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The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
Subject(s)
Humans , Consensus , Prone Position , Wakefulness , China , DyspneaABSTRACT
Interval timing is involved in a variety of cognitive behaviors such as associative learning and decision-making. While it has been shown that time estimation is adaptive to the temporal context, it remains unclear how interval timing behavior is influenced by recent trial history. Here we found that, in mice trained to perform a licking-based interval timing task, a decrease of inter-reinforcement interval in the previous trial rapidly shifted the time of anticipatory licking earlier. Optogenetic inactivation of the anterior lateral motor cortex (ALM), but not the medial prefrontal cortex, for a short time before reward delivery caused a decrease in the peak time of anticipatory licking in the next trial. Electrophysiological recordings from the ALM showed that the response profiles preceded by short and long inter-reinforcement intervals exhibited task-engagement-dependent temporal scaling. Thus, interval timing is adaptive to recent experience of the temporal interval, and ALM activity during time estimation reflects recent experience of interval.
Subject(s)
Animals , Mice , Reward , Time Factors , Cognition , Learning , Decision Making , Reinforcement, PsychologyABSTRACT
OBJECTIVE@#To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF).@*METHODS@#PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0.@*RESULTS@#Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model).@*CONCLUSIONS@#AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.
Subject(s)
Animals , Mice , Rats , Stroke Volume , Ventricular Function, Left , Heart Failure/drug therapy , Natriuretic Peptide, BrainABSTRACT
Acute coronary syndrome (ACS) is one of the leading causes of death in cardiovascular disease. Percutaneous coronary intervention (PCI) is an important method for the treatment of coronary heart disease (CHD), and it has greatly reduced the mortality of ACS patients since its application. However, a series of new problems may occur after PCI, such as in-stent restenosis, no-reflow phenomenon, in-stent neoatherosclerosis, late stent thrombosis, myocardial ischemia-reperfusion injury, and malignant ventricular arrhythmias, which result in the occurrence of major adverse cardiac events (MACE) that seriously reduce the postoperative benefit for patients. The inflammatory response is a key mechanism of MACE after PCI. Therefore, examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE. The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified. Many Chinese medicine (CM) preparations have been widely used in the treatment of CHD. Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone. The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE. The results provide a theoretical basis for further research and clinical treatment.
Subject(s)
Humans , Percutaneous Coronary Intervention/methods , Acute Coronary Syndrome/drug therapy , Coronary Disease , Treatment Outcome , Stents/adverse effectsABSTRACT
OBJECTIVE@#To investigate the effect of baicalin on the growth of extranodal NK/T cell lymphoma (ENKTCL) cells and its related mechanism.@*METHODS@#Normal NK cells and human ENKTCL cells lines SNK-6 and YTS were cultured, then SNK-6 and YTS cells were treated with 5, 10, 20 μmol/L baicalin and set control. Cell proliferation and apoptosis was detected by Edu method and FCM method, respectively, and expressions of BCL-2, Bax, FOXO3 and CCL22 proteins were detected by Western blot. Interference plasmids were designed and synthesized. FOXO3 siRNA interference plasmids and CCL22 pcDNA overexpression plasmids were transfected with PEI transfection reagent. Furthermore, animal models were established for validation.