1.Intervention Mechanism of Guizhi Fulingwan in Delaying Colitis-associated Colon Cancer via Modulating and Restoring MDSCs and Reshaping Immune Microenvironment
Yanwei HAO ; Chunrun LI ; Zhengwu QU ; Junmei TANG ; Jing GUO ; Yi ZHANG ; Fengming YOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):185-194
ObjectiveThis paper aims to investigate the efficacy and related actions of Guizhi Fulingwan in intervening in the mice with colitis-associated colon cancer (CAC) based on the immunosuppressive microenvironment associated with myeloid-derived suppressor cells (MDSCs). MethodsSixty male C57BL/6 mice were randomly assigned to a blank group, a model group, an aspirin group (0.04 g·kg-1), and low-, medium-, and high-dose Guizhi Fulingwan groups (4.87, 9.75, and 19.50 g·kg-1), with ten mice per group. The CAC mouse model was established via combined induction of azoxymethane (AOM)/dextran sulphate sodium (DSS). Drug intervention commenced in week five, with continuous intragastric administration for nine weeks. The food intake, body weight, fecal characteristics, and haematochezia were observed and recorded, and disease activity index (DAI) scores were calculated according to scoring criteria. Hematoxylin and eosin (HE) staining was used to observe the histopathological changes in the colon tissues of the mice. Immunohistochemistry was used to determine proliferating cell nuclear antigen-67 (Ki67) expression in the colon tissues, and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) in the serum of the mice. Flow cytometry was employed to determine the proportion levels of MDSCs, CD4+ T cells, and CD8+ T cells in the spleen tissues of the mice. The mRNA expressions of MDSC-associated effector molecules, including arginase 1 (Arg1) and inducible nitric oxide synthase (iNOS), were detected by real-time quantitative polymerase chain reaction (Real-time PCR). After that, an in vitro co-culture model of MDSCs and CD8+ T cells was established, and drug-containing serum of Guizhi Fulingwan was used for intervention. The Flow cytometry was employed to assess the effects of drug-containing serum of Guizhi Fulingwan with different concentrations on the levels of reactive oxygen species (ROS) and iNOS in MDSCs and the proliferation of CD8+ T cells. The levels of granzyme B (GZMB) and interferon-γ (IFN-γ) in cell supernatant were detected by ELISA. ResultsCompared with those in the control group, the mice in the model group exhibited significantly reduced body weight, elevated DAI scores, shortened colon length (P<0.01), increased number of tumors and Ki67 expression (P<0.01), and significantly elevated contents of IL-6, IL-1β, and TNF-α in the serum (P<0.01). Significant increases in the number of MDSCs were observed in mouse spleens, alongside marked reductions in the levels of CD4+ T and CD8+ T cells (P<0.01). Furthermore, the mRNA expressions of MDSC function-associated effector molecules Arg1 and iNOS were significantly upregulated (P<0.01). Compared with those in the model group, the mice in the middle-dose Guizhi Fulingwan group exhibited increased body weight and significantly decreased DAI scores (P<0.05, P<0.01). The mice in the middle- and high-dose Guizhi Fulingwan groups exhibited significantly improved colon shortening, significantly decreased number of tumors and Ki67 expression (P<0.05, P<0.01), and significantly decreased contents of IL-6, IL-1β, and TNF-α in the serum (P<0.05, P<0.01). Furthermore, administration of Guizhi Fulingwan markedly reduced MDSC infiltration in the spleen of the mice, with different degrees of increase in the levels of both CD4+ T and CD8+ T cells (P<0.05, P<0.01), alongside significant decreases in the mRNA expressions of Arg1 and iNOS (P<0.05, P<0.01). In vitro cell co-culture shows that administration of drug-containing serum of Guizhi Fulingwan significantly decreases the activity levels of ROS and iNOS in MDSCs and promotes the proliferation of CD8+ T cells and the secretion of GZMB and IFN-γ (P<0.05, P<0.01). ConclusionGuizhi Fulingwan can reduce pro-inflammatory cytokine secretion and inhibit tumor proliferation in the colon tissues of CAC mice. Its potential mechanism may involve reducing MDSC infiltration, enhancing effector T cells, particularly CD8+ T cell response, and improving the tumor immunosuppressive microenvironment.
