ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A （IDH3A） on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers （n=10） and patients with heart failure （HF） （n=10）， and in the myocardium of mice subjected to transverse aortic constriction （TAC） surgery and sham operation， as well as in phenylephrine （PE）-induced neonatal rat ventricular cardiomyocytes （NRVCs）， was assessed by real-time quantitative polymerase chain reaction （RT-qPCR） and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity， IDH3A_D208A， was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype， ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid （AKG） on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay， respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients， in the myocardium of TAC-operated mice， and in PE-induced NRVCs （P = 0.005 2，P = 0.026 6，P = 0.041 3 and P = 0.006 6， respectively）. Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs （P < 0.000 1， P = 0.000 1 and P = 0.000 2， respectively）. The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs （P = 0.001 2 and P<0.000 1， respectively）， whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could， but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level， providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

Objective:To investigate the risk factors for lymph node metastasis in patients with early gastric cancer and establish a model for prediction of risk.Methods:The cohort of this retrospective observational study comprised 1096 patients who had undergone radical gastric cancer surgery combined with standard D1 lymphadenectomy and been diagnosed with early gastric cancer by postoperative pathology in Zhongshan Hospital affiliated with Fudan University from January 2016 to July 2022. The patients were allocated to groups with and without lymph node metastases. Clinicopathological characteristics were compared between the two groups and multi-factor logistic regression analysis used to identify independent risk factors for lymph node metastasis in patients with early gastric cancer. Indications for endoscopic resection in the Japanese Gastric Cancer Association (JGCA) guideline were also incorporated into construction of the model. The patient cohort was divided into training and validation sets in a 6:4 ratio. The identified independent risk factors were used to construct a predictive nomogram. Receiver operating characteristic curves were plotted separately and the difference between them in predictive efficacy was compared using the area under the curve (AUC).Results:A total of 1,096 patients with early gastric cancer were included, with 750 males and 346 females. Their average age was (61.4±10.9) years old, and the mean tumor diameter was (23.8±11.4) mm. Among them, 188 patients (17.2%) had positive lymph node metastasis, with 109 cases in N1 stage, 42 cases in N2 stage, and 37 cases in N3 stage. Additionally, 462 patients were in T1a stage, while 634 patients were in T1b stage. Univariate analysis showed that tumor diameter, location, Lauren classification, gross morphology, histological type, intravascular invasion, ulceration, differentiation type and tumor T stage were associated with lymph node metastasis after radical gastrectomy for early gastric cancer (all P<0.05). Multifactorial analysis showed that the presence of intravascular invasion (OR=14.822, 95%CI: 9.323–23.572, P<0.001), undifferentiated type (OR=3.095, 95%CI: 1.649–5.811, P<0.001), tumor T1b (OR=1.798, 95%CI: 1.053–3.079, P=0.032), and tumor diameter ≥2 cm (OR=1.229, 95%CI: 1.031–1.469, P=0.022) were independent risk factors for lymph node metastasis. The baseline data of the training set and validation set were consistent in terms of balance (all P>0.05). We used the above variables to establish a predictive nomogram for lymph node metastasis in patients with early gastric cancer. The AUC values obtained from the validation of the model in the training and validation sets were 0.880 (95%CI: 0.849–0.911) and 0.881 (95%CI: 0.841–0.921), respectively, and were significantly better than the predictive efficacy based on the JGCA guideline (AUC=0.777, 95%CI: 0.746–0.809, P<0.001). Conclusions:Patients with early gastric cancer and intravascular invasion, undifferentiated tumors, tumor T1b, and diameter ≥2 cm are at higher risk of postoperative lymph node metastasis than other patients. The predictive model developed in this study more accurately predicts lymph node metastasis in patients with early gastric cancer than previously proposed methods.

