysis of the 74 genes identified 4 pos-sibly related genes FAM3B,JUNB,TMEM59,and KRT5.Comparison of the results of Mendelian randomization and univariate COX regression showed that KRT5 might be the most important gene influencing PCa.Conclusion:FAM3B,JUNB,TMEM59 and KRT5 may play a role in the progression of PCa,and KRT5 may potentially serve as a prognostic predictor and therapeutic target for the malig-nancy.

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ² test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.
Colectomy ; Colonic Neoplasms/surgery* ; Female ; Humans ; Laparoscopy ; Male ; Prognosis ; Propensity Score ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome

OBJECTIVE: To investigate the effect of dihydromyricetin (DHM) on cardiac insufficiency in diabetic rats and explore the underlying mechanism. METHOD: Twenty-four male SD rats were randomized equally into normal control group, type 2 diabetes (T2DM) group fed on a high-glucose and high-fat diet for 6 weeks with low-dose streptozotocin (STZ) injection, metformin (MET) group with daily intragastric administration of MET (150 mg/kg) for 8 weeks after T2DM modeling, and dihydromyricetin (DHM) group with daily intragastric administration of DHM (250 mg/kg) for 8 weeks after modeling. The levels of fasting blood glucose, low density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-C) and glycosylated hemoglobin (HbA1c) of the rats were measured, and plasma levels of insulin and high mobility group protein-1 (HMGB1) were detected with ELISA. The cardiac function of the rats was assessed using color echocardiography, ECG was measured using a biological signal acquisition system, and myocardial pathology was observed with HE staining. The protein expressions of HMGB1, nuclear factor-κB (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in the myocardial tissue were detected using Western blotting. RESULTS: Compared with the control group, the rats in T2DM group showed significant anomalies in cardiac function after modeling with significantly increased plasma HMGB1 level and expressions of HMGB1, NF-κB p65 and p-NF-κB p65 proteins in the myocardial tissue (P < 0.05 or 0.01). Treatment with DHM significantly improved the indexes of cardiac function of the diabetic rats (P < 0.05 or 0.01), decreased plasma HMGB1 level and down-regulated the protein expressions of HMGB1 and p-NF-κB p65 in the myocardial tissue (P < 0.05 or 0.01). CONCLUSION DHM treatment can improve cardiac function in diabetic rats possibly by down-regulation of HMGB1 and phospho-NF-κB p65 expressions in the myocardium.
Animals ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Flavonols ; HMGB1 Protein ; Heart Failure ; Male ; Metformin/therapeutic use* ; NF-kappa B/metabolism* ; Rats ; Rats, Sprague-Dawley

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.
Aging/pathology* ; Cellular Senescence ; Humans ; Lung/pathology* ; Lung Diseases/pathology* ; Respiration Disorders/pathology* ; Telomere ; Telomere Shortening

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l

In this paper, based on the supramolecular "Qi chromatography" of traditional Chinese medicine (TCM), combined with the characteristics of corona virus disease 2019 (COVID-19), the historical origin and characteristics of theoretical research on the treatment of epidemic diseases by TCM were analyzed retrospectively, and the key scientific problems for achieving its modernization were proposed, and the countermeasures were illustrated. In fact, the emergence and development history of TCM epidemic theory is a comprehensive and scientific understanding of biomolecular chemistry for epidemic caused by pathogen. From the exploration of the cause of abnormal Qi to the epidemic pathogenic factor, from the treatment based on syndrome differentiation by six meridians to by the defensive Qi and nutrient blood and the triple energizer, which is gradually close to the modern theoretical system of infectious diseases and immunology, all of which are stamped with brand of TCM supramolecular "Qi chromatography" theory. In the long history of biological evolution in nature, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as epidemic pathogenic factor in TCM, human body and Chinese materia medica are biological supramolecules at a specific stage of evolution in nature, which are controlled by the "imprinting templates" of molecular society in gradual biomolecules, with the unchanged laws of mutual advancement, mutation, suitability and mutual restriction. Based on the analysis of the law of supramolecular action hiding in the prevention and treatment of epidemic diseases dealt with TCM on procession of principle-method-recipe-medicines, this paper discusses the key scientific problems of its modernization and puts forward the solutions. It can not only clarify the scientific principle of the prevention and treatment with TCM, develop the multi-component Chinese medicine, accelerate the control of the epidemic situation, but also promote the solution of original frontier key scientific problems such as the material basis of meridians, viscera and syndromes, and the compatibility law of the TCM prescription, in order to protect the existing medical resources and open up a new situation in the modernization of TCM research.

