1.Latent profile analysis of self-care behavior in patients with chronic heart failure
Xinyue DONG ; Ying LIN ; Xiaoyan CHU ; Zhiyun SHEN ; Xiao CHEN ; Xian ZHANG ; Yike ZHU ; Zhenning LU ; Yuxia ZHANG
Chinese Journal of Practical Nursing 2024;40(30):2321-2329
Objective:To explore the characteristics and typology of self-care behavior among patients with chronic heart failure (CHF), and analyze their influencing factors.Methods:A cross-sectional study was used. A total of 318 patients with CHF who were hospitalized in the Heart Center of Zhongshan Hospital, Fudan University from November 2022 to July 2023 were selected by continuous enrollment method. The General Information Questionnaire, Heart Failure Self-care Index Scale, Brief Illness Perception Questionnaire, Self-efficacy for Managing Chronic Disease 6-item Scale, Perceived Social Support Scale, Atlanta Heart Failure Knowledge Test-V2 and Self-Care Confidence Scale were used to investigate. Latent profile analysis was utilized to delineate the characteristics and subtypes of self-care behaviors in CHF patients and examine the influencing factors.Results:A total of 291 patients were included in this study, including 190 males and 101 females, aged 67 (61, 74) years old. The analysis identified three latent categories of self-care behaviors among CHF patients: 26 cases in high self-care group, 131 cases in moderate self-care with deficiencies in maintenance and symptom perception group, and 134 cases in low self-care group.Ordered multicategorical Logistic regression analysis revealed that age ( OR=1.023, 95% CI 1.001-1.046, P<0.05), self-care confidence ( OR=0.859, 95% CI 0.817-0.904, P<0.01), and social support ( OR=0.966, 95% CI 0.940-0.993, P<0.05) were the factors influencing the potential categories of self-care behavior in CHF patients. Conclusions:The study identifies distinct categorical characteristics of self-care behaviors in patients with CHF. Healthcare professionals can leverage these findings to identify the self-care behavior characteristics and influencing factors for each patient category at an early stage, thereby providing personalized and precise support strategies to help patients enhance self-care behaviors.
2.Discussion on the Mechanism of Fire Needle in Treating Knee Osteoarthritis Based on p38MAPK Signaling Pathway
Tian WAN ; Yang XIAO ; Xinyue SHI ; Kunda HONG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(8):70-75
Objective To explore the mechanism of fire needle in treating cartilage degeneration in knee osteoarthritis(KOA)based on p38MAPK signaling pathway.Methods Totally 30 SPF grade male SD rats were randomly divided into blank group,model group and fire needle group,with 10 rats in each group.The model group and fire needle group established KOA models by injecting papain into the knee joint cavity.The fire needle group received fire needle intervention in"Neixiyan"and"Dubi",while the model group and blank group only received fixation and no intervention,once every 3 days,for 4 consecutive weeks.Morphological changes in the knee joint cartilage were observed using HE staining and safranine O-solid green staining,TUNEL staining was used to detect the apoptosis index of chondrocytes,immunohistochemical staining was used to detect the expressions of p-p38 and Fas protein,qPCR was used to detect the expressions of p38 and Fas mRNA.Results Compared with the blank group,the surface of the knee joint cartilage in the model group rats was uneven,with irregular and uneven arrangement of chondrocytes,lighter matrix red staining,and unclear tidal lines,the improved Mankin's score significantly increased(P<0.001),the apoptosis index of chondrocytes significantly increased(P<0.01),the expressions of p-p38 and Fas protein in knee joint cartilage tissue significantly increased(P<0.01),and the expressions of p38 and Fas mRNA significantly increased(P<0.001).Compared with the model group,the surface of the knee joint cartilage of the fire needle group rats was relatively flat,the arrangement of chondrocytes was generally normal,and the matrix staining was slightly lighter,the improved Mankin's score significantly decreased(P<0.001),the apoptosis index of chondrocytes significantly decreased(P<0.01),the expressions of p-p38 and Fas protein in knee joint cartilage tissue significantly decreased(P<0.01),and the expressions of p38 and Fas mRNA significantly decreased(P<0.001).Conclusion Fire needle may delay the progression of KOA by inhibiting the activation of p38MAPK signaling pathway and reducing chondrocyte apoptosis of knee joint.
