In recent years, the application of minimal residual disease (MRD) in solid tumors has gained widespread attention. MRD typically refers to the presence of residual cancer cells that remain undetectable by imaging after curative treatments, such as surgical resection. The presence of MRD post-surgery is significantly associated with an increased risk of tumor recurrence. In colorectal cancer, circulating tumor DNA (ctDNA) serves as an effective marker for assessing MRD, particularly in non-metastatic (stages I-III) colorectal cancer. As a real-time, accurate, and convenient biomarker, ctDNA can effectively predict tumor recurrence, guide postoperative adjuvant chemotherapy decisions, and provide crucial information for recurrence monitoring. The application prospects of ctDNA detection technology are vast, promising more precise and individualized treatment plans for colorectal cancer patients. This article comprehensively analyzes the progress in the application of ctDNA for detecting MRD in non-metastatic colorectal cancer patients, elaborates on its guiding role in clinical treatment decisions, and envisions the future development directions in this field.

In recent years, the application of minimal residual disease (MRD) in solid tumors has gained widespread attention. MRD typically refers to the presence of residual cancer cells that remain undetectable by imaging after curative treatments, such as surgical resection. The presence of MRD post-surgery is significantly associated with an increased risk of tumor recurrence. In colorectal cancer, circulating tumor DNA (ctDNA) serves as an effective marker for assessing MRD, particularly in non-metastatic (stages I-III) colorectal cancer. As a real-time, accurate, and convenient biomarker, ctDNA can effectively predict tumor recurrence, guide postoperative adjuvant chemotherapy decisions, and provide crucial information for recurrence monitoring. The application prospects of ctDNA detection technology are vast, promising more precise and individualized treatment plans for colorectal cancer patients. This article comprehensively analyzes the progress in the application of ctDNA for detecting MRD in non-metastatic colorectal cancer patients, elaborates on its guiding role in clinical treatment decisions, and envisions the future development directions in this field.

Objective:To characterize clinical and neuroimaging features, etiologies, and mechanisms of bilateral middle cerebellar peduncle (MCP) infarctions.Methods:Consecutive patients with bilateral MCP infarctions treated in the Beijing Tiantan Hospital, Capital Medical University between January 1, 2020 and April 30, 2022 were enrolled in this retrospective study. The demographic data, vascular risk factors, clincial manifestations and the National Institutes of Health Stroke Scale (NIHSS) scores were collected. Brain diffusion-weighted imaging was used to assess the regions of cerebral infarction, and the extracranial and intracranial segments of the vertebrobasilar artery were evaluated using magnetic resonance angiography, or computed tomography angiography. The stroke etiology and underlying mechanism were evaluated according to the Chinese Ischemic Stroke Subclassification.Results:Ten patients with bilateral MCP infarctions (8 men and 2 women) were analyzed ultimately. The onset age were 51.0-86.0 (64.8±11.4) years. NIHSS scores were 2.0-12.0 (4.9±2.9) points at admission. All patients had vascular risk factors, most of which were hypertension (10 cases) and dyslipoproteinemia (8 cases). The most common clinical manifestations were vertigo (10 cases), followed by ataxia (9 cases) and dysarthria (8 cases). Four cases were isolated bilateral MCP infarctions, while 6 patients were combined with other vertebrobasilar artery infarctions, 4 of which were combined with cerebellar hemisphere infarctions, consistent with the clinical symptoms. The etiology in all patients was large atherosclerosis (severe stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery; 9 cases). Five patients were classified as hypoperfusion/impaired emboli clearance, while 4 patients were considered as artery-to-artery embolism, and 1 was considered as the parent artery (plaque or thrombosis) occluding penetrating artery.Conclusions:Bilateral MCP infarctions are an extremely rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria. Cerebral infarction can be isolated or often combined with cerebellar hemisphere infarction. The etiology was mostly stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery.

