Objective To investigate the expression and significance of Th9, Th17 and CD4+CD25+Foxp3+regulatory T (Treg) cells as well as the related cytokines (IL-9, IL-17, TGF-β) in peripheral blood of patients with adult primary immune thrombocytopenia ( ITP) . Methods Peripheral blood samples were collected from 47 patients with ITP and 39 age-and sex-matched healthy subjects. The percentages of Th9, Th17 and CD4+CD25+Foxp3+Treg cells in peripheral blood samples were detected with flow cytometry. The levels of IL-9, IL-17 and TGF-βin serum samples were detected by enzyme linked immunosorbent assay ( ELISA) . Results Compared with healthy subjects, the percentages of Th9 and Thl7 cells and the concen-trations of IL-9 and IL-17 in patients with ITP were significantly increased [(1. 27±0. 31)% vs (0. 71± 0. 26)%, P<0. 05;(2. 01±0. 42)% vs (0. 97±0. 32)%, P<0. 05. (26. 52±7. 48) ng/L vs (16. 16± 5. 27) ng/L, P<0. 05;(10. 97±3. 94) ng/L vs (7. 14±2. 73) ng/L, P<0. 05]. The percentages of CD4+CD25+Foxp3+ Treg cells and the concentrations of TGF-β in patients with ITP were lower than those in healthy subjects [(4. 69±0. 85)% vs (7. 16±1. 92)%, P<0. 05. (3. 76±1. 28) μg/L vs (6. 41±1. 83)μg/L, P<0. 05]. Moreover, the blood platelet counts in patients with ITP were negatively correlated with the percentages of Th9 and Th17 cells and the concentrations of IL-9 and IL-17 (γs=-0. 349, P=0. 037;γs=-0. 392, P=0. 031;γs=-0. 436, P=0. 014;γs=-0. 401, P=0. 027), but were positively correlated with the percentages of CD4+CD25+Foxp3+ Treg cells and the concentrations of TGF-β (γs=0. 411, P=0. 024;γs=0. 407, P=0. 026). Conclusion The imbalanced distribution of Th9, Th17 and Treg cells and the abnormal expression of related cytokines (IL-9, IL-17 and TGF-β) in patients with ITP might be the possible immunological pathogenesis of ITP.

Objective To analyze the relationship between plasma concentration and efficacy , adverse drug reactions by monitoring vancomycin serum concentrations for appropriately treating the infections caused by methicillin‐resistant Staphylococcus aureus or other gram‐positive cocci .Methods Vancomycin concentration was monitored in the patients with indications for vancomycin therapy .Blood sample was taken after vancomycin was administered for at least 4 doses .The blood sample collected within 30 minutes before dosing was used to determine the trough blood concentration .The samples were taken within 30 minutes to 1 hour after infusion of vancomycin were used to estimate the peak concentration by fluorescence polarization immunoassay .The clinical data were collected at the same time to analyze clinical efficacy and safety .Results Vancomycin trough concentration ranged from 3 .22 mg/L to 50 .79 mg/L in 25 patients ,specifically ,＜ 5 mg/L in 3 cases ,5‐＜10 mg/L in 11 cases ,10‐15 mg/L in 3 cases ,and > 15 mg/L in 8 csaes .Peak concentration ranged from 13 .57 mg/L to 60 .47 mg/L ,specifically ,＜ 25 mg/L in 14 cases ,25‐40 mg/L in 7 cases ,and > 40 mg/L in 4 cases .The infection was cured in 80 .0% (20/25) of the patients .The gram‐positive cocci were eradicated in 87 .5% (21/24) of the patients .The dosage of vancomycin was adjusted in 13 patients according to the results of blood concentration monitoring .Majority of these patients (12/13 ,92 .3% ) were cured .Renal impairment was observed in 4 patients .Conclusions Vancomycin is safe and effective in treatment of methicillin‐resistant Staphylococcus aureus and other gram‐positive bacterial infections . Vacomycin concentration varies from person to person . Serum concentration monitoring is required to achieve best outcomes and the goal of individualized treatment of vancomycin.

