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.

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.

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*

Colorectal cancer is a common malignant tumor disease that poses a threat to human life. Its early stage is relatively concealed and often does not present specific clinical manifestations. Therefore, metastasis is the main factor leading to death. However, for colorectal cancer and all other tumor diseases, early identification and intervention have a significant impact on the prognosis, survival time and quality of life of patients. However, the current clinical examination and testing methods all have certain limitations, especially in terms of the sensitivity and specificity for indicating tumor occurrence and metastasis, which still need to be improved. Therefore, finding new biomarkers is of great significance, and the discovery of new biomarkers can also increase the risk stratification of screening. In recent years, with the deepening of research, chemokine CCL11 has gradually come into researchers′ view. CCL11 is an eosinophil chemotactic factor and was first reported in guinea pig allergic airway inflammation. With the progress of research, its important role in many tumor-related diseases has gradually emerged. This article will provide an overview of the correlation between CCL11 and colon cancer.

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.

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.

Objective:To review the application of pediatric magnetic resonance enterography (MRE) at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2012 to 2023, and to provide referenceable data for MRE use in complex pediatric clinical scenarios.Methods:This study was a cross-sectional study. The clinical and imaging data from children aged≤18 years who underwent MRE at Tongji Hospital between December 2012 and December 2023 were retrospectively analyzed. Out of 186 children who intended to receive the MRE examination, 12 failed, remainder 174 participants (mean age 14±4 years, range 1 month to 18 years) were included. Participants were categorized into an inflammatory bowel disease (IBD) group (118 cases) and a non-IBD group (56 cases), and further divided by age into infants (0-6 years, 8 cases), children (7-12 years, 37 cases), and adolescents (13-18 years, 129 cases). The overall image quality and the intestinal filling quality were scored using a 5-point scale. Statistical analyses included χ2 tests for age distribution, history of intestinal reconstruction surgery, and MRE success rates between IBD and non-IBD groups. Mann-Whitney U test was employed to compare subjective image quality scores between the abovementioned two groups. The Kruskal-Wallis test was used to detect the differences among the three age groups. Results:The success rate of MRE significantly increased with age: 66.7% (8/12) in infants, 88.1% (37/42) in children, and 97.7% (129/132) in adolescents ( χ2=15.39, P<0.001). A statistically significant difference in age distribution was observed between the IBD and non-IBD groups ( χ2=17.94, P<0.001). The proportion of infants in the non-IBD group was 14.3% (8/56), which was higher than that of the IBD group. The majority of the IBD group were adolescents, accounting for 78.8% (93/118). There was a statistically significant difference in the intestinal reconstruction surgery history ( χ2=2.83, P=0.005). The non-IBD group had a higher incidence of intestinal reconstructive surgery (21.4%, 12/56), compared to the IBD group (6.8%, 8/118). MRE intestinal filling quality or overall image quality scores between the IBD and non-IBD groups or among different age sub-groups were not statistically significant ( P>0.05). Conclusion:Juvenilization of non-IBD children and intestinal reconstructive surgery history could make the inspection more complex. High-quality imaging can still be achieved by adhering to technical specifications.

Objective:To compare the efficacy and impact on the quality of life of elderly patients of minimally invasive percutaneous nephrolithotomy(MPCNL)and retrograde intrarenal surgery(RIRS)in the treatment of unilateral upper ureteral calculi larger than 1.0 cm in diameter.Methods:A total of 104 patients were prospectively collected from January 2021 to December 2022 in the First Hospital of Shanxi Medical University.Based on the inclusion and exclusion criteria, 88 patients were finally included, 32 patients in the MPCNL group and 56 patients in the RIRS group, and the independent samples t-test, χ2 test, or Fisher's exact probability method were used to compare the differences in the general information, stone characteristics, and intraoperative and postoperative indexes between the two groups, and the quality-of-life scores were applied with the SF-36 Health Survey form. Results:There were no significant differences in age[(67.52±7.41)years and(67.38±7.25)years], gender[male/female: 19/13 cases and 36/20 cases], body mass index[(23.74±2.93)kg/m 2 and(23.70±2.57)], stone location(left/right: 20/12 cases and 38/18 cases), degree of hydronephrosis(mild/moderate/severe: 9/20/3 cases and 16/38/2 cases), stone maximum diameter[(14.12±3.69)mm and(13.34±2.99)mm], stone CT values[(1 035.7±275.7)HU and(973.3±253.8)HU]and postoperative complications[15.6%(5/32)and 14.3%(8/56)]between the two groups of patients( P>0.05).However, there were significant difference in stone clearance rate[96.9%(31/32) vs.80.4%(45/56)], and the operation time[(44.44±9.91)min vs.(54.69±11.94)min]between the two groups.The hospital stay in the RIRS group was shorter than that in the MPCNL group[(5.27±2.27)d vs.(8.00±2.19)d, P<0.05].There was no significant difference in the scores of eight dimensions between the two groups before surgery( P<0.05).At the day of discharge, patients in the MPCNL group had significantly lower mean scores than the RIRS group on six different subscales of the SF-36 questionnaire, namely, physical functioning, role-physical, bodily pain, social functioning, role-emotional and mental health.No differences in the mean scores for general health and vitality between the two groups were noted.In terms of SF-36 scores at one month after operation, the MPCNL group had lower scores in physical pain and social function than the RIRS group and the difference was statistically significant( P<0.05).No differences in the mean scores for other domains at one month after operation between patients undergoing MPCNL and those undergoing RIRS were noted. Conclusions:For patients with unilateral upper ureteral calculi larger than 1.0 cm in diameter, MPCNL has higher stone-free rate and shorter operation time than RIRS, but longer hospitalization time, and MPCNL has a greater impact on the quality of life of patients with ureteral calculi than RIRS in many aspects.

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.

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.