Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.
Humans ; Animals ; Periplaneta ; Sirtuin 1/genetics* ; K562 Cells ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Mammals

Buxue Yimu Pill (BYP) is a classic gynecological medicine in China, which is composed of Angelica sinensis (Oliv.) Diels, Leonurus japonicus Houtt, Astragalus membranaceus (Fisch.) Bunge, Colla corii asini and Citrus reticulata Blanco. It has been widely used in clinical therapy with the function of enriching Blood, nourishing Qi, and removing blood stasis. The current study was designed to determine the bioactive molecules and therapeutic mechanism of BYP against hemorrhagic anemia. Herein, GC-MS and UPLC/Q-TOF-MS/MS were employed to identify the chemical compounds from BYP. The genecards database (https: //www.genecards.org/) was used to obtain the potential target proteins related to hemorrhagic anemia. Autodock/Vina was adopted to evaluate the binding ability of protein receptors and chemical ligands. Gene ontology and KEGG pathway enrichment analysis were conducted using the ClusterProfiler. As a result, a total of 62 candidate molecules were identified and 152 targets related to hemorrhagic anemia were obtained. Furthermore, 34 active molecules and 140 targets were obtained through the virtual screening experiment. The data of molecular-target (M-T), target-pathway (T-P), and molecular-target-pathway (M-T-P) network suggested that 32 active molecules enhanced hematopoiesis and activated the immune system by regulating 57 important targets. Pharmacological experiments showed that BYP significantly increased the counts of RBC, HGB, and HCT, and significantly down-regulated the expression of EPO, IL-6, CSF3, NOS2, VEGFA, PDGFRB, and TGFB1. The results also showed that leonurine, leonuriside B, leosibiricin, ononin, rutin, astragaloside I, riligustilide and levistolide A, were the active molecules closely related to enriching Blood. In conclusion, based on molecular docking, network pharmacology and validation experiment results, the enriching blood effect of BYP on hemorrhagic anemia may be associated with hematopoiesis, anti-inflammation, and immunity enhancement.
Anemia/drug therapy* ; Drugs, Chinese Herbal ; Humans ; Molecular Docking Simulation ; Network Pharmacology ; Tandem Mass Spectrometry

BACKGROUND: Imprecise interpretation of coronary angiograms was reported and resulted in inappropriate revascularization. Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is a comprehensive system to evaluate the complexity of the overall lesions. We hypothesized that a real-time SYNTAX score feedback from image analysts may rectify the mis-estimation and improve revascularization appropriateness in patients with stable coronary artery disease (CAD). METHODS: In this single-center, historical control study, patients with stable CAD with coronary lesion stenosis ≥50% were consecutively recruited. During the control period, SYNTAX scores were calculated by treating cardiologists. During the intervention period, SYNTAX scores were calculated by image analysts immediately after coronary angiography and were provided to cardiologists in real-time to aid decision-making. The primary outcome was revascularization deemed inappropriate by Chinese appropriate use criteria for coronary revascularization. RESULTS: A total of 3245 patients were enrolled and assigned to the control group (08/2016-03/2017, n = 1525) or the intervention group (03/2017-09/2017, n = 1720). For SYNTAX score tertiles, 17.9% patients were overestimated and 4.3% were underestimated by cardiologists in the control group. After adjustment, inappropriate revascularization significantly decreased in the intervention group compared with the control group (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.73-0.95; P = 0.007). Both inappropriate percutaneous coronary intervention (adjusted OR: 0.82; 95% CI: 0.74-0.92; P < 0.001) and percutaneous coronary intervention utilization (adjusted OR: 0.88; 95% CI: 0.79-0.98; P = 0.016) decreased significantly in the intervention group. There was no significant difference in 1-year adverse cardiac events between the control group and the intervention group. CONCLUSIONS: Real-time SYNTAX score feedback significantly reduced inappropriate coronary revascularization in stable patients with CAD. CLINICAL TRIAL REGISTRATION Nos. NCT03068858 and NCT02880605; https://www.clinicaltrials.gov.

