BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

Cardiovascular diseases， a group of major non-infectious diseases， are characterized by high morbidity and mortality， significantly influencing patients' quality of life. Hence， it is imperative to discover a secure and efficacious treatment approach. As a form of programmed cell death， autophagy has been demonstrated to be associated with the pathogeneses of hypertension， diabetic cardiomyopathy， myocardial ischemia-reperfusion injury， heart failure， atherosclerosis， and other cardiovascular disorders. It serves as one of the potential targets for the clinical intervention in cardiovascular diseases by traditional Chinese medicine （TCM）. Autophagy exerts dual regulatory effects on the occurrence and development of cardiovascular diseases， and its specific effect predominantly depends on the extent of autophagy and the pathological stage of diseases. Recent studies have confirmed that TCM can prevent and treat cardiovascular diseases by directly regulating autophagy or interacting with oxidative stress， inflammation， and apoptosis under the regulation of autophagy， exhibiting the unique advantages of multiple targets， multiple components， and mild adverse reactions. This article reviews the experimental research progress in the role of autophagy and the intervention by active components and compound prescriptions of TCM and Chinese patent medicines in common cardiovascular diseases （such as diabetic cardiomyopathy， myocardial ischemia-reperfusion injury， heart failure， and atherosclerosis） in recent years and summarizes the research shortcomings， providing a theoretical basis and strategies for the clinical treatment of cardiovascular diseases.

Cardiovascular diseases， a group of major non-infectious diseases， are characterized by high morbidity and mortality， significantly influencing patients' quality of life. Hence， it is imperative to discover a secure and efficacious treatment approach. As a form of programmed cell death， autophagy has been demonstrated to be associated with the pathogeneses of hypertension， diabetic cardiomyopathy， myocardial ischemia-reperfusion injury， heart failure， atherosclerosis， and other cardiovascular disorders. It serves as one of the potential targets for the clinical intervention in cardiovascular diseases by traditional Chinese medicine （TCM）. Autophagy exerts dual regulatory effects on the occurrence and development of cardiovascular diseases， and its specific effect predominantly depends on the extent of autophagy and the pathological stage of diseases. Recent studies have confirmed that TCM can prevent and treat cardiovascular diseases by directly regulating autophagy or interacting with oxidative stress， inflammation， and apoptosis under the regulation of autophagy， exhibiting the unique advantages of multiple targets， multiple components， and mild adverse reactions. This article reviews the experimental research progress in the role of autophagy and the intervention by active components and compound prescriptions of TCM and Chinese patent medicines in common cardiovascular diseases （such as diabetic cardiomyopathy， myocardial ischemia-reperfusion injury， heart failure， and atherosclerosis） in recent years and summarizes the research shortcomings， providing a theoretical basis and strategies for the clinical treatment of cardiovascular diseases.

Vascular cognitive impairment(VCI)is a syndrome of cognitive decline attributed to vascular risk factors and cerebrovascular diseases.A range of pathophysiological processes induced by vascular injury,including inflammation,oxidative stress,cell death,disruption of the blood-brain barrier,and synaptic damage are intricately linked to the development of VCI.Nuclear factor E2-related factor 2(Nrf2),encoded by the NFE2L2 gene,is a potent transcription factor that plays a critical role in antioxidant defense.Extensive research has demonstrated that Nrf2 mitigates oxidative stress and inflammation by upregulating the expression of antioxidant response elements,thereby reducing the production of reactive oxygen species.Nrf2 also modulates programmed cell death,enhances blood-brain barrier integrity,and promotes synaptic plasticity,ultimately delaying the progression of VCI.This review examines the role of Nrf2 in VCI and highlights recent research on traditional Chinese medicines targeting Nrf2 for the prevention and treatment of VCI,thus providing novel insights and approaches for managing this condition.

Atherosclerosis(AS)is a chronic inflammatory disease involving various immune cells and is char-acterized by lipid deposition and inflammatory response.In recent years,the field of exosome research has been rapidly developed,thereby enhancing our comprehension of their role in AS.Immune cell-derived exosomes are extracellular vesi-cles secreted by immune cells that possess specificity,stability,and biocompatibility.These exosomes have the capacity to induce diverse responses including modulating gene transcription and regulating cytokine production,thereby influenc-ing the body's inflammatory and immune response.During AS progression,these exosomes primarily participate in patho-logical processes including endothelial dysfunction,lipid deposition,vascular calcification,and plaque rupture,all of which significantly influence the development of AS.This review is focused on exploring the role of exosomes derived from monocytes,macrophages,neutrophils,lymphocytes,as well as other immune cells(neutrophils,eosinophils,mast cells,and myeloid-derived suppressor cells)in AS,aiming to offer insights for diagnosis and clinical treatment.

