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Acute respiratory distress syndrome (ARDS), a common respiratory critical illness with multiple causes, is associated with high mortality. The high degree of heterogeneity may be the reason why it is lack of highly specific and sensitive biological biomarkers. Therefore, it is an urgent need to explore biomarkers, perform phenotypic analysis and establish risk stratification model for diagnosis, prognosis, and treatment of ARDS. Endothelial cells specificity molecular-1 (ESM-1, endocan), is a soluble dermatan sulfate proteoglycan, and be involved in regulating biological behaviors such as cell proliferation, differentiation and migration. Numerous studies have confirmed that ESM-1 is closely related to inflammation, endothelial activation and dysfunction. However, the role of ESM-1 in the initiating and developing process of ARDS is still unclear. To provide a scientific basis for its clinical applications in ARDS, such as early prognosis assessment and timely prevent strategies, this paper focuses on the biological properties and the clinical value of ESM-1 as a potential biomarker for ARDS.
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Objective:To describe the real experience of the elderly who has felt happy during the time they stayed at nursing homes, and discuss the meaning which is behind their experience during the COVID-19 pandemic, to provide scientific basis for improving their subjective well-being.Methods:Qualitative explanatory phenomenological analysis methods, and semi-structured in-depth interviews were used to interview 21 elderly people living in Guangzhou Songhe Nursing Home. Data analysis and subject extraction were carried out with reference to the Colaizzi 7-step analysis.Results:The real experience of subjective well-being of the elderly in nursing homes has six themes: be satisfied with the nursing home management service, be satisfied with harmonious interpersonal relationship, be satisfied with good health, be satisfied with family support, grateful and expectations for the social support system, be satisfied with and grateful for the epidemic prevention work during the COVID-19 epidemic.Conclusions:The elderly who live in a nursing home with perfect management and service, care for each other, are healthy, receive family and social support, are grateful, and understand family and social support will be more likely to feel happy. Improving the subjective well-being of the elderly in nursing homes requires the coordination and support of nursing homes, the elderly, families, society and other aspects.
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Mycena subpiligera, a new taxon in sect. Fragilipedes that can strongly enhance the germination efficiency of Gastrodia elata seeds, was discovered in subtropical areas of China. As revealed by a morphological comparison with related Mycena species as well as maximum likelihood (ML) and Bayesian phylogenetic analyses based on sequences of the internal transcribed spacer (ITS) and the large subunit (LSU) regions of nuclear ribosomal RNA, the new taxon can be distinguished from phenotypically similar and phylogenetically related species. Optimal cultural conditions for M. subpiligera basidiomata are reported, and the germination rate of the new species is compared with that of M. citrinomarginata.
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Objective@#To investigate the genotypes and prognosis of infants with definitive diagnosis of inherited metabolic diseases during neonatal screening in Zhejiang Province from 2009 to 2021, so as to provide insights into the management of birth defects.@*Methods@#The medical records of infants with definitive diagnosis of inherited metabolic diseases by tandem mass spectrometry during neonatal screening in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The prevalence, genotypes and prognosis of inherited metabolic diseases were analyzed. @*Results@#A total of 1 038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with an overall incidence rate of 1/4 535. There were 400 infants with amino acid metabolic disorders (AAD), 342 infants with fatty acid oxidation metabolic disorders and 296 infants with organic acid metabolic disorders (OAD), with incidence of 1/11 767, 1/13 763 and 1\15 902, respectively. There were 32 types of diseases, including 13 types of AAD, 8 types of FAOD and 11 types of OAD identified, and phenylketonuria and tetrahydrobiopterin deficiency (PKU/BH4D), primary carnitine deficiency (PCD) and methylmalonic academia (MMA) were detected as the most common forms of AAD, FAOD and OAD, with incidence of 1/20 827, 1/24 262 and 1\49 030, respectively. A total of 789 infants received genetic testing (76.01%), and genetic testing was performed among 70.00% of infants with AAD, 83.04% of infants with FAOD and 76.01% of infants with OAD. The c.728G >A (p.R243Q) variant was the most common mutation in infants with PKU (29.17%), c.1400C>G (p.S467C) variant was the most common mutation in infants with PCD (33.46%), c.609G>A (p.W203X) variant was the most common mutation in infants with combined MMA (40.00%), and c.1663G>A (p.A555T) variant was the most common mutation in infants with MMA (17.86%). Among the 997 infants (96.05%) with successful follow-up, 973 infants (93.74%) had normal intelligence and physical developments, and 41 infants died (3.95%), including 9 deaths due to AAD, 15 deaths due to FAOD and 17 deaths due to OAD. @*Conclusions @#The incidence of PKU, PCD and MMA was high among infants with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with c.728G>A (p.R243Q), c.1400C>G (p.S467C) and c.609G>A (p.W203X) variants as common gene mutations, respectively. Most infants with inherited metabolic diseases had a favorable prognosis; however, the mortality of OAD was relatively high.
