1.Mechanism of Shaoyaotang in Modulating MDSCs-related Immunosuppressive Microenvironment in Prevention and Treatment of Colitis-associated Carcinogenesis
Xue CHEN ; Chenglei WANG ; Bingwei YANG ; Haoyu ZHAI ; Ying WU ; Weidong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):10-19
ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis (CAC) based on myeloid-derived suppressor cells (MDSCs)-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups: Blank group, Shaoyaotang without model group (7.12 g·kg-1), model group, sulfasalazine group (0.52 g·kg-1), Shaoyaotang low-dose group (3.56 g·kg-1), Shaoyaotang medium-dose group (7.12 g·kg-1) and Shaoyaotang high-dose group (14.24 g·kg-1), with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline (10 mg·kg-1), while the other five groups were given a single intraperitoneal injection of azoxymethane (AOM) (10 mg·kg-1). After 1 week, the mice were given drinking water containing 2% dextran sulfate sodium (DSS) for 1 week, followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14th day of the experiment, followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28th and 98th days of the experiment. After dissection, the colon length, colon weight, spleen weight, tumor size, and tumor number were measured. Hematoxylin and eosin (HE) staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs, regulatory T cells (Tregs), CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated nuclear factor-κB (p-NF-κB), and hypoxia-inducible factor 1α (HIF-1α) in the colon tissue. ResultsOn day 14, compared with the blank group, the body weight of the model group was significantly reduced (P<0.01), reaching its lowest point on day 28 (23.39 ± 0.95 ) g. On days 28 and 98, compared with the blank group, the colon length in the model group was significantly shortened (P<0.01), the colon index significantly increased (P<0.01), the spleen index significantly increased (P<0.01), and the tumor load significantly increased (P<0.01). HE staining showed that in the model group, tumor cells, a large number of inflammatory cell infiltrates, goblet cell disappearance, and crypt loss were observed. In each dose group of Shaoyaotang, the damage to the colonic mucosa, inflammatory cell infiltration, and crypt structure destruction were alleviated. Compared with the model group, the body weight of mice in each dose group of Shaoyaotang increased. On day 98, the colon length was significantly increased (P<0.01), the colon index significantly decreased (P<0.01), the spleen index significantly decreased (P<0.01), and the tumor burden significantly decreased (P<0.01) in each Shaoyaotang dose group. On days 28 and 98, MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced (P<0.01), while CD4+ T cells and the CD4+/CD8+ T cell ratio were significantly increased (P<0.01). The proportion of CD8+ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees (P<0.05, P<0.01). On days 28 and 98, the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased (P<0.01), while the expression of p-NF-κB and HIF-1α was significantly reduced (P<0.01). ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.
2.Exploration on the Syndrome Differentiation and Treatment Strategies for Inflammation-Cancer Transformation in Inflammatory Bowel Disease Based on the Theory of Cold Qi-Induced Accumulation
Jiahe WU ; Muyao CUI ; Xue CHEN ; Bingwei YANG ; Haoyu ZHAI ; Chenglei WANG ; Ying WU ; Weidong LI
Journal of Traditional Chinese Medicine 2025;66(14):1489-1494
It is proposed that cold qi-induced accumulation encapsulates the core pathogenesis of the inflammation-cancer transformation in inflammatory bowel disease (IBD). Cold pathogens may serve as the initiating factor. When first invading the intestines, cold pathogens obstruct the flow of qi; over time, the lingering cold impairs the middle jiao (焦), eventually leading to the accumulation of cold-phlegm and blood stasis. Based on the progressive nature of this transformation, the process can be divided into three stages, active stage, remission stage, and carcinogenic stage. In the active stage, the main pathogenesis involves stagnation of cold qi and accumulation of damp-heat in the intestines; in the remission stage, cold qi impairs the spleen, disrupting its transport and transformation functions; and in the carcinogenic stage, the mechanisms include cold-induced accumulation, phlegm accumulation from cold, and stagnation of cold and blood stasis. Accordingly, the treatment strategies are proposed.In the active stage, regulating qi, relieving stagnation, and harmonizing cold and heat; in the remission stage, warming yang, dispersing cold, tonifying qi, and strengthening the spleen; and in the carcinogenic stage, promoting qi circulation, dispersing cold, resolving phlegm, activating yang, and eliminating stasis to remove accumulation. These approaches aim to interrupt the transformation of IBD into colorectal cancer.