Host cell residue DNA is one of the most common impurity which can affect the safety of biological products,therefore,domestic and international regulatory agencies have required the limit for host cell residue DNA in different biological products,either at the final product qualification or the appropriate intermediate control stage.The removal effect is verified by monitoring the residue DNA of products in different production stages,which is beneficial for assuring the scientificity and stability of the production process.In order to strengthen the understanding of control strategy about host cell residual DNA,the paper reviews progress in host cell residual DNA in biological products by authors'work experience and other's research,which provides reference for future work.

Objective:To investigate the risk factors for lymph node metastasis in patients with early gastric cancer and establish a model for prediction of risk.Methods:The cohort of this retrospective observational study comprised 1096 patients who had undergone radical gastric cancer surgery combined with standard D1 lymphadenectomy and been diagnosed with early gastric cancer by postoperative pathology in Zhongshan Hospital affiliated with Fudan University from January 2016 to July 2022. The patients were allocated to groups with and without lymph node metastases. Clinicopathological characteristics were compared between the two groups and multi-factor logistic regression analysis used to identify independent risk factors for lymph node metastasis in patients with early gastric cancer. Indications for endoscopic resection in the Japanese Gastric Cancer Association (JGCA) guideline were also incorporated into construction of the model. The patient cohort was divided into training and validation sets in a 6:4 ratio. The identified independent risk factors were used to construct a predictive nomogram. Receiver operating characteristic curves were plotted separately and the difference between them in predictive efficacy was compared using the area under the curve (AUC).Results:A total of 1,096 patients with early gastric cancer were included, with 750 males and 346 females. Their average age was (61.4±10.9) years old, and the mean tumor diameter was (23.8±11.4) mm. Among them, 188 patients (17.2%) had positive lymph node metastasis, with 109 cases in N1 stage, 42 cases in N2 stage, and 37 cases in N3 stage. Additionally, 462 patients were in T1a stage, while 634 patients were in T1b stage. Univariate analysis showed that tumor diameter, location, Lauren classification, gross morphology, histological type, intravascular invasion, ulceration, differentiation type and tumor T stage were associated with lymph node metastasis after radical gastrectomy for early gastric cancer (all P<0.05). Multifactorial analysis showed that the presence of intravascular invasion (OR=14.822, 95%CI: 9.323–23.572, P<0.001), undifferentiated type (OR=3.095, 95%CI: 1.649–5.811, P<0.001), tumor T1b (OR=1.798, 95%CI: 1.053–3.079, P=0.032), and tumor diameter ≥2 cm (OR=1.229, 95%CI: 1.031–1.469, P=0.022) were independent risk factors for lymph node metastasis. The baseline data of the training set and validation set were consistent in terms of balance (all P>0.05). We used the above variables to establish a predictive nomogram for lymph node metastasis in patients with early gastric cancer. The AUC values obtained from the validation of the model in the training and validation sets were 0.880 (95%CI: 0.849–0.911) and 0.881 (95%CI: 0.841–0.921), respectively, and were significantly better than the predictive efficacy based on the JGCA guideline (AUC=0.777, 95%CI: 0.746–0.809, P<0.001). Conclusions:Patients with early gastric cancer and intravascular invasion, undifferentiated tumors, tumor T1b, and diameter ≥2 cm are at higher risk of postoperative lymph node metastasis than other patients. The predictive model developed in this study more accurately predicts lymph node metastasis in patients with early gastric cancer than previously proposed methods.