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Objective: To explore the relationship between bisphenol A (BPA) exposure and obesity/overweight in children and adolescents through Dose-response Meta analysis. Methods: Articles published up to September 1st 2021 were systematically searched in PubMed, Web of science, Scopus, Embase, Cochrane library, CNKI, Wanfang databases and VIP Chinese Science and Technology Journal by using "bisphenol A" "BPA" "obesity" "weight" "fat""overweight" "body mass index" "BMI" "waist circumference" (both in English and in Chinese) as keywords. Use Stata 15.1 software to calculate the pooled OR (95%CI), perform heterogeneity test, subgroup analysis, sensitivity analysis, publication bias and the exposure-response relationship fitting. Results: A total of 9 English articles were included from 1 948 articles retrieved, including 8 articles from American and 1 article from China. 15 614 children/adolescents and 3 446 obese/overweight cases were further used for Meta-analysis of dose-response relationship. Meta-analysis results showed that there was heterogeneity among the highest dose groups in different studies(I2=52.1%, P=0.033). The random effect model-analysis found that compared with those in the lowest group, the OR(95%CI) for those in the highest group of urine BPA was 1.56(1.18-1.94)for the risk of obesity/overweight in children and adolescents, but there was no linear or nonlinear dose-response relationship. Sensitivity analyses showed that the results were robust, Egger's test(P=0.263) and Begg's test(P=0.348) showed that there was no publication bias. Conclusion: Bisphenol A exposure may increase the risk of obesity/overweight epidemics in children and adolescent.
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Adolescent , Child , Humans , Benzhydryl Compounds , Obesity/epidemiology , Overweight/epidemiology , PhenolsABSTRACT
To explore the biofilm inhibitory efficacy of perifosine against Pseudomonas aeruginosa (P. aeruginos) and its mechanisms. Twenty-fourwell plate was used to form biofilms at the bottom and crystal violet staining was used to determine the biofilm inhibitory effects of perifosine against P. aeruginosa, the wells without perifosine was set as control group. Glass tubes combined with crystal violet staining was used to detect the gas-liqud interface related bioiflm inhibitory effects of perifosine, the wells without perifosine was set as control group. Time-growth curved was used to detect the effects of perifosine on the bacteial planktonic cells growth of P. aeruginosa, the wells without perifosine was set as control group. The interaction model between perifosine and PqsE was assessed by molecular docking assay. The inhibitory effects of perifosine on the catalytic activity of PqsE was determined by detection the production of thiols, the wells without perifosine was set as control group. Binding affinity between perifosine and PqsE was detected by plasma surface resonance. The biofims at the bottom of the microplates and air-liquid interface were effectively inhibited by perifosine at the concentration of 4-8 μg/ml. There was no influence of perifosine on the cells growth of P. aeruginosa. The resuts of molecular docking assay indicates that perifosine could interacted with PqsE with the docking score of -10.67 kcal/mol. Perifosine could inhibit the catalytic activity of PqsE in a dose-dependent manner. The binding affinity between perifosine and PqsE was comfirmed by plasma surface resonance with KD of 6.65×10-5mol/L. Perifosine could inhibited the biofilm formation of P. aeruginosa by interacting with PqsE.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Biofilms , Molecular Docking Simulation , Phosphorylcholine/analogs & derivatives , Pseudomonas aeruginosa/metabolism , Quorum SensingABSTRACT
Objective: To observe the safety of the Song-Relaxing and Zhen-Vibrating abdomen manipulation in treating patients with prediabetes and its effects on blood glucose and lipid metabolism.Methods: One hundred and two patients with prediabetes were divided into a manipulation group and a control group according to the random number table method, with 51 cases in each group. All patients received the general behavioral intervention for prediabetes, with additional Song-Relaxing and Zhen-Vibrating abdomen manipulation in the manipulation group and oral metformin hydrochloride tablets in the control group. Both groups received the intervention for six months. Results: Fourteen patients dropped out during the treatment, and a total of 88 patients completed the trial, including 45 cases in the manipulation group and 43 cases in the control group. After the treatment, the prediabetes control rate was 93.3% in the manipulation group and 74.4% in the control group, and the difference between the two groups was statistically significant (P<0.05); no patient in the manipulation group progressed to diabetes, while the rate of conversion to diabetes in the control