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.

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.

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.

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.

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.

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.

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.

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.

Objective:To explore the clinical significance of the MYCN gene, PHOX2B gene and plasma cell-free DNA (cfDNA) in risk stratification and predicting the prognosis of high-risk neuroblastoma (NB). Methods:This was a prospective study involving 94 high-risk NB children admitted to Beijing Children′s Hospital, Capital Medical University from August 2017 to December 2018.Relative levels of MYCN and PHOX2B and cfDNA at diagnosis, and 4 and 6 cycles of chemotherapy were detected, and their differences were compared by the Chi- square test.Kaplan-Meier survival analysis was performed to explore their prognostic potential in high-risk NB. Results:Among the 94 high-risk NB children, 14 cases (14.9%) had MYCN amplification, 76 cases (80.8%) had positive expression of PHOX2B and 56 cases (59.6%) had cfDNA level higher than 100 μg/L.The proportion of high lactate dehydrogenase (LDH, ≥1 500 U/L) level in the MYCN gene amplification group (6/14 cases) was higher than that in the normal group (9/80 cases) ( P=0.009). The proportion of multi-site metastasis (54/76 cases) and high neuron specific enolase (NSE) level (NSE≥370 μg/L, 37/76 cases) in PHOX2B positive group were significantly higher than those in the negative group (5/14 cases, 2/14 cases) ( P=0.015, 0.020). The proportion of high LDH and high NSE in high cfDNA concentration (≥229.6 μg/L)group (13/37 cases, 28/37 cases) were significantly higher than those in low cfDNA concentration group (2/48 cases, 10/48 cases) (all P<0.001). With the decreased tumor burden during the treatment, the copy number of PHOX2B gene and cfDNA level were significantly lower than those at the initial diagnosis [0 (0-719.6) copies vs.1 723.5 (0-186 000.0) copies; 19.0 (1.1-225.5) μg/L vs.200.6 (8.0-5 247.4) μg/L, all P<0.001]. The 2-year event-free survival (EFS) rate of the MYCN gene amplification group was significantly lower than that of the normal group[(33.3±13.1)% vs.(58.5±7.1)%, P=0.020]. The 2-year EFS rate of PHOX2B positive group was significantly lower than that of the negative group[(47.9±7.1)% vs.(79.1±11.1)%, P=0.043]. EFS rate in high cfDNA concentration group was significantly lower than that in cfDNA low concentration group[(38.6±9.8)% vs.( 71.7±8.2)%, P=0.001]. After 6 cycles of chemotherapy, EFS rate in the PHOX2B positive group was significantly lower than that in the negative group [(16.7±14.4)% vs.( 60.6±6.6)%, P=0.014]; which was significantly lower in the Metaiodobenzylguanidine (MIBG) positive group than that of the negative group[(35.2±11.7)% vs.(65.8±7.1)%, P=0.037]. The MYCN gene and cfDNA concentration were not correlated with the prognosis of high-risk NB.Survival analysis of the combination of PHOX2B and MYCN gene ( PHOX2B+ /MIBG + , PHOX2B+ or MIBG + , PHOX2B-/MIBG -) showed a significant difference in the survival among three groups[0 vs.(53.6±1.2)% vs.(65.5±7.4)%, P=0.003]. Conclusions:The MYCN and PHOX2B gene and cfDNA concentration are of significance in risk stratification and predicting the prognosis of high-risk NB.Compared with the MYCN gene and cfDNA concentration, the PHOX2B gene is more suitable for monitoring the curative effect of chemotherapy on high-risk NB.A combined analysis of PHOX2B gene and MIBG before treatment can be more accurate in evaluating the treatment effect and residual lesions.

Objective:To summarize the clinical features of neuroblastoma (NB) with bone metastasis in infants and the prognostic factors.Methods:A retrospective analysis was performed on 32 patients aged ≤12 months who were enrolled in Beijing Children′s Hospital, Capital Medical University from January 2010 to December 2019 and had imaging findings suggesting signs of distant bone metastasis.The control group was included NB children, aged ≤12 months, who were admitted to Beijing Children′s Hospital, Capital Medical University during the same period, without signs of distant bone destruction.The clinical manifestations and auxiliary examinations of infants with bone metastasis were summarized, and the efficacy evaluation and survival analysis of infants with regular treatment and follow-up were conducted until December 31, 2020. Kaplan- Meier survival analysis was used for prognostic analysis, and Log Rank test was used for univariate prognostic analysis. Results:There were 32 NB infants with bone metastases, involving 12 males (37.5%) and 20 females (62.5%), accounting for 16.0% (32/200 cases) of infants diagnosed with NB du-ring the same period.The median age of onset was 9 (4.5-12.0) months.The main primary site included the retroperitoneal and adrenal region in 24 cases(75.0%) and mediastinum in 3 cases (9.4%). Among the 32 cases, 14 cases (43.8%) had simple bone metastasis, 19 cases (59.4%) had distant lymph nodes, 18 cases (56.3%) had bone marrow, and 3 cases (9.4%) had intracranial and meningeal metastasis.Bone metastasis mainly occurred in the skull, with 11 cases of single bone metastases and the remaining with 2 or more bone metastases.Compared with 168 NB infants without bone metastasis, the prognosis of those with bone metastasis was significantly worse [3-year overall survival(OS) rate 97.6% vs.82.7%, P=0.001]. Univariate analysis showed that the prognosis of NB children with bone marrow metastasis, meningeal and intracranial metastasis, MYCN gene amplification, and high-risk group was poor (all P<0.05). Two patients returned to the local hospital for treatment after diagnosis.A total of 30 children were recruited for efficacy evaluation and prognostic analysis.Twenty-nine children underwent surgery, of which 6 cases received surgery before chemotherapy and 23 cases received surgery after chemotherapy.One case received chemotherapy only.The mean course of chemotherapy was 6.2 (4-13) times.One case was treated with radiotherapy, 1 case was treated with Metaiodobenzylguanidine (MIBG) therapy, and 1 case was treated with stem cell transplantation.A total of 18 cases (62.1%) event-free survived, and 12 cases (40.0%) had a mean event at 7 (1.5-32.0) months.Among them, 7 cases survived and 5 cases died (16.7%). The expected 3-year event-free survival rate and OS rate were 57.1% and 82.7%, respectively. Conclusions:The most common sites of infant NB metastasis are bone and bone marrow, and the most common sites of bone metastasis are skull.Infants with bone metastasis had a worse prognosis than those without bone metastasis, and infants with bone and bone marrow metastasis had a worse prognosis than infants with single bone metastasis.