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.Molecular biological research and molecular homologous modeling of Bw.03 subgroup
Li WANG ; Yongkui KONG ; Huifang JIN ; Xin LIU ; Ying XIE ; Xue LIU ; Yanli CHANG ; Yafang WANG ; Shumiao YANG ; Di ZHU ; Qiankun YANG
Chinese Journal of Blood Transfusion 2025;38(1):112-115
[Objective] To study the molecular biological mechanism for a case of ABO blood group B subtype, and perform three-dimensional modeling of the mutant enzyme. [Methods] The ABO phenotype was identified by the tube method and microcolumn gel method; the ABO gene of the proband was detected by sequence-specific primer polymerase chain reaction (PCR-SSP), and the exon 6 and 7 of the ABO gene were sequenced and analyzed. Homologous modeling of Bw.03 glycosyltransferase (GT) was carried out by Modeller and analyzed by PyMOL2.5.0 software. [Results] The weakening B antigen was detected in the proband sample by forward typing, and anti-B antibody was detected by reverse typing. PCR-SSP detection showed B, O gene, and the sequencing results showed c.721 C>T mutation in exon 7 of the B gene, resulting in p. Arg 241 Trp. Compared with the wild type, the structure of Bw.03GT was partially changed, and the intermolecular force analysis showed that the original three hydrogen bonds at 241 position disappeared. [Conclusion] Blood group molecular biology examination is helpful for the accurate identification of ambiguous blood group. Homologous modeling more intuitively shows the key site for the weakening of Bw.03 GT activity. The intermolecular force analysis can explain the root cause of enzyme activity weakening.
3.Dispersion effect of bone cement after vertebroplasty using individualized unilateral external pedicle approach and bilateral pedicle approach
Lichuang ZHANG ; Wen YANG ; Guangjiang DING ; Peikun LI ; Zhongyu XIAO ; Ying CHEN ; Xue FANG ; Teng ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(4):800-808
BACKGROUND:According to existing clinical studies,vertebroplasty treatment with both the external pedicle approach and the pedicle approach can improve the pain and quality of life of patients with spinal compression fractures.Compared with the pedicle approach,the external pedicle approach has a freer puncture angle,and good bone cement dispersion effect can be obtained by adjusting the puncture angle. OBJECTIVE:To compare the impact of vertebroplasty through individualized unilateral external pedicle approach and bilateral pedicle approach on the treatment of spinal compression fractures by quantifying the dispersion effect of bone cement. METHODS:A total of 80 patients with thoracolumbar compression fracture were divided into two groups by random number table method.The bilateral pedicle group(n=40)underwent vertebroplasty through a bilateral pedicle approach,while the unilateral external pedicle group(n=40)underwent individualized vertebroplasty through a unilateral external pedicle approach.Anteroposterior and lateral X-rays of the affected vertebrae from two groups of patients were photographed to assess effect and type of bone cement dispersion within 3 days after surgery.Visual analog scale score,tenderness threshold around fracture,and Oswestry dysfunction index were assessed before,1,7 days,and 1 month after surgery. RESULTS AND CONCLUSION:(1)Dispersion effect of bone cement in unilateral external pedicle group was better than that in bilateral pedicle group(P<0.001),and the amount of bone cement perfusion was higher than that in bilateral pedicle group(P<0.001).In the bilateral pedicle group,the bone cement dispersion types were mainly concentrated in type Ⅰ and type Ⅲ,while in the unilateral external pedicle group,the bone cement dispersion types were mainly concentrated in type I and type Ⅱ,and there was a significant difference in bone cement dispersion types between the two groups(P<0.001).(2)Postoperative visual analog scale scores and Oswestry disability index of both groups were lower than those before surgery(P<0.001),and postoperative tenderness threshold around fracture showed a trend of decreasing first and then increasing.At the same time point after treatment,there were no significant differences in visual analog scale score,Oswestry disability index,and tenderness threshold around fracture between the two groups(P>0.05).(3)The results indicate that individualized vertebroplasty via unilateral external pedicle approach can achieve better bone cement dispersion,and the treatment effect is consistent with the vertebroplasty via classical bilateral pedicle approach.
4.Analysis of the nonlinear relationship between hypothermic machine perfusion parameters and delayed graft function and construction of an optimized predictive model based on sampling algorithms
Boqing DONG ; Chongfeng WANG ; Yuting ZHAO ; Huanjing BI ; Ying WANG ; Jingwen WANG ; Zuhan CHEN ; Ruiyang MA ; Wujun XUE ; Yang LI ; Xiaoming DING
Organ Transplantation 2025;16(4):582-590
Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.
5.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.