3.Effect of electroacupuncture on learning and memory abilities in vascular dementia rats via the NCOA4/FTH1 signaling pathway-mediated ferritinophagy.
Wei SUN ; Yinghua CHEN ; Tong WU ; Hongxu ZHAO ; Haoyu WANG ; Ruiqi QIN ; Xiaoqing SU ; Junfeng LI ; Yuanyu SONG ; Yue MIAO ; Xinran LI ; Yusheng HAN
Chinese Acupuncture & Moxibustion 2025;45(9):1271-1280
OBJECTIVE:
To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD.
METHODS:
A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot.
RESULTS:
Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01).
CONCLUSION
Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals
;
Electroacupuncture
;
Dementia, Vascular/genetics*
;
Male
;
Rats
;
Signal Transduction
;
Humans
;
Memory
;
Rats, Sprague-Dawley
;
Nuclear Receptor Coactivators/genetics*
;
Ferritins/genetics*
;
Learning
;
Hippocampus/metabolism*
;
Acupuncture Points
4.Analysis of the clinical effects of a three dimensional-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy
Peng GUO ; Tao LI ; Yutao PENG ; Wenqian WU ; Haoyu ZHANG ; Ziwen YANG ; Yinglun SONG ; Jinping LI
Chinese Journal of Surgery 2024;62(12):1120-1127
Objective:To explore the clinical effects of a 3D-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy (DC).Methods:This study is a retrospective cohort analysis. The clinical data of 35 patients who underwent DC at Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, from September 2020 to September 2023 were reviewed. The cohort included 24 males and 11 females, with an age of (48.7±14.9) years (range:17 to 74 years). Nineteen patients (experimental group) received the intracranial pressure balancing device fixed to the bone defect site post-DC. This device was made using medical-grade dicyanamide resin and was three dimensional printed based on postoperative CT scans of the patients. The remaining 16 patients (control group) did not receive the intracranial pressure balancing device, while other treatments and procedures were consistent with the experimental group. Data were compared using the χ2 test or Fisher′s exact probability method. Results:Out of the 35 patients, 30 cases (85.7%) experienced complications following DC. Specific complications included cerebral infarction in 3 cases (8.6%), intracerebral hemorrhage in 1 case (2.9%), subdural effusion in 27 cases (77.1%) with a median onset of (8.8±6.5) days (range: 1 to 23 days), brain tissue protrusion in 15 cases (42.9%) with a median onset of ( M(IQR)) 7.0 (21.0) days (range:2 to 106 days), and hydrocephalus in 6 cases (17.14%) with a median onset of 34.5 (111.0) days (range: 22 to 136 days). There were no significant differences in the occurrence of complications(all P>0.05). However, there was a significant reduction in the incidence of subdural effusion in the experimental group prior to cranioplasty ( P=0.013). No significant differences were noted in mRS scores between the two groups after cranioplasty ( P>0.05). Conclusions:The intracranial pressure balancing device has the effect of prevention and treatment of subdural effusion. However, it did not significantly improve patient prognosis post-DC, warranting further investigation.
