1.Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.
Xiu LIU ; Li ZHAO ; Deshen LIU ; Lingna ZHAO ; Yonghua TUO ; Qinbao PENG ; Fangze HUANG ; Zhengkun SONG ; Chuanjie NIU ; Xiaoxia HE ; Yu XU ; Jun WAN ; Peng ZHU ; Zhengyang JIAN ; Jiawei GUO ; Yingying LIU ; Jun LU ; Sijia LIANG ; Shaoyi ZHENG
Acta Pharmaceutica Sinica B 2025;15(7):3663-3684
This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.
2.Quality evaluation of Siraitiae fructus standard decoction based on UPLC fingerprint and multi-index determination
Fangping ZHANG ; Cuijie WEI ; Xiaoxia LIU ; Wenkai XIE ; Yuanyuan CHEN ; Zhiwen DUAN ; Yongwei FENG ; Minyou HE ; Roushan CHEN ; Dongmei SUN ; Lin ZHOU ; Zhenyu LI
China Pharmacist 2024;28(11):397-405
Objective To establish an ultra-high performance liquid chromatography(UPLC)fingerprint and multi-index content determination method of Siraitiae fructus standard decoction.Methods 15 batches of Siraitiae fructus from different producing areas were collected,Siraitiae fructus standard decoction was prepared according to Technical Requirements for Quality Control and Standardization of Traditional Chinese Medicine Formula Granules,and the extract rate was calculated.UPLC was used to establish the fingerprint of 15 batches of Siraitiae fructus standard decoction and determine the contents of 11-O-mogroside V,kaempferitrin and mogroside V,which were the main effective components.The chemometrics analysis was used to evaluate the quality of Siraitiae fructus standard decoction and find possible quality markers.Results The extraction rate of 15 batches Siraitiae fructus standard decoction ranged from 24.79%to 34.95%.There were 16 common peaks in the fingerprint,and 4 components were identified.The Siraitiae fructus standard decoction was divided into 2 categories by chemometrics analysis,among which samples from Liuzhou,Guangxi were in one category and samples from Guilin,Guangxi were in another category.Seven differential markers were screened out under the condition of variable importance projection value,and the order was as follows:peak 8>peak 7>peak 5>peak 12(kaempferitrin)>peak 1>peak 13>peak 4.The contents of kaempferitrin,11-O-mogroside V and mogroside V in samples from Guilin,Guangxi were slightly higher than those in samples from Liuzhou,Guangxi.Conclusion The UPLC fingerprint and content determination method established in this study are feasible,which can provide a basis for the quality evaluation of Siraitiae fructus.The results of principal component analysis show that kaempferol is likely to become a quality marker of Siraitiae fructus.
3.Study on the changes of chemical components of Aristolochia contorta before and after honey processing based on HPLC fingerprint and multivariate statistical analysis
Xiaoxia LIU ; Yongwei FENG ; Cuijie WEI ; Chunxiu WU ; Minyou HE ; Liye PAN ; Dongmei SUN ; Zhenyu LI
International Journal of Traditional Chinese Medicine 2024;46(11):1485-1492
Objective:To establish HPLC fingerprints of Aristolochia contorta and honey-processed Aristolochia contorta; To analyze the changes of chemical components before and after honey processing with multivariate statistics; To provide a reference for the study on the toxicity reduction of Aristolochia contorta.Methods:The fingerprints of 11 batches of Aristolochia contorta and honey-processed Aristolochia contorta were established through HPLC. Clustering analysis (HCA), principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and independent sample t-test were used to compare the changes of chemical components of Aristolochia contorta before and after honey processing.Results:The results showed that there were 14 common peaks in the fingerprints of Aristolochia contorta and Aristolochia contorta. 7 common peaks were identified. Both HCA and PCA could clearly distinguish the samples of Aristolochia contorta before and after honey processing. OPLS-DA found and screened 7 differential markers, and the order of difference significance was peak 3 > peak 7 (7-hydroxy aristolochic acid A) > peak 5 (aristolochic acid C)> peak 8 (aristolochic acid D) > peak 6 > peak 2 (Magnolia alkaloid) > peak 14 (aristolochic acid Ⅰ). After honey processing, the content of chemical components represented by peaks 2, 3, 5, 6, 7, 8 and 14 decreased ( P<0.05). Conclusion:This method is simple and specific, which can be used for the fingerprint analysis of Aristolochia contorta and honey-processed Aristolochia contorta, and can effectively distinguish Aristolochia contorta and honey-processed Aristolochia contorta, and provide a reference for the processing research of toxicity reduction of Aristolochia contorta honey processing.
