ObjectiveRepetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, offers a non-pharmacological therapeutic option for the management of Alzheimer’s disease (AD). Studies have demonstrated that ferroptosis plays a pivotal role in the pathological onset and progression of AD, and the inhibition of neuronal ferroptosis can significantly ameliorate cognitive impairments associated with AD. The imbalance of calcium ion (Ca²⁺) homeostasis is intimately associated with the pathology of AD and serves as a catalyst for the induction of ferroptosis through various pathways. This study is designed to investigate whether rTMS can ameliorate AD by inhibiting neuronal ferroptosis or maintaining calcium homeostasis, ultimately establishing a theoretical and experimental framework for the utilization of rTMS in AD treatment. MethodsAPP/PS1 AD mice were subjected to both 0.5 Hz low-frequency and 20 Hz high-frequency rTMS treatments, and the efficacy of these treatments was evaluated using novel object recognition and Morris water maze tests. ELISA was employed to quantify the levels of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), Fe²⁺ within the hippocampi of mice from each group. HT-22 cells were induced to undergo ferroptosis via Erastin treatment, and subsequent to high- and low-frequency magnetic stimulation, cell viability was assessed using CCK-8 assay, while intracellular calcium ion concentration fluctuations were monitored using Fluo-4 AM. ResultsThe findings revealed that, when compared to normal mice, AD mice displayed a notable decline in cognitive function, accompanied by a substantial increase in ferroptosis levels and intracellular calcium ion concentrations. Both high-frequency and low-frequency applications of rTMS were found to significantly ameliorate cognitive impairments in AD mice, while also effectively mitigating the abnormal augmentation of neuronal ferroptosis and intracellular calcium ion levels. ConclusionThe present study underscores that both high-frequency and low-frequency rTMS exhibit efficacy in alleviating cognitive dysfunction in AD mice, potentially through the modulation of ferroptosis and intracellular calcium ion homeostasis.

Dormant tumor cells constitute a population of cancer cells that reside in a non-proliferative or low-proliferative state, typically arrested in the G0/G1 phase and exhibiting minimal mitotic activity. These cells are commonly observed across multiple cancer types, including breast, lung, and ovarian cancers, and represent a central cellular component of minimal residual disease (MRD) following surgical resection of the primary tumor. Dormant cells are closely associated with long-term clinical latency and late-stage relapse. Due to their quiescent nature, dormant cells are intrinsically resistant to conventional therapies—such as chemotherapy and radiotherapy—that preferentially target rapidly dividing cells. In addition, they display enhanced anti-apoptotic capacity and immune evasion, rendering them particularly difficult to eradicate. More critically, in response to microenvironmental changes or activation of specific signaling pathways, dormant cells can re-enter the cell cycle and initiate metastatic outgrowth or tumor recurrence. This ability to escape dormancy underscores their clinical threat and positions their effective detection and elimination as a major challenge in contemporary cancer treatment. Hypoxia, a hallmark of the solid tumor microenvironment, has been widely recognized as a potent inducer of tumor cell dormancy. However, the molecular mechanisms by which tumor cells sense and respond to hypoxic stress—initiating the transition into dormancy—remain poorly defined. In particular, the lack of a systems-level understanding of the dynamic and multifactorial regulatory landscape has impeded the identification of actionable targets and constrained the development of effective therapeutic strategies. Accumulating evidence indicates that hypoxia-induced dormancy tumor cells are accompanied by a suite of adaptive phenotypes, including cell cycle arrest, global suppression of protein synthesis, metabolic reprogramming, autophagy activation, resistance to apoptosis, immune evasion, and therapy tolerance. These changes are orchestrated by multiple converging signaling pathways—such as PI3K-AKT-mTOR, Ras-Raf-MEK-ERK, and AMPK—that together constitute a highly dynamic and interconnected regulatory network. While individual pathways have been studied in depth, most investigations remain reductionist and fail to capture the temporal progression and network-level coordination underlying dormancy transitions. Systems biology offers a powerful framework to address this complexity. By integrating high-throughput multi-omics data—such as transcriptomics and proteomics—researchers can reconstruct global regulatory networks encompassing the key signaling axes involved in dormancy regulation. These networks facilitate the identification of core regulatory modules and elucidate functional interactions among key effectors. When combined with dynamic modeling approaches—such as ordinary differential equations—these frameworks enable the simulation of temporal behaviors of critical signaling nodes, including phosphorylated AMPK (p-AMPK), phosphorylated S6 (p-S6), and the p38/ERK activity ratio, providing insights into how their dynamic changes govern transitions between proliferation and dormancy. Beyond mapping trajectories from proliferation to dormancy and from shallow to deep dormancy, such dynamic regulatory models support topological analyses to identify central hubs and molecular switches. Key factors—such as NR2F1, mTORC1, ULK1, HIF-1α, and DYRK1A—have emerged as pivotal nodes within these networks and represent promising therapeutic targets. Constructing an integrative, systems-level regulatory framework—anchored in multi-pathway coordination, omics-layer integration, and dynamic modeling—is thus essential for decoding the architecture and progression of tumor dormancy. Such a framework not only advances mechanistic understanding but also lays the foundation for precision therapies targeting dormant tumor cells during the MRD phase, addressing a critical unmet need in cancer management.

