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Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.
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Objective To investigate the predictive value of serum oncogene[proliferation-related gene(C-myc),transformation gene(N-ras),silk/threonine kinase 1(PLK1),fibroblast growth factor 2(FGF2)]protein levels in patients with hepatitis B associated hepatocellular carcinoma(HCC)after hepatic arterial chemoem-bolization(TACE).Methods A total of 127 patients with hepatitis B-associated hepatocellular carcinoma ad-mitted to a hospital from July 2016 to January 2021 were selected and divided into death group and survival group according to the follow-up results.The serum oncogene C-myc,N-ras,PLK1 and FGF2 protein levels were determined by double-antibody sandwich enzyme-linked immunosorbent assay.Univariate and multivari-ate Cox analysis were used to analyze the risk factors of serum oncogene C-myc,N-ras,PLK1 and FGF2 pro-tein levels in patients with hepatitis B-associated hepatocellular carcinoma after TACE.The receiver operating characteristic curve was used to evaluate the prognostic value of the serum oncogene C-myc,N-ras,PLK1 and FGF2 protein levels,and the patients were divided into high expression group and low expression group ac-cording to the corresponding cutoff value.Kaplan-Meier survival curve was used to evaluate the prognosis of different serum oncogene C-myc,N-ras,PLK1 and FGF2 protein level.Results Multivariate Cox regression a-nalysis indicated that TNM stage Ⅲ to Ⅳ(HR=2.998,95%CI:1.239-7.257),portal vein metastasis(HR=3.737,95%CI:1.941-7.193),abdominal metastasis(HR=3.482,95%CI:1.709-7.097),Child-Pugh grade B(HR=2.587,95%CI:1.045-6.406),high serum oncogene C-myc protein level(HR=1.224,95%CI:1.090-1.374),high serum oncogene N-ras protein level(HR=1.218,95%CI:1.097-1.353),high serum oncogene PLK1 protein level(HR=1.237,95%CI:1.110-1.379)and high serum oncogene FGF2 protein level(HR=1.141,95%CI:1.060-1.228)were independent risk factors for the prognosis of hepatitis B-asso-ciated hepatocellular carcinoma patients after TACE(all P<0.05).The overall survival rate of low expression group of serum oncogene C-myc,N-ras,PLK1,FGF2 protein level was significantly higher than that of high expression group of serum oncogene C-myc,N-ras,PLK1,FGF2 protein level,the difference was statistically significant(all P<0.001).Conclusion Serum oncogene C-myc,N-ras,PLK1,FGF2 protein levels have predic-tive value for the prognosis of patients with HBV-related liver cancer after TACE.
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Objective To explore the correlation between the expression level of serum peptidylarginine deiminase type 2(PAD2)and acute physiology and chronic health evaluationⅡ(APACHE Ⅱ)scores in patients with septic shock.Methods A total of 103 patients with septic shock admitted to the First People's Hospital of Neijiang from June 2020 to June 22 were regarded as the study group.According to the severity of the condition,the APACHE Ⅱ scores were used to classify study group into mild group(n=39),moderate group(n=51)and severe group(n=13).In addition,103 healthy individuals who underwent physical examination in the hospital during the same period,whose general information matched the study group patients,were selected as the control group.Serum PAD2 expression level in patients with septic shock was determined by enzyme-linked immunosorbent assay.Spearman method was applied to analyze the correlation between serum PAD2 expression level and APACHE Ⅱ scores in patients with septic shock.Logistic regression was applied to analyze the factors affecting the severity of patients with septic shock.The diagnostic value of serum PAD2 in moderate and severe septic shock was evaluated using receiver operating characteristic(ROC)curve analysis.Results The differences in blood creatinine levels(137.52±9.01μmol/L vs 112.22±8.67μmol/L)and platelet counts(74.58±5.19 vs 86.02±5.34)×109/L between study group and control group were statistically significant(t=20.535,15.591,all P<0.05).The expression level of PAD2 in the study group(42.47±6.62 ng/ml)was higher than that in the control group(38.59±5.31 ng/ml),with significant difference(t=4.815,P<0.05).The expression level of serum PAD2 and APACHE Ⅱ scores in patients with septic shock gradually increased with the severity of the condition(F=3.777,176.582,all P<0.05).The expression level of serum PAD2 in patients with septic shock was positively correlated with APACHE Ⅱ scores(r=0.859,P<0.05).Serum creatinine(OR=1.927),PAD2(OR=1.803)and APACHE Ⅱscores(OR=1.657)were risk factors for moderate and severe septic shock(P<0.05),while platelet count(OR=0.781)was a protective factor(P<0.05).The area under the curve(AUC)of serum PAD2 in the diagnosis of moderate and severe septic shock was 0.880,and the sensitivity and specificity were 75.73%(95%CI:0.701~0.826)and 90.29%(95%CI:0.851~0.935),respectively,indicating it had high diagnostic value for moderate and severe septic shock.Conclusion The expression level of serum PAD2 was positively correlated with APACHE Ⅱ scores,and may have a good diagnostic value for moderate and severe septic shock.