Objective:To compare the application effects of three different extubation techniques in patients with mechanical ventilation in intensive care unit (ICU).Methods:A prospective randomized controlled study was conducted. Mechanical ventilation patients admitted to the critical care department of the First Affiliated Hospital of Guangxi Medical University from July to November 2023 were enrolled. According to the random number table generated by Excel, the patients were divided into negative pressure group, positive pressure group 1 and positive pressure group 2, with 45 cases in each group. On the basis of routine nursing, the negative pressure group used the negative pressure extubation technique to remove the tracheal catheter. In the positive pressure group, the pressure support (PS) and positive end-expiratory pressure (PEEP) of the positive pressure group 1 were 7 cmH 2O (1 cmH 2O≈0.098 kPa) and 5 cmH 2O, and the PS and PEEP of the positive pressure group 2 were 15 cmH 2O and 10 cmH 2O. The main outcome measures were extubation related complications, including tachypnea, severe cough, sore throat, upper airway obstruction spasm, extubation failure, hypoxemia, and hypercapnia. The secondary outcome measures were the variation of heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and blood oxygen saturation before and 1, 15 and 30 minutes after extubation. Results:Finally, 42 patients were included in each group. There were no significant differences in gender, age, catheter retention days, duration of mechanical ventilation, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), catheter model and diagnosis among the three groups, which were comparable. There were statistically significant differences in the incidence of tachypnea, severe cough, sore throat, upper airway obstruction spasm, hypoxemia and hypercapnia among the three groups, while there was no statistically significant difference in the failure rate of extubation. The incidence of tachypnea, severe cough, sore throat, upper airway obstruction spasm, hypoxemia and hypercapnia after extubation in positive pressure group 1 and positive pressure group 2 were lower than those in negative pressure group (7.14%, 9.52% vs. 33.33%; 7.14%, 4.76% vs. 28.57%; 61.90%, 52.38% vs. 88.10%; 11.90%, 19.05% vs. 45.24%; 7.14%, 7.14% vs. 30.95%; 4.76%, 2.38% vs. 28.57%; all P < 0.05). There were no significant differences in extubation related complications between group 1 and group 2. There were significant differences in the time effect of heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and blood oxygen saturation 30 minutes after extubation among three groups ( F values were 145.792, 49.749, 22.486, 23.622 and 242.664, respectively, all P < 0.01). The intergroup effect of blood oxygen saturation was statistically significant ( F = 3.835, P = 0.024), and the blood oxygen saturation in positive pressure group 1 and positive pressure group 2 were higher than those in negative pressure group 1 minute and 30 minutes after extubation (1 minute after extubation: 0.97±0.02, 0.97±0.02 vs. 0.95±0.02; 30 minutes after extubation: 1.00±0.01, 1.00±0.01 vs. 0.99±0.02, all P < 0.05). The interaction effects of heart rate and blood oxygen saturation were statistically significant ( F values were 3.512 and 7.226, respectively, both P < 0.01). Conclusions:Compared with negative pressure extubation, positive pressure extubation can effectively reduce extubation related complications in ICU mechanically ventilated patients. It is beneficial to maintain stable blood oxygen saturation within 30 minutes after extubation, and has better clinical application effects. It is recommended to use low pressure extubation.

Health behavior decision-making often involves the balance of gains and losses at different time points,which affects the choice and maintenance of health behaviors.As a cognitive processing method of"pre-experiencing"future events,Episodic Future Thinking(EFT)can promote the formation of health intentions and health behavior change by increasing the value of future health outcomes.This paper reviews the concept,intervention model and action effect of EFT in health behaviors,in order to provide references for nurses to innovate health education and behavior management from the perspective of behavioral economics.

Objective : To investigate the changes of iron and other metal elements and inflammatory factor γ interferon (IFN⁃γ) in the liver after taking deferiprone (DFP) in mice with chronic infection of Toxoplasma gondii , and to investigate the efficacy of DFP in the treatment of liver injury caused by chronic infection of Toxoplasma gondii. Methods : 6 ⁃week⁃old female C57BL/6 mice were randomly divided into four groups : control group , control + DFP group , TgCtWh6 group , TgCtWh6 + DFP group , with 6 mice in each group , and sterile gavage PBS in control group. Daily gavage was 50 μg/kg DFP in TgCtWh6 + DFP group , 20 toxoplasma cysts in TgCtWh6 group , 20 toxoplasmosis cysts in TgCtWh6 + DFP group , 20 toxoplasmosis cysts with daily gavage of 50 μg/kg DFP , and mice were sacrificed and liver tissues were taken after 45 days. Inductively coupled plasma mass spectrometry (ICP⁃MS) was used to detect the content of iron and other metal elements in mouse liver tissues. Real⁃time PCR (qRT⁃PCR) and Western blot were used to detect the mRNA levels and protein levels of IFN⁃γ and ferritin heavy chain (Fth) in mouse liver tissues , respectively. Results : Compared with the TgCtWh6 group , the Fth content in the liver (P < 0. 01) was significantly reduced in the liver of the TgCtWh6 + DFP group after taking DFP , the iron metabolism disorder was effectively improved , the IFN⁃γ content in the liver was significantly lowered (P < 0. 01) , and the inflammatory response of the liver was also reduced. Conclusion DFP can effectively improve iron metabolism disorders in the liver after infection with Toxoplasma gondii and reduce inflammatory damage in the liver.

