Lingguizhugan Decoction (LGZG) demonstrates significant efficacy in treating various cardiovascular diseases clinically, yet its precise mechanism of action remains elusive. This study aimed to elucidate the potential mechanisms and effects of LGZG on isoproterenol (ISO) continuous stimulation-induced chronic heart failure (CHF) in mice, providing direct experimental evidence for further clinical applications. In vivo, continuous ISO infusion was administered to mice, and ventricular myocytes were utilized to explore LGZG?s potential mechanism of action on the ?1-adrenergic receptor (?1-AR)/Gs/G protein-coupled receptor kinases (GRKs)/?-arrestin signaling deflection system in the heart. The findings reveal that LGZG significantly reduced the messenger ribonucleic acid (mRNA) expression of hypertrophy-related biomarkers [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] and improved cardiac remodeling and left ventricular diastolic function in mice with ISO-induced CHF. Furthermore, LGZG inhibited the overactivation of Gs/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling and downregulated the downstream transcriptional activity of cAMP-response element binding protein (CREB) and the expression of the coactivator CBP/P300. Notably, LGZG downregulated the expression of ?-arrestin1 and GRK 2/3/5 while upregulating the expression of ?1-AR and ?-arrestin2. These results suggest that LGZG inhibits Gs/cAMP/PKA signaling and ?-arrestin/GRK-mediated desensitization and internalization of ?1-AR, potentially exerting cardioprotective effects through the synergistic regulation of the ?1-AR/Gs/GRKs/?-arrestin signaling deflection system via multiple pathways.
Animals ; Heart Failure/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; G-Protein-Coupled Receptor Kinases/genetics* ; Mice, Inbred C57BL ; Humans ; Isoproterenol ; Arrestins/genetics* ; Chronic Disease

Objective: To investigate the interactive effects of prenatal and postnatal factors on overweight and obesity in preschool children, so as to provide evidence for subsequent planning of prevention strategies and intervention measures. Methods: Between October 2020 and June 2021, a convenience cluster sample of 918 preschool children from four kindergartens in Xuzhou urban area underwent questionnaire surveys and physical examinations. The Chi square test was used to compare intergroup differences in overweight and obesity prevalence. Multivariate Logistic regression analysis was employed to investigate the effects of prenatal and postnatal factors, as well as their interactions, on overweight and obesity in preschool children. Results: The prevalence of overweight and obesity among preschool children was 30.8%, with boys exhibiting a higher rate (37.0%) than girls (24.8%). Statistically significant differences in overweight and obesity prevalence were observed across age groups, genders, paternal pre pregnancy body mass index (BMI), paternal educational level, delivery mode, antibiotic use within the six months after birth, and rapid weight gain during infancy ( χ 2=5.08-17.67, all P <0.05). After adjusting for confounding factors such as age, gender, the only child, parental educational level and parental average monthly income, interaction analysis revealed that when the father was overweight or obese before conception, children delivered by caesarean section had an increased risk of overweight or obesity ( OR= 2.05 , 95%CI =1.02-3.39), and children with rapid weight gain during infancy also had an increased risk ( OR=2.05, 95%CI = 1.08 -3.88) (both P <0.05). Gender stratified analysis revealed that the interaction between paternal pre pregnancy BMI and mode of delivery on overweight and obesity was more pronounced among girls ( OR=4.00, 95%CI=1.51-10.58, P <0.05). While the interaction between the father s pre pregnancy BMI and rapid weight gain during infancy was more pronounced in boys ( OR= 2.85 , 95%CI=1.14-7.08, P <0.05). No significant interactions between prenatal and postnatal factors on overweight and obesity in preschool children were observed (all P >0.05). Conclusions Multiple prenatal and postnatal factors influence overweight and obesity in preschool children. Attention should be paid to mode of delivery and infant weight gain, particularly when the father is overweight or obese, to reduce the risk of overweight and obesity in preschool children.