Serine/arginine-rich splicing factor 6 (SRSF6) is a member of the serine and arginine-rich (SR) protein family,and it plays a crucial regulatory role in RNA splicing.Dysregulation of SRSF6 ex-pression or function can lead to aberrant alternative splicing of certain genes,and contribute to the devel-opment and progression of inflammatory diseases,including tumors,diabetes,and pleural fibrosis.How-ever,the role of SRSF6 in inflammation remains unclear.In this study,we found that the expression of inflammatory factors,including tumor necrosis factor-α(TNF-α) and cyclooxygenase-2 (COX-2),was induced by lipopolysaccharides (LPS) .Concurrently,both the levels of SRSF6 mRNA and protein ex-pression significantly increased with prolonged LPS stimulation (P<0.05) .Furthermore,we investigated the change of SRSF6 expression on the expression of inflammatory factors.The results showed that upreg-ulation of SRSF6 enhanced the expression of LPS-induced inflammatory factors (P<0.05),while down-regulation of SRSF6 inhibited their expression (P<0.05) .Additionally,the activation of the nuclear fac-tor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways was suppressed by SRSF6 knockdown (P<0.05),indicating that SRSF6 is involved in regulating inflammatory responses in macrophages.Myeloid differentiation factor 88 (MyD88) is a key adaptor protein in the TLR4 signaling pathway,with its splicing isoforms MyD88-L and MyD88-S exerting pro-inflammatory and anti-inflamma-tory effects,respectively.Analysis of RNA-binding protein database and RNA immunoprecipitation showed that SRSF6 binds to MyD88 mRNA.Splicing analysis indicated that downregulation of SRSF6 promoted the expression of the anti-inflammatory MyD88-S mRNA isoform (P<0.01) .Moreover,knock-down of MyD88-S could rescue the expression of inflammatory factors suppressed by SRSF6 downregula-tion.These findings suggest that SRSF6 regulates MyD88 alternative splicing in macrophages,thereby af-fecting the activation of inflammatory signaling pathways and the expression of inflammatory factors.This study provides a foundation for further elucidating the role of SRSF6 in inflammatory diseases.

Objective To explore the effect of a R language-based autoregressive integrated moving average(ARIMA)model for predicting the consumption of medical consumables.Methods The monthly consumption data of a certain type of pre-filled flush syringe from July 2018 to June 2023 was selected as the sample data,which underwent smoothness test and difference operation with R language.An ARIMA model was established and the optimal model was determined according to the Akaike and Bayesian information criteria.The corresponding data of the third quarter of 2023 was used as the validation set to predict the consumption,and the prediction result was compared with the actual values to evaluate the prediction effect of the ARIMA model.Results The ARIMA model with the best fitting was ARIMA(0,1,1)(1,0,0)12,all the predicted data were within 95％confidence interval,and its mean absolute percentage error MAPE was 9.92％.P-value proved to be higher than 0.05 when the residual series were tested using the Ljung-Box statistics,which meant the prediction result was satisfactory.Conclusion The R language-based ARIMA model behaves well in predicting the consumption of medical consumables,and provides references for demand planning,budgeting,purchasing and management of medical consumables.[Chinese Medical Equipment Journal,2024,45(10):84-87]