Objective To investigate the percentages of Th17 and CD4+CD25+FoxP3+ regulatory T(Tr) cells and the levels of related cytokines IL-6,IL-23,IL-17 and TGF-β in serum of patients with anlylosing spondylitis(AS).Methods Forty patients with AS and 37 age-matched healthy donors were studied.Flow cytometry Was used to analyze the percentages of blood Th17 and CD4+CD25+FoxP3+Tr cells.The levels of serum IL-6,IL-23,IL-17 and TGF-β were assayed by enzyme-linked immunosorbent assay ( ELISA).Results The proportion of Th17 cells in AS group was significantly higher than those in normal group [ (1.02±0.34)％ vs (0.68±0.29)％,P＜0.05) ],and the proportion of CD4+CD25+FoxP3+ cells was lower in AS group comparing with normal group [(3.77±0.81)％ vs (4.69±1.23)％,P＜0.05)].Meanwhile,serum levels of IL-6,IL-23 and IL-17 were significantly higher in AS group than those in normal group [ (6,15±2.71) ng/L vs (3.31±1.65) ng/L; (9.44±3.12) ng/ml vs (5.82±2.61) ng/ml;(10.53±4.97) ng/L vs (6.78±3.26) ng/L,all P＜0.01 ].In contrast,TGF-β level was decreased in AS group compares with the normal group [ ( 4.76±2.15) ng/ml vs (5.16±2.02) ng/ml,P＞0.05 ],but the difference was not significant.No associations of serum eytokine levels with clinical and laboratory parameters were found in AS.Conclusion The abnormality Th17 cells and Tr cells and their related cytokines IL-6,IL-23,IL-17 and TGF-β changes in patients with AS,which may be involved in immunological pathogenesis of AS.

Objective : o evaluate the association between Crohn's disease (CD) and frailty using a Mendelian randomization (MR) approach, so as to provide the evidence for prevention and control strategies. Methods: Genetic association data for CD were collected through the International Inflammatory Bowel Disease Genetics Consortium, with 20 883 samples and 12 276 506 single nucleotide polymorphism (SNP), and genetic association data for frailty were collected through a meta-analysis including 175 226 samples and 7 589 717 SNPs. A forward MR analysis was performed using the inverse-variance weighted (IVW) method with 37 CD-associated SNPs as instrumental variables, and frailty as the study outcome, and a reverse MR analysis was performed with 13 frailty-associated SNPs as instrumental variables and CD as the study outcome. The heterogeneity was assessed using the Cochran's Q test, and the horizontal pleiotropy was assessed using the MR-PRESSO global test and MR-Egger regression. In addition, the robustness of the results was verified with the leave-one-out. Results: Forward MR analysis results showed that patients with genetically predicted CD had an increased risk of frailty index relative to those without CD (β=0.018, 95%CI: 0.011-0.026, P<0.05). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Reverse MR analysis showed no association between frailty index and the risk of CD (OR=0.740, 95%CI: 0.206-2.661, P>0.05). Conclusions Genetically predicted CD is associated with an increased risk of frailty. It is suggested that screening and prevention of frailty should be reinforced among CD patients.

Objective : To examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients. Methods: Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method. Results: MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one. Conclusions Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.