@*RESULTS@#In control group and 5, 10, 20 μmol/L baicalin group, the proliferation rate of SNK-6 cells was (56.17±2.96)%, (51.92±4.63)%, (36.42±1.58)%, and (14.60±2.81)%, respectively, while that of YTS cells was (58.85±2.98)%, (51.38±1.32)%, (34.75±1.09)%, and (15.45±1.10)%, respectively. In control group and 5, 10, 20 μmol/L baicalin group, the apoptosis rate of SNK-6 cells was (5.93±0.74)%, (11.78±0.34)%, (28.46±0.44)%, and (32.40±0.37)%, respectively, while that of YTS cells was (7.93±0.69)%, (16.29±1.35)%, (33.91±1.56)%, and (36.27±1.06)%, respectively. Compared with control group, the expression of BCL-2 protein both in SNK-6 and YTS cells decreased significantly (P<0.001), and the expression of Bax protein increased in SNK-6 cells only when the concentration of baicalin was 20 μmol/L (P<0.001), while that in YTS cells increased in all three concentrations(5, 10, 20 μmol/L) of baicalin (P<0.001). The expression of FOXO3 protein decreased while CCL22 protein increased in ENKTCL cell lines compared with human NK cells (P<0.001), but the expression of FOXO3 protein increased (P<0.01) and CCL22 protein decreased after baicalin treatment (P<0.001). Animal experiments showed that baicalin treatment could inhibit tumor growth. The expression of CCL22 protein in ENKTCL tissue of nude mice treated with baicalin decreased compared with control group (P<0.01), while the FOXO3 protein increased (P<0.05). In addition, FOXO3 silencing resulted in the decrease of FOXO3 protein expression and increase of CCL22 protein expression (P<0.01, P<0.001).@*CONCLUSION@#Baicalin can inhibit proliferation and promote apoptosis of ENKTCL cell lines SNK-6 and YTS, up-regulate the expression of Bax protein, down-regulate the expression of BCL-2 protein, and down-regulate the expression of CCL22 protein mediated by FOXO3. Animal experiment shown that the baicalin can inhibit tumor growth. Baicalin can inhibit the growth and induce apoptosis of ENKTCL cells through FOXO3/CCL22 signaling pathway.
Subject(s)
Animals , Mice , Humans , Lymphoma, Extranodal NK-T-Cell/pathology , Forkhead Box Protein O3/metabolism , bcl-2-Associated X Protein/pharmacology , Mice, Nude , Signal Transduction , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolism , Chemokine CCL22/pharmacologyABSTRACT
OBJECTIVES@#To provide a guideline for genealogy inference and family lineage investigation through a study of the mismatch tolerance distribution of Y-STR loci in Chinese Han male lineage.@*METHODS@#Three Han lineages with clear genetic relationships were selected. YFiler Platinum PCR amplification Kit was used to obtain the typing data of 35 Y-STR loci in male samples. The variation of Y-STR haplotypes in generation inheritance and the mismatch tolerance at 1-7 kinship levels were statistically analyzed.@*RESULTS@#Mutations in Y-STR were family-specific with different mutation loci and numbers of mutation in different lineages. Among all the mutations, 66.03% were observed on rapidly and fast mutating loci. At 1-7 kinship levels, the number of mismatch tolerance ranged from 0 to 5 on all 35 Y-STR loci, with a maximum step size of 6. On medium and slow mutant loci, the number of mismatch tolerance ranged from 0 to 2, with a maximum step size of 3; on rapidly and fast mutant loci, the number of mismatch tolerance ranged from 0 to 3, with a maximum step size of 6.@*CONCLUSIONS@#Combined use of SNP genealogy inference and Y-STR lineage investigation, both 0 and multiple mismatch tolerance need to be considered. Family lineage with 0-3 mismatch tolerance on all 35 Y-STR loci and 0-1 mismatch tolerance on medium and slow loci can be prioritized for screening. When the number of mismatch tolerance is eligible, family lineages with long steps should be carefully excluded. Meanwhile, adding fast mutant loci should also be handled with caution.
Subject(s)
Male , Humans , Haplotypes , Chromosomes, Human, Y/genetics , Microsatellite Repeats , Mutation , Asian People/genetics , China , Genetics, PopulationABSTRACT
OBJECTIVE@#To explore the clinical features and genetic basis of a child with Galactosemia.@*METHODS@#A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing.@*RESULTS@#Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR).@*CONCLUSION@#Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.
Subject(s)
Child , Female , Humans , Galactosemias/genetics , Genetic Testing , Health Status , Methionine , Muscle Hypotonia , MutationABSTRACT
OBJECTIVE@#To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD).@*METHODS@#Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES).@*RESULTS@#All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant.@*CONCLUSION@#The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.
Subject(s)
Child , Humans , Acyl-CoA Dehydrogenase/genetics , Carnitine , Genetic Testing , Lipid Metabolism, Inborn Errors/genetics , Neonatal ScreeningABSTRACT
As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.
Subject(s)
Arsenic/analysis , Arsenicals/analysis , Sulfides , Arsenic Trioxide , Medicine, Chinese Traditional , Drugs, Chinese Herbal/analysis , Biological ProductsABSTRACT
This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.