Objective:To investigate the relationship between urinary polycyclic aromatic hydrocarbons(PAHs) metabolites and pulmonary function in community population.Methods:A total of 4 812 participants were recruited from two communities in Wuhan city from April to May 2011 and two communities in Zhuhai city in May 2012. Information of demographic characteristics and life style was collected by semi-structural questionnaire. Physical examination was performed and pulmonary function was measured. Morning urine was also collected. The concentration of 12 urinary PAHs metabolites was tested and classified into four types by chemical structure, including hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene and hydroxypyrene. The level of pulmonary function in different group of urinary PAHs metabolites was compared by using covariance analysis. The association of the urinary PAHs metabolites and pulmonary function was analyzed by using generalized linear model, and the interaction of different population characteristics and life style on the association was analyzed.Results:The age of participants was(51.99±13.64) years old, and 67.66% ( n=2 565) of the population were women. The M ( P25, P75) of concentration of total urinary PAHs metabolites was 5.72 (3.91,8.72) μg/mmol Cr. After controlling for variables including age, gender, city, Waist-to-Hip Ratio, smoking status, drinking situation, physical activity, cooking meals at home or not, kitchen ventilation and exposure to dust as confounding factors, generalized linear model showed that each 1-unit increase in log-transformed levels of hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene, hydroxypyrene and total PAHs was associated with 26.83 (95% CI: -48.18, -5.48) , 21.86 (95% CI: -40.49, -3.23), 26.18(95% CI: -48.27, -4.09), 34.95 (95% CI: -55.95, -13.94), and 35.23 (95% CI: -58.93, -11.54) ml reduction of FVC and 29.36 (95% CI: -47.23, -11.48), 20.79 (95% CI: -36.39, -5.19), 22.65 (95% CI: -41.15, -4.15), 31.44(95% CI: -49.03, -13.85), and 33.20 (95% CI: -53.04, -13.36) ml reduction of FEV 1 respectively (all P values<0.05). Compared to non-alcohol users and participants with home cooking, the association was more evident in alcohol users and participants without home cooking( P for interaction<0.05). Conclusion:The exposure to PAHs was associated with decreased pulmonary function, and the association was more evident in alcohol users and participants without home cooking.

Objective:To investigate the relationship between urinary polycyclic aromatic hydrocarbons(PAHs) metabolites and pulmonary function in community population.Methods:A total of 4 812 participants were recruited from two communities in Wuhan city from April to May 2011 and two communities in Zhuhai city in May 2012. Information of demographic characteristics and life style was collected by semi-structural questionnaire. Physical examination was performed and pulmonary function was measured. Morning urine was also collected. The concentration of 12 urinary PAHs metabolites was tested and classified into four types by chemical structure, including hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene and hydroxypyrene. The level of pulmonary function in different group of urinary PAHs metabolites was compared by using covariance analysis. The association of the urinary PAHs metabolites and pulmonary function was analyzed by using generalized linear model, and the interaction of different population characteristics and life style on the association was analyzed.Results:The age of participants was(51.99±13.64) years old, and 67.66% ( n=2 565) of the population were women. The M ( P25, P75) of concentration of total urinary PAHs metabolites was 5.72 (3.91,8.72) μg/mmol Cr. After controlling for variables including age, gender, city, Waist-to-Hip Ratio, smoking status, drinking situation, physical activity, cooking meals at home or not, kitchen ventilation and exposure to dust as confounding factors, generalized linear model showed that each 1-unit increase in log-transformed levels of hydroxynaphthalene, hydroxyfluorene, hydroxyphenanthrene, hydroxypyrene and total PAHs was associated with 26.83 (95% CI: -48.18, -5.48) , 21.86 (95% CI: -40.49, -3.23), 26.18(95% CI: -48.27, -4.09), 34.95 (95% CI: -55.95, -13.94), and 35.23 (95% CI: -58.93, -11.54) ml reduction of FVC and 29.36 (95% CI: -47.23, -11.48), 20.79 (95% CI: -36.39, -5.19), 22.65 (95% CI: -41.15, -4.15), 31.44(95% CI: -49.03, -13.85), and 33.20 (95% CI: -53.04, -13.36) ml reduction of FEV 1 respectively (all P values<0.05). Compared to non-alcohol users and participants with home cooking, the association was more evident in alcohol users and participants without home cooking( P for interaction<0.05). Conclusion:The exposure to PAHs was associated with decreased pulmonary function, and the association was more evident in alcohol users and participants without home cooking.

