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.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.
4.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.
5.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.
6.Morphological characteristics analysis for deposition sequencing of overlapping bloodstain patterns
Zunlei QIAN ; Lindi ZHANG ; Mengqi WU ; Haoyu WANG ; Zhao LIU ; Zhenjun JIA
Chinese Journal of Forensic Medicine 2024;39(3):299-303
Objective To explore the morphological characteristics of overlapping bloodstains and judge the deposition sequence of bloodstain patterns.Methods The overlapping bloodstains formed by drip stains and bloody shoe prints were simulated on ceramic tiles,and the morphological characteristic differences of 6 group overlapping bloodstain patterns were analyzed to screen effective indicative characteristics.A survey was held to measure the accuracy of the participants in judging the blood deposition sequence without and with information about the morphological characteristic guidance.Results After participants mastered morphological characteristics,the accuracy of judging deposition sequence increased from 59.5%to 89.0%,and the accuracy of judging dry and wet conditions of the primary bloodstains increased from 45.6%to 65.3%.Conclusion According to the morphological characteristics of bloodstains,not only the deposition sequence of bloodstains can be effectively judged,but also the dry and wet conditions of bloodstains can be judged,so as to infer the time interval of bloodstains deposition,which can provide technical support for the analysis and reconstruction of crime scene.
7.Possible mechanisms of multi-pathway biological effects of laser therapy for knee osteoarthritis
Xinqi LOU ; Hao ZHONG ; Xiyu WANG ; Haoyu FENG ; Pengcui LI ; Xiaochun WEI ; Yanqin WANG ; Xiaogang WU ; Weiyi CHEN ; Yanru XUE
Chinese Journal of Tissue Engineering Research 2024;28(34):5521-5527
BACKGROUND:Laser therapy is a non-invasive and painless treatment that is considered to be an effective method suitable for the treatment of osteoarthritis due to its simplicity and non-invasive nature.Currently,the mechanism of action of laser therapy is unclear and the results of studies on its clinical application are controversial. OBJECTIVE:To review and summarize the latest research progress of laser therapy on chondrocytes,animal experiments and clinical efficacy,and to explore the possible mechanism of laser-mediated multi-pathway biological effects,so as to provide a theoretical basis for further research on the laser treatment of osteoarthritis of the knee joint. METHODS:A literature search was performed in CNKI,WanFang Data,VIP and PubMed databases for relevant literature published from 2018 to 2023,with"laser therapy,low level laser therapy,high level laser therapy,photobiomodulation,knee osteoarthritis,chondrocytes"as the search terms in Chinese and English,respectively.Together with 14 articles searched manually,70 articles were finally included for review. RESULTS AND CONCLUSION:Laser therapy in the treatment of knee osteoarthritis is mainly categorized into two types:low-level laser therapy and high-level laser therapy.Differences in laser parameters and treatment protocols have a direct impact on laser efficacy.When appropriate parameters are used,low-level lasers show positive effects in cellular experiments,animal models,and clinical efficacy.High-level lasers have been less studied in the treatment of knee osteoarthritis,but some preliminary clinical studies have shown positive results.Cell experiments have shown that low-level laser promotes chondrocyte proliferation and cartilage matrix synthesis,thereby reducing inflammatory response.Animal experiments have shown that low-level laser can reduce the release of pro-inflammatory factors,promote cartilage matrix synthesis,inhibit matrix degradation,and effectively improve the repair process of cartilage tissue.Low-level laser is also able to reduce oxidative stress damage and relieve pain in knee osteoarthritis.In clinical trials,both low-and high-level laser can reduce patients'pain and improve functional activities.The combination of laser therapy and exercise therapy modalities may improve the therapeutic effect.Lasers may affect intracellular signaling and cellular functions through photobiological or thermodynamic effects.This provides direct evidence that laser promotes articular cartilage regeneration.