group was 6.9%, with a significant difference between the two groups (P<0.05). After the treatment, the body mass index (BMI), glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour postload plasma glucose (2hPG) level during an oral glucose tolerance test (OGTT), fasting insulin (FINS), homeostasis model assessment-2 of insulin resistance (HOMA2-IR), total cholesterol (TC), and triglycerides (TG) decreased in both groups versus baseline, with significant differences within the groups; the levels of all indicators were lower in the manipulation group than in the control group (P<0.05), and the differences between the two groups were more prominent at the sixth month (P<0.01). At the sixth month, the high-density lipoprotein cholesterol (HDL-C) in the manipulation group was increased, while there was no significant change in the control group. In the control group, three patients reported mild gastrointestinal reactions at the initial dosing, which improved after medication adjustment. No other adverse events were observed in either group. Conclusion: Both metformin hydrochloride tablets and the Song-Relaxing and Zhen-Vibrating abdomen manipulation can improve blood glucose and lipid metabolism and reduce insulin resistance and clinical discomfort in patients with prediabetes, but the Song-Relaxing and Zhen-Vibrating abdomen manipulation has higher efficacy and safety.
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We report the diagnosis and treatment of a case of reversible cerebral vasoconstriction syndrome characterized by postpartum thunderclap headache. The patient experienced a thunderclap headache on the second day after delivery, which gradually worsened. On postpartum day 4, she presented with sudden convulsion and hypertension on admission on May 19, 2020, and was initially diagnosed with postpartum eclampsia. We confirmed the diagnosis of reversible cerebral vasoconstriction syndrome based on the results of cranial magnetic resonance angiography (MRA) and other examinations and the consultation with neurologists. After antihypertensive and spasmolytic treatment, the patient's blood pressure returned to normal, and she was discharged on postpartum day 8. Reexamination with cranial MRA at 50 + days after delivery indicated that the cerebral vasospasm was relieved. No severe headaches or convulsions were observed during follow-up till June 2021.
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Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:An ambispective study was conducted on 123 AD patients treated with dupilumab in Department of Dermatology, the Second Xiangya Hospital of Central South University from July 2020 to March 2022, clinical data were collected, and efficacy and safety of dupilumab were evaluated. Primary outcomes included scores of eczema area and severity index (EASI) , patient-oriented eczema measure (POEM) , peak pruritus numerical rating scale (NRS) and dermatology life quality index (DLQI) before and after 4-, 8-, 12- and 16-week treatment, and adverse reactions and events were recorded. Comparison of scores before and after treatment was performed using paired t test or repeated measures analysis of variance, Mann-Whitney U test was used for the comparison of efficacy among patients with different types of skin lesions or different IgE levels, and multiple regression model based on robust standard errors was used to analyze factors influencing the efficacy. Results:Among the 123 AD patients, 107 were enolled into the efficacy analysis, and 85 (79.44%) completed at least 4 weeks of treatment, including 6 (7.06%) achieving EASI75 and 23 (27.06%) achieving EASI50, and the EASI, NRS, POEM, DLQI scores (10.41 ± 6.72, 4.12 ± 1.74, 8.60 ± 4.29, 7.81 ± 4.38, respectively) significantly decreased compared with those before treatment (18.08 ± 10.69, 7.21 ± 2.01, 16.88 ± 5.74, 12.95 ± 5.95, respectively; all P < 0.001) in the 85 patients. Among the 107 patients, 47 (43.93%) completed at least 16 weeks of treatment. Among the 47 patients, 23 (82.14%) of 28 adults and 17 (89.47%) of 19 adolescents and children achieved 75% or greater improvement in EASI score; the EASI, NRS, POEM and DLQI scores before the treatment all significantly differred from those 4, 8, 12, 16 weeks after the treatment (all P < 0.001) , and all the scores were significantly lower at weeks 4, 8, 12 and 16 than at the previous adjacent time points (all P < 0.05) . At week 4 during the treatment, the EASI improvement rate was significantly lower in the AD patients with prurigo nodularis than in those without ( U = 151.00, P = 0.006) , while there was no significant difference in the EASI improvement rate between the AD patients with xeroderma and those without ( P > 0.05) ; at week 16 during the treatment, there was no significant difference in the EASI improvement rate between patients with prurigo nodularis or xeroderma and those without (both P > 0.05) . Multiple regression analysis based on robust standard