3.Panax notoginseng saponins alleviate oral submucous fibrosis by inhibiting arecoline-induced oxidative stress in HaCaT cells via activating Nrf2/GCLC signaling pathway
Hong ZOU ; Shuo QI ; Fangping DENG ; Xinyue ZHANG ; Shuxin FU ; Mengqi GUO ; Yufeng XIAO ; Qun TANG
Chinese Journal of Pathophysiology 2024;40(5):908-916
AIM:To investigate the anti-fibrotic effect of Panax notoginseng saponins(PNS)in arecoline(ANE)-induced oral submucous fibrosis,and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glu-tamate-cysteine ligase catalytic subunit(GCLC)signaling pathway.METHODS:CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line Ha-CaT.The results of CCK-8 were used to select 75 mg/L arecoline,and 25,50 and 100 mg/L PNS as subsequent experi-mental concentrations.The cells were set as blank control group,model group,and low,medium and high doses(25,50 and 100 mg/L)of PNS groups.The protein and mRNA expressions of collagen type I(COL-I),E-cadherin,Nrf2,GCLC and glutathione reductase(GR)in each group were detected by Western blot and RT-qPCR.Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus.Biochemical kits were used to detect the content of glutathione(GSH),nicotinamide adenine dinucleotide phosphate(NADPH)and malondialdehyde(MDA),and superoxide dis-mutase(SOD)activity in each group of cells.DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species(ROS).RESULTS:Compared with the blank control group,the protein and mRNA expression of COL-I in the model group was up-regulated,and the protein and mRNA levels of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were down-regulated.The content of NADPH,MDA and ROS in the cells increased,and the content of GSH and the activity of SOD was significantly reduced.Compared with the model group,the protein and mRNA expression of COL-I was down-regulated,and the protein and mRNA expression of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups.Compared with the model group,the content of NADPH,MDA and ROS in cells decreased,and the content of GSH and the activity of SOD was significantly enhanced(P<0.05 or P<0.01).CON-CLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells,and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway,thereby resisting oxidative stress and improving oral submucosal fibrosis.
4.Research Progress on Mechanism of Flavonoids in Aurantii Immaturus in Lipid Metabolism
Wenjue LIU ; Zhongjie JI ; Xuyang CUI ; Xinyue YAN ; Xiao LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(12):3890-3898
As we all known,lipid metabolism participate in various diseases extensively.Abnormal lipid metabolism may contribute to hepatic adipose infiltration,diabetes,atherosclerosis and so forth.Accordingly,it is urgent to find chemicals that regulate lipid metabolism.A large number of experimental studies have shown that flavonoids in fructus aurantia are the active components of lowering blood lipids.This article will describe the concept,structure and classification of flavonoids.It will also introduce the mechanism of action of flavonoids in lipid metabolism from various diseases such as atherosclerosis,hypertension and type 2 diabetes.
