ObjectiveBased on the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway， this study aimed to observe the effect of the Huazhuo Jiedu prescription on renal fibrosis in 5/6 nephrectomy rats and explore its underlying mechanism. MethodsA total of 67 SPF-grade male SD rats were used， of which 11 were randomly selected as the normal group. A chronic renal failure （CRF） model was established using 5/6 nephrectomy. The successfully modeled rats were randomly assigned to the model group， losartan potassium group （4.5 mg·kg^-1）， and low- （1.175 g·kg^-1）， medium- （2.35 g·kg^-1） and high-dose （4.7 g·kg^-1） Huazhuo Jiedu prescription groups， with 9 rats per group. Each group received an equivalent volume of saline or the corresponding concentration of Huazhuo Jiedu prescription by gavage once daily for 8 weeks. Hematoxylin-eosin （HE） and Masson staining were used to observe renal tissue pathological changes. Transmission electron microscopy examined renal ultrastructure. Immunohistochemistry （IHC） detected expressions of α-smooth muscle actin （α-SMA） and transforming growth factor-β₁ （TGF-β₁）. Western blot analyzed expression levels of microtubule-associated protein Ⅰ light chain 3Ⅱ （LC3Ⅱ）， Beclin1， p62， AMPK， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultsCompared with the normal group， the model group exhibited glomerular shrinkage， mesangial and interstitial thickening， and tubular vacuolar degeneration， with no evident autophagosomes or autophagolysosome structures. Expression levels of α-SMA and TGF-β₁ were significantly increased （P0.01）， while p-AMPK/AMPK， Beclin1， and LC3Ⅱ were significantly decreased （P0.01）， and p-mTOR/mTOR and p62 were significantly increased （P0.01）. Compared with the model group， the medium- and high-dose Huazhuo Jiedu prescription groups and the losartan potassium group showed varying degrees of pathological improvement. Autophagosomes with double- or multiple-layer membranes and autophagolysosomes with monolayer membranes containing undegraded organelles were observed. Renal α-SMA and TGF-β₁ protein expression levels were markedly reduced （P0.05， P0.01）， p-mTOR/mTOR and p62 were significantly decreased （P0.05， P0.01）， and p-AMPK/AMPK， Beclin1， and LC3Ⅱ expression levels were significantly increased （P0.05， P0.01）. ConclusionHuazhuo Jiedu prescription may improve renal fibrosis in 5/6 nephrectomy rats by regulating the AMPK/mTOR signaling pathway and enhancing autophagy.

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

Objective To explore the risk factors for 28-day mortality of sepsis-associated acute kidney injury(SA-AKI)patients and to develop a nomogram risk prediction model.Methods A retrospective cohort study was conducted,involving 184 patients with SA-AKI admitted to the intensive care unit(ICU)of the 940th Hospital of Joint Logistic Support Force of PLA between January 2017 and December 2022.Patients were categorized into survival(n=135)and non-survival(n=49)groups based on 28-day mortality.Clinical data were collected,and statistically significant risk factors were preliminarily screened.Multivariate stepwise logistic regression analysis was performed to identify independent risk factors for 28-day mortality of SA-AKI patients.A nomogram predictive model was constructed using these factors,and internally validated with the Bootstrap method.The receiver operating characteristic curve(ROC curve)was drawn,and the area under the ROC curve(AUC)was calculated to verify the predictive value and accuracy of the model.Results The 28-day mortality rate among 184 SA-AKI patients was 26.6％(49/184).Multivariate stepwise logistic regression analysis identified multiple organ dysfunction syndrome(MODS)(OR=16.393,95％CI 4.317-62.254,P＜0.001),high acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score(OR=1.097,95％CI 1.036-1.161,P=0.002),low oxygenation index(OR=0.992,95％CI 0.986-0.998,P=0.015),low neutrophil count(OR=0.912,95％CI 0.860-0.968,P=0.002)and low fibrinogen concentration(OR=0.733,95％CI 0.549-0.978,P=0.034)as independent risk factors.The prediction model equation was P=1/1+e-logit(P),logit(P)=-1.626+2.797×MODS+0.092×AP ACHE Ⅱ+(-0.311)×fibrinogen+(-0.092)×neutrophil count+(-0.008)×oxygenation index.Internal validation with 1000 Bootstrap resamples showed high consistency between predicted and actual values.ROC analysis showed an AUC of 0.911(95％CI 0.868-0.955,P＜0.05)for the model,with 93.9％sensitivity and 78.5％specificity at a cut-off of 0.194.The Hosmer-Lemeshow test confirmed good calibration(P=0.62),and decision-making curve analysis demonstrated clinical utility within the high-risk threshold range(0.1-0.9).Conclusions MODS,high APACHE Ⅱ score,low oxygenation index,low neutrophil count,and low fibrinogen concentration are independent risk factors for 28-day mortality in SA-AKI patients.The developed nomogram risk prediction model may provide important guidance for predicting 28-day mortality in SA-AKI patients.