Objective:To investigate the influence of changes in the cognitive load of anesthesia residents on the teaching effectiveness of high-fidelity scenario simulation.Methods:Eighty-seven anesthesia residents in a grade-A tertiary hospital from February to November 2022 were divided into groups A, B, and C according to the random number method. Three cases were selected from the anesthesia crisis resource teaching case library for high-fidelity simulation training for the three groups, respectively, using the crossover design to control the order of the cases. Each round of training consisted of pre-training instruction, simulation teaching, and post-training summarization and analysis. After three rounds of simulation teaching, cognitive load, anxiety status, test scores, and non-technical skills were evaluated for all the study participants. SPSS 20.0 was used to perform analysis of variance with repeated measures and Pearson's correlation analysis.Results:All the three groups showed significantly higher cognitive load and anxiety scores during the first-round simulation training than during the second-round and third-round simulation trianing. The test scores were significantly lower in the first round [(87.07±5.66), (88.38±5.41), (89.07±6.17)] than in the second round [(95.69±2.29), (96.10±2.08), (96.07±2.60)] and the third round [(96.34±1.45), (96.38±1.50), (96.17±1.73); all P<0.05]. The non-technical skill scores were also significantly lower in the first round [(37.24±7.58), (38.69±7.27), (39.24±8.74)] than in the second round [(46.17±5.55), (47.07±5.59), (47.59±6.74)] and the third round [(47.17±5.21), (48.48±5.38), (48.24±6.83); all P<0.05]. For simulations with the same cases, the trainees showed significantly higher cognitive load and anxiety scores and significantly lower test scores and non-technical skill scores in the first round than in the second and third rounds ( P<0.05). Conclusions:Anesthesia residents have higher levels of cognitive load and anxiety in the first scenario simulation training, which can reduce learning outcomes, and repeated simulation training can reduce trainees' cognitive load and anxiety.

ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill （SQTLP） on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus （T2DM） mice based on nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） pathway. MethodA total of 60 7-week-old male db/db mice ［specific pathogen-free （SPF） grade］ were selected and fed for one week for adaption. They were divided into the model control group， SQTLP low-， medium- and high-dose （19， 38， and 76 g·kg^-1） groups and metformin group （0.26 g·kg^-1） by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose （FBG） was detected. Fasting serum insulin （FINS） levels were detected by enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment-insulin resistance （HOMA-IR） index and the homeostasis model assessment-insulin sensitivity index （HOMA-ISI） were calculated. Oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were conducted. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） and the contents of malondialdehyde （MDA） and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species （ROS） and 4-hydroxynonenal （4-HNE） in skeletal muscle tissue were detected by immunofluorescence （IF）. The expression levels of Nrf2， HO-1， NQO1 and glutamate-cysteine ligase catalytic subunit （GCLC） proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group， FBG， FINS and HOMA-IR in the model group were significantly increased （P<0.05）， while HOMA-ISI was decreased （P<0.05）. The results of OGTT and ITT showed that blood glucose was significantly increased at all time points （P<0.05）， and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased （P<0.05）， and MDA and NADPH contents were significantly increased （P<0.05）. In skeletal muscle tissues， the arrangement of muscle fibers was loose， the nucleus was disordered， and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly decreased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the metformin group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points （P<0.05）. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly increased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased （P<0.05）， and the NADPH content was decreased （P<0.05）. The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05）. Compared with those in the SQTLP low-dose group， FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05） in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice， and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway， promoting the expression of antioxidant enzymes， and thus improving the oxidative stress injury in the skeletal muscle.

AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.

When partial nephrectomy is performed by posterior abdominal approach, the surgical field is poorly exposed, resulting in increased surgical difficulty and risk of injury.In this study, 28 patients with T 1a stage kidney tumors underwent retroperitoneal laparoscopic partial nephrectomy. Intraoperatively, exposure of the surgical field was achieved using the percutaneous puncture of the renal fascia suspension technique. There were no dissatisfactory exposures due to peritoneal damage during the surgery, no additional tubes were inserted, and no conversions to open surgery were needed. The operation time was (76.5±20.3) minutes, blood loss was (92.1±18.7) ml, renal artery clamping time was (19.5±4.3) minutes. Postoperatively, there were no complications such as bleeding, infection, or hematuria.

