1.Research progress of hydrolases catalyzing amide drugs
Yuxiao WANG ; Xinhong WANG ; Limei WANG ; Zhixia QIU
Journal of China Pharmaceutical University 2025;56(2):244-251
Amide bond is formed by dehydration and condensation of amino and carboxyl groups in a molecule, which is used in structural design of drugs. The stability of the amide bond is affected by many factors, which make the pharmacokinetic behaviors of amide drugs complicated by metabolic heterogeneity. This review proposes that the expression and activity of hydrolase may be one of the important reasons for the obvious differences in the pharmacokinetics of amides among species, summarizes the common metabolic enzymes or proteins responsible for hydrolyzing amides so as to provide some reference for the structural design and further clinical study of amide drugs, and suggests that improper selection of in vitro evaluation systems may be an important cause for the inconsistency between between in vitro and in vivo pharmacokinetic characteristics of drugs, with a summary of the currently used in vitro drug metabolism systems for drug evaluation, aiming to provide a basis for preclinical evaluation of drugs.
2.Current status and influencing factors of frailty among elderly inpatients in Zunyi City
Shuang LI ; Xiaoli YUAN ; Zhixia JIANG ; Xiaoling YANG ; Heting LIANG ; Xiaoling ZHAO ; Chaoping WANG
Chinese Journal of Modern Nursing 2024;30(6):796-800
Objective:To explore the current status of frailty among elderly inpatients in Zunyi City and analyze its influencing factors.Methods:From October 2022 to March 2023, convenience sampling was used to select elderly patients who were hospitalized and treated at six hospitals, namely the Affiliated Hospital of Zunyi Medical University, the Second Affiliated Hospital of Zunyi Medical University, the First People's Hospital of Zunyi, Guizhou Aerospace Hospital, Zunyi Hospital of Traditional Chinese Medicine, and People's Hospital of Honghuagang District, Zunyi, as the research subject. The study subjects were surveyed using the General Information Questionnaire, Barthel Index, Pittsburgh Sleep Quality Index, Geriatric Depression Scale, and Fatigue, Resistance, Ambulation, Illness, Loss of Weight Scale. Multivariate Logistic regression was used to analyze the influencing factors of frailty in elderly inpatients in Zunyi City.Results:A total of 4 013 questionnaires were distributed and 3 853 valid questionnaires were collected, with an effective response rate of 96.01% (3 853/4 013). The incidence of frailty in elderly inpatients was 15.05% (580/3 853). Multivariate Logistic regression analysis showed that the coexistence of multiple diseases, types of long-term medication, activities of daily living, sleep quality, and depression were the influencing factors for frailty in elderly inpatients ( P<0.05) . Conclusions:The incidence of frailty in elderly inpatients was high. Medical and nursing staff should pay attention to elderly inpatients with the coexistence of multiple diseases, long-term use of multiple medications, decreased activities of daily living, poor sleep quality, and depressive emotions, and develop targeted intervention measures for them.
3.Analysis of clinical implementation of nursing group standard for oxygen therapy in adult patients
Xiaojiu QI ; Huiting WANG ; Yu XU ; Zheng HUANG ; Zhixia ZHANG ; Hongwen MA ; Yunyan XIANYU ; Su ZHANG
Chinese Journal of Nursing 2024;59(14):1726-1731
Objective To understand the implementation of the nursing group standards for oxygen inhalation therapy in clinical practice,and to provide a reference for improving the nursing practice of oxygen therapy.Methods A convenience sampling method was used to investigate nurses from 902 hospitals in 24 provinces and municipalities directly under the central government using a self-designed questionnaire from December 15th,2022,to January 14th,2023.The content of questionnaire included whether they had implemented the recommendations of the oxygen therapy standards,the knowledge of safety related to oxygen therapy,and the components of oxygen therapy prescriptions,the indications used for patients receiving oxygen therapy and practice status of oxygen therapy.Results A total of 10481 questionnaires were returned,of which 10447 were valid,with a valid questionnaire recovery rate of 99.68%.63.14%of the nurses indicated that the hospital had organized training on oxygen therapy standards.Only 47.82%of nurses know the correct use of the Venturi mask.41.90%of nurses could indicate the correct indicator of flow adjustment.31.88%of the nurses stated that they will adjust the oxygen flow rate based on the oxygenation status of carbon dioxide storage patients.Only 19.56%of nurses indicated that humidification is applied in oxygen therapy based on the oxygen flow and duration.Conclusion Even though nurses had received training related to oxygen therapy standards,the level of knowledge of oxygen therapy standards was still low;therefore continuous systematic training was needed,and the implementation of the content of oxygen therapy standards needed to be further standardized.Healthcare institutions would focus on organizing systematic training and maintaining the training effect,enhancing infrastructure and providing support for implementation.Recommendation to the nursing administration is to explore how to comprehensively and continuously implementing the oxygen therapy nursing standards with the ultimate goal of providing patients safer and more accurate oxygen therapy.
