This study aims to investigate the effect of anti-PD-1 antibody expressed in mouse mammary gland on the surface antigen protein of spleen T cells, cytokine expression, spleen CD4⁺ T cell proliferation and proliferation related pathways of transgenic mice at the cellular level. Transgenic mice expressing anti-human PD-1 antibody at 8 weeks of age without pregnancy and 18 weeks of age with lactation were divided into two groups, with transgenic negative mice in each group as the control. Spleen lymphocytes were extracted and the changes of spleen lymphocytes were detected. Compared with transgenic negative mice, the proportion of effector T cells of spleen T cells in the immune system of transgenic mice with anti-PD-1 antibody expressed in breast increased, the proportion of Treg cells decreased, and the IFN-γ, IL-17 and IL-2 expressed in CD4⁺ T cells increased in varying degrees. Moreover, IL-4, IL-10 and TGF-β in CD4⁺ T cells did not change, nor did some cell surface protein molecules related to T cell stimulate. There was no significant difference in T cell proliferation between transgenic positive and transgenic negative mice. In transgenic positive mice, the expression of phosphorylated proteins in PI3K/Akt/mTOR and RAS/MEK/ERK pathways were partially up-regulated, but the whole pathway was not completely up-regulated. Therefore, it is feasible to use transgenic mice as host to express monoclonal antibodies related to immune system such as anti-PD-1 antibody.
Mice ; Animals ; Female ; Mice, Transgenic ; Spleen/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cytokines/metabolism*

Objective:To study the role of myocardial work parameters in early identification of myocardial injury in neonatal asphyxia.Methods:From July 2020 to December 2021, neonates diagnosed with mild neonatal asphyxia admitted to the Department of Neonatology of our hospital within 24 h after birth were prospectively enrolled into the asphyxia group. Neonates without asphyxia during the same period were selected as the control group and matched with the asphyxia group for gender, gestational age and birth weight at a ratio of 1:1~1:2. The asphyxia group was subgrouped into preterm asphyxia group and term asphyxia group. All neonates received echocardiography within 24 h after birth. Multiple parameters were measured including M-mode, two-dimensional image, Doppler image, global longitudinal strain (GLS) and myocardial work parameters [global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE)]. The level of serum N-terminal pro brain natriuretic peptide (NT-proBNP) was recorded in the asphyxia group. The data were compared between the asphyxia group and the control group. Correlations between myocardial work parameters and other parameters were analyzed.Results:A total of 33 cases were in the asphyxia group and 43 cases were in the control group. The preterm asphyxia group (18 cases) showed significantly lower GWI and GCW than the preterm control group (18 cases) [GWI: (702±153) mmHg vs. (879±205) mmHg, GCW: (1 016±221) mmHg vs. (1 200±271) mmHg] ( P<0.05). No differences existed in GLS, GWW and GWE. The term asphyxia group (15 cases) showed significantly lower GWW than the term control group (25 cases) [45.0 (30.0, 65.0) mmHg vs. 71.0 (35.5,85.5) mmHg] ( P<0.05). No differences existed in GLS, GWI, GCW and GWE. GWI was negatively correlated with serum NT-proBNP level ( r=-0.327, P<0.05). Conclusions:GWI and GCW may indicate myocardial injury in preterm neonates with mild asphyxia.

Objective:To investigate the factors for serious complications within 30 days after surgery in elderly patients with advanced epithelial ovarian cancer(EOC)who undertook primary debulking surgery(PDS).Methods:The clinical data of International Federation of Gynecology and Obstetrics(FIGO)stage ⅢC/Ⅳ EOC patients aged≥60 years who received PDS in gynecological department of National Cancer Center and National Center of Gerontology between January 2014 and December 2018 were retrospectively analyzed.Clavien-Dindo scoring system was applied to grade the complications within 30 days after surgery.The serious early postoperative complications were those of grade Ⅲ or above occurred within 30 days after surgery.Multivariate Logistic regression analysis was used to screen the independent risk factors of serious complications within 30 days after surgery.Results:A total of 133 patients were included in this study and serious complications rated 11.3%(15/133). The mean age of patients in severe complication group was significantly higher than that in the control group[(69.80±6.56) vs.(65.87±5.14), t=2.699, P=0.008]. The proportion of patients with preoperative ECOG score≥2 was significantly higher in the severe complication group than that in the control group[26.7%(4/15) vs.5.9%(7/118), χ2=4.985, P=0.026], and the proportion of preoperative hypoalbuminemia(<35 g/L)was significantly higher in the severe complication group[20.0%(3/15) vs.3.4%(4/118), χ2=4.897, P=0.027]. However, there was no significant difference in intraoperative bleeding, R0 resection rate as well as surgical complexity( χ2=1.964, 0.330, 4.637, all P>0.05)between the two groups.Multivariate Logistic regression analysis showed that the independent factors for serious early postoperative complications were age≥70 years( OR=4.345, P=0.028), ECOG score≥2( OR=25.619, P=0.008)and preoperative albumin <35 g/L( OR=6.733, P=0.040). Conclusions:In the elderly ovarian cancer patients, individualized perioperative management should be strengthened for the patients with factors associated with serious early postoperative complications, in order to reduce severe complications and improve the prognosis.

