Background Vascular endothelial damage associated with endothelial progenitor cell dysfunction is considered as an initiating step of hypertension and target organ damage, in which oxidative stress plays a key role. High-intensity intermittent exercise is an effective prevention and treatment method of various chronic diseases; however, little attention has been paid to its effects and mechanisms on endothelial progenitor cells. Objective To observe the effect of high-intensity intermittent exercise on the function of endothelial progenitor cells in patients with hypertension and explore the mechanism of oxidative stress. Methods A total of 60 patients with essential hypertension were randomly divided into a control group and an exercise group. The control group received conventional drug treatment (including diuretics, calcium blockers, and beta-blockers), and the exercise group performed high-intensity intermittent exercise for 8 weeks (3 times·week⁻¹) in addition to the treatment plan of the control group. Before and after intervention, brachial artery flow-mediated vasodilation (FMD) was used to evaluate vascular endothelial function; venous blood was sampled to perfrom circulating endothelial progenitor cell counts; endothelial progenitor cells were cultured in vitro, and the modified Boyden chamber assay and Matrigel lumen formation assay were used to detect their migration and tube formation ability, superoxide fluorescent anion probe method to detect reactive oxygen species levels, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining method to detect cell apoptosis, Western blotting to determine protein expression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2, NADPH oxidase 4, and superoxide dismutase. Results Four patients (13.3%) in the control group and 2 patients (6.7%) in the exercise group dropped out; the completion rate of the exercise group's training plan was 94.9%. Compared with the before-intervention indicators, blood pressure decreased, brachial artery FMD increased, number of circulating endothelial progenitor cells increased, their migration and tube formation ability were enhanced, reactive oxygen species levels and cell apoptosis rate were reduced, NADPH oxidase 2 and NADPH oxidase 4 protein expressions were down-regulated, and superoxide dismutase protein expression was up-regulated in the after-intervention exercise group, and the differences were all statistically significant (P < 0.05). There was no significant difference in the above indicators in the control group between before and after intervention (P > 0.05). Conclusion High-intensity intermittent exercise regulates oxidative stress mediated by NADPH oxidase, improves endothelial progenitor cell function, and restores vascular endothelial disorders in patients with essential hypertension.

Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

Acute kidney injury （AKI） is a clinical syndrome characterized by a rapid decline in renal function over a short period due to various etiologic factors. If left untreated， AKI can progress to chronic kidney disease （CKD） or even end-stage renal disease （ESRD）. Although continuous renal replacement therapy （CRRT） can manage severe AKI， effective pharmacological treatments for AKI remain largely unavailable. Chinese medicine， with its multi-target and multi-pathway approaches， has accumulated substantial theoretical and practical knowledge in treating AKI and related complications. Rehmanniae Radix is a commonly used Chinese medicinal， known for its functions in clearing heat， cooling blood， nourishing yin， and promoting fluid production. The primary active ingredients of Rehmanniae Radix include catalpol， acteoside， and aucubin. In this study， we summarized recent research on the effect of the active ingredients of Rehmanniae Radix in preventing and treating AKI. We found that the key mechanisms underlying its anti-AKI effects include amelioration of inflammation， alleviation of oxidative stress， and inhibition of apoptosis. Additionally， the antifibrotic properties of the active ingredients of Rehmanniae Radix suggest its potential in slowing CKD progression. We reviewed the mechanisms of Rehmanniae Radix in treating AKI and its antifibrotic effects to provide a scientific basis for developing new AKI drugs， promoting the utilization of Rehmanniae Radix resources， and reducing the transition from AKI to CKD.