4.Study on the quality markers of Curcumae Radix standard decoction based on fingerprint and network pharmacology
Zhiwen DUAN ; Xiaoxia LIU ; Minyou HE ; Cuijie WEI ; Yongwei FENG ; Haibao QIU ; Ronghui ZHENG ; Dongmei SUN ; Xiangdong CHEN ; Zhenyu LI
International Journal of Traditional Chinese Medicine 2024;46(12):1622-1628
Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.
5.Effect of vitamin D3 supplementation in combination with adefovir dipivoxil and lamivudine on liver fibrosis indicators and cellular immunity in patients with hepatitis B cirrhosis
Yajuan MU ; Xiaoxia GAO ; Meng WANG ; Yani HE
Chinese Journal of Primary Medicine and Pharmacy 2024;31(6):858-862
Objective:To analyze the effect of vitamin D3 supplementation in combination with adefovir dipivoxil and lamivudine on liver fibrosis indicators and cellular immunity in patients with hepatitis B cirrhosis.Methods:A total of 150 patients with hepatitis B cirrhosis who received treatment at The First Hospital of Yulin from February 2021 to April 2023 were included in this study. They were randomly divided into two groups using the random number table method, with 75 patients in each group. Both groups received treatment with adefovir dipivoxil and lamivudine, but the observation group also received vitamin D3 supplementation. Before and after treatment, liver function indicators, liver fibrosis indicators, and cellular immunity were measured and compared between the two groups to evaluate the efficacy of the treatments. Adverse reactions such as gastrointestinal bleeding, hypophosphatemia, and headache were observed.Results:After treatment, alanine aminotransferase and aspartate aminotransferase levels in the observation group were significantly lower compared with the control group [(30.81 ± 3.24) U/L vs. (39.82 ± 4.07) U/L, (31.78 ± 3.19) U/L vs. (37.96 ± 3.89) U/L, t = 15.00, 10.64, both P < 0.001]. After treatment, the levels of serum hyaluronic acid and laminin in the observation group were significantly lower than those in the control group ( t = 4.13, 8.45, both P < 0.001). After treatment, the levels of CD 4+ and CD 4+/CD 8+ in the observation group were significantly higher than those in the control group, while the level of CD 8+ was significantly lower ( t = 6.32, 14.10, 8.10, all P < 0.001). The total response rate in the observation group was significantly higher than that in the control group [89.33% (67/75) vs. 70.67% (53/75), χ2 = 8.17, P < 0.05]. There was no statistically significant difference in the total incidence of adverse reactions such as gastrointestinal bleeding and headache between the control and observation groups ( χ2 = 0.32, P > 0.05). Conclusion:Vitamin D3 supplementation in combination with adefovir dipivoxil and lamivudine is remarkably effective in the treatment of hepatitis B cirrhosis. The combined therapy can efficiently correct cellular immune disorders in patients, mitigate liver fibrosis, enhance liver function, and is considered highly safe.
6.Construction and validation of a cognitive frailty risk prediction model in elderly patients with type 2 diabetes
Yun LIU ; Yuanyuan SUN ; Shen WANG ; Lirong WEI ; Yanan WANG ; Yan HE ; Qingxiu TIAN ; Xiaoxia DU ; Ridong XU
Chinese Journal of Modern Nursing 2024;30(31):4254-4261
Objective:To develop and validate a risk prediction model for cognitive frailty in elderly patients with type 2 diabetes.Methods:A total of 483 elderly patients with type 2 diabetes who visited Tianjin First Central Hospital from June to December 2022 were selected using convenience sampling. They were randomly divided into a modeling group ( n=338) and a validation group ( n=145). Data were collected using a self-designed general information questionnaire, the Short-Form Mini Nutritional Assessment (MNA-SF), the Geriatric Depression Scale-15 (GDS-15), the Frailty Phenotype (FP), the Montreal Cognitive Assessment (MoCA), and the Clinical Dementia Rating (CDR). Logistic regression analysis was performed to identify the influencing factors. A cognitive frailty risk prediction nomogram model was constructed based on the results. The model was validated in the validation group, and its predictive performance and clinical applicability were evaluated using the area under the receiver operating characteristic curve ( AUC), calibration curve, and clinical decision curve analysis. A total of 483 questionnaires were distributed and all were returned as valid, resulting in a 100.0% response rate. Results:The prevalence of cognitive frailty in the 483 elderly patients with type 2 diabetes was 20.3% (98/483). Age, regular exercise, duration of diabetes, HbA1c levels, depression and nutritional status were identified as predictive factors in the model. The AUC of the model was 0.886, and the Hosmer-Lemeshow test showed a χ 2 value of 8.004 ( P=0.433). The optimal cutoff value was 0.335, and the accuracy was 89.0%. Conclusions:The prediction model demonstrates good fit and strong predictive performance, and can intuitively and easily identify elderly patients with type 2 diabetes who are at high risk of cognitive frailty, providing a reference for early screening and intervention.