Objective To observe the transdifferentiation of renal tubular epithelial phenotype in allograft biopsy samples of patients with various rejections,and to analyze the association between rejection and transdifferentiation.Method Immunohistochemistry (SP method) was applied to detect α-SMA expression in tubular epithelial cells from 55 renal allograft biopsy samples with various rejection.Results Positive α-SMA expression was found in all the atrophic tubular epithelial cells adjacent to cytoplasm of basement membrane,which indicated the atrophic renal tubular epithelial cells appeared the phenotypic transdifferentiation.Positive α-SMA was also detected in some renal epithelial cells without atrophy.No phenotypic change was found in 7 cases without obviously rejection.Among 28 cases of acute T-cell-mediated rejection IA grade,α-SMA positive expression rate of non-atrophy renal epithelial cells was 25％-50％ in 1 case and 10％-25％ in 3 cases.Among 14 cases of more severe acute rejection group IB grade,α-SMA positive expression rate was over 50％ in 1 case,25％-50％ in 2 cases and 10％-25％ in 2 cases.Conclusion When acute T-cell-mediated rejection becomes more serious in renal allograft,the phenotype transdifferentiation aggravates in renal tubular epithelial cells.

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, the dose-dependent cardiotoxicity associated with DOX significantly limits its clinical application. In the present study, we investigated whether Rb1 could prevent DOX-induced apoptosis in H9C2 cells via aryl hydrocarbon receptor (AhR). H9C2 cells were treated with various concentrations (−μM) of Rb1. AhR, CYP1A protein and mRNA expression were quantified with Western blot and real-time PCR analyses. We also evaluated the expression levels of caspase-3 to assess the anti-apoptotic effects of Rb1. Our results showed that Rb1 attenuated DOX-induced cardiomyocytes injury and apoptosis and reduced caspase-3 and caspase-8, but not caspase-9 activity in DOX-treated H9C2 cells. Meanwhile, pre-treatment with Rb1 decreased the expression of caspase-3 and PARP in the protein levels, with no effects on cytochrome c, Bax, and Bcl-2 in DOX-stimulated cells. Rb1 markedly decreased the CYP1A1 and CYP1A2 expression induced by DOX. Furthermore, transfection with AhR siRNA or pre-treatment with AhR antagonist CH-223191 significantly inhibited the ability of Rb1 to decrease the induction of CYP1A, as well as caspase-3 protein levels following stimulation with DOX. In conclusion, these findings indicate that AhR plays an important role in the protection of Ginsenoside Rb1 against DOX-triggered apoptosis of H9C2 cells.
Apoptosis* ; Blotting, Western ; Cardiotoxicity ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cytochrome P-450 CYP1A1 ; Cytochrome P-450 CYP1A2 ; Cytochromes c ; Doxorubicin ; Myocytes, Cardiac ; Real-Time Polymerase Chain Reaction ; Receptors, Aryl Hydrocarbon* ; RNA, Messenger ; RNA, Small Interfering ; Transfection

Objective:To explore whether emotional motivation affects judgment of learning and its mechanism in short-term memory stage.Methods:Through the preliminary test and using E-Prime software, a set of suitable experimental procedures was compiled, and 134 middle school students were selected as subjects.Taking the instant judgment of learning after emotional video induction as the experimental paradigm, a four-factor mixed experiment of 2(emotional motivation direction: positive approach and negative avoidance) ×2(motivation intensity: high and low) ×2(word pair relevance: high and low) ×2(short-term memory load: more and less) was conducted to observe the subjects' judgment of learning scores.SPSS 23.0 software was used for repeated measurement analysis of variance.Results:Regarding learning judgment level, there was a significant interaction effect between emotional motivation direction and intensity( F=5.177, P=0.025, η2 =0.040). Emotional motivation intensity and direction both significantly interacted with short-term memory load capacity( F=4.778, P=0.031, η2=0.037 ; F=4.302, P=0.040, η2=0.034 ). Furthermore, emotional motivation direction( F=15.256, P<0.001, η2=0.110), motivation intensity( F=7.518, P=0.007, η2=0.057), short-term memory load( F=13.384, P<0.001, η2=0.097), and word pair relevance( F=212.238, P<0.001, η2 =0.631) all showed significant main effects.Regarding learning judgment accuracy, there was a significant interaction effect between emotional motivation direction and intensity( F=5.646, P=0.019, η2 =0.044). Both emotional motivation intensity and direction significantly interacted with short-term memory load capacity( F=4.593, P=0.034, η2 =0.036; F=4.033, P=0.047, η2 =0.031). Additionally, emotional motivation direction( F=15.318, P<0.001, η2=0.110), motivation intensity( F=7.572, P=0.007, η2=0.058), short-term memory load( F=11.119, P=0.001, η2=0.082), and word pair relevance( F=135.814, P<0.001, η2 =0.523) all showed significant main effects.Regarding recall performance, word pair relevance( F=416.326, P<0.001, η2=0.771) and short-term memory load( F=9.609, P=0.002, η2=0.772) showed significant main effects. Conclusion:The direction and intensity of emotional motivation have an impact on judgement of learning, emotional motivation and short-term memory jointly affect the level and accuracy of judgment of learning, and emotional motivation affects judgement of learning through clues related to the learning process in short-term memory stage.