Objective:To integrate qualitative research on the experience of type 2 diabetes patients using self-management APP, so as to provide evidence support for the design and promotion of highly accepted diabetes self-management APP.Methods:This study is a Meta-synthesis. Qualitative research on experience of type 2 diabetes patients using self-management APP was retrieved through computer in China National Knowledge Infrastructure (CNKI) , WanFang, VIP, China Biology Medicine disc Literature Database, PubMed, Web of Science, Cochrane Library, Embase, CINAHL, PsycINFO, Ovid (LWW Journals) , Scopus Chinese and English databases. The retrieval time limit was from the establishment of the database to April 30, 2022. According to the quality evaluation criteria for qualitative research of the Joanna Briggs Institute (JBI) Evidence-Based Health Care Center, the methodology of the included article was evaluated, and the included article was integrated with the method of pooled Meta-synthesis.Results:A total of 11 articles were included, 48 research findings were extracted and summarized into 3 integration results and 14 new categories. The integration results included that self-management APP promoted patients to form continuous self-management behavior and improved physical and mental health, obstacle factors that affected patients' use of APP, and patients' suggestions for improving the function of APP.Conclusions:Patients feel the benefits of self-management APP, such as correct understanding of diabetes, disease control, and improvement of psychological status. When developing relevant APP, we should pay attention to the change of patient behavior, design the APP function based on user needs, conduct cultural adjustment, improve training and technical support, and improve its acceptance and promotion.

Objective:To systematically review the risk prediction models for hypoglycemia in diabetic patients.Methods:The literatures published up to March 25, 2022 was retrieved from PubMed, Embase, Web of Science, Cochrane Library, CINAHL, MEDLINE, China National Knowledge Infrastructure, Wanfang, VIP and SinoMed. Two researchers independently screened the literatures, extracted information, and applied the PROBAST tool to evaluate the quality of the included models.Results:A total of 11 literatures and 13 models were included. The area under the receiver operating characteristic curve or C statistic of all models was 0.666-0.890, with a high risk of bias and a low risk of applicability, and the most included predictors were chronic kidney disease and age. The main reason for the bias in the model were insufficient number of events in the dependent variable, improper handling of continuous variables, and screening of predictors by single factor analysis. Conclusions:The existing hypoglycemia risk prediction models for diabetic patients are still in the development stage, and medical and nursing staff can choose the existing hypoglycemia models according to the results of this systematic review and clinical practice. In the future, we should improve the existing models based on tools or carry out large-sample, multi-center, prospective cohort studies, and build a high-quality hypoglycemia risk prediction model for diabetic patients that is more suitable for China based on more comprehensive and accurate statistical methods and clinical data.