Objective:To investigate the similarities and differences of Doppler echocardiographic parameters in healthy adults among Chinese (EMINCA study), Japanese (JAMP study) and Europeans (NORRE study).Methods:Based on the published Doppler echocardiographic data of JAMP and NORRE studies, the corresponding Doppler parameters were selected from the original database of EMINCA study and stratified by sex and age groups accordingly. Independent-samples t-test, summary t-test, and one-way analysis of variance (ANOVA) were used to test the differences between groups. Results:①Common Doppler parameters in three studies included: peak velocities of early diastolic (E) and late diastolic waves (A) of mitral valve inflow, E/A ratio, deceleration time (DT) of E wave, tissue velocities of early diastole (e′ ) and late diastole (a′ ) at both septal and lateral sites of the mitral annulus and the average value of e′ at both sites (average-e′), ratios of E to septal e′ (septal-E/e′), E to lateral e′ (lateral-E/e′), and E to average e′ (average-E/e′). ②Differences between genders: There existed significant gender differences for 5/10 of parameters in EMINCA study, 8/10 in JAMP study and 3/12 in NORRE study (all P<0.05). ③Stratification by sex and age groups: Except for DT for men in EMINCA study, significant differences were found in all 12 Doppler parameters both for men and women in all three studies (all P<0.05). ④Comparison between EMINCA and JAMP studies: There were statistically significant differences in 8/10 and 9/10 of parameters for men and women, respectively (all P<0.05). ⑤Comparison between EMINCA and NORRE studies: 7/12 of parameters both in men and women were significantly different between the two studies (all P<0.05). ⑥For the three studies, 6/10 of parameters both in men and women correlated positively with age ( r=0.12-0.66, all P<0.001), while 4/10 correlated negatively with age ( r=-0.27--0.72, all P<0.001). Conclusions:Doppler echocardiographic measurements in healthy adults are significantly different with genders, ages and races/nationalities. Therefore, gender, age and race/nationality-specific reference values of Doppler echocardiography parameters should be encouraged in clinical practice.

Metaverse technology, which fully combines virtual reality, augmented reality, digital twins, blockchain, Internet of Things and other technologies, enjoys promising prospects and advantages in medical care. This article reviews the types of Metaverse key technologies and their application status in medical care, proposes to develop "Metaverse + nursing" in the future, and looks forward to it, in order to promote the integration of Metaverse and nursing theory and practice and lay the foundation for subsequent research.

Objective:To establish a scientific, sensitive and practical sensitive index system for nutritional screening and nursing quality evaluation of maintenance hemodialysis patients, so as to provide reference for objective evaluation of nutritional screening and nursing quality evaluation of MHD patients.Methods:Based on Donabedian three-dimensional quality structure theory of "structure-process-result", the first draft of the index system was constructed through literature review and semi-structured interview. From September to October 2022, a total of 20 clinical nursing and nursing management experts from the field of hemodialysis in 12 Class Ⅲ Grade A hospitals were selected for two rounds of expert letter consultation to revise and confirm the indicator system.Results:The positive coefficient of the two rounds of expert correspondence were 95.00% and 100.00%, the expert authority coefficient were 0.813 and 0.818, the Kendall's harmony coefficients were 0.121-0.257 (all P<0.05), and the coefficient of variation of each index was less than 0.30. After 2 rounds of expert letter consultation, the sensitive index system for nutritional screening and evaluation of nursing quality for maintenance hemodialysis patients was finally constructed, including 1 structural index, 7 process index and 2 outcome index. Conclusions:In this study, a sensitive index system of nutritional screening and evaluation of nursing quality for maintenance hemodialysis patients with 10 indicators is established, which was scientific, practical and specialized and could be used to standardize the nutritional screening and evaluation nursing work in blood purification centers and promote the continuous improvement of nursing quality.

