OBJECTIVE To investigate the mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture based on the AMP-activated protein kinase （AMPK）/silencing information regulatory factor 1 （SIRT1）/ peroxisome proliferator activated-receptor-γ coactivator-1α （PGC-1α） signaling pathway. METHODS Rats with hip fracture surgery were assigned into model group， esketamine group （10 mg/kg）， inhibitor group （250 μg/mL AMPK inhibitor Compound C）， and esketamine+inhibitor group （10 mg/kg esketamine + 250 μg/mL Compound C）， and rats undergoing sham surgery were used as the control group， with 12 rats in each group. New object recognition and Barnes maze experiments were used to E-mail：448231@163.com evaluate cognitive function in rats. The levels of serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β），superoxide dismutase （SOD）， malondialdehyde （MDA）， gamma-aminobutyric acid （GABA）， dopamine （DA） and glutamate （Glu）， and the apoptosis of hippocampal neurons were detected. The pathological morphology of the hippocampal tissue and the ultrastructure of mitochondria were observed. The mRNA expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax），the mRNA and protein expression of AMPK， SIRT1 and PGC-1α， as well as the expression of phosphorylated （p）-AMPK in hippocampal tissue， were detected. RESULTS Compared with the control group， the hippocampal neurons in the model group of rats were disordered， with more neurons necrotic and swollen mitochondria；the new object recognition index， the SOD， GABA， DA levels， Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly reduced， while the latency and number of errors for locating unknown holes， the TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly increased/prolonged （P＜0.05）. Compared with the model group， the esketamine group showed reduced pathological damage to the hippocampal tissue of rats， and the new object recognition index， the SOD， GABA and DA levels， the Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly increased，while the latency and error frequency for locating unknown holes， TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly decreased （P＜0.05）；the inhibitor group showed the opposite trend of changes in these indicators compared to the esketamine group （P＜0.05）.AMPK inhibitor could reverse the improvement effect of esketamine on the above indicators after hip fracture surgery in rats （P＜0.05）. CONCLUSIONS Esketamine may improve postoperative inflammatory response and oxidative stress levels in rats with hip fracture by activating the AMPK/SIRT1/PGC-1α signaling pathway， inhibiting neuronal cell apoptosis， improving mitochondrial structure， and promoting postoperative cognitive function recovery.

OBJECTIVE: To investigate the antioxidant and osteogenic induction capabilities of calcium phosphate nanoflowers (hereinafter referred to as nanoflowers) in vitro at different concentrations. METHODS: Nanoflowers were prepared using gelatin, tripolyphosphate, and calcium chloride. Their morphology, microstructure, elemental composition and distribution, diameter, and molecular constitution were characterized using scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive spectroscopy. Femurs and tibias were harvested from twelve 4-week-old Sprague Dawley rats, and bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured using the whole bone marrow adherent method, followed by passaging. The third passage cells were identified as stem cells by flow cytometry and then co-cultured with nanoflowers at concentrations of 0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 2.8, 3.2, and 3.6 mg/mL. Cell counting kit 8 (CCK-8) assay was performed to screen for the optimal concentration that demonstrated the best cell viability, which was subsequently used as the experimental concentration for further studies. After co-culturing BMSCs with the screened concentration of nanoflowers, the biocompatibility of the nanoflowers was verified through live/dead cell staining, scratch assay, and cytoskeleton staining. The antioxidant capacity was assessed by using reactive oxygen species (ROS) fluorescence staining. The in vitro osteoinductive ability was evaluated via alkaline phosphatase (ALP) staining, alizarin red staining, and immunofluorescence staining of osteocalcin (OCN) and Runt-related transcription factor 2 (RUNX2). All the above indicators were compared with the control group of normally cultured BMSCs without the addition of nanoflowers. RESULTS: Scanning electron microscopy revealed that the prepared nanoflowers exhibited a flower-like structure; transmission electron microscopy scans discovered that the nanoflowers possessed a multi-layered structure, and high-magnification images displayed continuous atomic arrangements, with the nanoflower diameter measuring (2.00±0.25) μm; energy-dispersive spectroscopy indicated that the nanoflowers contained elements such as C, N, O, P, and Ca, which were uniformly distributed across the flower region; Fourier transform infrared spectroscopy analyzed the absorption peaks of each component, demonstrating the successful preparation of the nanoflowers. Through CCK-8 screening, the concentrations of 0.8, 1.2, and 1.6 mg/mL were selected for subsequent experiments. The live/dead cell staining showed that nanoflowers at different concentrations exhibited good cell compatibility, with the 1.2 mg/mL concentration being the best (P<0.05). The scratch assay results indicated that the cell migration ability in the 1.2 mg/mL group was superior to the other groups (P<0.05). The cytoskeleton staining revealed that the cell morphology was well-extended in all concentration groups, with no significant difference compared to the control group. The ROS fluorescence staining demonstrated that the ROS fluorescence in all concentration groups decreased compared to the control group after lipopolysaccharide induction (P<0.05), with the 1.2 mg/mL group showing the weakest fluorescence. The ALP staining showed blue-purple nodular deposits around the cells in all groups, with the 1.2 mg/mL group being significantly more prominent. The alizarin red staining displayed orange-red mineralized nodules around the cells in all groups, with the 1.2 mg/mL group having more and denser nodules. The immunofluorescence staining revealed that the expressions of RUNX2 and OCN proteins in all concentration groups increased compared to the control group, with the 1.2 mg/mL group showing the strongest protein expression (P<0.05). CONCLUSION The study successfully prepares nanoflowers, among which the 1.2 mg/mL nanoflowers exhibits excellent cell compatibility, antioxidant properties, and osteogenic induction capability, demonstrating their potential as an artificial bone substitute material.
Animals ; Osteogenesis/drug effects* ; Mesenchymal Stem Cells/drug effects* ; Calcium Phosphates/pharmacology* ; Rats, Sprague-Dawley ; Rats ; Antioxidants/chemistry* ; Cells, Cultured ; Cell Differentiation/drug effects* ; Nanostructures/chemistry* ; Tissue Engineering/methods* ; Bone Marrow Cells/cytology* ; Coculture Techniques ; Tissue Scaffolds/chemistry* ; Male ; Biocompatible Materials/chemistry* ; Cell Survival ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Cell Proliferation