5.Clinical application of multi-marker combined detection model in diagnosing type 4a myocardial infarction
Yujie WU ; Bo DENG ; Mingquan GUO ; Jue WANG ; Ye HE ; Haoyu MENG ; Liansheng WANG
Chinese Journal of Clinical Laboratory Science 2024;42(8):574-579
Objective To compare the diagnostic performance of a multi-marker panel(copeptin,cardiac troponin T[cTnT],and heart-type fatty acid-binding protein[HFABP])with the single marker cTnT in the diagnosis of type 4a acute myocardial infarction(AMI),and explore the application value of combined detectionmodel with the multiple markers.Methods The enrolled non-AMI pa-tients underwent elective percutaneous coronary intervention(PCI)at Nanjing Medical University First Affiliated Hospital during the period from March to December 2022 and were assessed as postoperative elevation of cTnT above the 99th percentile upper reference limit(URL).According to the Fourth Universal Definition of Myocardial Infarction,the patients were divided into non-type 4a AMI group and type 4a AMI group based on whether type 4a AMI occurred after surgery.The concentrations of AMI biomarkers were meas-ured using a chemiluminescent immuno-gold nanoassembly immunosensor array(chemiluminescent immuno-Gold,ciGold).Receiver operating characteristic(ROC)curves were used to analyze the performance of the diagnostic models with single and combined cardiac biomarkers.The sensitivity and specificity were also obtained from the ROC curves,and the area under the ROC curve(AUCROC)was calculated to evaluate respective diagnostic value.Kappa analysis was used to assess the consistency between the results combined de-tection model of multiple biomarkers and the diagnosis based on the Fourth Universal Definition of Myocardial Infarction.Results In this study,a total of 65 patients were included in whom females accounted for 23.1%.The ROC curve indicated that the combined de-tection model of multiple cardiac biomarkers showed specificity of 96.5%,sensitivity of 92.3%,agreement rate of 94.6%,positive pre-dictive value of 92.3%,negative predictive value of 96.2%,and AUCROC of 0.979.The single cTnT diagnostic model showed specificity of 94.2%,sensitivity of 100%,agreement rate of 95.7%,positive predictive value of 100%,negative predictive value of 94.9%,and AUCROC of 0.987.Although the combined detection model of multiple biomarkers had lower sensitivity(P=0.011),it showed higher specificity(P=0.016).The analysis of AUCROC differences between the two diagnostic models showed P>0.05,indicating no signifi-cantly statistical difference for the diagnostic accuracy.Kappa analysis demonstrated a strong consistency between the combined detec-tion model of multiple cardiac biomarkers and the diagnosis of type 4a AMI based on the Fourth Universal Definition of Myocardial In-farction with a Cohen's Kappa coefficient of 0.818.Conclusion The multi-marker combined detection model showed similar perform-ance of cTnT in diagnos of type 4a AMI with strong diagnostic consistency.However,the combined detection model exhibited an advan-tage of higher specificity.
6.Impact of changes in cognitive load of anesthesia residents on the effectiveness of high-fidelity scenario simulation teaching
Haoyu PEI ; Yi HU ; Li WANG ; Juan DAI ; Qi SUN ; Xing ZHU ; Xiaoli RAN ; Qiuping WU ; Qingxiang MAO
Chinese Journal of Medical Education Research 2024;23(4):548-555
Objective:To investigate the influence of changes in the cognitive load of anesthesia residents on the teaching effectiveness of high-fidelity scenario simulation.Methods:Eighty-seven anesthesia residents in a grade-A tertiary hospital from February to November 2022 were divided into groups A, B, and C according to the random number method. Three cases were selected from the anesthesia crisis resource teaching case library for high-fidelity simulation training for the three groups, respectively, using the crossover design to control the order of the cases. Each round of training consisted of pre-training instruction, simulation teaching, and post-training summarization and analysis. After three rounds of simulation teaching, cognitive load, anxiety status, test scores, and non-technical skills were evaluated for all the study participants. SPSS 20.0 was used to perform analysis of variance with repeated measures and Pearson's correlation analysis.Results:All the three groups showed significantly higher cognitive load and anxiety scores during the first-round simulation training than during the second-round and third-round simulation trianing. The test scores were significantly lower in the first round [(87.07±5.66), (88.38±5.41), (89.07±6.17)] than in the second round [(95.69±2.29), (96.10±2.08), (96.07±2.60)] and the third round [(96.34±1.45), (96.38±1.50), (96.17±1.73); all P<0.05]. The non-technical skill scores were also significantly lower in the first round [(37.24±7.58), (38.69±7.27), (39.24±8.74)] than in the second round [(46.17±5.55), (47.07±5.59), (47.59±6.74)] and the third round [(47.17±5.21), (48.48±5.38), (48.24±6.83); all P<0.05]. For simulations with the same cases, the trainees showed significantly higher cognitive load and anxiety scores and significantly lower test scores and non-technical skill scores in the first round than in the second and third rounds ( P<0.05). Conclusions:Anesthesia residents have higher levels of cognitive load and anxiety in the first scenario simulation training, which can reduce learning outcomes, and repeated simulation training can reduce trainees' cognitive load and anxiety.