Objective:To investigate the application effect of Mini-Clinical Evaluation Exercise (Mini-CEX) combined with direct observation of procedural skills (DOPS) in standardized training of emergency medicine guided by professional physician qualification examination.Methods:Based on the time of emergency medicine teaching reform in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, 32 standardized training residents in Emergency Department before September 2020 were included as control group and were given traditional teaching, and 32 standardized training residents after September 2020 were included as observation group and were given Mini-CEX combined with DOPS teaching under the guidance of professional physician qualification examination. The two groups were compared in terms of Mini-CEX score, DOPS score, assessment score of comprehensive emergency skills, pass rate of professional physician qualification examination, and comprehensive teaching quality. SPSS 25.00 was used to perform the t-test and the chi-square test. Results:Compared with the control group after training, the observation group had significantly higher scores of Mini-CEX, DOPS, and comprehensive emergency skill assessment ( P<0.05). There were no significant differences between the two groups in the pass rates of theoretical and practical examinations in professional physician qualification examination, and the observation group had a significantly higher total pass rate than the control group ( P<0.05). The observation group had significantly higher comprehensive teaching quality scores than the control group ( P<0.05). Conclusion:Mini-CEX combined with DOPS guided by professional physician qualification examination can help to improve the teaching effectiveness of standardized training residents in emergency, enhance their comprehensive skills and emergency professional skills, achieve a relatively high pass rate of professional physician qualification examination, and improve their post competency, and thus it holds promise for clinical application.

Objective:To investigate the effects of ceftriaxone(CTX) on nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4) pathway and ferroptosis in early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Forty-eight clean grade male SD rats were randomly divided into sham operation group (Sham group), SAH group, SAH+ CTX group and SAH+ CTX+ Nrf2 inhibitor group (SAH+ CTX+ ML385 group) according to the random number table with 12 rats in each group.Seven days before modeling, rats in SAH+ CTX+ ML385 group were injected intraperitoneally with ML385 (30 mg · kg -1) once a day for consecutive 7 days.And 5 days before modeling, rats in SAH+ CTX group and SAH+ CTX+ ML385 group were treated with CTX(200 mg · kg -1) by intraperitoneal injection once a day for five consecutive days.Rats in Sham group and SAH group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution.After 24 hours of modeling, the neurological function score and brain tissue water content of rats in each group were measured.HE staining was used to observe the morphology of neurons in CA1 and CA3 regions of hippocampus.Prussian blue staining was used to observe the iron deposition in cerebral cortex.Spectrophotometer was used to determine the iron content, malonic dialdehyde(MDA) content, glutathione(GSH) content and GPX4 activity in cerebral cortex.Western blot was used to detect the expression levels of Nrf2 and GPX4 proteins in cerebral cortex.SPSS 23.0 was used for statistical analysis.One-way ANOVA was used to compare the mean of multiple groups of samples, and Dunnett- t test was used for further pairwise comparison between groups. Results:There was a statistically significant difference in the neurological function scores of rats in the four groups 24 hours after SAH ( F=48.40, P<0.001). The neurological function score of rats in the SAH group 24 hours after SAH was significantly lower than those in Sham group and SAH+ CTX group (both P<0.05). The brain water content of rats in the four groups 24 h after SAH was statistically significant ( F=49.61, P<0.001). The brain water content of rats in the SAH group 24 h after SAH was significantly higher than that in Sham group and SAH+ CTX group(both P<0.05). There was statistically significant differences in the number of neuronal necrosis in CA1 and CA3 regions of hippocampus in the four groups 24 hours after SAH ( F=17.44, 246.50, both P<0.001). The numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH group were significantly higher than those in Sham group and SAH+ CTX group, and the numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH+ CTX+ ML385 group were significantly higher than those in SAH+ CTX group (all P<0.05). Twenty-four hours after SAH, the amount of iron deposited in the cerebral cortex of rats in the four groups was statistically significant ( F=2 363.0, P<0.001). The iron deposition in the cerebral cortex of rats in the SAH group was significantly higher than those in Sham group and SAH+ CTX group (both P<0.05). There were significant differences in iron content, MDA content, GSH content and GPX4 activity in the cerebral cortex of the four groups 24 h after SAH( F=2 380.0, 1 322.0, 789.1, 815.5, all P<0.001). The content of iron and MDA in the cerebral cortex of rats in SAH group were significantly higher than those in Sham group, while the content of GSH and the activity of GPX4 were significantly lower than those in Sham group (all P<0.05). The content of iron and MDA in the cerebral cortex of rats in SAH+ CTX group were lower than those in SAH group, and the content of GSH and the activity of GPX4 were higher than those in SAH group (all P<0.05). At 24 h after SAH, the expression levels of Nrf2 and GPX4 protein in the cerebral cortex of the four groups were statistically significant ( F=888.7, 1 556.0, both P<0.001). The protein expression levels of Nrf2 (0.382±0.014) and GPX4 (0.329±0.019) in the cerebral cortex in SAH group were lower than those in Sham group ((0.746±0.009), (0.953±0.009)) (both P<0.05). The expression levels of Nrf2 (0.631±0.006) and GPX4 (0.833±0.008) protein in the cerebral cortex in the SAH+ CTX group were significantly higher than those in the SAH group (both P<0.05). The expression levels of Nrf2 (0.427±0.009) and GPX4 (0.525±0.011) protein in the cerebral cortex in SAH+ CTX+ ML385 group were significantly lower than those in SAH+ CTX group (both P<0.05). Conclusion:Ceftriaxone may inhibit ferroptosis during EBI in SAH rats by regulating Nrf2/GPX4 signal axis.