Objective: To understand the status and related knowledge requirements of health emergency literacy among college students in Shaanxi Province, so as to provide the basis for improving college students health emergency literacy. Methods: A total of 2 723 students from 18 colleges and universities in Shaanxi Province were selected by multi stage random sampling and simple random sampling methods in November 2023, and the survey of health literacy in emergency and knowledge requirements of health emergency literacy was conducted. Statistical analysis was carried out by using χ 2 test, Wilcoxon rank sum test, Kruskal-Wallis H test and Logistic regression analysis. Results: About 28.98% of the surveyed college students had a high level of health emergency literacy, which varied by students whether being only one child, whether having left behind experience, with different personality types, whether being student cadres, and with different frequencies of community or social activities ( χ 2=9.15, 7.90, 32.73, 16.29 , 120.25, P <0.05). The equivalence scores of the four dimensions of health emergency literacy from high to low were poisoning and nuclear and radiation (0.84), medical rescue (0.83), infectious disease (0.82), and basic knowledge and behavior ( 0.77 ). Logistic regression analysis found that college students with left-behind experience were negatively correlated with health emergency literacy and its four dimensions ( OR =0.74, 0.72, 0.80, 0.80, 0.83), while personality type (rational type), community or social activity frequency were positively correlated with the cognitive levels of health emergency literacy and its four dimensions among college students ( OR =1.57, 1.50, 1.33, 1.27, 1.38)( P <0.05). There was a higher level of basic knowledge and behavioral cognition among only child college students ( OR =3.73), and female students had a higher level of health emergency literacy, as well as awareness of infectious disease outbreaks and medical rescue ( OR =1.21, 1.28, 1.21)( P <0.05). The radar map showed that the level of health emergency literacy was positive development radar map. About 67.68 % of the students had a high willingness to acquire health emergency literacy knowledge, and the demand for basic health emergency knowledge and behavioral knowledge was the highest (52.37%). Conclusions College students have insufficient health emergency literacy, but they have the highest demand for health emergency. Publicity and education should be strengthened for students with left behind experience, irrational type, and low frequency of community or social activities.

Objective:To summarize evidence for physical activity management in cancer patients based on the Joanna Briggs Institute (JBI) approach for evidence synthesis in health care, providing a scientific basis for the clinical standardization of physical activity management in cancer patients.Methods:Literature was searched according to the "6S" pyramid model of evidence, using BMJ Best Practice, UpToDate, JBI Evidence-Based Practice Database, Cochrane Library, global guideline websites, professional cancer association websites, and relevant Chinese and English databases for all evidence regarding physical activity in cancer patients. The search covered the period from February 13, 2018, to February 13, 2023. Guided by the JBI approach for evidence synthesis, two researchers independently evaluated the quality of the literature and extracted relevant evidence in accordance with clinical scenarios.Results:Thirty articles were included, comprising two guidelines, three expert consensuses, one evidence summary, 21 systematic reviews, and three randomized controlled trials. A total of 29 best evidence points were summarized in six aspects: benefits of physical activity, physically active people, pre-activity assessment, implementation of physical activity programs, safety monitoring of physical activity, and ongoing support strategies.Conclusions:This study supplements and updates 15 pieces of evidence based on existing evidence, ultimately forming a best evidence summary for the management of physical activity in cancer patients, providing evidence-based support for clinical management. Most evidence comes from international studies. It is recommended that Chinese researchers consider the activity ability and willingness of cancer patients when applying these findings in future research, and consider the specific clinical context, or conduct foundational research to further validate the evidence, to comprehensively improve the quality of life of cancer patients.

