Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To investigate the effects of Bruner's constructivist theory on the critical thinking and practice performance of nursing students interning in internal medicine.Methods:One hundred and fifty-three undergraduate nursing students practicing in the department of internal medicine of a Beijing grade A tertiary hospital were selected by convenience sampling and divided into control group ( n=76) and experimental group ( n=77) according to the order of rotation time. The experimental group received teaching based on Bruner's constructivist theory, while the control group was given traditional teaching. SPSS 24.0 was used to perform the t test. Results:Compared with the control group, the experimental group showed a significantly higher critical thinking score [(306.13±33.00) vs. (325.03±32.09)], a significantly higher exit theory assessment score [(94.74±3.24) vs. (96.94±1.79)], a significantly higher exit skills assessment score [(86.68±11.95) vs. (90.23±9.17)], and a significantly higher degree of satisfaction with teaching [(180.08±13.35) vs. (187.91±14.50); all P<0.05]. Conclusions:Bruner's constructivist theory can help nurse students improve their critical thinking, theoretical and practical performance, and satisfaction with teaching, which enhances the effects of internal medicine nursing teaching.

Objective:To study the effect of Wuzhi capsules on tacrolimus trough concentration in kidney transplant recipients with different CYP3A5 genotypes.Methods:From June 2015 to October 2019, 162 patients who underwent renal transplantation for the first time were retrospectively analyzed. The patients were divided into two groups, combined and uncombined, according to whether combined with Wuzhi capsules. There were 81 cases in the uncombined group (55 males and 26 females), and 81 in the combined group (62 males and 19 females). There was no significant difference between the two groups( P=0.219). The ages of the uncombined group and the combined group were (39.26±11.91) years old and (37.21±10.88) years old ( P=0.103), the weights were (62.39±11.64) kg and (66.18±13.89)kg ( P=0.298), systolic blood pressure were (147.28±20.24) mmHg and (145.00±16.42) mmHg (1 mmHg=0.133 kPa)( P=0.276), diastolic blood pressure were (92.25±13.87) mmHg and (92.20±12.53) mmHg ( P=0.886), alanine aminotransferase were (12.24±8.59) U/L and (17.06±13.11) U/L ( P=0.015), aspartate aminotransferase were (17.76±9.12) U/L and (16.57±8.37) U/L ( P=0.463), fasting blood glucose were (8.70±3.48) mmol/L and (7.18±2.74)mmol/L ( P=0.006), hemoglobin were (98.96±17.53) g/L and (101.05±18.67) g/L ( P=0.789), creatinine were (665.22±296.55) μmol/L and (797.32±279.32) μmol/L ( P=0.007), estimated glomerular filtration rate were (11.47±14.11) ml/(min·1.73m 2) and (8.85±3.71) ml/(min·1.73m 2) ( P=0.130)in the kidney transplant recipients before surgery. Among the 162 cases in this study, there were 86 cases (53.09%) of CYP3A5*1*3 genotype, 17 cases (10.49%) of CYP3A5*1*1 genotype, 59 cases (36.42%) of CYP3A5*3*3 genotype, and the minimum allele frequency of CYP3A5*1 was 37.04%. In the uncombined group, CYP3A5*1*3 genotype 39 cases (48.15%), CYP3A5*1*1 genotype 5 cases (6.17%), and CYP3A5*3*3 genotype 37 cases (45.68%). In the combined group, CYP3A5*1*3 genotype 47 cases (58.02%), CYP3A5*1*1 genotype 12 cases (14.81%), and CYP3A5*3*3 genotype 22 cases (27.16%), with statistically significant differences in the two groups ( P=0.024). The patients were treated with a triple immunosuppressive regimen (tacrolimus+ mycophenolate mofetil+ glucocorticoid) based on tacrolimus [initial dose: 0.15-0.30 mg/(kg·d)], combination of Wuzhi capsules in the combination group (11.25 mg, twice a day). The trough concentration of tacrolimus was detected by enzyme-linked immunosorbent assay, compare the difference in the trough concentration of tacrolimus between the two groups. The relationship between the effect of Wuzhi capsules and CYP3A5 gene polymorphism was compared, and compare the changes before and after the application of CYP3A5 genotype combined with Wuzhi Capsules. The influencing factors of tacrolimus trough concentration were analyzed by multiple linear regression. Results:In the combined with Wuzhi capsules, the dose corrected trough concentration (C 0/D) of tacrolimus was higher than that in patients without Wuzhi capsules, and the extent of increase was related to genotype. The C 0/D of tacrolimus in patients with CYP3A5*3*3 genotype in the combination and non-combination groups were (12.15±2.95) (ng·ml -1/0.1mg·kg -1·d -1) and (9.99±2.33) (ng·ml -1/0.1mg·kg -1·d -1) ( P=0.004), CYP3A5*1*3 genotype were (11.11±3.20) (ng·ml -1/0.1mg·kg -1·d -1) and (6.86±1.62) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001), and there were significant difference. However, CYP3A5*1*1 genotype were(8.29±2.64) (ng·ml -1/0.1mg·kg -1·d -1) and (6.16±2.87) (ng·ml -1/0.1mg·kg -1·d -1) ( P=0.160), there was no significant difference. The tacrolimus C 0/D of the combined group before and after the Wuzhi capsule were as follows: CYP3A5*3*3 genotype: (7.18±2.33)(ng·ml -1/0.1mg·kg -1·d -1) and (13.33±3.09) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001); CYP3A5*1*3 genotype: (5.14±2.14) (ng·ml -1/0.1mg·kg -1·d -1) and (10.61±3.20) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001); CYP3A5*1*1 genotype: (5.17±3.75) (ng·ml -1/0.1mg·kg -1·d -1) and (8.31±2.74) (ng·ml -1/0.1mg·kg -1·d -1)( P=0.002), and the differences were statistically significant. The results of multiple linear regression showed that the combination of Wuzhi capsules (β=0.508, P<0.001) and CYP3A5 genotype(CYP3A5*1*3 and CYP3A5*3*3: β=-0.361, P<0.001; CYP3A5*1*1 and CYP3A5*3*3: β=-0.425, P<0.001)could influence the trough concentration. The sex (β=-0.100, P=0.124) and age (β=-0.003, P=0.967) of renal transplant recipients had no statistical significance to tacrolimus C 0/D. Conclusions:In the renal transplant patients, CYP3A5 genotype and combined use of Wuzhi capsules are the main factors affecting tacrolimus C 0/D. In order to achieve the expected trough concentration as soon as possible, the interaction between CYP3A5 genotypes and drug combination should be considered.

【Objective】 To explore the relationship of fat mass and obesity-associated protein (FTO) with the m⁶A modification and expression level of DKK2 in the process of myocardial fibrosis. 【Methods】 Cardiac fibroblasts (CFs) were grouped as follows: Control group, AngⅡ-treated group, AngⅡ+EV group (transfected with empty vector and negative control siRNA and then treated with AngⅡ), AngⅡ+FTO-O group (transfected with FTO overexpression vector and then treated with AngⅡ), and AngⅡ+FTO-O+DKK2 siRNA group (treated with AngⅡ after co-transfection of FTO overexpression vector and DKK2 siRNA). Mice were divided into the following groups: Control group (sham operation group), AMI group (constructing acute myocardial infarction model), AMI+EV group (AMI mice were intraperitoneally injected with nanoparticles containing empty vector), and AMI+FTO-O group (AMI mice were intraperitoneally injected with nanoparticles containing FTO overexpression vector). Then, the expressions of FTO and DKK2 were detected by fluorescence quantitative PCR and Western blotting, the m⁶A modification level of DKK2 was detected by RNA binding protein immunoprecipitation, the cell viability was detected by CCK-8, the cardiac function of AMI mice was evaluated, and the cardiac pathological changes of mice were detected by HE and Masson staining. 【Results】 AngⅡ inhibited the expression of FTO, thereby enhancing the m⁶A modification level of DKK2 and downregulating the expression of DKK2 (P<0.05). AngⅡ promoted cell viability and enhanced the expressions of α-SMA, collagen Ⅰ and collagen Ⅲ (P<0.05). FTO overexpression significantly blocked the above-mentioned regulatory effects of AngⅡ (P<0.05), but DKK2 siRNA could antagonize the effect of FTO overexpression on AngⅡ. The expressions of FTO and DKK2 were downregulated in AMI mice, and the m⁶A modification level of DKK2 was increased (P<0.05). When FTO was overexpressed, the expressions of FTO and DKK2 in AMI mice were significantly restored, the m⁶A modification level of DKK2 and myocardial fibrosis were significantly reduced (P<0.05), and the cardiac pathological changes were significantly improved. 【Conclusion】 FTO can promote the expression of DKK2 by reducing the m⁶A modification level of DKK2, thereby inhibiting the progression of myocardial fibrosis. This indicates that FTO/DKK2 pathway is a key pathway in regulating myocardial fibrosis.

