ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

The neurophysiological mechanisms by which exercise improves cognitive function have not been fully elucidated. A comprehensive and systematic review of current domestic and international neurophysiological evidence on exercise improving cognitive function was conducted from multiple perspectives. At the molecular level, exercise promotes nerve cell regeneration and synaptogenesis and maintains cellular development and homeostasis through the modulation of a variety of neurotrophic factors, receptor activity, neuropeptides, and monoamine neurotransmitters, and by decreasing the levels of inflammatory factors and other modulators of neuroplasticity. At the cellular level, exercise enhances neural activation and control and improves brain structure through nerve regeneration, synaptogenesis, improved glial cell function and angiogenesis. At the structural level of the brain, exercise promotes cognitive function by affecting white and gray matter volumes, neural activation and brain region connectivity, as well as increasing cerebral blood flow. This review elucidates how exercise improves the internal environment at the molecular level, promotes cell regeneration and functional differentiation, and enhances the brain structure and neural efficiency. It provides a comprehensive, multi-dimensional explanation of the neurophysiological mechanisms through which exercise promotes cognitive function.
Animals ; Humans ; Brain/physiology* ; Cognition/physiology* ; Exercise/physiology* ; Nerve Regeneration/physiology* ; Neuronal Plasticity/physiology*

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objective To analyze the learning curve of Da Vinci robotic segmentectomy. Methods Cumulative sum analysis (CUSUM) was used to analyze the learning curve of Da Vinci robotic segmentectomy performed by the General Hospital of Northern Theater Command from February 2018 to December 2020. The learning curve was obtained by fitting, and R2 was used to judge the goodness of fitting. The clinical data of patients in different stages of learning curve were compared and analyzed. Results The first 50 patients who received Da Vinci robotic segmentectomy were included, including 24 males and 26 females, with an average age of 61.9±10.6 years. The operation time decreased gradually with the accumulation of operation patients. The goodness of fitting coefficient reached the maximum value when R2=0.907 (P<0.001), CUSUM (n) =0.009×n3−0.953×n2+24.968×n−7.033 (n was the number of patients). The fitting curve achieved vertex crossing when the number of patients reached 17. Based on this, 50 patients were divided into two stages: a learning and improving stage and a mastering stage. There were statistical differences in the operation time, intraoperative blood loss, postoperative drainage volume, number of lymph node dissection, postoperative catheter time, postoperative hospital stay, and postoperative complications between the two stages (P<0.05). Conclusion It shows that the technical competency for assuring feasible perioperative outcomes can be achieved when the cumulative number of surgical patients reaches 17.

Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33％and 25.00％,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To explore the application effect of multi-disciplinary team(MDT)model in hospital antimi-crobial management.Methods Relevant data on antimicrobial use in hospitalized patients in a hospital from January 2021 to December 2022 were analyzed retrospectively,January-December 2021 adopted conventional management mode and was as the control group,January-December 2022 adopted MDT management model and was as the inter-vention group.Antimicrobial therapy relevant indicators between two groups of patients were compared.Results After adopting the MDT management model,pathogen detection rate before the therapeutic antimicrobial use in the intervention group(73.62％)was higher than that in the control group(70.56％),difference was statistically sig-nificant(P＜0.001).Pathogen detection rate related to healthcare-associated infection diagnosis was 87.98％in the control group and 88.89％in the intervention group,with no statistically significant difference between two groups(P＞0.05).Pathogen detection rate before combined use of key antimicrobial agents in the intervention group(93.94％)was higher than that in the control group(92.00％),difference was statistically significant(P＜0.05).Antimicro-bial use rate in hospitalized patients and use rate of prophylactic antimicrobial agents in class Ⅰ incision surgery de-creased from 38.03％and 21.03％to 32.78％and 10.30％,respectively,with statistically significant differences(both P＜0.05).The amount and intensity of antimicrobial use in hospitalized patients in the intervention group de-creased.The implementation rate of bundled prevention and control measures for multidrug-resistant organism(MDRO)after intervention was significantly higher than that of the control group,with statistically significant differences(all P＜0.05).MDRO detection rate decreased from 34.70％to 32.37％,difference was statistically significant(P=0.027).there was no significant change in the MDRO case infection rate.Conclusion The MDT model can effectively improve the standardized management of antimicrobial agents,promote the rational use of anti-microbial agents in clinical practice,and prevent bacterial resistance.