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

Objective To explore the features of frontotemporal lobes'resting-state functional connectivity(rsFC)in preschool children with autism spectrum disorders(ASD)based on functional near-infrared spectroscopy(fNIRS)and to explore the possible neurological markers for early identification of ASD.Methods Sixty-three preschool ASD children and 72 typical development(TD)children were enrolled.Selected bilateral dorsolateral prefrontal cortex(DLPFC),bilateral premotor cortex(PMC),and bilateral temporal lobe(TL)cortex as the regions of interest(ROI).Changes of Oxyhemoglobin in the 6 ROIs in resting-state were measured by using functional near-infrared spectroscopy(fNIRS).Compared the frontotemporal rsFC strength and calculate the laterality index(LI)between two groups.Results Compared with the TD group,rsFC strength was significantly lower in the ASD group(P<0.05),and the differences existed mainly within the left ROIs(0.21±0.11 vs.0.32±0.18),right ROIs(0.16±0.16 vs.0.30±0.14),bilateral DLPFCs(0.20±0.14 vs.0.39±0.17;0.15±0.13 vs.0.36±0.13),bilateral TLs(0.15±0.14 vs.0.28±0.17;0.14±0.15 vs.0.31±0.17),and between the 10 groups of ROIs-ROIs(including right DLPFC-left DLPFC,right DLPFC-right PMC,right DLPFC-left PMC,right DLPFC-right TL,right DLPFC-left TL,left DLPFC-right PMC,left DLPFC-left PMC,left DLPFC-right TL,left DLPFC-left TL,right TL-left TL).There were a significant differences in the rsFC's laterality index of DLPFC and whole-brain between the two groups(t=2.002,P=0.047;t=3.003,P=0.003),and the ASD group showed left-lateralized connectivity.Conclusion Frontotemporal lobe's resting-state functional connectivity is abnormal in preschool children with ASD,characterized by low short-range functional connectivity of bilateral DLPFCs and TLs,low long-range functional connectivity associated with DLPFCs,and left-lateralized connectivity.

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTS^LepRb) neurons notably activated breathing. Moreover, stimulation of NTS^LepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTS^LepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTS^LepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTS^LepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca²⁺ transients in most NTS^LepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.
Leptin/pharmacology* ; Membrane Potentials ; Neurons/metabolism* ; Solitary Nucleus/metabolism*

Among current novel druggable targets, protein–protein interactions (PPIs) are of considerable and growing interest. Diacylglycerol kinase α (DGKα) interacts with focal adhesion kinase (FAK) band 4.1-ezrin-radixin-moesin (FERM) domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma (ESCC) cells. Chrysin is a multi-functional bioactive flavonoid, and possesses potential anticancer activity, whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC treatment. In this study, we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAK-controlled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo, whereas produced no toxicity to the normal cells. Molecular validation specifically demonstrated that Asp435 site in the catalytic domain of DGKα contributed to chrysin-mediated inhibition of the assembly of DGKα/FAK complex. This study has illustrated DGKα/FAK complex as a target of chrysin for the first time, and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.

