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.

At present, the C-arm structure accelerators commonly used in radiotherapy equipment are complex in operation and have potential safety hazards when realizing non-coplanar treatment. By combining with medical robotic arm technology, a spherical radiotherapy accelerator motion system is designed. The beam module is clamped by the medical robotic arm structure to achieve three-dimensional multi-angle irradiation treatment within the non-coplanar angle range. Firstly, the rotating mechanism, beam module, and MLC module of the spherical radiotherapy equipment are designed. Then, the double-plane counterweight method is used to calculate the dynamic balance of the equipment, ensuring that the beam center point does not rotate during the treatment process. Finally, the strength check and reliability analysis of the transmission component gear are conducted. The results show that the designed spherical radiotherapy accelerator motion system can meet the requirements of stable, accurate, and fast precision radiotherapy, which is conducive to improving the treatment efficiency.
Particle Accelerators/instrumentation* ; Equipment Design ; Reproducibility of Results ; Radiotherapy/instrumentation*

The latest research findings on bidirectional regulation of neuro-immunity through traditional neural circuits shed new light on the theoretical basis of the role of vidian neurectomy (VN). This article aims to provide a comprehensive understanding of VN, including the history of VN, the principle of neuroimmuno-interaction, the applied anatomy of VN as well as the methods of transnasal endoscopic surgery. Additionally, we introduce the concept of the nose-brain axis, which was proposed based on the advancement in the area of neuro-immune interactions.

ObjectiveTo observe the effects of Tongmai Kaiqiao pills on the hypoxia-inducible factor-1α （HIF-1α）/adenovirus E1B 19 kD-interacting protein 3 （BNIP3） signaling pathway and mitochondrial autophagy in the hippocampus of the rat model of vascular dementia （VD）. MethodNinety male SD rats underwent adaptive feeding for one week before the study. Ten rats were randomly assigned to the sham group， where the common carotid artery was isolated without ligation. The remaining rats were subjected to sequential ligation of the common carotid artery for the modeling of VD. The successfully modeled rats were randomly assigned into the following groups： model， high-， medium-， and low-dose （27.6， 13.8， 6.9 g·kg^-1， respectively） Tongmai Kaiqiao pills， donepezil hydrochloride （0.45 mg·kg^-1）， and combination （27.6 g·kg^-1 Tongmai Kaiqiao pills + 2.5 mg·kg^-1 HIF-1α inhibitor YC-1） groups. After 4 weeks of treatment， samples were collected. Nissl staining and hematoxylin-eosin staining were performed to observe the loss of neurons and pathological changes， respectively， in the hippocampal region. Western blot was employed to determine the protein levels of HIF-1α， BNIP3， Beclin-1， and microtubule-associated protein 1 light chain 3B （LC3B） in the hippocampal tissue. Transmission electron microscopy was used to observe the mitochondrial ultrastructure and the number of autophagosomes in the hippocampal tissue. Immunofluorescence was employed to observe the fluorescence intensity of HIF-1α， BNIP3， and LC3B in the hippocampal tissue. ResultCompared with the sham group， the model group showed prolonged escape latency （P<0.01）， decreased number of platform crossings （P<0.01）， reduced and disarranged neuronal layers in the hippocampal region， decreased number of Nissl bodies， disrupted mitochondrial cristae， damaged mitochondrial double-membrane structures， increased number of autophagosomes， upregulated expression of HIF-1α， BNIP3， beclin1， and LC3B （P<0.05， P<0.01）， and enhanced fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.05， P<0.01）. Compared with the model group， Tongmai Kaiqiao pills and donepezil hydrochloride shortened the searching time for the platform （P<0.01） and increased the number of platform crossings （P<0.01）. Moreover， the drugs increased the number of neurons with normal morphology and orderly arrangement and the number of Nissl bodies， alleviated the damage， increased the number of autophagosomes， upregulated the expression of HIF-1α， BNIP3， Beclin1， and LC3B （P<0.05， P<0.01）， and enhanced the fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.05， P<0.01）. Compared with high-dose Tongmai Kaiqiao pills， the combination group prolonged the escape latency （P<0.01）， reduced the number of crossing platforms （P<0.01）， decreased the number of hippocampal neurons， aggravated the damage， decreased the number of Nissl bodies and autophagosomes， downregulated the expression of HIF-1α， BNIP3， beclin1， and LC3B （P<0.01）， and decreased the fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.01）. ConclusionTongmai Kaiqiao pills may activate the HIF-1α/BNIP3 signaling pathway to promote the occurrence of mitochondrial autophagy， clear damaged mitochondria， provide energy for healthy cells， reduce neuronal cell death， and restore the brain function， thereby reducing ischemic damage to the hippocampal tissue， improving learning and memory abilities， and exerting therapeutic effects on VD in rats.