BACKGROUND: Feeding intolerance (FI) among intensive care unit (ICU) patients undergoing early continuous enteral nutrition (EN) is related to poor outcomes. This study aimed to explore the prevalence and risk factors of FI in ICU patients. METHODS: We retrospectively enrolled 1057 patients who received early continuous EN via a nasogastric tube between January 2014 and August 2019. The prevalence of FI during the first 7 days of ICU stay was calculated, and the risk factors were investigated using multivariate logistic regression analysis. RESULTS: The prevalence of FI during the first 7 days of ICU stay was 10.95%. FI occurred in 159 of 1057 (15.04%) patients on ICU day 2, 114 of 977 (11.67%) patients on ICU day 3, and 86 of 715 (12.03%) patients on ICU day 7. Mechanical ventilation (MV) (odds ratio [OR]: 1.928, 95% confidence interval [CI]: 1.064-3.493, P  = 0.03) was an independent risk factor for FI defined by a gastric residual volume (GRV) of 200 mL and/or vomiting, and acute renal failure (OR: 3.445, 95% CI: 1.115-10.707, P  = 0.032) was an independent risk factor of FI defined by a GRV of 500 mL and/or vomiting. Continuous renal replacement therapy (CRRT) was an independent predictor regardless of the FI defined by a GRV of 200 mL (OR: 2.064, 95% CI: 1.233-3.456, P  = 0.006) or 500 mL (OR: 6.199, 95% CI: 2.108-18.228, P  = 0.001) in the ICU patients. CONCLUSIONS FI occurs frequently in early ICU days, especially in patients receiving MV and CRRT. However, further investigation of a consensus definition of FI and risk factors is still warranted in future studies.
Critical Illness ; Enteral Nutrition/adverse effects* ; Humans ; Infant, Newborn ; Intensive Care Units ; Prevalence ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Vomiting/etiology*

Objective:To explore the risk factors of myelosuppression caused by nedaplatin in patients with lung cancer.Methods:The medical records of postoperative patients with advanced lung cancer and receiving nedaplatin-based chemotherapy in Shandong Provincial Qianfoshan Hospital from June 2015 to August 2018 were searched using hospital information system and analyzed retrospectively. According to sex, age (<60 years old, ≥ 60 years old), glutathione mercaptotransferase (GSTP) 1A313G genotype (AA or AG), pathological classification (non-small cell lung cancer, small cell lung cancer), having smoking history or not, being with or without liver injury and kidney injury, the patients were divided into 2 groups, respectively. The overall myelosuppression incidence and incidences of myelosuppression with different manifestations and different degrees were compared respectively between each 2 groups of patients with above-mentioned 7 different clinical features. The risk factors of nedaplatin-induced myelosuppression were analyzed using logistic regression.Results:A total of 46 patients were enrolled, including 34 males and 12 females. Among the 46 patients, 30 cases developed myelosuppression after administration of nedaplatin, and the overall incidence of myelosuppression was 65.2%, including 20 cases of grade Ⅰ-Ⅱ (43.5%) and 10 cases of grade Ⅲ-Ⅳ (21.7%). After administration of nedaplatin, the incidence of severe myelosuppression in patients with small cell lung cancer (3/5) was higher than that with non-small cell lung cancer (17.1%) ( P<0.05), showed by the univariate analysis; the overall incidence of leukopenia in males was higher than that in females (58.8% vs. 25.0%); the overall incidence of leukopenia and neutropenia was higher in patients with smoking history than that in patients without previous smoking history (68.0% vs. 28.6%, 0.01%, P=0.01; 64.0% vs. 33.3%, P=0.04); the overall incidence of thrombocytopenia in patients with small cell lung cancer was higher than that with non-small cell lung cancer (4/5 vs. 9.8%, P<0.01); the differences in the incidences of different degrees of neutropenia in patients with and without smoking history were statistically significant ( P=0.03); the differences in the incidences of different degrees of leukopenia, neutropenia, and thrombocytopenia in patients with different pathological