errors at week 16 showed that the improvement degree in the EASI score was not correlated with the type of skin lesions ( β = 3.20, P = 0.075) , but correlated with age ( β = -0.22, P = 0.030) , whether patients were in adulthood ( β = 9.54, P = 0.049) , immediate family history ( β = 7.46, P = 0.017) ; the improvement degree in the NRS score was correlated with the type of skin lesions ( β = 0.55, P = 0.032) , age ( β = -0.04, P = 0.033) , weight ( β = -0.05, P = 0.020) , whether patients were in adulthood ( β = 2.06, P = 0.003) and whether patients received combined treatment with antihistamines ( β = -1.91, P = 0.001) . Adverse reactions: among the 123 patients, 6 (4.88%) developed conjunctivitis, and 2 (1.63%) developed facial erythema. Adverse events: vitiligo-like changes occurred on the right forehead of 1 patient, and 3 patients discontinued the treatment with dupilumab due to Henoch-Sch?nlein purpura, distal axonal damage in peripheral nerves in both upper limbs, and epilepsy, respectively. The causal relationship between these adverse events and dupilumab was unclear. Conclusion:Dupilumab is effective in the treatment of AD with high overall safety, and can serve as a new treatment option for AD patients with an unsatisfactory response to traditional treatment.
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@#Due to the complex components of polysorbate 80, analysis is time-consuming and labor-intensive, so there is an urgent need to find a method for rapid analysis of polysorbate 80 components.In this study, 10 batches of samples collected from 3 domestic and foreign enterprises were analyzed by UHPLC-HRMS, with the being further results were analyzed by the ExcipientProfiler software and supplemented by the extended database.The results showed that the ExcipientProfiler software could quickly identify the [M+Na]+ peak in the mass spectrogram, and obtain the information of component distribution, the numbers of components and the degree of polymerization of the sample.Meanwhile, the numbers of components obtained by the ExcipientProfiler software could be used to distinguish the injection grade samples from the ordinary grade samples by systematic clustering analysis.In addition, it was found through further supplement that the sample contained other fatty acid ester components by manually searching the relevant extended database.The polyoxyethylene sorbitan tetraoleate components were found in the sample according to the analysis of mass spectrum data.Therefore, although this method is fast and simple, it is necessary to add polyoxyethylene sorbitan tetraoleate components and other fatty acid ester components to further supplement the information in the ExcipientProfiler software, so that it can be better used for the analysis of polysorbate 80.
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Four compounds were isolated from the 70% EtOH extract of Ardisia crispa by using various chromatographic techniques, including silica gel, ODS and semi-preparative HPLC. The structures of 1-4 were elucidated based on physicochemical properties and spectroscopic data. These compounds were defined as crispalactone A (1), (+)-pinoresinol (2), 3,5-dimethoxy-4- hydroxyphenol-1-O-β-D-glucopyranoside (3) and (+)-schizandriside (4). Compound 1 is a new γ-valerolactone derivative, and compounds 2-4 are firstly isolated from Ardisia crispa.
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Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.
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OBJECTIVE To isolate and ide ntify the chemical constituents of the root of Ardisia virens and preliminarily evaluate the in vitro anti-inflammatory activity of the compounds. METHODS The ethyl acetate extraction part from 70% ethanol extract of the root of A. virens were separated and purified by silica gel column chromatography ,ODS column chromatography , etc. The structures of the compounds were identified according to physical and chemical properties and spectral data. The inflammation model of RAW 264.7 cells was induced by lipopolysaccharide ,and anti-inflammatory activity of the compound was investigated by MTT assay. RESULTS A total of 11 compounds were isolated from the ethyl acetate extraction part ,and were identified as cyclamiretin A (1),α-spinasterol (2),(3S,5R,6S,7E)-3,5,6-trihydroxy-7-megastigmen-9-one (3), (+)-angelicoidenol(4),octadeca-dienoic acid- 2,3-dihydroxypropyl ester (5),α-linolenic acid (6),glycerol monooleate (7),5, 5′-(4,7-hexadecadlene-1,16-diyl)bisresorcinol(8),1-(3,5-dihydroxyphenyl)heptan-1-one(9),5-heptylresorcinol and (10) 5-n-nonylresorcinol(11). The in vitro anti-inflammatory results showed that 80,40,20,10,5 μg/mL of compounds 2,8,9 and 10 could reduce the cell survival rate in different degrees. CONCLUSIONS Compounds 1-11 are isolated from this plant for the first time,and compound 8 is a new natural product. Compound 2,8,9 and 10 show certain anti-inflammatory activity in vitro .