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Objective:To carry out evidence-based nursing for standardized management of stress hyperglycemia in perioperative period of gastrointestinal tumor patients, and to formulate indicators, analyze obstacles and promoting factors, formulate action strategies.Methods:Guided by the Johns Hopkins evidence-based nursing model, evidence were searched, evaluated and summarized. Clinical indicators and review methods were formulated to carry out quality review. From November 2021 to April 2022, the medical staff and patients in the gastrointestinal surgery department of the First Affiliated Hospital of Anhui Medical University who met the inclusion criteria were conducted, and the incidence of compliance rate was calculated. Based on the results of the baseline review, the obstacles and contributing factors were analyzed.Results:A total of 26 pieces of best evidence were included and 14 indicators were formulated for 48 medical staff and 45 patients to clinical review, among which the compliance rate of 7 indicators was less than 60%. The main obstacle factors were lack of procedures and instruments for management of perioperative stress hyperglycemia in gastrointestinal tumor patients, lack of knowledge of medical staff, etc. The main promoting factors were organizational support, good atmosphere of medical team cooperation, strong willingness to change, etc.Conclusions:There is a big gap between the clinical practice and the best evidence of perioperative stress hyperglycemia management in patients with gastrointestinal tumor. Action strategies should be put forward for obstacles and promoting factors to promote evidence transformation.
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Objective To investigate the effect of a three-tier delirium care management process in patients with acute stroke in neurology intensive care unit(NICU).Methods A total of 50 patients with acute stroke admitted to the NICU of the Fourth Hospital of Changsha from May to September 2021 were assigned to the control group.The patients in the control group received routine NICU nursing care to prevent delirium.Another 50 patients with acute stroke admitted to the NICU from December 2021 to April 2022 were assigned to the trial group.They were managed with the three-tier delirium nursing management process on top of the routine NICU nursing care for the control group.The incidence of ICU delirium(DICU),duration of DICU,length of stay in NICU and the incidence of delirium-related adverse events were compared between the two groups.The degree of delirium and cognitive function before and after the intervention were compared between the two groups as well.Results The trial group had significantly shorter duration of DICU and NICU stay(both P<0.05)and lower incidence rate of delirium-related adverse events(P<0.05)compared to the control group.After the intervention,the trial group showed significantly lower scores on the intensive care delirium screening checklist(ICDSC)and significantly higher scores of cognitive function compared to those of the control group(both P<0.05).Conclusion The three-tier delirium nursing management process can lower the occurrence of delirium in NICU patients with acute stroke,shorten the NICU stay,reduce the safety risk in nursing,and improve the cognitive function.