[Objective]To investigate the therapeutic effect and molecular mechanism of Chinese medicine Saffron on Parkinson's disease(PD)based on network pharmacology and molecular docking.[Methods]The pharmacodynamic components of Saffron included in the analysis were determined through the pharmacological database and literature research of the Chinese medicine system.With the help of compound target database and disease target database,the corresponding targets of saffron components and PD targets were predicted,respectively.Enrichment analysis of compound-disease intersection targets was made by using R procedures and referencing correlated R-packages.Construction of protein-protein interaction(PPI)networks and analysis of node-related topological parameters.Simulate molecular docking to verify binding properties of representative compounds and key targets.The pharmacodynamic properties of Saffron acid on key targets were preliminarily evaluated by experiments.[Results]The 8 components of saffron with druggable potential corresponded to 279 targets,PD had 2 183 disease targets,and a total of 98 intersection targets of compounds and diseases were obtained.Enrichment analysis showed that the compound-disease intersection target was involved in biological processes such as reactive oxygen radical synthesis and metabolism,neuroinflammation and mitogen-activated protein kinase(MAPK)signaling pathway.The key targets identified by PPI network analysis were tumor necrosis factor(TNF)and signal transducer and activator of transcription 3(STAT3).Molecular docking showed that saffron glycosides and saffron acids had stronger binding activity with TNF.Experiments had shown that saffron acid can reduce the transcription levels of lipopolysaccharide-induced cytoinflammatory factor TNF,interleukin-1β(IL-1β)and inducible nitric oxide oxide synthase(iNOS).[Conclusion]Saffron can be used as a candidate for PD treatment,and its neuroprotective effect may involve the interaction and synergy of many targets and signaling pathways,which deserves special attention to the activity of saffron acid against central nervous system inflammation.

Motor imagery (MI) is an important paradigm of driving brain computer interface (BCI). However, MI is not easy to control or acquire, and the performance of MI-BCI depends heavily on the performance of the subjects' MI. Therefore, the correct execution of MI mental activities, ability evaluation and improvement methods play important and even critical roles in the improvement and application of MI-BCI system's performance. However, in the research and development of MI-BCI, the existing researches mainly focus on the decoding algorithm of MI, but do not pay enough attention to the above three aspects of MI mental activities. In this paper, these problems of MI-BCI are discussed in detail, and it is pointed out that the subjects tend to use visual motor imagery as kinesthetic motor imagery. In the future, we need to develop some objective, quantitatively visualized MI ability evaluation methods, and develop some effective and less time-consumption training methods to improve MI ability. It is also necessary to solve the differences and commonness of MI problems between and within individuals and MI-BCI illiteracy to a certain extent.
Algorithms ; Brain-Computer Interfaces ; Electroencephalography ; Humans ; Imagery, Psychotherapy ; Imagination