Objective:To establish an index system for frailty risk assessment of maintenance hemodialysis patients, and scientifically evaluate frailty risk status of maintenance hemodialysis patients.Methods:With the biopsychosocial medical model as the theoretical framework, semi-structured interview method and Delphi expert consultation method were used to establish and screen indicators and analytic hierarchy process was used to determine the weight of indicators, and an indicator system for frailty risk assessment of patients with maintenance hemodialysis was constructed.Results:The effective recovery rates of the two rounds of expert consultation questionnaires were respectively 100.00% (22/22) and 95.45% (21/22), the expert authority coefficients were respectively 0.85 and 0.84, the Kendall's harmony coefficients of the importance of expert opinions were respectively 0.149 and 0.201, and the Kendall's harmony coefficients of the feasibility of expert opinions were respectively 0.134 and 0.175. Finally, the frailty risk evaluation system for maintenance hemodialysis patients was established, including 3 primary indexes, 8 secondary indexes and 36 tertiary indexes.Conclusions:The established frailty risk evaluation index system for patients with maintenance hemodialysis is scientific and practical and comprehensive in content, which can better reflect the specialty characteristics and provide a basis for frailty risk assessment for maintenance hemodialysis patients.

Objective:To observe the effect of irradiation on the production of IL-8 in lung cancer cell line A549 and explore its possible mechanism.Methods:A549 cells irradiated with different doses of X-rays were used to collect cell supernatant, cellular RNA and protein at different time points after irradiation. The expression level of IL-8 mRNA in A549 cells after irradiation was detected by RT-PCR, which was further validated by real-time quantitative PCR. The expression level of IL-8 in the cell supernatant was quantitatively measured by ELISA. The expression levels of cellular signaling pathway molecules in A549 cells after irradiation were detected by Western Blot. The A549 cells were pretreated with p38 MAPK inhibitor, NF-κB inhibitor and ROS scavenger. The effect of these inhibitors on the expression of IL-8 in A549 cells induced by irradiation was evaluated by ELISA.Results:Irradiation up-regulated the expression of IL-8 in A549 cells in a dose-and time-dependent manner. Irradiation activated the p38 MAPK and NF-κB signaling pathway in A549 cells. p38 MAPK and NF-κB inhibitors blocked the induction of IL-8 of A549 cells by irradiation. Inhibition of ROS failed to inhibit the induction of IL-8 of A549 cells by irradiation.Conclusion:Irradiation can increase the production of IL-8 in lung cancer cells A549, possibly through the activation of p38 MAPK and NF-κB signaling pathways in a ROS-independent pattern.

Phosphatidylinositol 3-kinase (PI3K) signaling plays an important role in the regulation of cellular lipid metabolism and non-alcoholic fatty liver disease (NAFLD). However, little is known about the role of the regulatory subunits of PI3K in lipid metabolism and NAFLD. In this study, we characterized the functional role of PIK3R3 in fasting-induced hepatic lipid metabolism. In this study, we showed that the overexpression of PIK3R3 promoted hepatic fatty acid oxidation via PIK3R3-induced expression of PPARα, thus improving the fatty liver phenotype in high-fat diet (HFD)-induced mice. By contrast, hepatic PIK3R3 knockout in normal mice led to increased hepatic TG levels. Our study also showed that PIK3R3-induced expression of PPARα was dependent on HNF4α. The novel PIK3R3-HNF4α-PPARα signaling axis plays a significant role in hepatic lipid metabolism. As the activation of PIK3R3 decreased hepatosteatosis, PIK3R3 can be considered a promising novel target for developing NAFLD and metabolic syndrome therapies.
Animals ; Diet, High-Fat ; Fatty Liver ; Lipid Metabolism ; Mice ; Non-alcoholic Fatty Liver Disease ; Phenotype ; Phosphatidylinositol 3-Kinase

Objective: This paper analyzed the present clinical researches of traditional Chinese medicine (TCM) in the treatment of heart failure caused by coronary heart disease and discusses the ideas and methods of evidence-based optimization. Methods: PubMed, EMBASE, Cochrane Library, CNKI, WanFang, VIP and CBM were searched to screen the clinical studies of TCM for treating heart failure caused by coronary heart disease. The problems and solutions were discussed by evaluating the risk of bias of the studies and analyzing the outcomes compared with the Cochrane systematic reviews of chronic heart failure. Results: A total of 32 clinical researches were included and the methodological quality of the studies was generally low. In addition, few studies assessed the endpoint events, mortality and readmission, as the primary outcomes in their trials, which is significantly different from the outcomes concerned in the Cochrane systematic reviews. Conclusion: It is really critical to improve the methodological quality of the trials and to choose the endpoint events as the primary outcomes in the evidence-based optimization of the prevention and treatment of TCM for heart failure caused by coronary heart disease Chinese medicine.