Vascular cognitive impairment (VCI) denotes a wide range of cognitive deficiencies resulting from cerebrovascular risk factors and cerebrovascular diseases. Sirtuin 1 (SIRT1), as a deacetylase, can mediate the deacetylation of histones and non-histone proteins. It is involved in regulating multiple pathophysiological processes of VCI, including neuroinflammation reduction, oxidative stress inhibition, cell apoptosis decrease, and blood-brain barrier protection, serving as a target for VCI treatment. This paper summarizes SIRT1 and the molecular mechanisms of targeting SIRT1 in order to provide a reference for the clinical treatment of VCI.

PD is a neurodegenerative disease characterized by degenerative death of dopaminergic neurons in the substantia nigra,exhibiting a range of motor and non-motor symptoms with serious effects on quality of life.circRNA is a covalently closed-loop non-coding RNA that plays a major role in PD progression.This article reviews the involvement of circRNA in oxidative stress,regulation of transcription,neuroinflammation,autophagy,and α-synuclein.

Parkinson's disease(PD)is a common neurodegenerative disease with a complex pathogenesis,and a large number of studies have shown that mitochondrial dysfunction is an important causative factor for PD,whereas dysregulation of mitochondrial quality control is a key factor leading to mitochondrial dysfunction,and that aberrant mitochondrial biogenesis,fusion/fission imbalance,and mitochondrial hyperautophagy are closely associated with the onset of PD,but the role of the mitochondrial quality control system in the progression of PD is unclear.Therefore,this paper reviews the mechanism of mitochondrial quality control system in PD,with the aim of providing new ideas and theoretical basis for the clinical prevention and treatment of PD.

Objective:To discuss the effect of Fuzheng Ruanjian Anticancer Formula on the malignant biological behaviors of the hepatocellular carcinoma HepG2 cells by requlating protein kinase B(Akt)/murine double minute 2(MDM2)/P53 signaling pathway.Methods:The HepG2 cells were treated with 0,0.05,0.10,0.20,0.40,0.80,1.60,3.20,and 6.40 g·mL-1 Fuzheng Ruanjian Anticancer Formula for 48 h.CCK-8 method was used to detect the survival rates of the HepG2 cells in various groups,and the concentrations of Fuzheng Ruanjian Anticancer Formula for the subsequent experiments were screened.The HepG2 cells were divided into control group,low dose of Fuzheng Ruanjian Anticancer Formula group(0.2 g·mL-1),medium dose of Fuzheng Ruanjian Anticancer Formula group(0.4 g·mL-1),high dose of Fuzheng Ruanjian Anticancer Formula group(0.8 g·mL-1),SC79 group(8 mg·L-1 SC79),and high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group(0.8 g·mL-1 Fuzheng Ruijian Anticancer Formula+8 mg·L-1 SC79).CCK-8 method was used to detect the proliferation activities of the HepG2 cells in various groups;clone formation assay was used to detect the clone formation rates of the HepG2 cells in various groups;flow cytometry was used to detect the apoptotic rates of the HepG2 cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion HepG2 cells in various groups;Western blotting method was used to detect the expression levels of proliferating cell nuclear antigen(PCNA),cysteine aspartate specific proteinase(Caspase-3),matrix metalloproteinase(MMP)-2,MMP-9,phosphorylated Akt(p-Akt),phosphorylated MDM2(p-MDM2),and P53 proteins in the HepG2 cells in various groups.Results:As the increasing of concentrations of Fuzheng Ruanjian Anticancer Formula(0,0.05,0.10,0.20,0.40,0.80,1.60,3.20,and 6.40 g·mL-1),the surival rates of the HepG2 cells were gradually decreased(P<0.05),and 0.2,0.4,and 0.8 g·mL-1 Fuzheng Ruanjian Anticancer Formula were selected for the subsequent experiments.The CCK-8 assay results showed that compared with control group,the proliferation activities of the HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05),in a dose-dependent manner,while the proliferation activity of the cells in SC79 group was significantly increased(P<0.05).Compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the proliferation activity of the HepG2 cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly increased(P<0.05).The clone formation assay results showed that compared with control group,the clone formation rates of the HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the clone formation rate of the cells in SC79 group was significantly increased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the clone formation rate of the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly increased(P<0.05).The flow cytometry results showed that compared with control group,the apoptotic rates of the HepG2 cells in low,medium,and high doses of Fuzheng Ruijian Anticancer Formula groups were significantly increased(P<0.05)in a dose-dependent manner,while the apoptotic rate of the cells in SC79 group was significantly decreased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the apoptotic rate of the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion HepG2 cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the numbers of migration and invasion cells in SC79 group were significantly increased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the numbers of migration and invasion HepG2 cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in low,medium,and high doses of Fuzheng Ruanjian Anticancer Formula groups were significantly decreased(P<0.05)in a dose-dependent manner,while the expression levels of Caspase-3 and P53 proteins were significantly increased(P<0.05)in a dose-dependent manner,while the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in SC79 group were significantly increased(P<0.05),and the expression levels of Caspase-3 and P53 proteins were significantly decreased(P<0.05);compared with high dose of Fuzheng Ruanjian Anticancer Formula group,the expression levels of PCNA,MMP-2,MMP-9,p-Akt,and p-MDM2 proteins in the cells in high dose of Fuzheng Ruanjian Anticancer Formula+SC79 group were significantly increased(P<0.05),while the expression levels of Caspase-3 and P53 proteins were significantly decreased(P<0.05).Conclusion:Fuzheng Ruanjian Anticancer Formula may inhibit the proliferation,migration,and invasion of the HepG2 cells and promote the apoptosis,and its mechanism may be related to suppressing the Akt/MDM2 signaling pathway and upregulating the P53 proteim expression.