Objective:To investigate the clinical efficacy of ex vivo liver resection and autotransplantation (ELRA) for liver complex space-occupying lesions.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 50 patients with liver complex space-occupying lesions who underwent ELRA in the First Hospital Affiliated to Army Medical University between June 2009 and May 2017 were collected. There were 36 males and 14 females, aged from 13 to 69 years, with a median age of 51 years. All patients underwent ELRA. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination or telephone interview. Patients were followed up according to the individual follow-up plan in the first 6 months after discharge, and then once every 3 to 6 months to detect tumor recurrence and survival up to May 2019. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-rank test was used for survival analysis. Results:(1) Surgical situations: all the 50 patients underwent ELRA successfully, and postoperative pathological examination showed the R 0 resection rate was 100%(50/50). The operation time of the 50 patients were (630±186)minutes, of which 9 patients with liver benign occupation had the operation time of (684±168)minutes and 41 patients with liver malignant tumor had the operation time of (618±190)minutes. The operation time of temporary reconstruction of inferior vena cava and portacaval shunt, time of anhepatic phase, volume of intraoperative blood loss of the 50 patients were (35±9)minutes, (256±71)minutes, 2 000 mL(range, 400-10 000 mL), respectively. The remnant liver mass to standard liver mass ratio of the 50 patients was 65%±16%, of which 9 patients with liver benign occupation had the remnant liver mass to standard liver mass ratio of 63%±14% and 41 patients with liver malignant tumor had the remnant liver mass to standard liver mass ratio of 65%±17%. Of the 50 patients, 35 had vascular invasion (7 cases with liver benign occupation, 28 cases with liver malignant tumor), of which 24 (6 cases with liver benign occupation, 18 cases with liver malignant tumor) underwent in vitro vascular reconstruction, 12 (5 cases with liver benign occupation, 7 cases with liver malignant tumor) had bile duct invasion and underwent choledochojejunostomy due to the inability of the common bile duct to anastomose the ends. Two cases with liver metastasis of gastric cancer, one case with liver metastasis of colon cancer and one case with liver metastasis of pancreatic cancer underwent radical gastrectomy, radical resection of colon cancer, and pancreaticoduodenectomy, respectively. (2) Postoperative situations: the duration of postoperative hospital stay of the 50 patients were 25 days (range, 11-169 days). Of the 50 patients, 12 had pleural effusion who were treated with pleural puncture drainage, 10 had bile leakage who were treated with abdominal puncture drainage, 3 had bile duct anastomotic leakage who were treated with endoscopic nasobiliary drainage or biliary stent implantation, 6 underwent reoperation among which 4 underwent exploratory laparotomy due to abdominal hemorrhage, 1 underwent portal vein reconstruction due to abdominal hemorrhage combined with portal vein thrombosis, and 1 underwent salvage liver transplantation due to liver failure. Nine of the 50 patients died within 90 days after surgery, all of whom had liver malignant tumor. Among them, 3 died of multi-organ dysfunction syndrome caused by severe infection, 3 died of acute liver failure, 2 died of abdominal hemorrhage and 1 died pulmonary embolism. (3) Follow-up: all the 50 patients were followed up for 1 to 119 months. The overall survival time, 1-, 3-, 5-year overall and tumor-free survival rates of the 50 patients after operation were 17 months (range, 1-119 months), 68.0%, 45.9%, 41.1% and 41.9%, 33.4%, 30.8%, respectively. The overall survival time, 1-, 3-, 5-year overall and tumor-free survival rates of the 9 patients who with liver benign occupation after operation were 68 months (range, 10-114 months), 88.9%, 88.9%, 88.9% and 88.9%, 88.9%, 88.9%, respectively. The overall survival time, 1-, 3-, 5-year overall and tumor-free survival rates of the 41 patients who with liver malignant tumor after operation were 15 months (range, 1-119 months), 63.4%, 36.6%, 31.0% and 31.5%, 21.0%, 18.0%, respectively. There were significant differences in the overall and tumor-free survival rates between patients who with liver benign occupation and patients who with liver malignant tumor ( χ2=7.626, 11.766, P<0.05). Conclusions:ELRA can be applied in the treatment of liver complex space-occupying lesions. The selection criteria of patients with liver malignant tumor should be more rigorous to reduce perioperative mortality.