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OBJECTIVE@#To conduct eukaryotic expression of the leucine-rich repeat containing 15 (LRRC15), a differentially expressed protein in excretory secretory antigens of Taenia solium cysticercus, and predict its antigen epitope.@*METHODS@#The molecular weight, stability, amino acid sequence composition, isoelectric point and T lymphocyte epitope of the LRRC15 protein were predicted using the bioinformatics online softwares ExPASy-PortParam and Protean. The full-length splicing primers were designed using PCR-based accurate synthesis, and the LRRC15 gene was synthesized. The recombinant pcDNA3.4-LRRC15 plasmid was constructed and transfected into HEK293 cells to express the LRRC15 protein. In addition, the LRRC15 protein was characterized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting.@*RESULTS@#The recombinant pcDNA3.4-LRRC15 plasmid was successfully constructed, which expressed the target LRRC15 protein with an approximately molecular weight of 70 kDa. Bioinformatics prediction with the ExPASy-PortParam software showed that LRRC15 was a hydrophilic protein, which was consisted of 644 amino acids and had a molecular weight of 69.89 kDa and an isoelectric point of 5.6. The molecular formula of the LRRC15 protein was C3073H4942N846O953S28 and had an instability coefficient is 50.3, indicating that LRRC15 was an instable protein. Bioinformatics prediction with the Protean software showed that the dominant T-cell antigen epitopes were located in 292 to 295, 353 to 361, 521 to 526 and 555 to 564 amino acids of the LRRC15 protein, and the T-cell antigen epitopes with a high hydrophilicity, good flexibility, high surface accessibility and high antigenicity index were found in 122 to 131, 216 to 233, 249 to 254, 333 to 343, 358 to 361, 368 to 372, 384 to 386, 407 to 412, 445 to 450, 469 to 481, 553 to 564, 588 to 594, 607 to 617 and 624 to 639 amino acids. Following transfection of the recombinant pcDNA3.4-LRRC15 plasmid into HEK293 cells, SDS-PAGE and Western blotting identified LRRC15 proteins in cell secretory culture media, cell lysis supernatants and sediments. The LRRC15-His fusion protein was purified from the cell culture medium, and SDS-PAGE identified a remarkable band at approximately 70 kDa, while Western blotting successfully recognized the band of the recombinant LRRC15 protein.@*CONCLUSIONS@#The eukaryotic expression and antigen epitope prediction of the LRRC15 protein in the excretory secretory antigens of T. solium cysticercus have been successfully performed, which provides insights into further understandings of its biological functions.
Subject(s)
Animals , Humans , Amino Acids , Antigens, Helminth/genetics , Cysticercus/genetics , Epitopes/genetics , Eukaryota , HEK293 Cells , Leucine-Rich Repeat Proteins , Membrane Proteins , Taenia solium/geneticsABSTRACT
Objective: To investigate the role and mechanism of tumor-derived mesenchymal stem cells in regulating the M2 polarization of macrophages within gastric cancer microenvironment. Methods: Gastric cancer tissues and the adjacent non-cancerous tissues were collected from patients underwent gastric cancer resection in the First People's Hospital of Lianyungang during 2018. In our study, THP-1-differentiated macrophages were co-cultured with gastric cancer-derived mesenchymal stem cells (GC-MSCs). Then, the M2 subtype-related gene, the markers expressed on cell surface and the cytokine profile were analyzed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry and Luminex liquid chip, respectively. The key cytokines mediating the inducing effect of GC-MSCs on macrophage