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Exosome is an excellent vesicle for in vivo delivery of therapeutics, including RNAi and chemical drugs. The extremely high efficiency in cancer regression can partly be attributed to its fusion mechanism in delivering therapeutics to cytosol without endosome trapping. However, being composed of a lipid-bilayer membrane without specific recognition capacity for aimed-cells, the entry into nonspecific cells can lead to potential side-effects and toxicity. Applying engineering approaches for targeting-capacity to deliver therapeutics to specific cells is desirable. Techniques with chemical modification in vitro and genetic engineering in cells have been reported to decorate exosomes with targeting ligands. RNA nanoparticles have been used to harbor tumor-specific ligands displayed on exosome surface. The negative charge reduces nonspecific binding to vital cells with negatively charged lipid-membrane due to the electrostatic repulsion, thus lowering the side-effect and toxicity. In this review, we focus on the uniqueness of RNA nanoparticles for exosome surface display of chemical ligands, small peptides or RNA aptamers, for specific cancer targeting to deliver anticancer therapeutics, highlighting recent advances in targeted delivery of siRNA and miRNA that overcomes the previous RNAi delivery roadblocks. Proper understanding of exosome engineering with RNA nanotechnology promises efficient therapies for a wide range of cancer subtypes.
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Objective: To investigate the relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status. Methods: The demographic data and biochemical indicators of the adult population who had received physical examination in the Second Medical Center of the PLA General Hospital from January 2018 to December 2021 were collected. The subjects were divided into two groups according to the level of serum uric acid: the normal uric acid group and the hyperuricemia group. The relationship between hemoglobin (stratified into four levels of Q1 to Q4 by the quartile) and serum uric acid was quantified by using Pearson correlation and logistic regression analysis. The effects of age and glucose metabolism status on the relationship between hemoglobin and serum uric acid were analyzed. Results: A total of 33 183 adults were enrolled with age (50.6±10.0) years. The level of hemoglobin in the normal uric acid group (142.61±14.24) g/L was significantly lower than that in the hyperuricemia group [(151.79±11.24) g/L, P<0.001]. Univariate Pearson correlation analysis showed that hemoglobin was positively associated with serum uric acid (r=0.444, P<0.001). After adjusting for related confounding factors, multivariate logistic regression analysis showed that hemoglobin was associated with serum uric acid, and the OR values (95%CI) of hemoglobin Q2 to Q4 group were 1.29 (1.13-1.48), 1.42 (1.24-1.62) and 1.51 (1.32-1.72), respectively (Ptrend<0.001) when compared with hemoglobin Q1 group. Subgroup analysis and hierarchical interaction analysis suggested that with the increase of hemoglobin, the serum uric acid in the age<60 years subgroup, normal glucose subgroup and prediabetes subgroup increased gradually (Ptrend<0.05 and Pinteraction<0.001). Conclusion: The association between hemoglobin and serum uric acid in adults is affected by age and glucose metabolism status.