5.Mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma cells
Jiali WU ; Jiahui ZHANG ; Ping ZHANG ; Xinyue XIAO ; Rui LI ; Hongyu ZHANG
Journal of International Oncology 2023;50(7):413-418
Objective:To investigate the inhibitory effect and killing mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma (NK/TCL) .Methods:Human NK cell leukemia cell line YT and human NK/TCL cell line NK92 cells were treated with 0, 0.05, 0.10, 0.20, 0.30, 0.40, 0.50 μmol/L BDA-366. CCK-8 assay was used to calculate the half inhibitory concentration (IC 50) value of BDA-366 on these cells. The apoptosis levels of cells in control group and IC 50 BDA-366 treated group were detected by flow cytometry. Western blotting was used to detect the expression levels of apoptosis-related proteins in cells of control group and 1/2 IC 50, IC 50, 2× IC 50 BDA-366 treated groups. TMRE and Fluo-3 fluorescent probe were used to detect mitochondrial membrane potential of control group and IC 50 BDA-366 treated group, and the intracellular Ca 2+ concentration of control group, IC 50, 2× IC 50 BDA-366 treated groups. NOD-SCID mice in control group and 10 mg/kg BDA-366 intraperitoneal injection group were weighed and HE staining was performed to evaluate the toxicity of BDA-366 in vivo. Results:The IC 50 of BDA-366 for YT and NK92 cells were 0.065 and 0.086 μmol/L respectively. The apoptosis rates of YT cells in the control group and 0.065 μmol/L BDA-366 group were (6.62±1.59) % and (34.60±3.06) % respectively. The apoptosis rates of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were (5.57±0.88) % and (29.18±0.90) % respectively, both with statistically significant differences ( t=14.05, P<0.001; t=32.58, P<0.001). The relative expression of Bax in NK92 cells of the control group, 0.043, 0.086 and 0.172 μmol/L BDA-366 groups were 0.85±0.00, 1.26±0.04, 1.51±0.18, 1.15±0.10 ( F=20.70, P<0.001), the relative expression of Bax in BDA-366 groups were higher than that in the control group (all P<0.05). The fluorescence intensity of TMRE of YT cells in the control group and 0.065 μmol/L BDA-366 group were 8 372.00±330.47 and 6 419.67±311.34, and that of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were 9 169.00±535.72 and 7 311.67±295.52 respectively, and there were statistically significant differences ( t=7.45, P=0.002; t=5.26, P=0.006). In YT cells, the intracellular Ca 2+ concentrations of 0.065 and 0.130 μmol/L BDA-366 groups were significantly higher than that of the control group (5 791.67±220.45, 6 729.33±585.39, 4 874.67±112.61, F=19.16, P=0.003) ( P=0.039; P=0.002). In NK92 cells, the intracellular Ca 2+ concentrations of 0.086 and 0.172 μmol/L BDA-366 groups were significantly higher than that of the control group (4 553.67±17.62, 4 740.33±254.50, 4 185.67±17.67, F=10.96, P=0.010) ( P=0.039; P=0.007). There was no statistically significant difference in body weight change on day 12 compared with day 0 of NOD-SCID mice between BDA-366 group and control group [ (3.18±0.01) g vs. (2.73±0.58) g, t=0.60, P=0.570], and HE staining showed no abnormal morphology of heart, liver, spleen, lung and kidney in BDA-366 group. Conclusion:BDA-366 promotes NK/TCL cells apoptosis in vitro, but does not cause weight loss and morphological changes of organs by HE staining in vivo. The inhibitory effect of BDA-366 on NK/TCL cells may be achieved by increasing Bax expression, inducing Ca 2+ release and reducing mitochondrial membrane potential.
6.Novel mutation c.1210-3C > G in cis with a poly-T tract of 5T affects CFTR mRNA splicing in a Chinese patient with cystic fibrosis.
Xinyue ZHAO ; Keqiang LIU ; Wenshuai XU ; Meng XIAO ; Qianli ZHANG ; Jiaxing SONG ; Keqi CHEN ; Yaping LIU ; Xinlun TIAN ; Kai-Feng XU ; Xue ZHANG
Frontiers of Medicine 2022;16(1):150-155
Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G > A, p.Gly970Asp in exon 18 and c.1210-3C > G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C > G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C > G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.