Subject(s)
Female , Mice , Animals , Glucose Transporter Type 1/genetics , Network Pharmacology , Animal Experimentation , Saline Solution , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Signal Transduction , Glycolysis , RNA, Messenger , Neoplasms/drug therapy , Molecular Docking SimulationABSTRACT
Objective To conduct a survey on the status of noise hazards in Tianjin in 2020, to analyze the main distribution characteristics of noise hazards, and to put forward corresponding preventive and control measures. Methods A unified questionnaire was used to investigate the city-wide enterprises with more than 5 employees, normal production and operation, and noise hazards. The χ2 test was used to analyze the survey results. Results There were 8 560 enterprises with noise hazards, which were concentrated in the five outer suburban districts, the four districts around the city and the Binhai New Area, mainly small and medium-sized enterprises. Totally, 223 800 people were exposed to noise. The rates of noise hazard detection and physical examination of workers were 25.88% and 17.66%, and the rate of over standard detection and the rate of abnormal physical examination were 13.09% and 1.62%, respectively. The differences in noise detection rate, over standard detection rate and physical examination rate were significant in different administrative regions, enterprise scales and industries. The detection rate and physical examination rate of enterprises in the five outer suburban districts, micro-scale enterprises, and paper products industries were the lowest, while the rate of exceeding standards was the highest in the railway, shipping, aerospace and other transportation equipment manufacturing industries. Conclusion Noise is a common occupational hazard in enterprises in Tianjin. There are a large number of people who are exposed to noise. The detection rate and physical examination rate of noise are at a low level. Individual industries have a high rate of exceeding the standard. The current situation of noise hazard prevention and control is not optimistic. It is recommended to pay attention to it and take effective intervention measures.
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Ulcerative colitis (UC) is one of the chronic refractory inflammatory bowel diseases characterized by abdominal pain, diarrhea, and mucus, pus and blood in the stool. In recent years, with changes in human life style and improvements of the diagnosis, the incidence and prevalence of UC have been increasing. The pathogenesis of UC is closely related to intestinal mucosal immune dysfunction, intestinal flora disturbance, and abnormal bile acid secretion. Patients with UC have abnormal bile acid secretion and intestinal flora imbalance. A large number of studies have found that abnormal bile acid secretion inhibits immune function, affects signal transduction, and destroys the intestinal mucosal barrier. Intestinal flora disturbance has an important impact on the occurrence and development of inflammation, immune homeostasis, and stress. Bile acids indirectly or directly affect the structure and function of intestinal flora, and at the same time, they produce secondary bile acids under the modification of intestinal flora, entering the liver through enterohepatic circulation. Therefore, the complex dialogue mechanism of bile acid-intestinal flora axis is closely related to the occurrence and development of UC. Based on the basic theory of traditional Chinese medicine(TCM) and clinical research, it is found that emotion is an important factor that induces this disease, spleen and stomach weakness is the root of the disease, and liver depression and spleen deficiency are the key pathogenesis of UC. Combined with modern medicine and molecular biology research, it is believed that abnormal secretion of bile acids is a microscopic manifestation of liver depression in TCM, and intestinal flora disturbance is the biological basis of spleen deficiency. In the pathogenesis of UC, the imbalanced bile acid-intestinal flora axis is consistent with the pathogenesis of liver depression and spleen in TCM. The exploration of the biological connotation of the pathogenesis of UC with liver depression and spleen deficiency from the perspective of bile acid-intestinal flora axis can better explain the scientific nature of its pathogenesis, which provides new clinical solutions and reliable references for studying the pathogenesis of UC with liver depression and spleen deficiency and finding representative prescriptions to prevent and treat this disease.