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Humans , Adult , Middle Aged , Uric Acid , Hyperuricemia/epidemiology , Hemoglobins , Prediabetic State , Glucose , Risk FactorsABSTRACT
Objective: To investigate the clinical characteristics of hospitalized children infected with the Omicron variant in Kunming after the withdrawal of non-pharmaceutical interventions (NPI) and analyze the risk factors of severe cases. Methods: Clinical data was retrospectively collected from 1 145 children with SARS-CoV-2 Omicron infection who were hospitalized in six tertiary grade A hospitals in Kunming from December 10th, 2022 to January 9th, 2023. According to clinical severity, these patients were divided into the general and severe SARS-CoV-2 groups, and their clinical and laboratory data were compared. Between-group comparison was performed using t-test, chi-square test and Mann-Whitney U test. Spearman correlation test and multivariate Logistic regression analysis were used to determine the risk factors of severe illness. Results: A total of 1 145 hospitalized patients were included, of whom 677 were male and 468 female. The age of these patients at visit was 1.7 (0.5, 4.1) years. Specifically, there were 758 patients (66.2%) aged ≤3 years at visit and 387 patients (33.8%) aged >3 years. Of these children, 89 cases (7.8%) had underline diseases and the remaining 1 056 cases (92.2%) had no combined diseases. Additionally, of all the patients, 319 cases (27.9%) were vaccinated with one or two doses of SARS-CoV-2 vaccine, 748 cases (65.3%) had acute upper respiratory tract infection (AURTI), and six cases died (0.5%). A total of 1 051 cases (91.8%) were grouped into general SARS-CoV-2 group and 94 cases (8.2%) were grouped into severe SARS-CoV-2 group. Compared with the general cases, the severe cases showed a lower rate of SARS-CoV-2 vaccination and younger median age, lower lymphocyte count, as well as proportions of CD8+T lymphocyte (36 cases (38.3%) vs. 283 cases (26.9%), 0.5 (2.6, 8.0) vs. 1.6 (0.5, 3.9) years, 1.3 (1.0, 2.7) ×109 vs. 2.7 (1.3,4.4)×109/L, 0.17 (0.12, 0.24) vs. 0.21 (0.15, 0.16), respectively, χ2=4.88, Z=-2.21,-5.03,-2.53, all P<0.05). On the other hand, the length of hospital stay, proportion of underline diseases, ALT, AST, creatine kinase isoenzyme, and troponin T were higher in the severe group compared to those in the general group ((11.6±5.9) vs. (5.3±1.8) d, 41 cases (43.6%) vs. 48 cases (4.6%), 67 (26,120) vs. 20 (15, 32) U/L, 51 (33, 123) vs. 44 (34, 58) U/L、56.9 (23.0, 219.3) vs. 3.6 (1.9, 17.9) U/L, 12.0 (4.9, 56.5) vs. 3.0 (3.0, 7.0) ×10-3 pg/L,respectively, t=-20.43, χ2=183.52, Z=-9.14,-3.12,-6.38,-3.81, all P<0.05). Multivariate regression analysis indicated that increased leukocyte count (OR=1.88, 95%CI 1.18-2.97, P<0.01), CRP (OR=1.18, 95%CI 1.06-1.31, P<0.01), ferritin (OR=1.01, 95%CI 1.00-1.00, P<0.01), interleukin (IL)-6 (OR=1.05, 95%CI 1.01-1.08, P=0.012), D-dimer (OR=2.56, 95%CI 1.44-4.56, P<0.01) and decreased CD4+T lymphocyte (OR=0.84, 95%CI 0.73-0.98, P=0.030) were independently associated with the risk of severe SARS-CoV-2 in hospitalized children with Omicron infection. Conclusions: After the withdrawal of NPI, the pediatric inpatients with Omicron infection in Kunming were predominantly children younger than 3 years of age, and mainly manifested as AURTI with relatively low rate of severe SARS-CoV-2 infection and mortality. Elevated leukocyte counts, CRP, ferritin, IL-6, D-dimer, and decreased CD4+T lymphocytes are significant risk factors for developing severe SARS-CoV-2 infection.
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Humans , Child , Female , Male , COVID-19 , COVID-19 Vaccines , Retrospective Studies , SARS-CoV-2 , Ferritins , Interleukin-6ABSTRACT
Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P>0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population (P<0.01), imatinib treatment group (P=0.044) and no imatinib treatment group (P<0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS (P=0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.