polarization into the M2 subtype were detected and screened by Luminex liquid chip, which were further confirmed by the neutralizing antibody test. The expressions of macrophage proteins involved in M2 polarization-related signaling pathways under the different co-culture conditions of GC-MSCs were detected by western blot. Results: In Mac+ GC-MSC-culture medium (CM) group, the expression levels of Ym-1 and Fizz-1 (1.53±0.32 and 13.22±1.05, respectively), which are markers for M2 subtype, were both significantly higher than those of Mac group (1.00±0.05 and 1.21±0.38, respectively, P<0.05). The level of iNOS in Mac+ GC-MSC-CM group (0.60±0.41) was significantly lower than that of Mac group (1.06±0.38, P=0.023). In Mac+ GC-MSC-Transwell (TW) group, the expression levels of Ym-1 and Fizz-1 (1.47±0.09 and 13.16±2.77, respectively) were both significantly higher than those of Mac group (1.00±0.05 and 1.21±0.38, respectively, P<0.05). The level of iNOS in Mac+ GC-MSC-CM group (0.56±0.03) was significantly lower than that of Mac group (1.06±0.38, P=0.026). The ratios of CD163(+) /CD204(+) cells in Mac+ GC-MSC-CM and Mac+ GC-MSC-TW groups (3.80% and 4.40%, respectively) were both remarkably higher than that of Mac group (0.60%, P<0.05). The expression levels of IL-10, IL-6, MCP-1 and VEGF in Mac+ GC-MSC-CM group were (592.60±87.52), (1 346.80±64.70), (11 256.00±29.03) and (1 463.90±66.67) pg/ml, respectively, which were significantly higher than those of Mac group [(41.03±2.59), (17.35±1.79), (5 213.30±523.71) and (267.12±12.06) pg/ml, respectively, P<0.05]. The levels of TNF-α, IP-10, RANTES and MIP-1α were (95.57±9.34), (410.48±40.68), (6 967.30±1.29) and (1 538.70±283.04) pg/ml, which were significantly lower than those of Mac group [(138.01±24.31, (1 298.60±310.50), (14 631.00±4.21) and (6 633.20±1.47) pg/ml, respectively, P<0.05]. The levels of IL-6 and IL-8 in GC-MSCs [(11 185.02±2.82) and (12 718.03±370.17) pg/ml, respectively] were both strikingly higher than those of MSCs from adjacent non-cancerous gastric cancer tissues [(270.71±59.38) and (106.04±32.84) pg/ml, repectively, P<0.05]. The ratios of CD86(+) cells in Mac+ IL-6-blocked-GC-MSC-CM and Mac+ IL-8-blocked-GC-MSC-CM groups (28.80% and 31.40%, respectively) were both higher than that of Mac+ GC-MSC-CM group (24.70%). Compared to Mac+ GC-MSC-CM group (13.70%), the ratios of CD204(+) cells in Mac+ IL-6-blocked-GC-MSC-CM and Mac+ IL-8-blocked-GC-MSC-CM groups (9.90% and 8.70%, separately) were reduced. The expression levels of p-JAK2 and p-STAT3, which are proteins of macrophage M2 polarization-related signaling pathway, in Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, respectively) were significantly higher than those of Mac group (0.50±0.01 and 0.82±0.01, respectively, P<0.05). The expression levels of p-JAK2 in Mac+ IL-6-blocked-GC-MSC-CM group (0.47±0.02) were significantly lower those that of Mac+ GC-MSC-CM group (0.86±0.01, P<0.05). The expression levels of p-JAK2 and p-STAT3 in Mac+ IL-8-blocked-GC-MSC-CM group (0.50±0.01 and 0.85±0.01, respectively) were both significantly lower than those of Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, P<0.05). The expression levels of p-JAK2 and p-STAT3 in Mac+ IL-6/IL-8-blocked-GC-MSC-CM group (0.37±0.01 and 0.65±0.01, respectively) were both significantly lower than those of Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, P<0.05). Conclusion: GC-MSCs promote the activation of JAK2/STAT3 signaling pathway in macrophages via high secretions of IL-6 and IL-8, which subsequently induce the macrophage polarization into a pro-tumor M2 subtype within gastric cancer microenvironment.