4.Exploring the Protective Effect of Modified Taoren Chengqi Decoction on Ventilator-induced Lung Injury in Rats Based on the Nrf2/GPX4-ferroptosis Pathway
Zhixia SUN ; Lihui WANG ; Hongliang SUO ; Hua LI ; Qian CHEN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1281-1288
Objective To explore the protective effect of modified Taoren Chengqi Decoction on ventilator-induced lung injury(VILI)in rats based on the nuclear factor-erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)-ferroptosis pathway.Methods Rats were randomly separated into the control group,the model group,the modified Taoren Chengqi Decoction group,the ML385(Nrf2 inhibitor)group,and the modified Taoren Chengqi Decoction+ML385 group,with 12 rats in each group.The rats in control group underwent tracheal intubation and kept spontaneous breathing.The rats of other groups were subjected to mechanical ventilation for 4 hours.Seven days before mechanical ventilation,medication treatment was carried out once a day for seven days.After mechanical ventilation,ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin 6(IL-6)in bronchoalveolar lavage fluid(BALF).Lung wet/dry weight ratio and lung tissue pathology of rat were detected.The reagent kit was applied to detect the content of glutathione(GSH),malonaldehyde(MDA),and Fe2+in rat lung tissue.The relative fluorescence intensity of reactive oxygen species(ROS)and 4-hydroxynonenal(4-HNE)in lung tissue was detected by immunofluorescence staining.The mRNA and protein expressions of solute carrier family 7 member 11(SLC7A11),Nrf2,GPX4 were detected.Results Compared with the control group,the lung tissue of rats in model group was severely damaged,the levels of TNF-α and IL-6 in BALF increased,lung wet/dry weight ratio,content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE increased,but the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 decreased(P<0.01).Compared with the model group,the pathological damage of lung tissue in the modified Taoren Chengqi Decoction group was improved,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,content of MDA and Fe2+,the relative fluorescence intensity of ROS and 4-HNE decreased,the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 increased(P<0.01).However,an opposite trend for corresponding indicators in the ML385 group was found(P<0.01).The pathological injury of lung tissue was alleviated,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE decreased,GSH content,the mRNA expression of Nrf2,SLC7A11 and GPX4,as well as the protein expression of Nrf2 and GPX4 increased in modified Taoren Chengqi Decoction+ML385 group(P<0.01,P<0.05).Compared with ML385 group,the pathological injury of lung tissue was alleviated,the levels of TNF-α and IL-6 in BALF decreased,lung wet/dry weight ratio,the content of MDA and Fe2+,and the relative fluorescence intensity of ROS and 4-HNE decreased,GSH content,the mRNA and protein expression of Nrf2,SLC7A11 and GPX4 increased in modified Taoren Chengqi Decoction+ML385 group(P<0.01).Compared with the modified Taoren Chengqi Decoction group,the pathological damage in lung tissue of rats was intensified,the levels of TNF-α and IL-6 in BALF increased,lung wet/dry weight ratio,the content of MDA and Fe2+,the relative fluorescence intensity of ROS and 4-HNE increased,the content of GSH,the mRNA and protein expressions of Nrf2,SLC7A11,and GPX4 decreased(P<0.01)in modified Taoren Chengqi Decoction+ML385 group.Conclusion Modified Taoren Chengqi Decoction may improve rat VILI by activating the Nrf2/GPX4 pathway to inhibit ferroptosis.