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Male , Female , Humans , Middle Aged , Gastrointestinal Stromal Tumors/surgery , Retrospective Studies , Antineoplastic Agents/therapeutic use , Prognosis , Imatinib Mesylate/therapeutic use , Mutation , Proto-Oncogene Proteins c-kit/geneticsABSTRACT
Objective To understand the distribution and changes in antimicrobial resistance of clinically isolated Pseudomonas aeruginosa(P.aeruginosa)in the member hospitals of Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods Antimicrobial susceptibility testing by disk diffusion or automa-ted instrument was performed on clinical isolates.Testing results were determined according to the standards of 2022 edition from American Clinical Laboratory Standards Institute(CLSI).Statistical analysis was performed by WHONET 5.6 software.Data were analyzed by trend test(Cochran-armitage)and Chi-square test with SPSS.Results A total of 176 441 strains of P.aeruginosa were surveilled by Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021.99.4%of the strains were isolated from hospitalized patients,and about 70%of the strains were isolated from respiratory specimens.8.4%of P.aeruginosa were from children(0-17 years old),91.6%were from adults.Antimicrobial susceptibility testing results showed that P.aeruginosa was most sensitive to polymyxin B over 10 years,with a resis-tance rate of less than 6%.Resistance rates to piperacil-lin,piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,imipenem,amikacin,gentamicin,tobramycin,cip-rofloxacin,levofloxacin,and polymyxin B all showed downward trends.A total of 29 920 carbapenem-resistant P.aeruginosa(CRPA)strains were detected.The average isolation rate of CRPA in this province was 18.0%over 10 years.CRPA detection rate from adult was 18.5%,higher than that from children(12.3%),and both showing downward trends.Conclusion The resistance rate of clinically isolated P.aeruginosa in Hunan Province to most commonly used antimicrobial agents is decreasing.
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Radiation-induced brain injury (RBI) is one of the complications after radiotherapy for head and neck malignant tumors, which seriously affects the quality of life of patients. The pathophysiological mechanism of RBI is not completely clear. Current studies suggest that it is involved in a variety of cells in the central nervous system (CNS), whereas astrocyte, as the largest number of glial cells in the CNS, plays an important role in maintaining the CNS homeostasis and responding to CNS injury. In this article, the role of astrocytes in RBI was reviewed.
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@#Objective ( ) To investigate the association between urinary polycyclic aromatic hydrocarbons PAHs metabolites - Methods and high normal blood pressure in coke oven workers. A total of 433 coke oven workers were selected as the study - subjects using convenient sampling method. They were divided into normal blood pressure group and high normal blood pressure group according to their blood pressure level. The levels of ten kinds of urinary hydroxylated PAHs metabolites were measured by - Results - high performance liquid chromatography mass spectrometry. Among the subjects,57.5% had high normal blood - , - , - pressure. The levels of 1 hydroxynathalene 2 hydroxyphenanthrene 1 hydroxyphenanthrene and the metabolite of total PAHs - ( P ) in the high normal blood pressure group were higher than those in the normal blood pressure group all <0.05 . The results of - , - , - , the multivariate logistic regression analysis showed that urinary 1 hydroxynathalene 2 hydroxyfluorene 3 hydroxychrysene - ( P ), and metabolite of total PAHs were all risk factors for high normal blood pressure in coke oven workers all <0.05 after , , , , , adjusting for confounding factors such as gender length of service body mass index smoking index alcohol consumption tea , , , Conclusion consumption night shift exercise frequency and other PAHs metabolites. Exposure to PAHs in coke oven plants may increase the risk of elevated blood pressure within the normal range among coke oven workers.