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Objective: To evaluate the value of nasal nitric oxide (nNO) measurement as a diagnostic tool for Chinese patients with primary ciliary dyskinesia (PCD). Methods: This study is a retrospective study. The patients were recruited from those who were admitted to the respiratory Department of Respiratory Medicine, Children's Hospital of Fudan University from March 2018 to September 2022. Children with PCD were included as the PCD group, and children with situs inversus or ambiguus, cystic fibrosis (CF), bronchiectasis, chronic suppurative lung disease and asthma were included as the PCD symptom-similar group. Children who visited the Department of Child health Care and urology in the same hospital from December 2022 to January 2023 were selected as nNO normal control group. nNO was measured during plateau exhalation against resistance in three groups. Mann-Whitney U test was used to analyze the nNO data. The receiver operating characteristic of nNO value for the diagnosis of PCD was plotted and, the area under the curve and Youden index was calculated to find the best cut-off value. Results: nNO was measured in 40 patients with PCD group, 75 PCD symptom-similar group (including 23 cases of situs inversus or ambiguus, 8 cases of CF, 26 cases of bronchiectasis or chronic suppurative lung disease, 18 cases of asthma), and 55 nNO normal controls group. The age of the three groups was respectively 9.7 (6.7,13.4), 9.3 (7.0,13.0) and 9.9 (7.3,13.0) years old. nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls (12 (9,19) vs. 182 (121,222), 209 (165,261) nl/min, U=143.00, 2.00, both P<0.001). In the PCD symptom-similar group, situs inversus or ambiguus, CF, bronchiectasis or chronic suppurative lung disease and asthma were significantly higher than children with PCD (185 (123,218), 97 (52, 132), 154 (31, 202), 266 (202,414) vs. 12 (9,19) nl/min,U=1.00, 9.00, 133.00, 0, all P<0.001). A cut-off value of 84 nl/min could provide the best sensitivity (0.98) and specificity (0.92) with an area under the curve of 0.97 (95%CI 0.95-1.00, P<0.001). Conclusions: nNO value can draw a distinction between patients with PCD and others. A cut-off value of 84 nl/min is recommended for children with PCD.
Subject(s)
Humans , Child , Adolescent , Nitric Oxide , Retrospective Studies , Cystic Fibrosis , Bronchiectasis/diagnosis , Asthma/diagnosis , Hospitals, Pediatric , Ciliary Motility Disorders/diagnosisABSTRACT
Objective:To investigate the expressions of eukaryotic initiation factor-4B (eIF4B) and eukaryotic initiation factor-5A (eIF5A) in papillary thyroid carcinoma tissues, and to analyze their regulatory effects on cell proliferation in vitro.Methods:The clinical data of 61 patients diagnosed with papillary thyroid carcinoma who received surgical resection at Yuncheng Central Hospital from January 2020 to October 2021 were retrospectively analyzed. The postoperative tumor tissues and paracancerous normal thyroid tissues (>1 cm from the margin of the mass) were retained. Immunohistochemistry was used to detect the expressions of eIF4B, eIF5A and proliferating cell nuclear antigen (PCNA) in different tissues. The correlation of eIF4B, eIF5A expressions with the clinicopathological characteristics of patients, and the relationship between eIF4B, eIF5A and PCNA were analyzed. The thyroid cancer cell line SW1736 and normal thyroid cell line HT-ori3 were selected. The expressions of eIF4B mRNA and eIF5A mRNA were detected by using real-ime quantitative polymerase chain reaction (qRT-PCR). After the small interfering RNA (siRNA) of siRNA-eIF4B and siRNA-eIF5A were synthesized, the interfering plasmids were constructed, and SW1736 cells were transfected, siRNA-eIF4B group and siRNA-eIF5A group were obtained; the empty plasmid transfection group and the blank control group without transfection intervention were established. The cell proliferation activity was detected by using CCK-8 assay, and the expression of PCNA mRNA was detected by using qRT-PCR.Results:The positive rates of eIF4B and eIF5A in papillary thyroid cancer tissues were higher than those in paracancerous normal thyroid tissues [65.57% (40/61) vs. 29.51% (18/61), 57.38% (35/61) vs. 9.84% (6/61), P < 0.001]. The positive rates of eIF4B and eIF5A were statistically different in patients with different tumor diameter [>3 cm vs. ≤3 cm: 88.89% (16/18) vs. 55.81% (24/43),77.78% (14/18) vs. 48.84% (21/43), all P < 0.05], lymph node metastasis [with vs. without: 85.00% (17/20) vs. 56.10% (23/41), 80.00% (16/20) vs. 46.34% (19/41), all P < 0.05] and the number of different nodes [multiple vs. single: 86.67% (13/15) vs. 58.70% (27/46), 86.67% (13/15) vs. 47.83% (22/46), all P < 0.05]; there were no statistically significant differences in the positive rates of eIF4B and eIF5A among patients with different age and gender (all P > 0.05). Positive correlation was found between eIF4B score and the positive cell proportion of PCNA ( r = 0.66, P = 0.0324), eIF5A score and the positive cell proportion of PCNA ( r = 0.62, P = 0.024), eIF4B score and eIF5A score ( r = 0.63, P = 0.021). The expression levels of eIF4B mRNA and eIF5A mRNA in thyroid cancer cell line SW1736 cell was higher than that of HT-ori3 cell in normal thyroid (all P < 0.05). The cell proliferation activity of SW1736 and PCNA mRNA expression level in siRNA-eIF4B group and siRNA-eIF5A group were lower than those in the empty vector transfected group and the blank control group (all P < 0.05). Conclusions:eIF4B and eIF5A are expressed elevated in papillary thyroid carcinoma, and both are involved in tumor development and progression. The role of eIF4B and eIF5A may be related to promoting the proliferation of tumor cells.