Objective To compare the clinical efficacy of ankle arthroscopy combined with closed reduction guide and conventional surgical incision in the treatment of trimalleolar fracture.Methods A total of 60 patients with ankle fracture were divided into two groups according to different surgical plans:the ankle arthroscopy combined with closed reduction guide surgery group(arthroscopy group)and the conventional incision surgery group(incision group),with 30 cases in each group.The operative time,intraoperative blood loss and complications of the two groups were observed and compared.Pain and functional recovery of patients were evaluated by the American Orthopaedic Foot&Ankle Society(AOFAS)ankle and hind foot scores and Foot and Ankle Disability Index(FADI)scores.Results All 60 patients were followed up.Compared with the arthroscopy group,patients in the incision group had a longer surgical time,a shorter incision length in the medial malleolus,a reduced number of cases of skin numbness and reduced bleeding(P＜0.05).The AOFAS score and the FADI score at 12 months after surgery were higher in the arthroscopic group than those of the incision group(P＜0.05).After 12 months of surgery,the AOFAS score in patients without cartilage injury of the arthroscopic group were higher than those of patients with cartilage injury(P＜0.05),while there were no significant differences in pain and force line scores between patients with cartilage injury and patients without cartilage injury(P＞0.05).Conclusion The application of ankle arthroscopy combined with closed reduction guide in the treatment of trimalleolar fracture can achieve better postoperative results,but it has no obvious advantages in operation time and incision infection compared with the incision surgery.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To explore the impact of Cullin5 on the radiosensitivity of glioblastoma multiforme cell and its underlying mechanisms.Methods:Glioblastoma U251 cells were transfected with flag-NC plasmids and overexpression plasmids (flag-Cullin5), and divided into the flag-NC group and flag-Cullin5 group. The expression levels of Cullin5 and programmed death ligand 1 (PD-L1) mRNA and protein were assessed using real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. After exposing U251 cells to 0, 2, 4, and 8 Gy X-ray radiation, cell viability was evaluated via the CCK-8 assay, and apoptosis rates were measured using flow cytometry. Co-immunoprecipitation was used to detect the interaction between Cullin5 and PD-L1, and ubiquitination assays were conducted to investigate the ubiquitination effect of Cullin5 on PD-L1. Cells were further transfected with PD-L1 overexpression (oe-PD-L1) and flag-Cullin5 and assigned into the flag-Cullin5 group, flag-Cullin5+oe-NC group, and flag-Cullin5+oe-PD-L1 group. qRT-PCR and Western blot were used to measure the expression levels of Cullin5 and PD-L1 mRNA and protein post-X-ray radiation in these groups. Cell survival rates and apoptosis rates were measured following radiation. Statistical differences between two or among multiple groups were analyzed using LSD- t test or one-way ANOVA. Results:Compared with the flag-NC group, the flag-Cullin5 group showed increased expression levels of Cullin5 mRNA and protein, and decreased PD-L1 protein expression (all P<0.05). Following radiation doses of 4 and 8 Gy, there was a reduction in cell survival rates and an increase in apoptosis rates (both P<0.05). Co-immunoprecipitation assay revealed the presence of PD-L1 in the Cullin5 immunoprecipitate and vice versa. Ubiquitination levels of PD-L1 protein were higher in the flag-Cullin5 group compared to those in the flag-NC group. Additionally, compared to the flag-Cullin5 group, the flag-Cullin5+oe-PD-L1 group exhibited increased PD-L1 mRNA and protein levels (both P<0.05), and following radiation doses of 4 and 8 Gy, these cells showed higher survival rates and lower apoptosis rates (both P<0.05). Conclusion:Cullin5 enhances the radiosensitivity of glioblastoma multiforme cells to radiation therapy through mediating the ubiquitination degradation of PD-L1.

Objective:To investigate the application value of nectin-4 targeting radiotracer 68Ga-N188 in the diagnosis of pancreatic cancer. Methods:The prospective study was conducted. The clinicopathologic data of 16 patients diagnosed as pancreatic cancer on enhanced computed tomography (CT) who were admitted to the Peking University First Hospital from August to December 2022 were collected. There were 9 males and 7 females, aged (62±8)years. All patients underwent 18F-flurodeoxyglucose ( 18F-FDG) and 68Ga-N188 positron emission tomography (PET)/CT examination. Observation indicators: (1) distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients; (2) expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer; (3) comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages. Results:(1) Distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients. Results of PET/CT examination showed that in 1 hour after injection, the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) of 68Ga-N188 in fat, muscle, skin, and brain tissues of 16 patients were 0.40±0.16 and 0.25±0.09, 0.68±0.20 and 0.44±0.12, 0.39±0.14 and 0.28±0.11, 0.09±0.04 and 0.05±0.02, respectively. In the tissues of the esophagus, liver, spleen, and pancreas, the above indicators were 1.53±0.48 and 1.16±0.31, 1.49±0.45 and 0.91±0.30, 1.40±0.30 and 1.02±0.24, 1.24±0.31 and 0.96±0.25, respectively. In tumor primary lesion, the above indicators were 3.28±1.02 and 2.14±0.62, respectively, showing significant differences in SUVmax and SUVmean compared with pancreatic tissue ( t=8.03, 6.75, P<0.05). The tumor background ratio in tumor primary lesion based on SUVmax was 1.82±0.58. (2) Expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer. Results of immunohistochemical staining in 16 patients showed that there were 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression. Results of PET/CT examination showed that the SUVmax of 68Ga-N188 in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 3.77±1.10 and 2.64±0.68, showing a significant difference between them ( t=2.64, P<0.05). The SUVmax of 18F-FDG in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 6.73±3.24 and 6.43±3.45, showing no significant difference between them ( t=0.17, P>0.05). (3) Comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Of the 16 patients, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 14 and 11, respectively, for the 14 pancreatic cancer patients diagnosed by postoperative histopathology. Among them, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 3 and 1 for the 3 pancreatic cancer patients receiving evaluation for chemotherapy. The SUVmax of 18F-FDG in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 2.80±0.69 and 6.97±2.11, showing a significant difference between them ( t=3.29, P<0.05). The SUVmax of 68Ga-N188 in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 3.38±1.12 and 2.93±0.50, showing no significant difference between them ( t=0.66, P>0.05). Cases with positive results of lymph node metastases in 68Ga-N188 and 18F-FDG PET/CT were 6 and 4, respectively, for the 6 pancreatic cancer patients diagnosed with lymph node metastases by postoperative histopathology, and the SUVmax of 68Ga-N188 and 18F-FDG in lymph node metastases were 2.25±1.12 and 4.02±1.27. Conclusion:68Ga-N188 PET/CT can be used for imaging diagnosis of tumor primary lesion and lymph node metastases of pancreatic cancer.