7.Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China: Findings from real-world data
Ruoxi HE ; Xiaoxia REN ; Ke HUANG ; Jieping LEI ; Hongtao NIU ; Wei LI ; Fen DONG ; Baicun LI ; Ye WANG ; Ting YANG ; Chen WANG
Chinese Medical Journal 2024;137(10):1179-1189
Background::Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD.Methods::Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared.Results::Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34%-3.10%), 2.09% (95% CI: 1.76%-2.43%), and 1.25% (95% CI: 0.99%-1.51%), respectively. In multivariable models, age ≥60 years (60-69 years, odds ratio [OR]: 1.90, 95% CI: 1.11-3.25; ≥80 years, OR: 2.00, 95% CI: 1.06-3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96-13.21), urban residence (OR: 1.69, 95% CI: 1.07-2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21-2.58; senior high school or above, OR: 2.61, 95% CI: 1.69-4.03), former smoking (OR: 1.79, 95% CI: 1.15-2.79), and regular inhaled medication treatment (OR: 3.28, 95% CI: 2.29-4.70) were positively associated with vaccination. Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated (OR: 0.65, 95% CI: 0.45-0.96). Compared with unvaccinated participants, vaccinated participants adhered better to pharmacological and non-pharmacological treatment.Conclusions::Influenza and pneumococcal vaccination coverage are extremely low. Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.
8.Effect of computer-assisted training on post-stroke dysarthria
Tianyuan WEI ; Yufan LIN ; Yi HE ; Mingjie SONG ; Chaojinzi LI ; Qingsu ZHANG ; Xiaoxia DU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(5):520-525
Objective To compare the effect of routine speech training and computer-assisted training on post-stroke dysarthria. Methods From March,2021 to April,2023,72 patients with post-stroke dysarthria in Beijing Bo'ai Hospital were ran-domly divided into control group(n=36)and experimental group(n=36).Both groups received routine rehabili-tation,while the control group received routine speech training,and the experimental group received computer-assisted training,for four weeks.They were assessed with modified Frenchay Dysarthria Assessment(m-FDA)and Speech Intelligibility(SI)before and after intervention. Results Eight cases in the control group and one case in the experimental group dropped down.The scores of m-FDA and SI improved in both groups after treatment(|Z|>4.183,P<0.001),and there was no significant difference between two groups(|Z|<1.598,P>0.05).Noninferiority of m-FDA was found between two groups(|t|>3.656,P<0.001). Conclusion Computer-assisted training could improve the speech function of patients with post-stroke dysarthria,simi-lar to routine speech training.