5.Impact of ultrasonic image quality on the consistency of artificial intelligence assisted diagnosis system and manual measurements of biological indicators in children with developmental dysplasia of hip
Shuangshuang ZHANG ; Xiaoyi CHEN ; Wei SHI ; Ziyi WANG ; Tong HAN ; Xin YANG ; Dong NI ; Bingxuan HUANG ; Zhixia WU ; Na XU
Chinese Journal of Medical Imaging Technology 2024;40(7):1067-1071
Objective To observe the impact of ultrasonic image quality on the consistency of artificial intelligence(Al)assisted diagnosis system and manual measurements of biological indicators of developmental dysplasia of hip(DDH).Methods Hip ultrasonic data of 75 DDH and 345 non-DDH children were retrospectively analyzed,and the quality of ultrasonic images were subjectively scored.An evaluation model of ultrasonic image quality was constructed based on 140 ultrasonic images acquired from 140 cases(group A,containing 25 DDH and 115 non-DDH)using entropy weighting method,the weight of anatomic structures and impact factors related to DDH were obtained.The comprehensive image quality scores of other ultrasonic images acquired from 280 cases(group B,including 50 DDH and 230 non-DDH)were calculated,and the images in group B were classified into grade A,B and C in descending order.The consistency of AI and manual measurements of DDH biological indicators in group B was assessed.Results The weight of each anatomic structure and impact factors of DDH obtained with the model were as follows:The lower edge of iliac branch>ilium>glenoid labrum>bony margin>femoral head>motion artifacts.In group B,grade A was observed in 67(9 DDH and 58 non-DDH),grade B was found in 160(26 DDH and 134 non-DDH),while grade C was noticed in 53(15 DDH and 38 non DDH)images.Except for β,femoral head coverage(FHC)and femoral head length diameter,the consistencies between AI and manual measurements of other indicators of DDH were grade A>B>C.In group B,AI and manual measurements were more consistent in DDH than in non-DDH cases.Conclusion Ultrasonic image quality affected the consistency between AI and manual measurements of biological indicators of DDH.When image quality was not good enough,further attention should be paid to measurement of FHC and sizes of femoral head.
6.Current situation and influencing factors of nurses' willingness to engage in telecare in county-level hospitals in Henan Province
Cancan DU ; Zhixia WANG ; Jiaqi WANG ; Shaoxia WANG ; Xiaoyan ZHENG ; Yajuan WEN ; Tianyun ZHAO ; Lina YANG
Chinese Journal of Modern Nursing 2023;29(36):4981-4986
Objective:To understand the current situation of nurses' willingness to engage in telecare in county-level hospitals in Henan Province and analyze its influencing factors.Methods:Using the convenient sampling method, a total of 1 300 clinical nurses from 6 Class Ⅱ Grade A county-level hospitals in Zhengzhou, Hebi, Zhoukou and other cities in Henan Province were selected as the research objects from August 2022 to January 2023. General Data Questionnaire and Clinical Nurses' Willingness to Engage in Telecare Questionnaire were used to investigate the research objects. Non-parametric test and multiple linear regression were used to analyze the influencing factors of clinical nurses' willingness to engage in telecare.Results:A total of 1 300 questionnaires were sent out in this study, and 1 183 were effectively collected, with an effective recovery rate of 91.00% (1 183/1 300). The total score of Clinical Nurses' Willingness to Engage in Telecare Questionnaire of 1 183 nurses in county-level hospitals was [105.00 (98.00, 112.00) ] points, and all items were scored [3.50 (3.27, 3.73) ]. Multiple linear regression analysis showed that professional title, post, whether they knew about telecare, and the number of times of receiving training on nursing information each year were the influencing factors of nurses' willingness to engage in telecare in county-level hospitals ( P<0.05) . Conclusions:In Henan Province, 1 183 nurses in county-level hospitals have a high willingness to engage in telecare. Relevant departments should further strengthen the publicity of relevant contents of telecare, carry out practical operation training related to nursing information, improve the nursing information ability of nurses in county-level hospitals and strengthen the awareness of health management services, so as to promote the successful implementation of telecare services in rural areas.