7.Prediction of Microvascular Complications in Type 2 Diabetes Mellitus Based on Deep Belief Network
Ruiyao LI ; Jingyi XU ; Haoyu DAI ; Huiwen SUN ; Ying BAO ; Lvchun HUA ; Tianxing WU
Journal of Medical Informatics 2024;45(7):68-73
Purpose/Significance A prediction model is constructed based on real-world data to achieve prediction and early screening of type 2 diabetic microvascular complications.Method/Process Based on the real world data of Nanjing Drum Tower Hospital in the past 10 years,a particle swarm optimization based deep belief network(PSO-DBN)prediction model for microvascular complica-tions in type 2 diabetes mellitus is constructed by taking test results and medical record documents into consideration.Result/Conclusion The PSO-DBN model can predict diabetic microvascular complications,and the performance is better than that of random forest and sup-port vector machine(SVM)benchmark models,it provides references for the research of disease prediction model of real-world data.
8.Satisfaction survey on infectious diseases online teaching for medical interns
Zeqian WU ; Haoyu CHEN ; Yusheng JIE ; Bingliang LIN ; Shaoquan ZHANG ; Lei TAN
Modern Hospital 2024;24(8):1309-1312
Objective To investigate the satisfaction degree among medical interns with the effect of infectious diseases online teaching.Methods A questionnaire survey was conducted among 172 interns from a 5-year clinical medicine program who were doing internship with infectious diseases in the Third Affiliated Hospital of Sun Yat-Sen University in the spring and fall semesters of 2022.The survey aimed to investigate the advantages and disadvantages of online teaching for medical interns com-pared with traditional offline teaching.Results In terms of the advantages,online internship online teaching saved commuting time among 95.4%(164/172)of the students,enhanced self-management ability among 41.9%(72/172)of the students,en-riched teaching elements among 71.5%(123/172),promoted reviewing and consolidation of clinical knowledge among 38.4%(66/172)of the students.As regarding the disadvantages,online internship decreased clinical situational experience among 83.7%(144/172)students,reduced teaching-student interactions among 76.2%(131/172)of the students,decreased learn-ing efficiency among 51.7%(89/172)of the students and lowered quality of learning among 59.3%(102/172)of the students due to frequent network inefficiency.For prospection,37.8%(65/172)of the students expressed their wish to resume the tradi-tional offline teaching model continue and 57.6%(99/172)of them suggested that the combination of online and offline teaching mode should be adopt.Conclusion The inevitability and possibility of online internship of infectious diseases are gradually in-creasing.Compared with offline internships in infectious disease,students welcome a hybrid model of internships that combines online and offline models.