classification were statistically significant ( P<0.01 for all). The binary logistic regression analysis showed that the risk of thrombocytopenia in patients with small cell lung cancer was higher than that with non-small cell lung cancer ( OR=25.00, 95 %CI:2.20-284.61, P=0.01). The orderial logistic regression analysis showed that a pathological classification of small cell lung cancer was a risk factor for severe myelosuppression, leukopenia, neutropenia, and thrombocytopenia ( OR=13.20, 95 %CI: -4.67-0.49, P=0.02; OR=22.20, 95 %CI: -5.37-0.83, P=0.01; OR=19.49, 95 %CI: -5.11-0.82, P=0.01; OR=13.87, 95 %CI: -4.89-0.38, P=0.02). Conclusions:A pathological classification of small cell lung cancer is an independent risk factor for severe myelosuppression in lung cancer patients after taking nedaplatin. Male patients with a history of smoking are more likely to have leukopenia/neutropenia.

Objective:To explore the risk factors of myelosuppression caused by nedaplatin in patients with lung cancer.Methods:The medical records of postoperative patients with advanced lung cancer and receiving nedaplatin-based chemotherapy in Shandong Provincial Qianfoshan Hospital from June 2015 to August 2018 were searched using hospital information system and analyzed retrospectively. According to sex, age (<60 years old, ≥ 60 years old), glutathione mercaptotransferase (GSTP) 1A313G genotype (AA or AG), pathological classification (non-small cell lung cancer, small cell lung cancer), having smoking history or not, being with or without liver injury and kidney injury, the patients were divided into 2 groups, respectively. The overall myelosuppression incidence and incidences of myelosuppression with different manifestations and different degrees were compared respectively between each 2 groups of patients with above-mentioned 7 different clinical features. The risk factors of nedaplatin-induced myelosuppression were analyzed using logistic regression.Results:A total of 46 patients were enrolled, including 34 males and 12 females. Among the 46 patients, 30 cases developed myelosuppression after administration of nedaplatin, and the overall incidence of myelosuppression was 65.2%, including 20 cases of grade Ⅰ-Ⅱ (43.5%) and 10 cases of grade Ⅲ-Ⅳ (21.7%). After administration of nedaplatin, the incidence of severe myelosuppression in patients with small cell lung cancer (3/5) was higher than that with non-small cell lung cancer (17.1%) ( P<0.05), showed by the univariate analysis; the overall incidence of leukopenia in males was higher than that in females (58.8% vs. 25.0%); the overall incidence of leukopenia and neutropenia was higher in patients with smoking history than that in patients without previous smoking history (68.0% vs. 28.6%, 0.01%, P=0.01; 64.0% vs. 33.3%, P=0.04); the overall incidence of thrombocytopenia in patients with small cell lung cancer was higher than that with non-small cell lung cancer (4/5 vs. 9.8%, P<0.01); the differences in the incidences of different degrees of neutropenia in patients with and without smoking history were statistically significant ( P=0.03); the differences in the incidences of different degrees of leukopenia, neutropenia, and thrombocytopenia in patients with different pathological classification were statistically significant ( P<0.01 for all). The binary logistic regression analysis showed that the risk of thrombocytopenia in patients with small cell lung cancer was higher than that with non-small cell lung cancer ( OR=25.00, 95 %CI:2.20-284.61, P=0.01). The orderial logistic regression analysis showed that a pathological classification of small cell lung cancer was a risk factor for severe myelosuppression, leukopenia, neutropenia, and thrombocytopenia ( OR=13.20, 95 %CI: -4.67-0.49, P=0.02; OR=22.20, 95 %CI: -5.37-0.83, P=0.01; OR=19.49, 95 %CI: -5.11-0.82, P=0.01; OR=13.87, 95 %CI: -4.89-0.38, P=0.02). Conclusions:A pathological classification of small cell lung cancer is an independent risk factor for severe myelosuppression in lung cancer patients after taking nedaplatin. Male patients with a history of smoking are more likely to have leukopenia/neutropenia.