6. Mechanism of ellagic acid improving cognitive dysfunction in APP/PS double transgenic mice based on PI3K/AKT/GSK-3β signaling pathway
Li-Li ZHONG ; Xin LU ; Ying YU ; Qin-Yan ZHAO ; Jing ZHANG ; Tong-Hui LIU ; Xue-Yan NI ; Li-Li ZHONG ; Yan-Ling CHE ; Dan WU ; Hong LIU
Chinese Pharmacological Bulletin 2024;40(1):90-98
Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg
7.Clinical Observation on Abdominal Penetrating Moxibustion Combined with Acupuncture at Four Chong Acupoints for the Treatment of Stroke in the Convalescent Stage
Nan YU ; Jie HU ; Hai-Ning LI ; Shan-Shan SONG ; De-Song ZHENG ; Xin-Hong XUE ; Ying GAO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):116-122
Objective To observe the effects of abdominal penetrating moxibustion combined with acupuncture at the"four chong points"on balance,walking function and trunk control in patients recovering from stroke.Methods Seventy-eight patients recovering from stroke were randomly divided into an observation group and a control group,with 39 patients in each group.The control group was given conventional rehabilitation exercises,while the observation group was given abdominal penetrating moxibustion combined with acupuncture at the"four chong points"on the basis of the control group.Both groups were treated for 2 consecutive months.After 2 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Berg Scale score and the Timed Up and Go Test(TUGT)were observed before and after treatment.The changes in the National Institutes of Health Stroke Scale(NIHSS)scores were compared before and after treatment between the two groups.The Sheikh Trunk Control Scale scores were also evaluated.Results(1)The total effective rate of the observation group was 94.87%(37/39),and the total effective rate of the control group was 80.00%(31/39),and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the Berg scores of the patients in the two groups were significantly increased(P<0.05),and the Berg scores of the observation group were higher than those of the control group,and the difference was statistically significant(P<0.05).(3)After treatment,the TUGT time and NIHSS score of patients in the two groups were significantly improved(P<0.05),and the TUGT time of the observation group was shorter than that of the control group,and the NIHSS score was lower than that of the control group,and the difference was statistically significant(P<0.05).(4)After treatment,the Sheikh trunk control scores of the two groups were significantly increased(P<0.05),and the Sheikh trunk control score of the observation group was higher than that of the control group,and the difference was statistically significant(P<0.05).Conclusion Abdominal penetrating moxibustion method combined with acupuncture at the four chong points for the treatment of stroke recovery can effectively restore the patients'balance and walking function,improve the patients'trunk control ability,and the therapeutic effect is precise.
8.The Mechanism of miR-124 in Depression
Yan XUE ; De-Zhu LI ; Hui-Ying XIE ; Chuan-Miao JIANG ; Jun-Fang ZHANG
Progress in Biochemistry and Biophysics 2024;51(6):1316-1326
Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.
9.46XY simple gonadal hypoplasia: 2 case reports and literature review
Xue LI ; Mengfan DING ; Fei TENG ; Yanfang ZHANG ; Ying LUO ; Yongxiu ZHENG ; Jin CUI ; Huiying ZHANG
Clinical Medicine of China 2024;40(1):65-69
46XY simple gonadal hypoplasia, also known as Sweyer syndrome, patients often due to primary amenorrhea or pubertal secondary sex characteristics do not develop the doctor, its combined gonadal tumor is more likely, in the treatment process is often recommended prophylactic removal of gonads, postoperative hormone replacement therapy. We describe two patients diagnosed with Sweyer syndrome, one with gonadowlastoma and mature teratoma, and one with nodular Leydig cell hyperplasia and ectopic adrenal tissue, and reviews the literature.
10.Relationship between occupational stress and sleep quality among locomotive engineers: Mediating role of response strategy and moderating role of overcommitment
Hongjing LI ; Xiping SHEN ; Ying XUE
Journal of Environmental and Occupational Medicine 2024;41(5):512-518
Background The occurrences of occupational stress and sleep disorders are closely related. As a high-risk group of occupational stress, the sleep quality of locomotive engineers is of great significance for road traffic safety. Objective To explore the direction and degree of occupational stress affecting the sleep quality among locomotive engineers, and to analyze potential mediating and moderating roles of response strategy and overcommitment in the relationship. Methods From July 1st to July 31st, 2022, a total of 6219 locomotive engineers from three locomotive depots of China Railway Lanzhou Group Corporation were selected. We conducted an online survey on occupational stress, overcommitment, response strategy and sleep quality using the Effort-Reward Imbalance, Personal Resources Questionnaire, and Pittsburgh Sleep Quality Index. Single factor analysis and correlation analysis were conducted using SPSS 25.0 software, mediation and moderation models were constructed using the Process V3.3 macro program plugin, and Harman's single factor test was used for common method bias testing. Results A total of 6219 questionnaires were distributed, and 5738 valid questionnaires were collected, with an effective response rate of 92.27%. The average locomotive engineers' occupational stress score (1.22±0.29), overcommitment score (16.38±3.55), response strategy score (50.00±10.00), and sleep quality score (11.51±3.95) were calculated. The Pearson correlation analysis results showed that occupational stress was positively correlated with overcommitment and sleep quality (r=0.435, 0.321, P<0.01), and negatively correlated with response strategy (r=−0.286, P<0.01); overcommitment was positively correlated with sleep quality (r=0.367, P<0.01), and negatively correlated with response strategy (r=−0.210, P<0.01); there was a negative correlation between response strategy and sleep quality (r=−0.244, P<0.01). Occupational stress positively associated with sleep quality in locomotive engineers (b=3.658, t=21.177, P<0.001); response strategy exhibited a partial mediating role between occupational stress and sleep quality, with an effect size of 0.581, accounting for 15.88% of the total effect; overcommitment presented a significant moderating effect in the first half of the mediating process of "occupational stress-response strategy-sleep quality" (P<0.001). Conclusion Occupational stress has an impact on the sleep quality of locomotive engineers through the mediating effect of response strategy, and the first half of this mediating pathway is moderated by overcommitment.

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