Zhenwutang is the classic formula of Wenyang Lishui in " Treatise on Febrile Diseases" . It consists of five kinds of medicines, namely Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma Recens, Atractylodis Macrocephalae Rhizoma, Poria, Paeoniae Radix Alba or Paeoniae Radix Rubra. It has been included in the Catalogue of Ancient Classics (The First Batch) issued by the State Administration of Traditional Chinese Medicine in 2018.There are two articles in the " Treatise on Febrile Diseases" about the syndromes of Zhenwutang. On the basis of Article 82 of the Chapter of Taiyang disease, the Taiyang disease is demonstrated by sweating, but after that the patient still suffers from fever, epigastric throb, dizziness and shiver, this shall be treated with Zhenwutang. According to Article 316 of the chapter of Shaoyin disease, Shaoyin disease lasts for two or three days, until the fourth and fifth days, and is demonstrated by abdominal pain, difficult urination, severe pain in the limbs and diarrhea, the patient have a cough, diuresis, diarrhea and vomit, this shall be treated with Zhenwutang. The original texts discuss the basic pathogenesis is edema syndrome due to Yin and Yang deficiency, with symptoms of unfavorable urination, heavy limbs or edema, pale tongue, white moss and heavy pulse as dialectical points. In terms of the compatibility of prescriptions, usage and dosage, and the interpretation of prescriptions, this paper examines Zhenwutang syndromes in " Treatise on Febrilediseases" , summarizes the material basic research of Zhenwutang, and provides the basis for the quality control of its compound pharmacodynamics. This study summarizes the progress of pharmacological research for Zhenwutang in recent years, finds that Zhenwutang has many efficacies, such as cardiotonic, diuretic, lowering lipid, anti-oxidation, improving renal function and balancing of water and liquid metabolism, lists traditional Chinese medicine(TCM) syndromes treated with Zhenwutang, such as heart palpitations, edema, cough, abdominal pain, sipping, dizziness, and Western medicine diseases, like congestive heart failure, pulmonary heart disease, bronchial asthma, chronic colitis, cirrhosis, ascites, chronic glomerulonephritis, chronic renal failure, benign prostatic hyperplasia and Meniere's syndrome, expounds the principle of Zhenwutang for " treating different diseases with the same therapy" , in order to provide useful reference for the research and development and clinical application of Zhenwutang and more classic prescriptions.

BACKGROUND: Resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for the study of brain function. Typically, rs-fMRI is performed on anesthetized animals. Although different functional connectivity (FC) in various anesthetics on whole brain have been studied, few studies have focused on different FC in the aged brain. Here, we measured FC under three commonly used anesthesia methods and analyzed data to determine if the FC in whole brain analysis were similar among groups. METHODS: Twenty-four male aged Wistar rats were randomly divided into three groups (n = 8 in each group). Anesthesia was performed under either isoflurane (ISO), combined ISO + dexmedetomidine (DEX) or α-chloralose (AC) according to the groups. Data of rs-fMRI was analyzed by FC in a voxel-wise way. Differences in the FC maps between the groups were analyzed by one-way analysis of variance and post hoc two-sample t tests. RESULTS: Compared with ISO + DEX anesthesia, ISO anesthesia caused increased FC in posterior brain and decreased FC in the middle brain of the aged rat. AC anesthesia caused global suppression as no increase in FC was observed. CONCLUSION ISO could be used as a substitute for ISO + DEX in rat default mode network studies if the left temporal association cortex is not considered important.
Anesthesia ; Animals ; Brain/diagnostic imaging* ; Brain Mapping ; Isoflurane ; Magnetic Resonance Imaging ; Male ; Rats ; Rats, Wistar