9.Predicting the histological type of thymoma based on CT radiomics nomogram
Qingsong BU ; Haoyu ZHU ; Tao WANG ; Lei HU ; Xiang WANG ; Xiaofeng LIU ; Jiangning DONG ; Xingzhi CHEN ; Shujian WU
Journal of Practical Radiology 2024;40(10):1615-1619
Objective To investigate the value of a nomogram model based on contrast-enhanced CT radiomics in predicting the histological type of thymoma.Methods A total of 154 patients(101 in low-risk group and 53 in high-risk group)with thymoma confirmed by pathology were retrospectively selected.The cases were randomly divided into training set(n=107)and validation set(n=47)at a ratio of 7∶3.The three-dimensional volume of interest(VOI)of the whole lesion on the image from the arterial phase of contrast-enhanced CT was manually delineated,and the radiomics features were extracted.Based on the selected radiomics features,the radiomics model was constructed and the model Radiomics score(Radscore)was calculated.Clinical risk factors were screened to construct a clinical model,and a nomogram model was constructed by fusing Radscore and clinical risk factors.The receiver operating characteristic(ROC)curve,area under the curve(AUC),accuracy,sensitivity and specificity were compared to analyze the predictive efficacy and difference of different models for high-risk and low-risk thymoma.The decision curve and calibration curve were drawn to evaluate the clinical value and fitting performance of the nomogram model.Results Eleven radiomics features were selected to construct the radiomics model,and five clinical risk factors[myasthenia gravis(MG),morphology,border,surrounding tissue invasion and CT value in arterial phase]were used to construct the clinical model.In the training set,the AUC of the nomogram model(0.88)was higher than that of the radiomics model(0.80)and the clinical model(0.79),and the difference was statistically significant(Z=2.233,2.713,P=0.026,0.007,respectively).In the validation set,the AUC of the nomogram model was higher than that of the radiomics and clinical models,but the difference was not statistically significant.The calibration curve showed that the nomogram model had good fitting performance,and the decision curve showed that the nomogram model had high clinical benefit.Conclusion The nomogram model based on contrast-enhanced CT can effectively predict high-risk and low-risk thymoma,which is helpful to guide clinicians to make relevant decisions.
10.Analysis of the clinical effects of a three dimensional-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy
Peng GUO ; Tao LI ; Yutao PENG ; Wenqian WU ; Haoyu ZHANG ; Ziwen YANG ; Yinglun SONG ; Jinping LI
Chinese Journal of Surgery 2024;62(12):1120-1127
Objective:To explore the clinical effects of a 3D-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy (DC).Methods:This study is a retrospective cohort analysis. The clinical data of 35 patients who underwent DC at Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, from September 2020 to September 2023 were reviewed. The cohort included 24 males and 11 females, with an age of (48.7±14.9) years (range:17 to 74 years). Nineteen patients (experimental group) received the intracranial pressure balancing device fixed to the bone defect site post-DC. This device was made using medical-grade dicyanamide resin and was three dimensional printed based on postoperative CT scans of the patients. The remaining 16 patients (control group) did not receive the intracranial pressure balancing device, while other treatments and procedures were consistent with the experimental group. Data were compared using the χ2 test or Fisher′s exact probability method. Results:Out of the 35 patients, 30 cases (85.7%) experienced complications following DC. Specific complications included cerebral infarction in 3 cases (8.6%), intracerebral hemorrhage in 1 case (2.9%), subdural effusion in 27 cases (77.1%) with a median onset of (8.8±6.5) days (range: 1 to 23 days), brain tissue protrusion in 15 cases (42.9%) with a median onset of ( M(IQR)) 7.0 (21.0) days (range:2 to 106 days), and hydrocephalus in 6 cases (17.14%) with a median onset of 34.5 (111.0) days (range: 22 to 136 days). There were no significant differences in the occurrence of complications(all P>0.05). However, there was a significant reduction in the incidence of subdural effusion in the experimental group prior to cranioplasty ( P=0.013). No significant differences were noted in mRS scores between the two groups after cranioplasty ( P>0.05). Conclusions:The intracranial pressure balancing device has the effect of prevention and treatment of subdural effusion. However, it did not significantly improve patient prognosis post-DC, warranting further investigation.

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