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Objective:To investigate the expression of fibrinogen-like protein 1 (FGL1) in clear cell renal cell carcinoma (ccRCC) and its correlation with clinicopathological characteristics of patients with ccRCC.Methods:The clinicopathological data of 242 patients with ccRCC who were diagnosed and treated surgically from January 2015 to December 2018 were retrospectively analyzed. The cancerous tissues and paracancerous tissues (2 cm away from the edge of cancerous tissues) of patients were collected. The expression of FGL1 protein was detected by using immunohistochemistry, and the relative expression level of FGL1 mRNA was detected by using reverse transcription polymerase chain reaction (RT-PCR). Cox proportional risk model was used to make univariate and multivariate analysis of the influencing factors of progression-free survival (PFS).Results:The positive rate of FGL1 protein in ccRCC tissues was higher than that in paracancerous tissues [28.5% (69/242) vs. 2.1% (5/242)], and the difference was statistically significant ( χ2 = 65.34, P < 0.001); the relative expression level of FGL1 mRNA in ccRCC tissues was higher than that in paracancerous tissues (1.67±0.12 vs. 0.60±0.15), and the difference was statistically significant ( t = 25.33, P < 0.001). The expression of FGL1 was positively correlated with pathological staging ( r = 0.164, P = 0.011), renal vascular tumor thrombus ( r = 0.130, P = 0.043), regional lymph node metastasis ( r = 0.153, P = 0.018), and distant metastasis ( r = 0.160, P = 0.012). Univariate analysis showed that the tumor diameter, regional lymph nodes metastasis, pathological staging, distant metastasis, and FGL1 expression were factors influencing the PFS of ccRCC patients (all P < 0.05). Multivariate regression results showed that high expression of FGL1 ( HR = 11.679, 95% CI 7.432-15.673, P = 0.015), pathological staging of Ⅲ-Ⅳ ( HR = 13.654, 95% CI 8.765-18.761, P = 0.013), and distant metastasis ( HR = 11.387, 95% CI 7.662-14.831, P = 0.038) were independent risk factors for PFS in patients. Conclusions:FGL1 is highly expressed in ccRCC, which is correlated with pathological staging, renal vascular tumor thrombus, regional lymph nodes metastasis, and distant metastasis. The high expression of FGL1 is a risk factor affecting the prognosis of patients with ccRCC.