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ObjectiveTo observe the clinical efficacy of modified Tuoli Xiaodusan (TLXDS) in adjuvant treatment of Helicobacter pylori (Hp)-positive peptic ulcer (PU) with cold-heat complex syndrome and explore its regulating effect on invasive/protective factors. MethodA total of 136 patients were randomly assigned into the control group (68 cases, including 4 cases missing, 3 cases eliminated, and 61 cases completed) and the TLXDS group (68 cases, including 4 cases missing, 1 case eliminated, and 63 cases completed). Both groups adopted the quadruple therapy of acid suppression and Hp eradication. The patients in the control group received Weinai'an capsules orally at 4 capsules/time and 3 times/day, and those in the TLXDS group took modified TLXDS orally at 1 dose/day. The administration of both groups lasted for 8 consecutive weeks and the follow-up lasted for 12 months. Electronic gastroscopy was carried out before and after treatment for evaluating the healing of ulcer, the score of mucosal morphology, and the maturity of regenerated mucosa. The Hp infection and the score of cold-heat complex syndrome were evaluated before and after treatment. The serum levels of gastrin (GAS), prostaglandin E2 (PGE2), pepsinogen (PG)-Ⅰ, PG-Ⅱ, epidermal growth factor (EGF), and trefoil factor 2 (TFF-2) were determined before and after therapy. The recurrence of Hp and PU was recorded, and the drug safety was evaluated. ResultAfter treatment, the mucosal morphology score and the traditional Chinese medicine (TCM) syndrome score in the TLXDS group were lower than those in the control group (P<0.01). The levels of GAS, PG-Ⅰ, and PG-Ⅱ in the TLXDS group were lower than those in the control group (P<0.01), whereas those of PGE2, EGF, and TFF-2 showed an opposite trend (P<0.01). After treatment, the Hp eradication rate in the TLXDS group was 95.24% (60/63), higher than that (83.61%, 51/61) in the control group (χ2=4.467, P<0.05). The total effective rate of TCM syndromes in the TLXDS group was 98.41% (62/63), higher than that (81.97%, 50/61) in the control group (χ2=9.589, P<0.01). The total effective rate of the TLXDS group under gastroscopy was 98.41% (62/63), higher than that (86.89%, 53/61) in the control group (χ2=4.525, P<0.05). The excellent and good rate of regenerated mucosal maturity in the TLXDS group was 92.06% (58/63), also higher than that (73.77%, 45/61) in the control group (χ2=7.372, P<0.01). After 12 months of follow-up, the TLXDS group had lower PU recurrence rate [19.05% (12/63) vs 37.70% (23/61), χ2=5.325, P<0.05] and lower Hp recurrence rate [15.00% (9/60) vs 33.33% (17/51), χ2=5.165, P<0.05) than the control group. No adverse reactions related to TLXDS were detected. ConclusionModified TLXDS-assisted quadruple therapy demonstrates significant short-term clinical efficacy and high Hp eradication rate for Hp-positive PU (cold-heat complex syndrome) patients. Moreover, it can adjust the levels of invasive/protective factors to facilitate ulcer healing and reduce the recurrence rates of Hp and PU in a long term, with good clinical safety.
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Objective:To explore the progression of diabetic macrovascular disease and the effects of Didangtang at different doses on it. Method:Four-week-old male apolipoprotein-E knockout (ApoE<sup>-/-</sup>) mice with diabetic macrovascular disease induced by exposure to high-fat diet combined with streptozotocin (STZ) were randomly divided into the model, simvastatin, as well as high-, medium-, and low-dose Didangtang groups. The age-matched ApoE<sup>-/-</sup> mice of the same batch only fed with a high-fat diet were classified into the ApoE<sup>-/-</sup> (model control) group, and C57BL/6 mice with the same genetic background receiving a regular diet into the normal group. The sampling was conducted at the 8th and 20th weeks of the experiment for observing the pathological characteristics of the aorta and the proportion of plaque area in mice of each group at different time points, followed by the comparison of blood glucose, blood lipid, and oxidized low-density lipoprotein (ox-LDL) levels. The aortic NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate-specific proteinase-1 (Caspase-1) protein expression was detected by Western blot assay, and the serum interleukin-1<italic>β</italic> (IL-1<italic>β</italic>), interleukin-18 (IL-18), interleukin-1<italic>α</italic> (IL-1<italic>α</italic>), and tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>) levels by enzyme-linked immunosorbent assay (ELISA). Result:The comparison with the normal group revealed that the proportions of plaque area in the ApoE<sup>-/-</sup> group and the model group were increased (<italic>P</italic><0.01), while the proportion of plaque area in each administration group was significantly reduced in contrast to that of the model group (<italic>P</italic><0.05). The aortic NLRP3 and Caspase-1 protein expression levels as well as the serum IL-1<italic>β</italic>, IL-18, IL-1<italic>α</italic>, and TNF-<italic>α </italic>levels in the ApoE<sup>-/-</sup> group and the model group were significantly higher than those in the normal group (<italic>P</italic><0.01). Compared with the model group, each administration group exhibited a significant reduction in aortic NLRP3 and Caspase-1 protein expression and serum IL-1<italic>β</italic>, IL-18, IL-1<italic>α</italic>, and TNF-<italic>α</italic> levels (<italic>P</italic><0.05), with the strongest inhibitory effect detected in the medium-dose Didangtang group (<italic>P</italic><0.05). Conclusion:Didangtang directly alleviates diabetic macrovascular disease possibly by down-regulating NLRP3 and Caspase-1 protein expression and easing the inflammatory cascade.