Subject(s)
Humans , Interleukin-6/genetics , Interleukin-8/pharmacology , Janus Kinase 2/metabolism , Macrophages/metabolism , Mesenchymal Stem Cells , STAT3 Transcription Factor/metabolism , Signal Transduction , Stomach Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
Objective:To establish a quantitative detection method for the main components of dust mite allergens Der p 1, Der p 2 specific immunoglobulin E (sIgE) by using the nano-magnetic particle chemiluminescence immunoassay.Methods:The performance indexes of the established method were evaluated after setting up and optimizing the chemiluminescence detection system and immune reaction conditions of sIgE for dust mite allergen. Serum sIgE levels of 50 suspected allergic patients with dust mite were determined by this chemiluminescence method. At the same time, this method was compared with the Phadia kit and the consistency was analyzed by Kappa test. Results:The optimal amount of magnetic beads was 25 μg, the optimal reaction buffer (pH=7.4) contained 0.1 mol/L Tris-HCl and 0.25%( W/ W) casein, the optimal coating solution contatined 20 mmol/L phosphate buffer (PB) and 1%( W/ W) bovine serum albumin (BSA), and the luminescence enhancement solution contained 0.05%( V/ V) Triton X-100. The two-step immunoreaction was adopted, and the detection could be completed with 20 μl sample at the optimal reaction temperature of 37℃. The limit of detection (LOD) of the established nano-magnetic particle chemiluminescence system in detecting Der p 1 and Der p 2 sIgE antibodies were both less than 0.01 kU/L, with the linear range of 0.2-100.0 kU/L, the precision of less than 7%, and the cross contamination rate of 0.19% and 0.21%. Compared with the Phadia system, the positive and negative coincidence rate of Der p 1 were 78.0%(32/41) and 9/9 with good consistency ( Kappa=0.65, P=0.008), and the positive and negative coincidence rate of Der P 2 were 93.3%(28/30) and 85.0%(17/20) with good consistency ( Kappa=0.79, P=0.003). Conclusion:The nano-magnetic particle chemiluminescence immunoassay is successfully established for detecting dust mite allergen sIgE, which has good detection performance and good consistency with Phadia system.
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Objective:To investigate the diagnosis and treatment of posterolateral elbow dislocation in children.Methods:A total of 19 children with posterolateral elbow dislocation were diagnosed and treated at Department of Children's Orthopedics, Sichuan Orthopedic Hospital from April 2018 to April 2021. They were 12 boys and 7 girls, aged from 7 to 14 years (average, 10.9 years). Internal epicondyle avulsion fracture of the humerus was complicated in 11 cases, external epicondyle avulsion fracture of the humerus in 5 cases, capitulum avulsion fracture of the humerus in 3 cases, and fracture of the ulna coronoid process in 4 cases. After evaluation of the elbow stability, stable elbows were treated nonsurgically while the unstable ones complicated with fracture were treated with open reduction and internal fixation. After treatment, the injured limbs were fixated with elbow flexion 90° in forearm pronation position for 4 to 6 weeks.Results:In this group, 4 children received nonsurgical treatment and 15 ones were treated surgically. Internal epicondyle fractures of the humerus were treated by open reduction and internal fixation with Kirschner wire and hollow screws, and external epicondyle avulsion fractures or capitulum avulsion fractures of the humerus by suture fixation with Kirschner wire tension band or absorbable anchors. Three coronal process fractures were treated with plate internal fixation but one coronal process fracture was not treated with internal fixation. All the children were followed up for 6 to 30 months (average, 13.3 months). The last follow-up showed that fractures got united in all children, with no ectopic ossification, fine anatomical relationship of the elbow, and no recurrence of elbow dislocation or instability. The last follow-up showed that the Mayo elbow performance scores (MEPS) ranged from 75 to 100 points, averaging 93.2 points.Conclusions:In the treatment of posterolateral elbow dislocation in children, the key point is to rebuild the stability of the elbow. Non-surgical treatment is recommended for cases of a stable elbow with posterolateral rotation and dislocation while surgical treatment for cases of an unstable elbow because surgery leads to fine functional recovery and efficacy in children.