Facing of mounting resource constraints and rising demands for personalization in medical education,regional anatomy teaching urgently requires transformation.In this paper,we focus on the regional anatomy of the thoracic wall,in order to explore a novel AI-driven teaching paradigm.Anchored in the core principle of"virtual-real integration with cadaveric dissection as the cornerstone,"the paradigm redefines educational objective and constructs an intelligent,closed-loop teaching model integrating students,computers,and instructors.Leveraging the robust support of digital intelligence(e.g.,DeepSeek),this paradigm incorporates interactive method including group collaboration,branching instruction,and gamified assessments.It achieves a comprehensive intelligent transformation of the entire teaching process-from goal setting and plan customization to activity implementation,task completion,outcome exchange,multidimensional evaluation,and reflective iteration.This new paradigm centers on medical students and leverages digital intelligence to activate deep personalized learning potential.It seamlessly integrates fundamental anatomical knowledge with clinical scenarios(e.g.,key anatomy in breast cancer surgery,flap design in breast reconstruction),and significantly enhances clinical decision-making abilities,scientific research and innovative thinking,as well as medical humanistic literacy,paving a new path for intelligent medical education.

Objective To explore the integration value of mobile virtual reality devices in the classroom teaching of human anatomy,and to evaluate their potential impact on the in-depth construction of human anatomy knowledge,the cultivation of spatial cognitive ability,and the transformation of teaching paradigms from the perspectives of cognitive load theory and situated learning.Methods The undergraduate students majoring in clinical medicine in Peking University were selected as the research objects.Among them,students in grade 2019 were the control group,and students in grade 2022 were the experimental group,introducing movable virtual anatomy equipment and other teaching auxiliary method in theory and practice courses.The final exam scores of the two groups of students were compared,and a questionnaire survey was conducted for the experimental group after the course,and the survey result were statistically analyzed.Results The final examination result showed that the average score of the experimental group was 82.47±10.19,and the average score of the control group was 74.82±16.56,which was significantly higher in the experimental group than in the control group,with statistical significance(P＜0.05).The questionnaire survey result showed that compared with traditional classroom teaching,94.62％of students preferred the new auxiliary teaching mode such as VR,96.77％of students believed that VR assisted teaching could achieve the traditional teaching effect or better,95.7％of them think that it improved students' interest in learning human anatomy,and 98.92％thought that it improved students' knowledge of anatomy.Conclusion The application of mobile virtual reality devices in anatomy classroom teaching provides immersive and interactive 3D visualization teaching scenarios,effectively reducing students' cognitive load on abstract and complex anatomical structures,promoting spatial understanding and knowledge internalization,significantly improving teaching effectiveness and self-learning ability,thus changing the traditional anatomy teaching mode and laying a solid foundation for the development of future medical education and the cultivation of medical talents.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Osteoporosis is an important cause of internal fixation loosening after spinal surgery.Cement-augmented pedicle screw instru-mentation(CAPSI)technique is the most widely used technique in clinical practice to improve the stability of pedicle screw,mainly applied in osteoporosis and revision surgery,which included conventional solid pedicles crews and fenestrated/cannulated pedicle screws technique.CAPSI technique may cause cement leakage and pulmonary embolism,and there is no consensus on its indications or technical points.Therefore,this article reviews the research progress of CAPSI,in order to provide relevant reference for clinical practice.

Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Objective To establish an acute exposure model of extreme plateau hypobaric hypoxia environment and explore transcriptomic changes related to learning and memory impairment in rats.Methods Healthy male SD rats aged 6-weeks,200-250 g,were selected and divided into control group and plateau group.The control group was treated with normal pressure and oxygen(19 rats),and the plateau group was placed in a hypobaric hypoxia chamber(19 rats)at a simulated altitude of 8000 meters and treated for 72 hours.Behavioral changes were detected with 16 animals from each group using contextual fear conditioning and Morris water maze(8 rats each).Three hippocampal tissues were extracted from each group for transcriptomic sequencing,and the molecular mechanism of learning and memory impairment induced by extreme plateau environment was analyzed by Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene set enrichment analysis(GSEA)enrichment.Results The behavioral result showed that compared with the control group,the fear memory and spatial learning memory abilities of rats in plateau group were decreased.GO and KEGG analyses showed that the extreme altitude environment reshaped the hippocampal microenvironment and affected the intercellular signal transmission,while GSEA analysis showed that the extreme altitude environment up-regulated the gene set related to the plasma membrane and extracellular matrix.Conclusion The extreme plateau environment at an altitude of 8000 meters could affect the microenvironment of rat hippocampus,destroy intercellular connections and impair intercellular communication and then induce learning and memory impairment.