Objective To investigate the predictive effect of multiple serological indicators on the occurrence of heart failure (HF) after percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI). Methods A retrospective study was conducted on 276 elderly AMI patients. Based on whether HF occurred within 6 months, they were divided into HF group (n=65) and non-HF group (n=211). Multivariate Logistic regression was used to screen the influencing factors of AMI complicated with HF. The receiver operating characteristic (ROC) curve was applied to evaluate the efficacy of serological indicators in predicting HF. Results Age, uric acid, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), systemic immune-inflammation index (SII) and level of interleukin-6 (IL-6) in the HF group were significantly higher than those in the non-HF group, while the left ventricular ejection fraction and the proportion of TIMI grade 3 blood flow in the HF group were significantly lower (P < 0.05). Multivariate Logistic regression analysis showed that age (OR=1.401, 95%CI, 1.103 to 1.937), hs-CRP (OR=1.428, 95%CI, 1.108 to 1.839), SII (OR=1.645, 95%CI, 1.262 to 2.145), uric acid (OR=1.376, 95%CI, 1.123 to 1.685) and TIMI grade 3 blood flow (OR=0.502, 95%CI, 0.335 to 0.752) were independent influencing factors for HF after PCI in AMI patients. The ROC curve demonstrated that the area under the curve (AUC) of hs-CRP, SII and uric acid for predicting HF after PCI in AMI patients were 0.694 (95%CI, 0.619 to 0.768), 0.854 (95%CI, 0.796 to 0.912) and 0.716 (95%CI, 0.646 to 0.786), respectively, with sensitivities of 75.38%, 81.54% and 66.15%, and specificities of 57.32%, 74.88% and 73.93%. Conclusion SII has the highest predictive value for HF after PCI in elderly AMI patients, which is helpful for assisting clinical management of high-risk HF populations.

Objective:To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods:The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened. The GeneCards, OMIM, TTD, DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. The Cytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-disease network diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-in was used to screen core active components and targets. The bioenrichment analysis of GO and KEGG was carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram was drawn, and the core active components and core targets were docked in PyMOL and AutoDockTools 1.5.7.Results:A total of 102 potentially active components and 62 intersection targets were obtained, and 8 active components and 7 core targets were screened. Enrichment analysis showed that the key targets were mainly enriched through the signaling pathways of fluid shear stress and atherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biological processes such as the response to nutritional levels and the regulation of small molecule metabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion:The main active components of Linggui Zhugan Decoction are quercetin, kaempferol and naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid and atherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.

ObjectiveTo build an evaluation index system for traditional Chinese medicine （TCM） medicated diet， promoting the scientific and standardized development of medicated diet in TCM. MethodsThe framework of the evaluation index system was constructed through literature review and Delphi expert consultation method. The analytic hierarchy process was used to construct a hierarchical structure model. Pairwise comparisons between the indicators were conducted using the Saaty 1-9 scale method， and the weight of each indicator was calculated using Yaahp 10.3. ResultsThe response rates for the two rounds of expert consultation were 93.33% and 100%， respectively. The Kendall's W coefficients for the first-level and second-level indicators in the second round were 0.270 and 0.281， respectively （both P＜0.001）. Finally， an evaluation index system for TCM medicated diet therapy was constructed， consisting of 6 primary indicators and 27 secondary indicators. The weightings of the primary indicators were as follows： sensory appearance （0.1843）， health value （0.3569）， ingredient compatibility （0.1271）， packaging （0.0370）， production and preparation （0.1005）， and reliability （0.1940）. ConclusionA comprehensive and universally applicable evaluation index system for TCM medicated diet has been developed， taking into conside-rations of color， taste， appearance， efficacy， preparation， quality and others. This system can provide valuable reference for the evaluation of the value of medicated diet as well as its development.