Objective To evaluate and summarize the evidence related to the prevention of parenteral nutritional support complications in inpatients,and to provide an evidence-based basis for guiding healthcare professionals to prevent parenteral nutritional support complications in a scientific and standardized manner.Methods Computerized search was conducted in UpToDate,BMJ Best Clinical Practice,Centre for Evidence-Based Health Care database of the Joanna Briggs Institute in Australia,Ontario Registered Nurses Association website in Canada,National Institute for Health and Clinical Excellence website in the United Kingdom,Scottish Intercollegiate Guidelines Network,Guidelines International,New Zealand Guidelines Collaborative,American Society for Parenteral and Enteral Nutrition website,European Society for Clinical Nutrition and Metabolism Society website,International Practice Guidelines Registry Platform China Clinical Guidelines Repository,Medical Pulse,PubMed,Cochrane Library,Web of Science,CINAHL,Embase,China Biomedical Literature Database,CNKI,Wanfang Database,etc.The search period was from the time of database construction to October 2023.After literature screening and quality evaluation,the evidence extraction and integration were carried out.Results A total of 16 papers were included,including 3 clinical decision-making,1 evidence summary,4 guidelines,6 expert consensuses,and 2 systematic evaluations.27 pieces of best evidence were extracted from 3 areas,namely metabolic complications,mechanical complications,and infectious complications.Conclusion This study summarized the evidence related to the prevention and management of complications of parenteral nutrition support in adult inpatients,aiming to provide an evidence-based basis for healthcare professionals to develop scientific and standardized measures for the prevention and management of complications of parenteral nutrition support.

Objective:To explore whether cytoplasmic linker protein 170(CLIP170)affects papillary thyroid cancer(PTC)cell metastasis and invasion and clarify the underlying mechanisms.Methods:We analyzed CLIP170 expression levels in PTC using GEO and TCGA data and con-structed CLIP170 knockdown(CLIP170KD)cells using lentiviral transfection.Then,we evaluated their functions through Transwell transfer and invasion assays.We assessed how CLIP170 affected the cellular actin structure via immunofluorescence analysis.We detected transforming growth factor-β 1(TGF-β1)release in the cell culture medium using enzyme-linked immunosorbent assay(ELISA).We also assessed epithelial-mesenchymal transition(EMT)and TGF-β signaling pathway molecule expression using immunoblotting and reverse-transcription quantitat-ive fluorescence PCR and validated the results in a nude mouse lung metastasis model.Results:CLIP170 expression level in PTC was lower than that in normal thyroid tissue.Regarding the function,CLIP170KD significantly enhanced PTC cell metastasis both in vitro and in vivo.Re-garding the underlying mechanism,CLIP170KD triggered TGF-β pathway activation,subsequently promoted tumor cell migration and invasion.The inhibitor of TGF-β effectively inhibited TGF-β activation,and this inhibition significantly reversed the CLIP170KD-induced tumor metastasis.Conclusions:CLIP170 could be a promising therapeutic target to mitigate metastatic tendencies in PTC.