Objective:To investigate protective effect of Pinus massoniana needle extract (PMNE) against oxidative stress in human dermal papilla cells (HDPC) , and to explore its mechanisms. Methods:As research objects, some cultured HDPC were treated with H 2O 2 at different concentrations of 0 (control group) , 0.1, 0.2, 0.4, 0.8 and 1.0 mmol/L, in order to establish the optimal condition for in vitro oxidative stress in HDPC; some other HDPC were transfected with nuclear factor-erythroid 2-related factor 2 (Nrf2) specific small interfering RNAs (siRNA1, siRNA2, siRNA3) or a Nrf2-overexpressing plasmid (pCMV6-XL5-Nrf2) , the HDPC transfected with a scrambled-siRNA and an empty plasmid pCMV6-XL5 served as the control siRNA group and control plasmid group respectively, and HDPC subjected to conventional culture served as the blank group; after the above treatment, real-time fluorescence-based quantitative PCR and Western blot analysis were performed to determine Nrf2 mRNA and protein expression, respectively; cell viability and apoptosis were detected in the above transfected cells after the treatment with H 2O 2 at an optimal concentration. In the subsequent experiment, some HDPC were divided into several groups: control group subjected to conventional culture, dihydrotestosterone group treated with 0.03 μg/ml dihydrotestosterone, proanthocyanidin group treated with 0.03 μg/ml dihydrotestosterone and 6.00 μg/ml proanthocyanidin B2, PMNE groups treated with 0.03 μg/ml dihydrotestosterone and PMNE at different concentrations of 1, 5, 25 and 100 μg/ml; after the above treatment, cell viability and apoptosis were detected, relative fluorescence intensity of intracellular reactive oxygen species (ROS) , malondialdehyde (MDA) content, mRNA and protein expression of Nrf2, quinone oxidoreductase 1 (NQO1) , heme oxygenase 1 (HO-1) , Kelch-like ECH-related protein 1 (Keap1) , transforming growth factor (TGF) -β1, Sma- and Mad-related protein 2/3 (Smad2/3) , phosphorylated Smad2/3 (p-Smad2/3) were determined in HDPC. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference- t test for multiple comparisons. Results:The viability of HDPC ranged from 75% to 85% after the treatment with 0.4 mmol/L H 2O 2, which was selected as the optimal condition for in vitro oxidative stress in HDPC. Compared with the blank group and control siRNA group, the Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups showed significantly decreased Nrf2 mRNA and protein expression (all P < 0.05) , but significantly increased apoptosis rate (Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups, blank group and control group: 12.50% ± 0.05%, 26.07% ± 0.05%, 58.44% ± 1.03%, 10.38% ± 0.64%, 13.05% ± 0.12%, respectively; all P < 0.05) . Nrf2 protein expression was the lowest in the Nrf2-siRNA2 group, so Nrf2-siRNA2 was selected as the optimal interfering fragment for subsequent experiments. Compared with the blank group and control plasmid group, the Nrf2 overexpression group showed significantly increased Nrf2 mRNA and protein expression (both P < 0.05) , but a significantly decreased apoptosis rate (all P < 0.05) . After the treatment with 0.4 mmol/L H 2O 2, the Nrf2 overexpression group showed a significantly decreased apoptosis rate, but significantly increased cell viability compared with the empty vector group ( t = 3.66, 40.40, respectively, both P < 0.001) ; the Nrf2-siRNA2 group showed a significantly increased apoptosis rate, but significantly decreased cell viability compared with the control group ( t = 13.13, 67.37, respectively, both P < 0.001) . In the PMNE treatment experiment, the proanthocyanidin group and PMNE groups showed significantly increased cell viability, but significantly decreased apoptosis rates compared with the dihydrotestosterone group (all P < 0.01) ; proanthocyanidin and PMNE at different concentrations could significantly inhibit dihydrotestosterone-induced overexpression of ROS and MDA in HDPC (all P < 0.01) ; the protein expression of Nrf2, NQO1 and HO-1 was significantly higher in the proanthocyanidin group, 5-, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) , while the protein expression of Keap1 and TGF-β1, and the Smad2/3 phosphorylation level were significantly lower in the proanthocyanidin group, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) . Conclusion:Nrf2 plays an important role in protecting against oxidative damage in HDPC, and PMNE may exert marked protective effect on HDPC by activating the Nrf2-antioxidant responsive element signaling pathway.