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (I_Na.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC₅₀) values of Mel on transient sodium current (I_Na.T) and specific I_Na.L opener 2 nmol·L^-1 sea anemone toxins II (ATX II) increased I_Na.L were 686.615 and 7.37 μmol·L^-1, respectively. Mel did not affect L-type calcium current (I_Ca.L), transient outward current (I_to), and AP. In addition, 16 μmol·L^-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking I_Na.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na⁺ and K⁺ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na⁺ and K⁺ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.

Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

Objective:To compare and analyze the therapeutic effects of open, laparoscopic and interventional treatments for refractory lymphatic leakage after radical neck dissection in thyroid cancer, and the feasibility of interventional treatment for refractory lymphatic leakage.Methods:Totally 41 patients with refractory lymphatic leakage after radical neck dissection in thyroid cancer at thyroid surgery department of First Affiliated Hospital of Zhengzhou University from Jan.2018 to Dec.2023 were retrospectively enrolled. They were divided into open surgery group ( n=18), interventional surgery ( n=14), and laparoscopic surgery group ( n=9) based on surgical methods. The drainage volume, extubation time, hospital stay, and cost on the 1st, 3rd, and 5th day after surgery were recorded. Inter group comparison was conducted using analysis of variance and independent sample Kruskal-Wallis test. The effects of different groups on incurable lymphatic leakage after radical neck dissection in thyroid cancer were compared and analyzed. Results:The treatment of refractory lymphatic leakage after radical neck dissection in thyroid cancer using open, endoscopic, and interventional methods all improved. On the 1st, 3rd and 5th day after surgery, the drainage volumes were (96.67±46.40) mL, (64.44±30.46) mL, (72.86±57.70) mL, P=0.197, (43.89±25.70) mL, (33.33±12.25) mL, (39.29±36.68) mL, P=0.653, and (22.50±19.42) mL, (16.67±15.61) mL, (20.00±27.39) mL, P=0.806, respectively, and the differences were not statistically significant. The cost of open surgery was lower than that of the other groups (0.33±0.75 vs 0.56±0.70,0.76±0.84, F=126.245, P<0.01) and postoperative hospital stay for interventional surgery was lower than the other groups [ (2.36±0.50) d vs (4.67±1.14) d, (4.56±1.13) d, P<0.01]. Conclusion:Interventional therapy could be used to treat incurable lymphatic leakage after radical neck dissection in thyroid cancer.

Objective:To investigate the relationship between phase angle (PA) and nutritional status,duration of mechanical ventilation,length of intensive care unit (ICU) stay,and clinical outcomes in patients with severe acute pancreatitis (SAP) complicated with ARDS. Methods:The clinical data of patients with SAP complicated with ARDS admitted to the surgical ICU,Jinling hospital,medical school of Nanjing University,from July 2023 to March 2024 were retrospectively collected. Patients are divided into low-PA group and normal-PA group based on phase angle. The correlation analysis between phase angle,nutritional status,and clinical outcomes,and evaluation of risk factors for mortality in patients with SAP combined with ARDS were performed. Result:A total of 83 patients with SAP complicated with ARDS were included in this study. PA was negatively correlated with nutritional risk scores (rs=-0.352,P=0.001),duration of mechanical ventilation (rp=-0.475,P<0.001),length of ICU stay (rp=-0.313,P=0.004),and mortality (rs=-0.371,P=0.001). Univariate analysis showed statistically significant differences in age,PA value,and duration of mechanical ventilation for predicting mortality (P<0.05);Multivariate analysis showed that the PA value was an independent risk factor for mortality (P<0.05). Conclusion:PA is significantly correlated with clinical outcomes,such as nutritional risk,duration of mechanical ventilation,length of ICU stay and mortality,and may be a promising biomarker in future.