Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

OBJECTIVE: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). METHODS: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. RESULTS: C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts ( n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. CONCLUSION We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
Humans ; Colorectal Neoplasms/diagnosis* ; Cyclin-Dependent Kinase 4/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/genetics* ; Aged ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

Objective:To explore the effect of psychological nursing on the prognosis of male patients with urethral riding inju-ry treated by ureteroscopic urethral catheter implantation(UCI).Methods:This study included 63 male patients with urethral strad-dle injury treated in the General Hospital of Southern Theater Command from February 2020 to March 2023.We divided the patients into a control(n=29)and an experimental group(n=34)according to the odd-or even-numbered days of admission and treated them by ureteroscopic UCI.Meanwhile those of the former group received routine nursing care and the latter underwent psychological nursing intervention in addition.We obtained the Self-Rating Anxiety Scale(SAS)and Self-Rating Depression Scale(SDS)scores of the patients,recorded their postoperative pain scores,catheter-removal time,hospitalization days,postoperative complications and o-verall recovery status,and compared the data collected between the two groups.Results:At 3 days after surgery,both the SAS and SDS scores were significantly lower in the experimental group than in the control(SAS:45.2±2.9 vs 50.4±3.6,P<0.05;SDS:41.9±2.5 vs 48.3±4.0,P<0.05),and so were the pain scores at24 hours(6.2±0.6 vs 6.8±0.9,P<0.05),48 hours(4.9±0.7 vs 6.1±0.8,P<0.05)and 72 hours after surgery(2.5±0.6 vs 3.9±0.9,P<0.05).The hospitalization time was remarkably shorter in the experimental than in the control group([14.1±2.9]vs[16.1±3.4]d,P<0.05),but there was no statistically significant difference in the time of postoperative catheterization between the two groups of patients([19.3±3.7]vs[19.6±4.4]d,P>0.05).A30-day postoperative follow-up found2 cases of difficult urination in the control group but no com-plications in the experimental group.Conclusion:Ureteroscopic UCI is a safe,effective and minimally invasive treatment method for male urethral riding injury,and psychological nursing helps not only shorten the time of catheterization and hospitalization but also a-void postoperative complications.

Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.

Objective To evaluate the process risk of the implementation of prevention and control measures for surgical site infection(SSI)after colorectal surgery,and explore the application effect of failure mode and effects analysis(FMEA)based on action priority.Methods FMEA based on action priority was adopted to evaluate the whole process of the implementation of prevention and control measures for SSI after colorectal surgery.Prioritiza-tion ranking was conducted according to whether optimized measures were taken.Standard-reaching rate of comp-liance to SSI prevention and control measures as well as SSI incidence before and after the implementation of FMEA were compared.Results After evaluation,there were 7 high-priority and 22 medium-priority prevention and control measures for SSI.The control of medium-priority measures was strengthened,with a focus on developing further preventive and detectable measures for high-priority measures.The re-evaluation results after improvement showed that 7 high-priority measures have been downgraded to medium priority,and 16 medium-priority measures have been downgraded to low priority.Standard-reaching rate of compliance to SSI prevention and control measures in-creased from 77.15％(2 566/3 326)to 92.47％(3 096/3 348),and SSI incidence decreased from 6.04％(58/960)to 2.54％(60/2 364).Conclusion Application of FMEA based on action priority can effectively evaluate the risk of prevention and control process of SSI after colorectal surgery,and adopting preventive risk control measures accord-ing to the current situation can reduce the incidence of SSI after colorectal surgery.

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]

Objective To analyze the disposition of medical support equipment support units for medical service support of the synthetic battalion to carry out efficiently demand matching and replenishment for war loss,so as to enhance the efficiency of deployment and decision making of medical support equipment.Methods War loss of the medical support equipment was analyzed with queuing theory with the support service of the synthetic battalion as the basic research framework and desired equipment intact rate in the battlefield as the goal.A M/M/1/∞/∞ model and a M/M/c/∞/∞ model were established to investigate the disposition process of medical support equipment support units by simulating actual conditions of the battlefield.Multi synthetic battalions were assumed to be deployed to carry out 2 missions with different tasks and combat intensities,of which 40 synthetic battalions were involved in for mission 1 and 35 synthetic battalions for mission 2.The disposition of medical support equipment support units was calculated with the two models constructed.Results With the M/M/c/∞/∞ model it's suggested 5 medical support equipment support units be deployed to serve for 40 synthetic battalions;with the M/M/1/∞/∞ model only one unit was employed to support 35 battalions.The two models both met the requirements of 90％intact rate.Conclusion The research contributes to the decision making of medical support equipment support forces during synthetic battalion medical support and enhances the precision support of medical support equipment.[Chinese Medical Equipment Journal,2024,45(4):83-87]

Objective To explore the thoughts and medication rules of the contemporary inheritors of Lingnan LUO's Gynecology in differentiating and treating menopausal syndromes based on data mining technology.Methods The medical records of menopausal syndrome differentiated and treated by the contemporary inheritors of Lingnan LUO's Gynecology in clinic were collected.The Ancient and Modern Medical Records Cloud Platform(V2.3.5)was used to perform frequency statistics,association rule analysis,cluster analysis and complex network analysis of the data of medical records.Results A total of 191 medical records and 191 prescriptions were finally included,involving 160 kinds of Chinese medicinals.The statistics of four-examination information and syndrome types showed that the pathogenesis of menopausal syndrome was characterized by deficiency of the origin,which resulted in the dysfunction of healthy qi and the disturbance of the pivot,and then multiple viscera were involved;among the syndrome types,liver and kidney yin deficiency syndrome was the most common type.There were 26 high-frequency Chinese medicinals with the frequency being or over 40 times,and the top 5 Chinese medicinals were Lilii Bulbus,Codonopsis Radix,Corni Fructus,Paeoniae Radix Alba,and Rehmanniae Radix Praeparata.Most of the medicines were sweet in flavor and mild in nature,and had the meridian tropism of the liver,heart,kidney and spleen meridians.A total of 15 pairs of high-confidence drug combinations were obtained after association rule analysis.Cluster analysis of high-frequency Chinese medicinals yielded 5 core drug combinations.The complex network analysis revealed the core prescription which was composed of Rehmanniae Radix Praeparata,Corni Fructus,Cuscutae Semen,Lilii Bulbus,Ziziphi Spinosae Semen,Salviae Miltiorrhizae Radix et Rhizoma,and Margaritifera Concha.The association rule analysis showed that the drug pairs with high frequency of use were Ligustri Lucidi Fructus-Corni Fructus,Ligustri Lucidi Fructus-Salviae Miltiorrhizae Radix et Rhizoma.Conclusion For the treatment of menopausal syndrome,the contemporary inheritors of Lingnan LUO's Gynecology take the therapy of nourishing liver and kidney as the key,and also adopt the therapies of nourishing the heart and calming the mind,benefiting qi and invigorating the spleen,and harmonizing the pivot.The medicines prescribed by the inheritors mostly are sweet-light and mild tonics,and their prescription and medication rules are consistent with Professor LUO Yuan-Kai's academic thoughts.