China
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Cystic Fibrosis/genetics*
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Cystic Fibrosis Transmembrane Conductance Regulator/genetics*
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Humans
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Mutation
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Poly T
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RNA, Messenger/genetics*
7.Correlation between serum concentration of angiogenic suppressor protein 1 and urinary albumin creatinine ratio in patients with type 2 diabetes mellitus and diabetic nephropathy
Zhifeng WANG ; Qiumei LI ; Xiao JIANG ; Xinyue XU
Clinical Medicine of China 2022;38(3):268-273
Objective:To investigate the correlation between serum concentration of vasohibin-1 (VASH-1) and urinary albumin creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy.Methods:The clinical data of 196 patients with T2DM from February 2017 to December 2020 were analyzed retrospectively. According to whether diabetic nephropathy (DN) was combined, 33 patients without DN of T2DM were divided into the control group,and 163 patients with DN of T2DM were divided into the case group, and the case group was divided into four groups:normal albuminuria group (groupⅠ, UACR <30 mg/g, 21 cases),microalbuminuria group (groupⅡ, UACR ≥30-≤300 mg/g, 50 cases), clinical albuminuria group (group Ⅲ, UACR>300 mg/g, 43 cases), and clinical albuminuria hypertensive group (groupⅣ, UACR >300 mg/g with hypertension, 49 cases). Serum levels of VASH-1,C-reactive protein(CRP), erythrocyte sedimentation rate (ESR) and transforming growth factor β1 (TGF-β1) with other biochemical indicators were measured. T-test was used for comparison between measurement data groups in accordance with normal distribution, one-way ANOVA was used for comparison between multiple groups, q-test was used for pairwise comparison, and χ2 test was used for comparison between counting data groups. The influencing factors were analyzed by multivariate Logistic regression.Pearson correlation analysis was used to analyze the correlation between vash-1 and UACR. Results:UACR((1 175.9±120.4) mg/g), CRP((9.80±2.01) mg/L), ESR((20.61±2.20) mm/h),TGF-β1((16.75±2.05) μg/L), VASH-1((645.3±183.5) ng/L) in case group were higher than that in the control group((11.5±2.0) mg/g, (4.77±1.34) mg/L, (8.33±1.56) mm/h, (10.63±1.97) μg/L, (416.3±162.1) ng/L), and there were significant differences between the two groups ( t=123.39,13.76,30.54,15.75,6.66; all P<0.001). Multivariate logistic regression analysis showed that VASH-1 ( OR=1.881,95% CI 1.146-3.089), UACR( OR=1.511,95% CI 1.064-2.146), TGF-β1( OR=1.846,95% CI 1.135-3.001)were all risk factors for DN of T2DM ( P values were 0.009, 0.022 and 0.012). Serum VASH-1 ((693.5±201.4), (709.8±214.7) ng/L] in group Ⅲ and group Ⅳ were higher than those in group Ⅰ and group Ⅱ ((585.3±162.1), (632.9±165.5) ng/L). There was significant difference between the two groups ( F=129.46, P<0.001). The CRP ((7.08±1.36), (8.99±3.72), (10.58±3.48), (11.64±3.50) mg/L), ESR ((17.36±1.76), (19.05±4.12), (21.45±5.74), (22.69±9.13) mm/h) and TGF- β1 ((14.75±1.97), (16.50±1.90), (17.06±1.23), (18.39±1.46) μg/L) of groupⅠ, groupⅡ, groupⅢ and groupⅣ increased gradually, and there were significant differences between the four groups ( F values were 73.48, 156.61, 25.83; all P<0.001). Pearson correlation analysis showed that there was a significant positive correlation between VASH-1 and UACR ( r=0.532, P=0.008). Conclusion:The concentration of VASH-1 in serum of patients with T2DM complicated with DN increased with the increase of UACR. VASH-1 may become a new marker for predicting early DN of T2DM.