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Objective:To prepare a recombinant hemagglutinin trimer (HA-Tri) vaccine against influenza viruses and to study its immunogenicity in a mouse model.Methods:A stable CHO cell line that could express HA-Tri was constructed. Western blot, single radial immunodiffusion, protein particle size detection and N-glycosylation site analysis were performed for qualitative and quantitative analysis of the recombinant protein. According to the different treatment conditions such as dosage and adjuvant, BALB/c mice were divided into 11 groups and subjected to consistent immunization procedures. Serum neutralizing antibody titers were measured on 56 d after the first immunization to evaluate the immunogenicity of HA-Tri.Results:The constructed CHO cells could secret and express HA-Tri proteins. The HA-Tri proteins were biologically active and capable of forming precipitation rings in the single radial immunodiffusion. The particle size of HA-Tri was approximately 18.79 nm and 10 N-glycosylation sites were detected, including high mannose, complex glycoforms and heterozygous glycoforms. After prime-boost immunization, there was no statistically significant difference in the titers of neutralizing antibodies induced in mice by 3.75 μg of HA-Tri in combination with RFH01 adjuvant and 15 μg of monovalent vaccine stock solution ( P=0.431 2, U=36). Serum antibody titers in the HA-Tri+ RFH01 groups were higher than those in the corresponding HA-Tri groups without RFH01 adjuvant, and the highest titer was induced in the 15 μg HA-Tri+ RFH01 group, which was 1 280. Conclusions:The recombinant HA-Tri protein was successfully prepared. HA-Tri in combination with RFH01 adjuvant could induce humoral immune responses against influenza viruses in BALB/c mice, which would provide reference for the development of influenza virus recombinant subunit vaccines.
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Objective:To observe any effect of high-intensity interval training on the blood pressure and renal function of Wistar-Kyoto rats modeling spontaneous hypertension (SHR) and to explore the mechanism of the renal renin-angiotensin system′s (RAS′s) role in this process.Methods:Twenty male SHR were randomly divided into a sedentary group and an exercise group, each of 10. Another 10 Wistar-Kyoto rats formed a normotensive control group. The rats in the normotensive and hypertensive sedentary groups were fed quietly in their cage, while the hypertensive exercise group performed high-intensity interval training for 8 weeks. After the last exercise, blood pressure, renal function, the kidney levels of nitric oxide and interleukin-6 (IL-6) and the protein expressions of angiotensin converting enzyme (ACE), ACE2, angiotensin type 1 receptor (AT1R), AT2R and Mas receptor (MasR) were measured.Results:Compared with the normotensive group, the hypertensive sedentary group showed a significant increase in average blood pressure, IL-6, ACE and AT1R protein and the ratio of AT1R to AT2R. There was a significant decrease in the renal function, the average NO level and the expression of ACE2, AT2R and MasR protein. That group also showed a significant decrease in blood pressure, IL-6, ACE and AT1R protein expression and the AT1R: AT2R ratio compared with the hypertensive sedentary group, but a significant increase in renal function, average NO content and the expression of ACE2, AT2R and MasR protein.Conclusion:Eight weeks of high-intensity interval training has a protective effect on the kidneys by regulating the renin-angiotensin system, at least in rats.
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Objective:To explore any effect of regular aerobic exercise on renal fibrosis and apoptosis in rats with spontaneous hypertension.Methods:Thirty 6-week-old male spontaneously hypertensive rats were randomly divided into a sedentary group (group HS) and an exercise group (group HE). Ten age- and sex-matched Wistar-Kyoto rats formed a control group. The rats in group HE underwent 12 weeks of swimming exercise lasting 60 minutes, five times a week, while the other two groups were kept quiet in their cages. Before and after the training, the tail artery blood pressure of each rat was measured. Renal function was evaluated after the experiment by measuring 24h urine protein, blood urea nitrogen and serum creatinine levels, while the degree of renal interstitial fibrosis was measured using Masson staining and the collagen volume fraction was calculated. The number of apoptotic cells in the renal tubular epithelial tissue was recorded by TUNEL staining and the apoptosis rate was calculated. The expression of renal transforming growth factor β1 (TGF-β1), Smad2/3, Smad7, Bax and Bcl-2 protein were detected using western blotting.Results:After the intervention, the average systolic and diastolic blood pressure and mean arterial pressure of group HS had increased significantly, while those of group HE had decreased significantly, with no significant changes in those measurements among the control group. Compared with the control group, after the intervention, the average blood pressure, 24h urinary protein, blood urea nitrogen and serum creatinine, as well as the cell apoptosis rate and expression of TGF-β1, Smad2/3 and Bax had increased significantly, and that of Smad7 and Bcl-2 had decreased significantly in group HS. And compared with group HS, in group HE the average blood pressure, 24h urinary protein, blood urea nitrogen, serum creatinine and the cell apoptosis rate had decreased significantly, together with the expression of TGF-β1, Smad2/3 and Bax, but the average expression of Smad7 and Bcl-2 had increased significantly.Conclusion:Regular aerobic exercise can relieve the renal dysfunction seen in spontaneous hypertension, at least in rats, by inhibiting renal fibrosis and apoptosis.