7.Path analysis of positive and negative affect and associated factors among patients with systemic lupus erythematosus
Zhixia WANG ; Yanling CHEN ; Hong CHEN
Chinese Journal of Practical Nursing 2023;39(28):2191-2198
Objective:To investigate the positive and negative affect of patients with systemic lupus erythematosus (SLE), explore the effect of social support, self-efficacy and psychological resilience on positive and negative affect and relationships among these factors, and provide reference for improving the emotional health of SLE patients.Methods:This was a cross-sectional survey. From February to May 2021, 142 SLE patients attending the outpatient clinic of the Department of Rheumatology and Immunology of West China Hospital, Sichuan University were selected by convenience sampling. Participants were investigated by the general information questionnaire, Perceived Social Support Scale, General Self-efficacy Scale, Connor-Davidson Resilience Scale, and Positive and Negative Affect Schedule. And path analysis was performed to analyze the effect of social support, self-efficacy and psychological resilience on positive and negative affect.Results:A total of 127 valid questionnaires were collected, with an effective response rate of 89.44%. The positive and negative affect scores of 127 SLE patients were (28.09±7.31) and (25.83±8.10) points. And the positive rate (ratio of positive to negative affect) was 1.09; positive affect was positively correlated with social support, self-efficacy and psychological resilience ( r=0.412, 0.448, 0.533, all P<0.01), and negative affect was negatively associated with social support, self-efficacy and psychological resilience ( r=-0.313, -0.239, -0.382, all P<0.01); the results of the path analysis showed that the standardized total effects of social support, self-efficacy and psychological resilience on positive and negative affect in SLE patients were 0.341, 0.313, 0.632 and -0.237, -0.218, -0.439, respectively. There were significant mediating effects between social support and positive and negative affect (95% CI 0.035 -0.111, -0.087- -0.026) mediated by self-efficacy and psychological resilience. Social support could affect positive and negative affect through psychological resilience ( β=0.104, -0.080, both P<0.01) and through self-efficacy and psychological resilience ( β=0.065, -0.050, both P<0.01). Conclusions:Social support, self-efficacy and psychological resilience are the primary factors influencing positive and negative affect in SLE patients. Increasing social support to encourage patients to take social participation more actively and improving the self-efficacy as well as psychological resilience are ought to do for promoting their emotional health.
8.Effect of Jiawei Taoren Chengqi Decoction on autophagy in rats with mechanical ventilation-induced lung injury
Zhixia SUN ; Lihui WANG ; Hongliang SUO ; Qian CHEN
Tianjin Medical Journal 2023;51(12):1349-1355
Objective To explore the impact of Jiawei Taoren Chengqi Decoction on autophagy in rats with mechanical ventilation-induced lung injury(VILI)through adenylate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Sixty SPF male rats were randomly grouped into the sham operation group,the model group,the low-dose Jiawei Taoren Chengqi Decoction group(TCM-L group,2.85 g/kg),the high-dose Jiawei Taoren Chengqi Decoction group(TCM-H group,8.55 g/kg)and the high-dose Jiawei Taoren Chengqi Decoction + AMPK inhibitor Compound C group(TCM-H+CC group,Jiawei Taoren Chengqi Decoction 8.55 g/kg+ Compound C 250μg/kg),12 in each group.Oxygenation index(OI)was measured immediately after intubation and at 1 h,2 h and 4 h after mechanical ventilation.Bronchoalveolar lavage fluid(BALF)was collected after mechanical ventilation,levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-18 in BALF were detected by enzyme-linked immunosorbent assay(ELISA).Rats were sacrificed,and lung tissue was taken to measure the wet/dry weight(W/D)ratio.HE staining was used to observe pathological changes of lung tissue in each group of rats.Lung injury scores were carried out.Morphology of alveolar epithelial cells was observed by transmission electron microscopy.RT-qPCR was applied to detect mRNA expression levels of AMPK and mTORC1 in rat lung tissue.Western blot assay was applied to detect expression levels of AMPK,p-AMPK,mTORC1,p-mTORC1 and autophagy-related proteins in rat lung tissue.Results Compared with the sham group,the pathological damage of lung tissue was serious,lung W/D,levels of TNF-α,IL-1β and IL-18 in BALF,lung injury score,mTORC1 mRNA expression level,and p-mTORC1 protein expression were increased in the model group(P<0.05).OI values at 2 h and 4 h of mechanical ventilation,AMPK mRNA expression level,p-AMPK,LC3-II/LC3-I and Beclin-1 protein expression in lung tissue were decreased(P<0.05).Compared with the model group,the pathological damage of lung tissue was alleviated in the Chinese medicine-H group,and the trend of changes in related indexes was opposite to the above(P<0.05).Autophagosomes in alveolar epithelial cells were increased.Compound C attenuated the protective effect of Jiawei Taoren Chengqi Decoction on VILI rats(P<0.05).Conclusion Jiawei Taoren Chengqi Decoction may promote autophagy and reduce VILI in rats by activating AMPK/mTOR signaling pathway.