2.Analysis on Theoretical Model and Pharmacological Mechanism of Staged Treatment of Severe Acute Pancreatitis with "Strengthening Healthy Qi to Eliminate Pathogenic Factors"
Wei JIN ; Quanyu DU ; Yang SONG ; Yong CHEN ; Junfeng MO ; Xiaochuan PAN ; Chunrun LI ; Peishu LAN ; Shaohong CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):195-204
Severe acute pancreatitis (SAP) is closely related to dysfunction of the spleen-stomach ascent and descent. Due to the influence of modern lifestyle and dietary factors, Qi deficiency in the spleen and stomach has become the pathological basis of SAP. Its pathogenesis is characterized by dampness, heat, pathogenic factors, stasis, stagnation, obstruction, Fu-organs Qi obstruction, pathogenic excess, and healthy Qi deficiency. At different stages of the disease course of SAP, there is a focus on both pathogenic excess and healthy Qi deficiency. It is specifically manifested as Fu-organs stagnation and heat accumulation, as well as pathogenic excess and healthy Qi deficiency, during the systemic inflammatory response phase, intermingling of blood stasis and pathogenic factors, as well as Qi deficiency and blood stasis, during the infection period, and weakness of the spleen and stomach, as well as healthy Qi deficiency and lingering pathogenic factors, during the residual infection period. Based on the theory that "the spleen and stomach are the acquired foundation", a staged treatment method centered on the core principle of "strengthening healthy Qi to eliminate pathogenic factors" was developed. The staged treatment method included "clearing the Fu-organs to expel turbidity, replenishing Qi to harmonize the stomach, activating blood circulation to expel pathogenic factors, replenishing Qi to relieve pain, promoting digestion to stimulate appetite, and replenishing Qi to invigorate the spleen". In clinical practice, Hewei Tongxie mixture, Yikang mixture, and Shiwei Jianpi Xiaoshi powder were selected for staged treatment of SAP. This article systematically summarized the theoretical basis of traditional Chinese medicine, Western medicine foundation, modern pharmacological mechanisms, and clinical application experience of the staged treatment of SAP with "strengthening the healthy Qi to eliminate pathogenic factors", providing new ideas for the treatment of SAP with traditional Chinese medicine.
3.Impact on ovarian reserve function by different homostasis methods during laparoscopic cystectomy in treatment of ovarian endometrioma
Changzhong LI ; Deying WEI ; Fei WANG ; Hongqing WANG ; Chunrun YANG
Chinese Journal of Obstetrics and Gynecology 2013;(1):11-15
Objective To investigate the impact on ovarian reserve function by different hemostasis methods during laparoscopic surgery in treatment of ovarian endometrioma.Methods From September 2008 to February 2010,162 cases with ovarian endometrioma undergoing laparoscopic surgery in Shandong Provincial Hospital were enrolled in this study.At the 3rd day of the menstrual cycle before surgery and the 1 st,3rd,6th and 12th cycle after surgery,serum FSH and anti-mullerian hormone(AMH) and ultrasound basal antral follicle count (AFC) and peak systolic velocity (PSV) were examined and compared.Based on hemostasis method,those patients were divided into 3 groups,including 54 cases in bipolar hemostasis,54 cases in ultrasonic scalpel hemostasis and suture after excision of endometrioma.Results (1) Before surgery:no significant different factors among three groups before surgery were observed,including age,size of endometrioma,the level of FSH,AMH,AFC,PSV (P > 0.05).(2) Ovarian reserve function after surgery:①FSH:at the 1st,3rd,6th and 12th month follow-up,the FSH in the bipolar group was (11.7 ±4.0),(9.9 ± 4.0),(9.5 ± 4.3),(9.5 ± 3.9) U/L,and the FSH in ultrasonic scalpel group was (11.4 ±4.3),(9.7 ± 4.0),(9.2 ± 3.7),(9.9 ± 4.6) U/L,were significantly higher than (9.3 ± 3.8),(6.7 ±3.0),(6.5 ± 3.2),(6.4 ± 2.2) U/L in suture group respectively (all P < 0.05).()AMH:at the 1 st,3rd,6th and 12th month follow-up,the AMH in the bipolar group was (1.8 ±0.9),(1.8 ± 1.0),(1.9 ±1.0),(2.0 ± 1.0) μg/L,and the AMH in the ultrasonic scalpel group was (1.6 ±± 0.8),(1.8 ± 1.0),(2.0 ± 1.1),(2.1 ± 1.0) μg/L,which were significantly lower than (2.8 ± 1.7),(2.9 ± 1.6),(3.0 ±1.3),(3.2 ± 1.5) μg/L in suture group,respectively (all P < 0.05).③AFC:there was no significant difference of APC among the three groups in the 1st month after surgery.However,at the 3rd,6th and 12th month follow-up,the AFC of 4.8 ± 1.4,5.9 ± 1.5,6.1 ± 1.5 in the suture group was significant higher than 3.7 ± 1.4,4.1 ± 1.4,4.0 ± 1.5 in bipolar group and 3.6 ± 1.3,4.0 ± 1.1,3.9 ± 1.5 in ultrasonic group,respectively (all P < 0.05).④PSV:at the 1 st,3rd,6th and 12th month follow-up,the PSV of the bipolar group(7.9 ±3.5),(8.1 ±3.3),(8.4 ±3.1),(8.6±3.0) cm/s in bipolar group and (8.1 ±3.5),(8.0 ± 3.0),(7.9 ± 3.2),(8.0 ± 2.9) cm/s in ultrasonic group were significant lower than (10.9 ± 3.3),(12.0 ± 3.2),(11.8 ± 3.0),(12.1 ± 4.1) cm/s in suture group,respectively.(allP<0.05).Conclusions Bipolar or ultrasonic scalpel hemostasis during laparoscopic excision of ovarian endometrioma is associated with a significant reduction in ovarian reserve.Electrocoagulation of the ovarian tissue should be avoided.

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