9.Monitoring and occupational health risk assessment of key volatile organic compounds in workplace air based on qualitative monitoring
Xiaoxia XIANG ; Xuejian ZHANG ; Yang LIU ; Liu HE ; Jun LUO
Journal of Environmental and Occupational Medicine 2024;41(11):1246-1250
Background Occupational hazards in the workplace are often determined through on-site investigations and recognized hazards to determine monitoring items, and occupational health risk assessments are rarely carried out on the monitoring results. Objective Based on the qualitative results of volatile organic compounds, to monitor 8 types of volatile organic compounds in workplace air, and conduct occupational health risk assessments for workstations with disqualified results. Methods This study selected 29 enterprises from 12 key industries listed in the Work Plan for Monitoring Occupational Disease Hazards in Workplaces in Chongqing (2023) in 5 districts and counties of Chongqing. A total of 49 key workstations, including spray painting, glue brushing, glue adjustment, adhesion, printing, bonding, packing, oil film, feeding, material preparation,dispersion, and immersion, were selected for air sampling and chemical headspace treatment. The volatile organic compounds in the headspace were separated with a gas chromatography capillary column and sequentially entered into a mass spectrometer for detection. Qualitative analysis of each component was conducted using the National Institute of Technical Standards and Technology standard spectrum library and retention time. Based on the qualitative results, chemical hazards and related workstations were determined, then quantitative evaluation was conducted for key hazards in workplace air, and followed by occupational health risk assessment for the disqualified workstations using semi-quantitative exposure ratio. Results One or more of the 8 key chemical hazards were positive in the 29 enterprises, among which xylene (89.7%) and toluene (86.2%) had the highest positive rates, followed by benzene (34.5%), 1,2-dichloroethane (31.0%), ethylbenzene (20.7%), n-hexane (10.3%), and trichloromethane (6.9%), and trichloroethylene was negative. In the quantitative evaluation for occupational hazards in workplace air, the highest positive rates of chemical hazards were xylene (70.6%) and ethylbenzene (83.3%), and the highest disqualification rate of chemical hazards was 1,2-dichloroethane (50.0%). Out of the 29 enterprises, 8 reported disqualified air key chemical hazards, mainly in the workstations of spray painting and immersion. One spray painting workstation reported 3 disqualified chemical hazards, and one spary painting workstation reported 2 disqualified chemical hazards. The risk level of 1,2-dichloroethane in the spary painting workstations of 3 enterprises was high. The joint risk of 2 enterprises with multiple disqualified chemical hazards was high. Conclusion The positive rates of benzene derivatives and 1,2-dichloroethane in workplace chemicals are high in this study. The risk level of 1,2-dichloroethane in the spary painting workstations of 3 companies is high, and this substance needs special attention in future monitoring.
10.Influencing factors of memory impairment in elderly stroke patients and construction of prediction model
Xiao FEI ; Xiaoxia GAO ; Jianan ZHANG ; Xiaoping YUN ; Zejia HE ; Yu ZHANG ; Jing GUO ; Fan XIE ; Yi ZHANG
Chinese Journal of Geriatrics 2024;43(9):1149-1154
Objective:To examine the factors that contribute to memory impairment in elderly stroke patients and develop a predictive model.Methods:One hundred stroke patients from the First People's Hospital of Changzhou were selected to assess the incidence of memory impairment using the Montreal cognitive assessment memory index score(MoCA-MIS).Univariate analysis and multivariate Logistic regression were performed to determine the factors influencing memory impairment in these patients.Additionally, the correlation among relevant scale scores was examined, and a prediction model was developed.Results:In the study, 49 patients(49.0%)did not exhibit memory impairment.Patients with memory impairment were found to have higher proportions of individuals over 75 years old, elevated levels of triglyceride(TG), total cholesterol(TC), low-density lipoproteins cholesterol(LDL-C), and National Institute of Health Stroke Scale(NIHSS)scores compared to those without memory impairment.Conversely, patients without memory impairment had higher proportions of individuals with more than 9 years of education, higher levels of high-density lipoprotein cholesterol(HDL-C), mini-mental state examination(MMSE)scores, Rivermead behavioural memory test-Ⅱ(RBMT-Ⅱ)scores, and picture-based memory impairment screen(PMIS)scores(all P<0.05).Furthermore, Montreal cognitive assessment-memory index(MoCA-MIS)scores in stroke patients with memory impairment showed negative correlations with NIHSS scores, TG, and LDL-C, while showing positive correlations with HDL-C, MMSE scores, RBMT-Ⅱ scores, and PMIS scores(all P<0.05).Multifactorial Logistic regression analysis indicated that years of education, TG, HDL-C, NIHSS score, MMSE score, RBMT-Ⅱ score, PMIS score, and the location of the lesion in the cortex or temporal lobe were significant factors influencing memory impairment in stroke patients(all P<0.05).The receiver operating characteristic curve(ROC)analysis revealed an area under curve(AUC)of 0.955(95% CI: 0.921-0.977)for the prediction model of memory impairment in stroke patients, with a Yoden index of 0.841. Conclusions:The risk of memory impairment in stroke patients is associated with education years and blood lipid levels.Factors such as high education level, active cognitive function, and memory training serve as protective factors against memory impairment.The prediction model developed using these influencing factors demonstrates high predictive accuracy for post-stroke memory impairment.

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