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OBJECTIVE Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease lacking efficacy therapeutics. Therefore, it urgently needs to develop safe and effective drugs for PAH treatment. Osthole derived from Cnidium monnieri (L.) Cusson (Shechuangzi) or Angelica pubescens Maxim (Duhuo) has the capacity to alleviate PAH by decreasing pulmonary arterial pressure and alleviating pulmonary vascular remodeling in rats, which is a candi?date drug for the prevention of PAH, but the underlying modulatory mechanism is still unclear. Our study aims at investi?gating the metabolic modulatory mechanism of osthole against PAH employing functional metabolomics strategy. METH?ODS PAH model rats were successfully established with MCT, following osthole administration, then functional metabo?lomics based on untargeted metabolomics assay, targeted lipidomics analysis, qRT-PCR, Western blotting and ELISA were performed to investigate the modulatory mechanism of osthole against pulmonary arterial pressure and pulmonary vascular remodeling in PAH. RESULTS Untargeted metabolomics results found that sphingosine 1-phosphate (S1P) was the differential metabolites characterized PAH and reversed by osthole treatment. S1P is a crucial sphingolipid metabolite catalyzed by sphingosine kinases1 (Sphk1) and functions as promoting PASMCs proliferation contributing to pulmonary vascular remodeling and pulmonary arterial pressure increase. We revealed that osthole reversed high level of S1P by modulating metabolic enzyme Sphk1 via inactivating microRNA-21-PI3K/Akt/mTOR signal pathway to decrease pulmonary arterial pressure in rats with PAH. Then, targeted phospholipid metabolomics results uncovered that decadienyl-L-carnitine (C10:2) was the differential metabolite characterized PAH and corrected by osthole treatment in rat with PAH. C10:2 is the intermediate metabolite of fatty acid oxidation (FAO), and C10:2 accumulation indicated mitochondrial dysfunction and FAO increase. CONCLUSION Osthole could block lipid metabolic reprogramming through functional modulating the expression of fatty acid translocase, fatty acid synthase, phospholipase A2, carnitine palmitoyltransferase 1A to inhibit C10:2, thus to improve mitochondrial dysfunction and inhibit utilizing lipid to biosyn?thesize necessary essence for pulmonary artery smooth muscle cells (PASMCs) proliferation. Moreover, we delineated that C10:2 and metabolic reprogramming enzymes were modulated by miRNA-22-3p which was involved in PASMCs proliferation and pulmonary vascular remodeling. Therefore, osthole inhibited miRNA-22-3p mediated lipid metabolic reprogramming to ameliorate pulmonary vascular remodeling.
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Signaling pathways in innate and adaptive immunity play vital roles in pathogen recognition and the functions of immune cells. Higher-order assemblies have recently emerged as a central principle that governs immune signaling and, by extension, cellular communication in general. There are mainly two types of higher-order assemblies: 1) ordered, solid-like large supramolecular complexes formed by stable and rigid protein-protein interactions, and 2) liquid-like phase-separated condensates formed by weaker and more dynamic intermolecular interactions. This review covers key examples of both types of higher-order assemblies in major immune pathways. By placing emphasis on the molecular structures of the examples provided, we discuss how their structural organization enables elegant mechanisms of signaling regulation.