9.Establishment and validation of population pharmacokinetic model of docetaxel in malignant tumor patients
Junping WANG ; Zhengyu WU ; Zhixia LOU ; Yuan YAO ; Tingting WU ; Zongtao HU
China Pharmacy 2022;33(18):2261-2265
OBJECTIVE To establis h and validate a population pharmacokinetic model of docetaxel in malignant tumor patients. METHODS The clinical data of malignant tumor patients treated with chemotherapy regimen containing docetaxel in our hospital from June 2019 to December 2021 were retrospectively collected . According to the results of blood concentration detection , based on the three -compartment model the nonlinear mixed effect model (NONMEM)was used ;covariates(age,weight,height, body surface area ,Karnofsky performance scale ,total protein ,albumin,total bilirubin ,aspartate aminotransferase ,alanine aminotransferase and serum creatinine )affecting clearance (CL)were screened by “forward inclusion and backward exclusion ”; the population pharmacokinetic model of docetaxel was established . The model was tested for goodness -of-fit diagnosis and internal validation by Bootstrap . RESULTS A total of 264 measured blood concentrations of 132 patients with malignant tumors during chemotherapy were included . The covariates that had significant effect on CL of docetaxel were serum creatinine and total bilirubin (P<0.01). The results of Bootstrap analysis (parameter median values and 95% confidence intervals )were close to predict results of the established model ;the final model estimated that the population typical value of docetaxel CL was 37.82 L/h. CONCLUSIONS The population pharmacokinetic model of docetaxel in malignant tumor patients is established successfully , which can be used for the formulation and optimization of clinical individualized regimen .
10.Clinical status and related factors of subclinical hypothyroidism in patients with abnormal glucose metabolism
Jin WANG ; Weici XIE ; Wen LIU ; Zhixia BIE
Journal of Public Health and Preventive Medicine 2022;33(2):145-148
Objective To analyze the clinical situation and related factors of subclinical hypothyroidism in patients with abnormal glucose metabolism, and to provide theoretical basis for the prevention and treatment of subclinical hypothyroidism in patients with abnormal glucose metabolism. Methods A total of 428 patients with abnormal glucose metabolism who were treated in the Department of Endocrinology of Tianmen First People's Hospital from March 2018 to March 2020 were selected, and serum FT3, FT4 and TSH levels were determined by automatic immune analysis system. Automatic analyzer was used to measure the levels of FBG, HbA1c, TC, TG, LDL-C and UA. A self-made questionnaire was used to investigate the basic information of all subjects, including gender, age, abnormal course of glucose metabolism, BMI and blood pressure. The survey method was combined with telephone inquiry and field investigation. Logistic regression was used to analyze the independent risk factors for subhypothyroidism in patients with abnormal glucose metabolism. Results Among 428 patients with abnormal glucose metabolism, 89 patients were accompanied by subclinical hypothyroidism, including 39 males and 43 females, with an average age of (45.12±8.13) years. The prevalence of subhypothyroidism in females was higher than that in males, and the difference was statistically significant (χ2=4.353 , P<0.05). There was no significant difference in serum FT3 and FT4 levels between the two groups (P>0.05). The serum TSH level in experimental group was significantly higher than that in control group (P<0.05). Univariate analysis showed statistically significant differences in age, gender, abnormal course of glucose metabolism, BMI, BMI, FBG, HbA1c, UA, TC, LDL-C and SBP between the two groups (P<0.05). Logistic regression analysis showed that old age, high levels of FBG, TC, SBP and UA were independent risk factors for subclinical hypothyroidism in patients with abnormal glucose metabolism (P<0.05). Conclusion The incidence rate of patients with abnormal glucose metabolism complicated with subclinical hypothyroidism is high. The biochemical indexes such as blood glucose, blood lipid, blood pressure and uric acid should be monitored regularly. The early regulation of glucose metabolism disorder is an effective way to prevent and treat subclinical hypothyroidism.


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