Objective:To investigate the efficacy of intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia caused by multidrug-resistant Gram-negative (G -) bacteria. Methods:A observational study was conducted. The clinical data of 45 patients with pneumonia due to multidrug-resistant G - bacteria admitted to intensive care unit of Fujian Medical University Union Hospital from January to October in 2020 were analyzed. According to the different use methods of polymyxin B, 25 patients who received single intravenous drip (the first dose was 2.0 mg/kg, then 1.25 mg/kg, once every 12 hours) from January to April in 2020 were enrolled in the routine group, and 20 patients who received intravenous drip combined with aerosol inhalation (25 mg once every 12 hours, sputum in the airway was sucked and then sprayed aerosol) from May to October in 2020 were enrolled in the combination group. After the treatment course of polymyxin B, the total bacterial clearance rate, total clinical efficiency rate, recovery time of body temperature, time of bacterial clearance and the change of serum procalcitonin (PCT) level before and after treatment were compared between the two groups. Moreover, the incidence of adverse reactions during treatment in the two groups was observed. Results:The results of sputum culture in the routine group were Acinetobacter baumannii in 13 patients, Klebsiella pneumoniae in 5 patients, Pseudomonas aeruginosa in 6 patients, Enterobacter cloacae in 1 patient; the sputum culture results of the combination group showed that there were 5 patients of Acinetobacter baumannii, 9 Klebsiella pneumoniae and 6 Pseudomonas aeruginosa. There was no significant difference in the results of sputum culture between the two groups ( P > 0.05). The total bacterial clearance rate and the total clinical efficiency rate of the combination group were significantly higher than those in the routine group (total bacterial clearance rate: 70.0% vs. 40.0%, total clinical efficiency rate: 75.0% vs. 40.0%, both P < 0.05). The recovery time of body temperature and the time of bacterial clearance of the combination group were significantly shorter than those in the routine group [recovery time of body temperature (days): 6.0±3.9 vs. 10.2±7.3, time of bacterial clearance (days): 6.1±5.2 vs. 11.5±6.8, both P < 0.05]. No significant difference was found in serum PCT level before treatment between the two group. There was no significant difference in serum PCT level before and after treatment in the routine group [μg/L: 0.85 (0.44, 2.87) vs. 1.43 (0.76, 5.30), P > 0.05]. The serum PCT level after treatment in the combination group was significantly lower than that before treatment [μg/L: 0.27 (0.10, 0.70) vs. 0.91 (0.32, 3.53), P < 0.05], and it was significantly lower than that in the routine group [μg/L: 0.27 (0.10, 0.70) vs. 0.85 (0.44, 2.87), P < 0.01]. The incidence of renal toxicity of polymyxin B between the combination group and the routine group was not significantly different (5.0% vs. 4.0%, P > 0.05). Conclusions:The efficacy of intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia due to multidrug-resistant G - bacteria is better than that of intravenous drip of polymyxin B only. The aerosolized polymyxin B will not increase the risk of renal injury.

Objective:To explore the feasibility of fetal intelligent navigation echocardiography (FINE) in automatic quantitation of cardiac axis (CA).Methods:A total of 62 pregnant women of which 2 with twins′ pregnancy in the second and third trimesters from May to June 2020 in Sir Run Run Shaw Hospital Zhejiang University College of Medicine were enrolled in this non-selective and prospective study. After excluding those who could not be analyzed, they were assigned into four groups according to their CA measuring methods: ①Group with manual measuring CA in systole (CAS); ②Group with manual measuring CA in diastole(CAD); ③Group with CA measured by FINE in three-steps; ④Group with CA measured by FINE in seven-steps. The CAS among groups were compared in order to analyze the consistency and correlation of CAS achieved by different methods, meanwhile, the intra-observer and inter-observer consistency and repeatability were also evaluated.Results:A total of 64 fetuses with 187 volume data were collected, of which 60 cases of fetal data can be included in the study, 57 cases of normal CA, 3 cases of abnormal CA, a total of 158 volume data can be used for data analysis, the success rate was about 84.5%. Because of the small number of abnormal CA cases (3 cases), only 57 cases of normal CA were statistically analyzed in this study. Three-step and seven-step FINE automatic quantitative CA showed significantly different from those obtained with manual measurements of CAD ( P=0.005, P<0.001). There were no significant differences in quantitative analysis of CA between three-step or seven-step FINE and manual measurements of CAS ( P=0.458, 0.883), however, there was no correlation between CA using three-step FINE and manual measurement of CAS ( rs=0.056, P=0.679), but there was a positive correlation between CA using seven-step FINE and manual measurement of CAS ( rs=0.599, P<0.001). The linear regression equation was constructed as follows: Y=10.96+ 0.73 X ( R2=0.431, P<0.001). There was no correlation between three-step method and seven-step method for automatic quantitative CA ( rs=0.158, P=0.241). There was significant difference( P<0.001), but strong correlation between manual measurement of CAS and manual measurement of CAD ( rs=0.973, P<0.001), the average difference was ΔCA=(4.5± 3.8)°. The linear regression equation was constructed as follows: Y=-2.94+ 0.96 X ( R2=0.950, P<0.001). Intra-observer and inter-observer measurements had shown no significant difference in consistency and repeatability (all P>0.05). Conclusions:The measurement of fetal CA by seven-step FINE is superior to the three-step FINE when the fetal CA is in normal range. This may be considered a promising aspect that seven-step FINE automatic quantitation of fetal CA can replace the manual measurement of CAS. Future research is needed to deliminate the reliability of automatic quantification of fetal CA by seven-step FINE with the CA in abnormal range.