Objective:To explore the management effect of information nurses in the reception of new surgical instruments and to provide a reference for improving the quality of instrument management in central sterile supply department.Methods:This was a quasi-experimental study. A total of 45 packages of 227 pieces received from January to July 2021 in central sterile supply department of the First Affiliated Hospital of Zhengzhou University were selected as the control group by convenience sampling method, and the conventional mode was used to receive new surgical instruments. Another 51 packages of 259 pieces received from November 2021 to June 2022 were selected as the observation group, and the information nurse management system was set up to receive new surgical instruments. The observation and comparison of the time to complete the receipt of new surgical instruments in central sterile supply department, the incidence of adverse events in the operation process and the satisfaction of medical and nursing staff with the management of new surgical instruments were conducted.Results:The receiving time for newly added surgical instruments of the observation group was 6.00(5.00, 8.00) hours and that of the control group was 28.00(20.00, 42.50) hours, with a statistically significant difference between the two groups ( Z = - 8.26, P<0.01). The incidence of adverse events of new surgical instruments was 0.4%(1/259) in the observation group and 6.2%(14/227) in the control group, there was significant difference between the two groups ( χ2 = 13.52, P<0.01). The satisfaction degree of medical staff in the observation group was 100% (50/50), higher than 72% (36/50) in the control group, and the difference between the two groups was statistically significant ( χ2 = 16.28, P<0.01). Conclusions:The implementation of the post of information nurse in the special post responsibility system in the management of new surgical instruments can effectively manage the specifications of surgical instruments, reduce the receiving time and the occurrence of adverse events, improve the satisfaction of medical staff.

Background: in vitro culture of preantral follicles is a promising technology for fertility preservation. Objectives: This study aims to investigate an optimized three-dimensional (3D) fetal bovine serum (FBS)-free preantral follicle culture system having a simple and easy operation. Methods: The isolated follicles from mouse ovaries were randomly divided in an ultra-low attachment 96-well plates supplement with FBS or bovine serum albumin (BSA) culture or encapsulated with an alginate supplement with FBS or BSA culture. Meanwhile, estradiol (E 2 ) concentration was assessed through enzyme-linked immunosorbent assay of culture supernatants. The diameter of follicular growth was measured, and the lumen of the follicle was photographed. Spindle microtubules of oocytes were detected via immunofluorescence.The ability of oocytes to fertilize was assessed using in vitro fertilization. Results: The diameters were larger for the growing secondary follicles cultured in ultra-low attachment 96-well plates than in the alginate gel on days 6, 8, and 10 (p < 0.05). Meanwhile, the E 2 concentration in the BSA-supplemented medium was significantly higher in the alginate gel than in the other three groups on days 6 and 8 (p < 0.05), and the oocytes in the FBS-free system could complete meiosis and fertilization in vitro. Conclusions The present study furnishes insights into the mature oocytes obtained from the 3D culture of the preantral follicle by using ultra-low attachment 96-well plate with an FBSfree system in vitro and supports the clinical practices to achieve competent, mature oocytes for in vitro fertilization.

Objective:To explore the effect of out-of-hospital nursing based on gratitude extension-construction theory on self-management efficacy of young and middle-aged patients undergoing percutaneous coronary intervention (PCI) .Methods:A total of 136 young and middle-aged patients who underwent PCI in Coronary Heart Disease Ward of Department of Cardiology in Henan Provincial People's Hospital were selected as the research objects by the convenient sampling method. The patients were randomly divided into the control group and the observation group by the envelop method, with 68 patients in each group. The control group received routine out-of-hospital nursing, while the observation group received out-of-hospital nursing based on gratitude extension-construction theory. Self-management efficacy was compared before and after intervention between the two groups.Results:After intervention, the scores for self psychological management, self-management confidence, self-management behavior, self-management cognition and self-management information in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.01) . Conclusions:Out-of-hospital nursing based on gratitude extension-construction theory can significantly improve self-management efficacy of young and middle-aged patients undergoing PCI.