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree

Objective To investigate the incidence and bacterial etiology of stent associated respiratory tract infec-tion (SARTI) caused by two types of airway stents.Methods Silicone and coated metal airway stent were placed into patients with central airway stenosis caused by varied pathologies. The incidence of stent related respiratory tract infection,bacteria etiology of SARTI and improved dyspnea score were compared between two groups receiving different airway stent.Results 1)Totally 171 patients received airway stents, and among them, 39 patients (22.81%) developed SARTI.2)The incidence of SARTI in metal stent group and silicone stent group was 29.21% (26/89) vs.15.85% (13/82),P<0.05;3)Bacterial spectrum of SARTI was different in metal and silicone stent groups:staphylococcus aureus was 38.46% vs. 69.23%,respectively;candida albicans was 23.08% vs. 0%,re-spectively;Singular proteus was 7.26% vs.0%,respectively;4)The narrowed lumen was improved from 74.27%± 7.13% to 17.64%±6.22%in the metal stent group,while the data was improved from 74.94%±9.18% to 12.68%± 8.32% in the silicone stent group (P<0.01). Accordingly, the dyspnea symptomscore was improvedfrom 2.85 ± 0.89 to 0.85±0.68 in metal stent group,and from 2.88±0.91 to 0±0.61 in the silicone stent group (P<0.05). Conclusions Compared with metal airway stents,silicone stents have a lower incidence of SARTI,which mightbe due to the projections in the silicon stent surface and wider expanded in the bronchial stenosis.

OBJECTIVE: To investigate the effects of Toll like receptors on the osteogenesis of human pe-riodontal ligament stem cells (hPDLSCs) and probable molecular mechanism. METHODS: Real-time PCR and flow cytometry were applied to test the expression of TLRs in hPDLSCs and the positive cell percentage of TLR. hPDLSCs were cultured in osteogenic medium for 7 to 14 days with different TLR agonists at various concentrations . The effect of different TLR on osteogenic differentiation of hPDLSCs was evaluated by alizarin red S staining, alkaline phosphatase (ALP) staining and ALP activity assay. Western blotting was used to analyze the phosphorylation levels of extracellular regulated protein kinases (ERK), c-Jun N-terminal protein kinase (JNK), P38, AKT and expression of Runx2 an osteogenic related gene after treatment with TLR agonists, compared with the effect of inhibitors of mitogen activated protein kinase (MAPK) or protein kinase B (PKB or AKT) on Runx2 expression of hPDLSCs cultured in osteogenic medium. RESULTS: Higher expressions of TLR1,3,4,6 were found in hPDLSCs through real-time PCR. Positive cell percentage of TLR was determined by flow cytometry and described as TLR1: 2.82%±0.68%; TLR2: 1.26%±0.09%; TLR3: 13.23%±2.05%; TLR4: 3.64%±0.79%; TLR6: 3.21%±1.64%, whose tendency was comparable to their mRNA expression in hPDLSCs. Most TLR ligands had no effect on the ALP staining, activity and mineralization of hPDLSCs at lower concentration except for 0.1 mg/L PolyI:C could induce the osteogenic ability of hPDLSCs. On the contrary, Higher concentration of TLR ligands (PolyI:C: 10 mg/L, LPS: 10 mg/L , Pam3CSK4: 1 mg/L, FSL-1: 50 μg/L) had obviously inhibitory effect on osteogenic differentiation of hPDLSCs. Activation of TLR using higher concentration of TLR ligands could downregulate the phosphorylation levels of ERK, P38, JNK and AKT, and also reduced the expression of Runx2, compared with the untreated control. The inhibitors of MAPK (U0126, SP600125,SB203580) and inhibitor of AKT (perifosine) could also inhibit Runx2 expression. CONCLUSION Higher concentration of TLR ligands could inhibit osteogenic differentiation of hPDLSCs. This inhibitory effect seemed to be related to decreased phosphorylation of MAPK and AKT.
Cell Differentiation ; Cells, Cultured ; Humans ; Ligaments ; Mitogen-Activated Protein Kinases/metabolism* ; Osteogenesis ; Periodontal Ligament/metabolism* ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism* ; Stem Cells ; Toll-Like Receptors/metabolism*

As the largest research-oriented specialty department in national traditional Chinese medicine hospitals, the Department of Critical Care Medicine in Guangdong Provincial Hospital of Chinese Medicine insists on the development mode combined with clinical medicine and scientific research. By taking clinical and basic researches for integrative medicine preventing and treating acute myocardial in-farction and sepsis as a breakthrough, authors explored key problems of Chinese medicine in improving the prognosis related diseases and patients' quality of life. In recent 3 years our department has successively become the principal unit of the national key specialties cooperative group of critical care medicine (awarded by State Administration of Traditional Chinese Medicine), the key clinical specialties (awarded by National Health and Family Planning Commission), and Guangzhou key laboratory construction unit, and achieved overall lap in clinical medical treatment, personnel training, scientific research, and social service.
Biomedical Research ; China ; Clinical Medicine ; Critical Care ; Hospital Departments ; organization & administration ; Humans ; Integrative Medicine ; Medicine, Chinese Traditional ; Quality of Life