Objective:To construct a rat model of hypothalamic obesity by two point electrical damage to the ventromedial hypothalamus and arcuate nucleus.Methods:Twenty adult male SD rats of SPF grade were randomly divided into experimental group and sham operation group.A 25GA (0.45 mm) solid iron needle was used, the needle was coated with an insulating layer, and the tip exposed a 0.5 mm conductive area.With reference to The Rat Brain in Stereotaxic Coordinates and using the stereotactic instrument (AP: -2.6 mm, ML: ± 0.6 mm, DV: -9.6 mm) as the coordinate, 1.5 mA current was continuously applied for 25 s, the ventromedial nucleus (VMH) and arcuate nucleus (ARC) of bilateral brain in SD rats was damaged.During the experiment, the body weight(BW), food intake(FI) and water intake(WI) of the two groups were recorded regularly.The rats were sacrificed on the 28th day after the operation, and the changes of periprenal fat mass and body length were measured.The changes of liver and adipose tissue were detected by HE staining method, leptin by ELISA, leptin receptor(LEPR) by Western blot.Results:(1) The body weight of rats in the experimental group ((427.5±17.7)g) and weight gain ((208.5±14.8)g) were significantly increased compared with the rats in the control group((349.2±17.7)g), ((136.2±21.4)g)on the 28th day after operation ( t=7.661, 6.806, both P<0.001). (2) The daily food intake of rats in the experimental group ((44.2±6.6)g) on the 28th day after surgery was significantly higher than that in the control group ((23.0±3.6)g) ( t=6.918, P<0.001). There was no significant difference of the daily drinking water of rats between experimental group((37.5±12.1)ml) and the control group ((35.0±11.8)ml) ( t=0.361, P=0.726). (3) Perikidney fat mass of experimental group rats ((13.4±2.7)g) significantly increased 28 days after operation compared with control group rats((6.3±0.9)g)( t=4.250, P<0.05). The naso-anal length of experimental group((21.8±0.4)cm) was significantly decreased compared with the control group ((23.4±0.2)cm) ( t=-6.788, P<0.01). The Lee index of the experimental group (348.9±8.5) was significantly higher than that of the control group(305.5±4.3)( t=7.898, P<0.01). (4) The serum leptin content ((8 324.10±159.00)μg/L) of the experimental group rats at 28 days after surgery was significantly higher than that of the control group((2 705.31±407.10)μg/L) ( t=25.712, P<0.001). The lateral hypothalamus area (LHA) LEPR protein expression (1.3±0.1) in the experimental group was significantly higher than that in the control group (0.9±0.1) ( t=4.932, P<0.01). Conclusion:Two-point electrical damage to bilateral VMH and ARC of rats can establish hypothalamic obese rat model.

OBJECTIVE: To investigate the mechanism by which doublecortin promotes the recovery of cytoskeleton in arginine vasopressin (AVP) neurons in rats with electrical lesions of the pituitary stalk (PEL). METHODS: Thirty-two SD rats were randomized into PEL group with electrical lesions of the pituitary stalk through the floor of the skull base (=25) and sham operation group (=7), and the daily water consumption (DWC), daily urine volume (DUV) and urine specific gravity (USG) of the rats were recorded. Four rats on day 1 and 7 rats on each of days 3, 7 and 14 after PEL as well as the sham-operated rats were sacrificed for detection of the expressions of β-Tubulin (Tuj1), doublecortin and caspase- 3 in the AVP neurons of the supraoptic nucleus using immunofluorescence assay and Western blotting. RESULTS: After PEL, the rats exhibited a typical triphasic pattern of diabetes insipidus, with the postoperative days 1-2 as the phase one, days 3-5 as the phase two, and days 6-14 as the phase three. Immunofluorescent results indicated the repair of the AVP neurons evidenced by significantly increased doublecortin expressions in the AVP neurons following PEL; similarly, the expression of Tuj1 also increased progressively after PEL, reaching the peak level on day 7 after PEL. The apoptotic rates of the AVP neurons exhibited a reverse pattern of variation, peaking on postoperative day 3 followed by progressive reduction till day 14. Western blotting showed that the expressions of c-Jun and p-c-Jun were up-regulated significantly on day 3 ( < 0.05) and 7 ( < 0.01) after PEL, while an upregulated p-JNK expression was detected only on day 3 ( < 0.05), as was consistent with the time-courses of neuronal recovery and apoptosis after PEL. CONCLUSIONS JNK/c-Jun pathway is activated after PEL to induce apoptosis of AVP neurons in the acute phase and to promote the repair of neuronal cytoskeleton by up-regulation of doublecortin and Tuj1 expressions.
Animals ; Apoptosis ; Arginine Vasopressin ; pharmacology ; Cytoskeleton ; metabolism ; MAP Kinase Signaling System ; Neurons ; cytology ; Pituitary Gland ; cytology ; injuries ; Proto-Oncogene Proteins c-jun ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Tubulin ; metabolism