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Objective:To investigate the clinical value of contrast-enhanced ultrasonography in the diagnosis of inflammatory hepatocellular adenoma.Methods:100 patients with inflammatory hepatocellular adenoma who received treatment in the Department of Oncology, Zhejiang Quhua Hospital, between March 2018 and March 2021, were included in this study. These patients were divided into < 5 cm group (control group, n = 65) and ≥ 5 cm group (observation group, n = 35) according to maximum tumor diameter. Routine ultrasonography and contrast-enhanced ultrasonography findings were compared between the two groups. Results:Pathological findings and immunohistochemical staining results confirmed all patients had inflammatory hepatocellular adenoma. There were 65 patients with maximum tumor diameter < 5 cm in the control group and 35 patients with maximum tumor diameter ≥ 5 cm in the observation group. Routine ultrasonography findings revealed there were no significant differences in internal echo, border, shape, and blood flow distribution between control and observation groups ( χ2 = 0.45, 0.08, 3.12, 3.54, all P > 0.05). In the control group, 56 (86.15%) patients had a uniform echo and 9 (13.85%) patients had an uneven echo. In the observation group, 19 (54.29%) patients had a uniform echo and 16 (45.71%) patients had an uneven echo. There were significant differences in the number of patients having a uniform echo or an uneven echo between the two groups ( χ2 = 12.32, P < 0.05). There were no significant differences in contrast-enhanced ultrasonography results in terms of arterial phase enhancement mode, portal phase enhancement performance, delayed phase enhancement performance, and presence of a vessel sign under the capsule between the two groups ( χ2 = 0.65, 0.40, 1.75, 2.07, all P > 0.05). In the control group, 55 (84.62%) patients had a uniformly contrast-enhanced area, and 10 (15.38%) patients had a non-uniformly contrast-enhanced area, in the arterial phase at the peak intensity. In the observation group, 16 (45.71%) patients had a uniformly contrast-enhanced area, and 19 (54.29%) patients had a non-uniformly contrast-enhanced area, in the arterial phase at the peak intensity. There was a significant difference between the two groups ( χ2 = 16.52, P < 0.05). No patients from the control group had an internal perfusion defect, and 12 (34.29%) patients from the observation group had an internal perfusion defect. There was significant difference in the number of patients having an internal perfusion defect ( χ2 = 25.32, P < 0.05). High contrast enhancement in the arterial phase appeared in two groups. Conclusion:Contrast-enhanced ultrasonography can display the imaging features of inflammatory hepatocellular adenoma, which reflects the hemodynamic differences among foci of different sizes and helps diagnose and treat inflammatory hepatocellular adenoma.
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Objective:To observe the application effect of simulation medicine teaching in clinical practice teaching of respiratory department.Methods:A total of 96 five-year undergraduate students of clinical medicine specialty from Batch 2018 were randomized into in two groups in average. The traditional teaching group conducted bedside teaching according to traditional teaching outline, and the simulation medicine group used simulated medical teaching method. The performances of theoretical knowledge and skill operations and the teaching satisfaction with the department were evaluated between the two groups. SPSS 22.0 was used for t test and chi-square test. Results:There was no significant difference in theoretical knowledge between the two groups, but the results of skill operation test and satisfaction with the department of the simulation medicine group were significantly better than those of the traditional teaching group, and the difference was statistically significant [(80.92±5.99) vs. (87.71±4.95), P<0.050; χ2=26.14, P<0.05]. Conclusion:Simulation medicine teaching is better than traditional teaching in clinical practice teaching of respiratory department, which can improve students' clinical skills and operation level, cultivate good clinical thinking for students, and improve their learning interests.
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Objective To evaluate the characteristics of exposure to micro- and nano-plastics (MPs) via food ingestion and inhalation among Chinese children including 6-7 years old school children in Pudong New Area of Shanghai. Methods Articles published until March 2021 were searched on PubMed, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang and Weipu databases. The exposure levels of MPs by food ingestion and inhalation pathways were estimated by referring to the Chinese children food consumption and breathing rates data. The characteristics of children’s exposure to MPs in China were compared with that in the United States. In addition, the consumption of bottled water, tap water and salt intake among children aged 6-7 years was determined in a cohort of children and adolescents in Pudong New Area of Shanghai. The characteristics of exposure to MPs through food intake and inhalation among them were investigated. Results A total of 5 786 samples from 38 studies were retrieved. Annual intake of MPs among Chinese children was estimated to range from 159 400 to 204 637 MPs from food ingestion, depending on age and sex. When inhalation exposure is also considered, the annual MPs intake increased to 164 635 to 213 032 MPs, which were larger than the values in American persons. Ingestion of MPs posed the largest health risk to male Chinese adults. With the questionnaire survey data, the estimated annual total exposure amount through food intake alone is 116 272‒120 334 MPs for 6 to 7 years old school children in Pudong New Area. With addition of inhalation exposure, the annual total exposure amount is 121 300‒125 983 MPs, which is lower than the average exposure level in the whole country. The discrepancy could be mainly due to the different drinking habits between the local children and others. Overall, tap drinking water, seafood,bottled water, and air represented four substantial vectors of daily MPs exposure in Chinese children. Conclusion Ingestion and inhalation of MPs pose higher health risk to Chinese children in comparison to American children. The level of exposure to MPs among 6 to 7 years old school children in Pudong New Area of Shanghai is lower than that in the same age group of children across the whole country. The attempt to lower the MPs levels in drinking water and seafood would represent the most effective means to help reduce the MPs exposure risk to Chinese children.