Objective: To evaluate the feeding effect of not monitoring gastric residual volume in ICU patients receiving continuous enteral feeding,including complications and calorie intake. Methods: We searched for relevant studies in China national knowledge internet(CNKI), Wanfang Data, PubMed, Embase, Cochrane library. We included all Randomized controlled trials (RCTs) and pre-post studies related to the feeding effect of not monitoring gastric residual volume in ICU patients receiving continuous enteral feeding. Two researchers independently screened, appraised and extracted data, and meta-analysis was conducted via RevMan 5.3 software. Results: 3 RCTs and 2 pre-post studies with 1 000 patients were included. Not monitoring gastric residual volume increase the rate of vomiting [OR=1.35, 95%CI(1.02, 1.80), Z=2.08, P=0.04], decrease the proportion of intolerance to enteral nutrition [OR=0.35, 95%CI(0.26, 0.46), Z=7.29, P<0.01], there were no significant differences in diarrhea [OR=1.14, 95%CI(0.78, 1.67), Z=0.67, P=0.51] and distention[OR=1.24, 95%CI(0.76, 2.03), Z=0.87, P=0.38]. The cumulative calorie deficit between targeted volume and provided volume in not monitoring gastric residual volume group was significantly lower than the control group[MD=-0.29, 95%CI(-0.47, -0.11), Z=3.23, P=0.001], daily provided calorie amount was also significantly higher than the control group [MD=0.35, 95%CI(0.10, 0.59), Z=2.75, P=0.006]. Conclusions Not monitoring gastric residual volume in ICU patients increase calorie intake and have better enteral nutrition provision, decrease the proportion of intolerance to enteral nutrition. Monitoring gastric residual volume should not be taken as a routine task in critical care nursing.

Objective: To investigate the distribution of polymorphisms of glucagon-like peptide-1 receptor gene (GLP-1R) rs10305420 and rs3765467 in Chinese Han type 2 diabetic patients, and the effects on body weight, blood glucose and serum lipid levels. Methods: Two SNPs of GLP-1R rs3765467 and rs10305420 were genotyped by Sanger dideoxy termination sequencing method. The racial difference and the association between the gene polymorphisms and the metabolic markers including BMI, serum lipids and blood glucose were analyzed. Results: The distribution of gene polymorphisms was consistent with the Hardy-Weinberg equilibrium. High-density lipoprotein (HDL-C) levels were significantly lower in the rs10305420 T allele carriers than in the CC genotype (1.00±0.18 vs 1.09±0.22, P=0.02). The triglyceride (TG) level of the rs3765467 A allele carrier was higher than that of the GG type (2.75±2.19 vs 2.07±1.36, P=0.03). The allele frequency of rs10305420 C/T was highly statistically significant compared with European population (P=0.000 3). The allele frequency of rs3765467 G/A was statistically different from that of European and African populations (P<0.01). Conclusions The two genetic polymorphisms were significantly associated with lipid levels in patients with type 2 diabetes, and there was a significant racial difference in the frequency distribution of the two variants.