8.Construction of digital intelligent minimally invasive research-oriented hepatobiliary and pancreatic surgery discipline
Jian YANG ; Xiwen WU ; Wen ZHU ; Haoyu HU ; Nan XIANG ; Ning ZENG ; Zhihao LIU ; Xuequan FANG ; Chihua FANG
Chinese Journal of Digestive Surgery 2024;23(1):91-97
The emergence and evolution of digital intelligent technology has profoundly influenced the development of minimally invasive research-oriented hepatobiliary and pancreatic surgery discipline. Over various periods, our team has always adhered to the principle of "being oriented by clinical issues and driven by clinical needs", continuously carried out innovative research across interdisciplinary boundaries, propelling the evolution of digital intelligent technology. Spanning over two decades, this journey includes the progression from digital virtual human, three-dimensional visualization, molecular fluorescence imaging, augmented reality and mixed reality, artificial intelligence, to the realm of human visualization meta-universe. This evolution facilitates the shift from two-dimensional empirical diagnoses of hepatobiliary and pancreatic surgical diseases to deep learning intelligent diagnostics, the transition from morphology-based tumor diagnoses to molecular imaging-based diagnostics, and from conventional empirical surgery to intelligent navigation surgery. The authors provide a comprehensive review of our developmental process and achievements within the realm of digital intelligent diagnostic and therapeutic technologies, with the aims to promote the development and application of digital intelligent medicine.
9.Application of diffusion tensor imaging scanning of conus medullaris in lower urinary tract dysfunction
Haoyu SUN ; Yi GAO ; Juan WU ; Limin LIAO ; Huafang JING ; Siyu ZHANG ; Dong LI ; Chunsheng HAN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(3):333-338
Objective To investigate the signal abnormality of conus medullaris in patients with overactive bladder(OAB)and un-deractive bladder(UAB)by MRI diffusion tensor imaging(DTI). Methods From May,2021 to April,2023,23 patients with lower urinary tract dysfunction without trauma and supraspi-nal lesions were enrolled(case group).All patients underwent imaging urodynamics and pelvic floor electromy-ography.Based on the bladder contraction during the filling phase of urodynamics,the patients were divided into UAB group and OAB group.Eight healthy subjects were included as the control group.All participants under-went T10 to L5 spinal segment MRI scans and DTI scans.The position of conus medullaris was determined by comparing the DTI sequences with the MRI scans.The fractional anisotropy(FA),apparent diffusion coefficient(ADC),and relative anisotropy(RA)of the conus medullaris intermediate segment were compared. Results Twelve cases were in UAB group,and eleven in OAB goup.Abnormalities were found in the pelvic floor elec-tromyography in the case group.There was significant difference in sacral reflex arc nerve conduction testing be-tween UAB and OAB groups(P = 0.036).Compared with the control group,ADC increased(t = 2.185,P = 0.037)in the case group;FA decreased(t = 3.439,P = 0.005)and ADC increased(t = 4.582,P<0.001)in UAB group. Conclusion DTI is helpful to find the potential lesion of spinal cord in patients with lower urinary tract dysfunction.FA and ADC are valuable indicators for the diagnosis of conus medullaris injury.
10.Discussion and treatment of late onset hypogonadism in male based on " tian gui out of time sequence"
Hui WU ; Gang NING ; Bonan LI ; Ajian PENG ; Haoyu WANG ; Ruobing SHI ; Xing ZHOU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1501-1505
The unique advantages of traditional Chinese medicine (TCM) in treating late onset hypogonadism in male have gradually emerged with the continuous deepening of the understanding and research on late onset hypogonadism in male. Time sequence is a general summary of the natural growth and operational laws. Tian gui and testosterone have their normal time sequences, and they may be associated with each other. A man′s tian gui follows the regular time sequence from " inception" to " exhaustion" throughout " eight" under normal physiological conditions. " Tian gui out of time sequence" includes the loss of tian gui exuberance (dysfunction of viscera dominated by the liver) and exhaustion in the time sequence (pathological deficiency of viscera dominated by the kidney), resulting in " tian gui exhaustion" in advance of " eight eight". Tian gui and testosterone are key concepts in Chinese and Western medicine for understanding late onset hypogonadism in male. The theory of " tian gui out of time sequence" may be closely related to the core pathogenesis of this condition, particularly in cases of liver depression and kidney deficiency. This study suggests that restoring the normal time sequence of tian gui while treating the liver and kidney simultaneously through time-sharing treatment should be effective. The use of Xiongcan Yishen Formula has shown promising therapeutic result, offering new insights and references for treating late onset hypogonadism in male using TCM.


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