Objective:To document any effect of repeated high-frequency repetitive transcranial magnetic stimulation (rTMS) using double-cone coils on the lower limb motor function of stroke survivors.Methods:A total of 40 stroke survivors were randomly divided into an rTMS group and a sham stimulation group, each of 20. The rTMS group received rTMS at 10Hz with a double-cone coil, while a coil that produced sound but no magnetic stimulation was used with the sham group. The treatments were administered daily, five times a week, for three weeks. Before as well as after 1, 2 and 3 weeks of treatment, lower limb motor function, balance, and the root mean square (RMS) and median frequency (MF) of the rectus femoris and tibialis anterior muscles were evaluated using the Fugl-Meyer lower extremity assessment (FMA-LE), the Berg Balance Scale (BBS), the Modified Barthel Index (MBI), Brunnstrom staging, the TecnoBody balance assessment system, and surface electromyography.Results:Compared with the sham stimulation group, the BBS score of the rTMS group was significantly higher after 2 weeks of treatment, and both the FMA-LE and BBS scores were significantly higher after 3 weeks. The average Brunnstrom stage in the sham group had increased significantly after 3 weeks, but in the rTMS group it had increased after 2 weeks. By 3 weeks there were no significant differences between the two groups. In terms of movement control, the average motion ellipse area in the rTMS group was significantly smaller than among the sham group after 2 weeks, and after 3 weeks the average motion trajectory length was significantly shorter than in the sham group. The average RMS of the rectus femoris in the rTMS group was significantly higher than the sham group′s average after 3 weeks of treatment, indicating improved muscle activation.Conclusions:High-frequency rTMS using a conical coil can effectively improve the lower limb motor function and balance ability of stroke survivors, demonstrating promising clinical application potential.

Objective:To document any effect of repeated high-frequency repetitive transcranial magnetic stimulation (rTMS) using double-cone coils on the lower limb motor function of stroke survivors.Methods:A total of 40 stroke survivors were randomly divided into an rTMS group and a sham stimulation group, each of 20. The rTMS group received rTMS at 10Hz with a double-cone coil, while a coil that produced sound but no magnetic stimulation was used with the sham group. The treatments were administered daily, five times a week, for three weeks. Before as well as after 1, 2 and 3 weeks of treatment, lower limb motor function, balance, and the root mean square (RMS) and median frequency (MF) of the rectus femoris and tibialis anterior muscles were evaluated using the Fugl-Meyer lower extremity assessment (FMA-LE), the Berg Balance Scale (BBS), the Modified Barthel Index (MBI), Brunnstrom staging, the TecnoBody balance assessment system, and surface electromyography.Results:Compared with the sham stimulation group, the BBS score of the rTMS group was significantly higher after 2 weeks of treatment, and both the FMA-LE and BBS scores were significantly higher after 3 weeks. The average Brunnstrom stage in the sham group had increased significantly after 3 weeks, but in the rTMS group it had increased after 2 weeks. By 3 weeks there were no significant differences between the two groups. In terms of movement control, the average motion ellipse area in the rTMS group was significantly smaller than among the sham group after 2 weeks, and after 3 weeks the average motion trajectory length was significantly shorter than in the sham group. The average RMS of the rectus femoris in the rTMS group was significantly higher than the sham group′s average after 3 weeks of treatment, indicating improved muscle activation.Conclusions:High-frequency rTMS using a conical coil can effectively improve the lower limb motor function and balance ability of stroke survivors, demonstrating promising clinical application potential.

Vascular cognitive impairment(VCI)is a syndrome of cognitive decline attributed to vascular risk factors and cerebrovascular diseases.A range of pathophysiological processes induced by vascular injury,including inflammation,oxidative stress,cell death,disruption of the blood-brain barrier,and synaptic damage are intricately linked to the development of VCI.Nuclear factor E2-related factor 2(Nrf2),encoded by the NFE2L2 gene,is a potent transcription factor that plays a critical role in antioxidant defense.Extensive research has demonstrated that Nrf2 mitigates oxidative stress and inflammation by upregulating the expression of antioxidant response elements,thereby reducing the production of reactive oxygen species.Nrf2 also modulates programmed cell death,enhances blood-brain barrier integrity,and promotes synaptic plasticity,ultimately delaying the progression of VCI.This review examines the role of Nrf2 in VCI and highlights recent research on traditional Chinese medicines targeting Nrf2 for the prevention and treatment of VCI,thus providing novel insights and approaches for managing this condition.

Atherosclerosis(AS)is a chronic inflammatory disease involving various immune cells and is char-acterized by lipid deposition and inflammatory response.In recent years,the field of exosome research has been rapidly developed,thereby enhancing our comprehension of their role in AS.Immune cell-derived exosomes are extracellular vesi-cles secreted by immune cells that possess specificity,stability,and biocompatibility.These exosomes have the capacity to induce diverse responses including modulating gene transcription and regulating cytokine production,thereby influenc-ing the body's inflammatory and immune response.During AS progression,these exosomes primarily participate in patho-logical processes including endothelial dysfunction,lipid deposition,vascular calcification,and plaque rupture,all of which significantly influence the development of AS.This review is focused on exploring the role of exosomes derived from monocytes,macrophages,neutrophils,lymphocytes,as well as other immune cells(neutrophils,eosinophils,mast cells,and myeloid-derived suppressor cells)in AS,aiming to offer insights for diagnosis and clinical treatment.