8.Control strategy for the limit of aldehydes in polysorbates based on genotoxicity and influence on the aggregation of monoclonal antibody
Jue WANG ; Ying JIANG ; Xinyue XIAO ; Rui YANG ; Huimin SUN ; Jiasheng TU
Journal of China Pharmaceutical University 2022;53(1):67-73
An HPLC pre-column derivatization detection method was established to detect and analyze the formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 from different manufacturers.The effects of aldehyde and acetaldehyde on the aggregation of adalimumab under different conditions were monitored.Based on the control of genotoxic impurities and the influence on the stability of monoclonal antibody preparations, the control limits of the two chemicals were preliminarily obtained.2, 4-dinitrophenylhydrazine (2, 4-DNPH) was applied as the derivatization reagent in HPLC pre-column derivatization; acetonitrile and water were used as mobile phase to perform a gradient elution on a C8 (4.6 mm × 150 mm, 5 μm) chromatographic column.The detection wavelength was 360 nm, and the external standard method was used for quantification.Verification results showed that the method was suitable for the quantitative analysis of trace formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 . The detection and analysis of formaldehyde or acetaldehyde in different batches of polysorbate 80 and polysorbate 20 from different manufacturers showed that the content of formaldehyde and acetaldehyde were quite different. The content of formaldehyde and acetaldehyde in polysorbate 80 were significantly higher than those of polysorbate 20. After monitoring the changes of adalimumab aggregates treated by formaldehyde and acetaldehyde by size exclusion chromatography (SEC), it was found that the effect of formaldehyde on adalimumab aggregation was significantly higher than that of acetaldehyde.According to the requirements of ICH M7 (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk), the impurity limits of formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 for monoclonal antibody preparations were calculated from the perspective of risk assessment.Combined with the influence on the aggregation stability of monoclonal antibodies, the preliminary limis for acetaldehyde and acetaldehyde were recommended to be ≤ 7 μg/g and ≤ 765 μg/g, respectively.
9.Mechanism of action of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in liver diseases
Yan YANG ; Feilin GE ; Qian HUANG ; Xinyue ZHANG ; Rui ZENG ; Xiaohe XIAO ; Zhaofang BAI ; Qin SUN
Journal of Clinical Hepatology 2022;38(4):942-946
Inflammasomes play an important role in the innate immunity of the liver; however, the excessive activation of inflammasomes can lead to liver inflammation and injury. The mechanism of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated liver injury has been extensively studied. Related studies have shown that the development of various liver diseases may be associated with the excessive activation of inflammasomes, especially NLRP3 inflammasome. This article reviews inflammasomes, the activation mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in different liver diseases, so as to provide a reference for the treatment targets of liver diseases from the perspective of NLRP3 inflammasome.
10.Analysis on adolescent healthcare capacity at health centers for women and children at district and county level in Chongqing
Dan HE ; Xia WEN ; Haiyan ZHANG ; Xinyue WANG ; Nian XIAO
Chinese Journal of Hospital Administration 2022;38(4):299-303
Objective:To analyze and evaluate the capacity of adolescent healthcare at health centers for women and children at district and county level in Chongqing, for theoretical basis in promoting adolescent healthcare.Methods:From January to February 2021, a unified questionnaire was used to collect the information of adolescent healthcare and data of human resources from 39 health centers for women and children at district and county level in Chongqing. The survey data were analyzed by descriptive statistics.Results:Among the 39 health centers for women and children at district and county level in Chongqing, 32 (82.1%) institutions maintain adolescent outpatient clinics, most of which under gynecology (40.6%) instead of independent departments. 37(94.9%) institutions could provide health care services for adolescents, and 26 (66.7%) institutions could provide the services both in and out-institution services. All the institutions could provide services of prevention and treatment for regular reproductive health diseases, but the numbers of institutions providing such services as nutritional assessment, common problems consultation and guidance, psycho-behavioral screening, mental health consultation and guidance, accidental injury prevention and guidance, violence injury prevention and guidance, as well as Internet addiction assessment and guidance, were 25, 20, 16, 10 and 8, respectively. There were 273 medical workers engaged in adolescent healthcare, mostly part-time (98.9%).Conclusions:The construction of outpatient clinics for adolescent health care is expected to be strengthened at health centers for women and children at district and county level in Chongqing. Meanwhile, services provision and human resources of medical workers for adolescent health care are inadequate.

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