Objective:To investigate the association between triglyceride-glucose (TyG) index and all-cause mortality in elderly patients with hypertension and coronary artery disease.Methods:This was a retrospective cohort study, a total of 5 640 elderly inpatients (≥65 years) with hypertension and coronary artery disease who were admitted to the Department of Cardiology, Liberation Army General Hospital from August 2008 to July 2018 were enrolled in this study. The baseline clinical data of the patients were collected and the TyG index was calculated. Patients were divided into four groups according to their TyG index quartiles: TyG index<8.31 ( Q1 group, n=1 392), 8.31≤TyG index<8.67 ( Q2 group, n=1 417), 8.67≤TyG index<9.07 ( Q3 group, n=1 427), and TyG index≥9.07 ( Q4 group, n=1 404). All patients were followed up by obtaining outpatient/rehospitalization records or by telephone. The primary endpoint was all-cause mortality. Log-rank test was used to compare the cumulative all-cause mortality among groups. Cox proportional hazard regression model was used to analyze the risk of all-cause mortality in each group (the Q2 group with the lowest all-cause mortality was used as a reference), after adjusting for confounding factors, Restricted cubic spline analysis (RCS) was used to determine the association between TyG index and risk of all-cause mortality. Results:During a follow-up of 6.44 (4.70, 8.85) years, 1 037 all-cause deaths (18.39 %) were documented. The cumulative all-cause mortality in Q1- Q4 groups was 16.52%, 16.51%, 17.59% and 22.93%, respectively, and the difference was statistically significant ( χ2=26.49, P<0.01). In the Cox regression model, compared with Q2 group (reference), the HR (95% CI) for all-cause mortality was 1.06 (0.88-1.28) in the Q1 group, 1.23 (1.02-1.48) in the Q3 group and 1.48 (1.23-1.77) in the Q4 group, respectively ( P for trend<0.01). RCS curve analysis showed that when the TyG index was greater than 8.67, the risk of all-cause mortality increased with the TyG index, and there was a linear relationship between TyG index and all-cause mortality in this patient cohort (non-linearity P=0.31). Conclusion:The elevated TyG index is significantly associated with a higher risk for all-cause mortality in elderly hypertension and coronary artery disease patients.