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Objective:To explore the effect of supplementing stem cell therapy with aerobic exercise in left ventricle remodeling after myocardial infarction.Methods:Sixty 6-week-old male Wistar rats had acute myocardial infarction induced by ligation of the anterior descending coronary artery. They were then randomly divided into a model group, a stem cell group, an exercise group and an observation group. Another ten healthy Wistar rats formed a sham operation group. The rats in the stem cell and observation groups were infused with a suspension of bone marrow mesenchymal stem cells through the tail vein. Beginning four weeks later, the exercise and observation groups underwent 60 minutes of aerobic treadmill exercise 5 days per week for 8 weeks. At the beginning and end of the eight weeks the rats′ exercise performance was evaluated using a graded treadmill exercise test. And after the last training session cardiac structure and function were detected using ultrasound imaging. Tissue was then collected from the left ventricles and the collagen volume fractions were calculated. The expression of myocardial brain natriuretic peptide (BNP), heavy chain β-myosin (β-MHC) and α-MHC mRNA was detected using real-time fluorescence quantitative PCRs.Results:Compared with the sham operation group, the time and distance to exhaustion shortened significantly in the model group, with a significant decrease in the average maximum running speed, left ventricle ejection fraction (LVEF), left ventricle shortening fraction (LVFS), expression of α-MHC and the α-MHC/β-MHC ratio. There was a significant increase in the average resting heart rate, collagen volume fraction, expression of BNP and β-MHC in the model group. Compared with the model group, there was a significant increase in the average LVEF and LVFS of the stem cell group as well as in the time and distance to exhaustion, maximum running speed, expression of α-MHC and in the α-MHC/β-MHC ratio of the observation group, but a significant decrease in the average collagen volume fraction of the stem cell group compared with the observation group, together with the resting heart rate, collagen volume fraction, the expression of BNP and of β-MHC. Compared with the stem cell group, the observation group showed a significant increase in the average time and distance to exhaustion, maximum running speed, expression of α-MHC and the α-MHC/β-MHC ratio, with a significant decrease in the average resting heart rate, collagen volume fraction, expression of BNP and β-MHC.Conclusion:Aerobic exercise or stem cell therapy alone can inhibit left ventricular remodeling and improve cardiac function after myocardial infarction, at least in rats. The combination of the two treatments has a synergistic effect and can further enhance the effect of stem cell therapy.
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Objective:To investigate the risk factors of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in plain-sand areas and loess hilly areas of Gansu province.Methods:A total of 1 599 T2DM patients who participated in chronic disease and risk factors monitoring and basic public health service management were selected by multi-stage stratified random sampling method in the sandy plain areas and loess hilly areas of Gansu province. Questionnaire survey, physical measurement and laboratory tests were performed. Multivariate binary logistic model was used to analyze the influencing factors.Results:The prevalence of DKD was 22.1% (174/787) among T2DM patients in the sandy plain areas and 19.1%(155/812) in the loess hilly area, respectively. Hypertension ( OR=3.022), hyperuricemia ( OR=2.114) and HbA1c≥7%( OR=2.231) were the risk factors for DKD in the plain-sand areas, and the risk of DKD increased with age. In the loess hilly areas, female sex ( OR=0.379) was the protective factor for DKD; while duration of disease≥10 years ( OR=2.476), hyperuricemia ( OR=1.907), HbA1c≥7% ( OR=1.927) were the risk factors for DKD; and the risk of DKD increased with the increase of age, and decreased with the increase of per capita monthly income. Conclusions:The prevalence of DKD and its influencing factors are different between sandy plain areas and loess hilly areas in Gansu province. The prevention and treatment of hypertension should be given more attention in sandy plain areas. In addition, the screening of DKD should be conducted among T2DM patients, particularly for those with old age, hyperuricemia and HbA1c≥7% in both areas of the province.