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Pulmonary arterial hypertension (PAH) is a devastating pulmonary circulation disease lacking high-efficiency therapeutics. The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata, a well-known traditional chinese medicine with cardiopulmonary protection capacity, on PAH by exploiting functional lipidomics. The rat model with PAH was successfully established for first, following Rhodiola crenulata water extract (RCE) treatment, then analysis of chemical constituents of RCE was performed, additional morphologic, hemodynamic, echocardiographic measurements were examined, further targeted lipidomics assay was performed to identify differential lipidomes, at last accordingly mechanism assay was done by combining qRT-PCR, Western blot and ELISA. Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls, mostly assigned to acylcarnitines, phosphatidylcholines, sphingomyelin associated with the PAH development. Excitingly, RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH. Furthermore, RCE was observed to reduce autophagy, confirmed by significantly inhibited PPARγ, LC3B, ATG7 and upregulated p62, and inactivated LKB1-AMPK signal pathway. Notably, we accurately identified the constituents in RCE, and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy. Altogether, RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH. This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.
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@#Objective To explore the effects of perioperative autologous platelet transfusion on postoperative complications and prognosis of adult cardiac surgery patient. Methods Using the method of systematic review of Cochrane Collaboration, we searched PubMed, Web of Science, EMbase, The Cochrane Library, CNKI and Wangfang databases, retrieving the literature from January 1970 to June 2020 to collect clinical randomized controlled trials on the effects of autologous platelet transfusion on complications and prognosis of adult cardiac surgery patients. The extracted valid data was analyzed by RevMan5.3 software. Results Ten studies were included, with a total of 1 083 patients. The results of meta-analysis showed that there were statistical differences in the perioperative blood loss (MD=−195.15, 95%CI − 320.48-−69.83, P=0.002) and perioperative blood transfusion (MD=−0.88, 95%CI −1.23-−0.52, P<0.001). There was no statistical difference in the death rate 30 days after the operation (RR=0.90, 95%CI 0.48-1.70, P=0.75), reoperations (OR=0.48, 95%CI 0.23-1.02, P=0.06), postoperative myocardial infarction (OR=1.29, 95%CI 0.48-3.51, P=0.61), postoperative infection (OR=1.71, 95%CI 0.89-3.29, P=0.11) or postoperative ICU retention time (MD=−0.31, 95%CI − 0.67-0.05, P=0.09). Conclusion Perioperative autologous platelet transfusion can reduce perioperative blood loss and blood transfusion in adult cardiac surgery patients, but has no significant impact onprognosis and postoperativecomplications, which indicates that perioperative autologous platelet transfusion is a safe and beneficial blood protection measure for patients undergoing cardiac surgery.
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Radiation-induced brain injury is a neurological injury caused by radiation therapy of head and neck tumors. The pathogenesis is still unclear. It is hypothesized that immune cells play an important role in radiation-induced brain injury. The excessive activation of microglia in the central nervous system and the migration of peripheral immune cells into the brain collectively promote the incidence and development of radiation-induced brain injury. In this article, the immunological mechanism underlying the radiation-induced brain injury was reviewed.
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OBJECTIVE@#To study the changes and clinical significance of amplitude-integrated electroencephalography (aEEG) in preterm infants with bronchopulmonary dysplasia (BPD).@*METHODS@#A total of 156 preterm infants with a gestational age of ≤ 32@*RESULTS@#Compared with the non-BPD group, the BPD group had a significantly lower total aEEG score at the corrected gestational age of 33-34@*CONCLUSIONS@#Preterm infants with BPD (especially moderate to severe BPD) have a lower aEEG score than those without BPD, suggesting that their nervous system development may lag behind that of non-BPD preterm infants with the same gestational age. Therefore, early nervous system evaluation and intervention are necessary for preterm infants with BPD.