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.Programmed Cell Death in Endometriosis and Traditional Chinese Medicine Intervention: A Review
Zuoliang ZHANG ; Wanrun WANG ; Wen LI ; Xue HAN ; Xiaohong CHEN ; Nan SU ; Huiling LIU ; Quansheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):48-57
Endometriosis (EMT) is a common disease with frequent occurrence and difficult to be cured in modern clinical practice of obstetrics and gynaecology. It is characterized by progressively worsening dysmenorrhoea, pelvic mass, and infertility. The incidence of EMT is growing and increasingly younger patients are diagnosed with this disease, which poses a serious threat to the reproductive and psychological health of women of childbearing age and adolescent females. However, the pathogenesis of EMT is still not completely clear, and the disease has a long course. Therefore, developing new therapies is an urgent clinical problem to be solved. Great progress has been achieved in the treatment of EMT with traditional Chinese medicine (TCM), while the underlying mechanism remains in exploration. Programmed cell death (PCD) is a cell death mode mediated by a variety of bio-molecules with specific signaling cascades. The known PCD processes include apoptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis, which all play a pivotal role in the development of EMT. Researchers have made achievements in the treatment of EMT with TCM, which regulates PCD via multiple pathways, routes, targets, and mechanisms. However, the progress in the regulation of PCD in the treatment of EMT with TCM remains to be reviewed. This paper reviews the research progress in the treatment of EMT with TCM from five PCD processes (apoptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis), with the aim of providing a theoretical basis for the clinical prevention and treatment of EMT.
3.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
4.Analyzing Differences in Volatile Components of Citri Reticulatae Pericarpium Before and After Being Stir-fried with Halloysitum Rubrum Based on HS-GC-MS and Intelligent Sensory Technology
Li XIN ; Jiawen WEN ; Wenhui GONG ; Beibei ZHAO ; Shihao YAN ; Huashi CHEN ; Haiping LE ; Jinlian ZHANG ; Yanhua XUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):157-162
ObjectiveTo analyze the differences in color, odor and volatile components of Citri Reticulatae Pericarpium(CRP) before and after being stir-fried with Halloysitum Rubrum, and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the volatile components were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). According to the principle of variable importance in the projection(VIP) value>1.5, volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose, the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum, of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected, including α-pinene, β-myrcene, linalool, sabinene, ocimene isomer mixture, A-ocimene, and δ-elemene. After being processed with Halloysitum Rubrum, the brightness value(L*), yellow-blue value(b*) and total chromatic value(E*ab) of CRP were decreased(P<0.01), and red-green value(a*) was increased(P<0.01), the response values of S4, S5, S10 and S13 sensors were significantly increased(P<0.05), and the response values of S3 and S8 sensors were significantly decreased(P<0.05). Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L* and E*ab, but positively correlated with a*. Sabinene was positively correlated with L* and E*ab. Linalool was positively correlated with L* and E*ab, and negatively correlated with a*. The ocimene isomer mixture was positively correlated with the L*. ConclusionAfter being processed with Halloysitum Rubrum, the appearance color, odor and volatile components of CRP change significantly, and α-pinene, β-myrcene, sabinene, linalool and A-ocimene are the characteristic volatile components before and after processing, which can provide references for the quality evaluation and clinical application of CRP and its processed products.
5.Regulation of Tumor Immune Homeostasis by Programmed Cell Death and Intervention Effect of Traditional Chinese Medicine Under Theory of Regulating Qi and Resolving Toxins
Bingwei YANG ; Xue CHEN ; Chenglei WANG ; Haoyu ZHAI ; Weidong LI ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):212-220
Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death (PCD) is a kind of regulable cell death including various forms such as apoptosis, autophagy, pyroptosis, necrosis, and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years, modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation, PCD can control tumor development in time by playing a specific immune clearance role, while in the later tumorigenic stage, PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment, resulting in carcinogenic effects. Therefore, PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui, the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins'', the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis, while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis, which led to the escape and development of tumor cells. Therefore, under the guidance of ''regulating Qi and removing toxins'', the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation, the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage, the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells, with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.
6.Clinical efficacy of escitalopram combined with transcutaneous cervical vagus nerve stimulation therapy for patients with major depressive disorder and its effect on plasma IL-6 and IL-10 levels
Jin LI ; Jinbo SUN ; Di WU ; Wenjun WU ; Runzhu SUN ; Shanshan XUE ; Yapeng CUI ; Huaning WANG ; Yihuan CHEN
Sichuan Mental Health 2025;38(1):7-13
BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression, which may contribute to the anti-inflammatory properties of vagus nerve stimulation (VNS), whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation (tcVNS) in treating major depressive disorder (MDD) and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression, anxiety and sleep quality as well as the plasma levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in MDD patients, in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21, 2019 to April 17, 2024, 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group (n=23) and control group (n=22) using random number table method. All patients were treated with escitalopram. On this basis, study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation, and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment, Hamilton Depression Scale-17 item (HAMD-17) was used to assess depressive symptoms, and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score, anxiety/somatization subfactor score and insomnia subfactor score in both groups (Wald χ2=315.226, 495.481, 82.420, P<0.01). After 4 weeks of treatment, HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group, with statistically significant differences (Wald χ2=4.967, 32.543, P<0.05 or 0.01), while no statistically significant difference was found in the insomnia subfactor score between two groups (Wald χ2=0.819, P=0.366). Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups (Wald χ2=21.792, 5.242, P<0.05 or 0.01). Compared with baseline data, a reduction in plasma IL-6 levels was detected in both groups (Wald χ2=22.015, 6.803, P<0.01), and an increase in plasma IL-10 levels was reported in study group (Wald χ2=5.118, P=0.024) after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms, anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally, it helps reduce plasma IL-6 levels and increase IL-10 levels. [Funded by Shaanxi Provincial Key Research and Development Program-General Project (number, 2023-YBSF-185), www.clinicaltrials.gov number, NCT04037111]
7.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
8.Analyzing Differences in Volatile Components of Citri Reticulatae Pericarpium Before and After Being Stir-fried with Halloysitum Rubrum Based on HS-GC-MS and Intelligent Sensory Technology
Li XIN ; Jiawen WEN ; Wenhui GONG ; Beibei ZHAO ; Shihao YAN ; Huashi CHEN ; Haiping LE ; Jinlian ZHANG ; Yanhua XUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):157-162
ObjectiveTo analyze the differences in color, odor and volatile components of Citri Reticulatae Pericarpium(CRP) before and after being stir-fried with Halloysitum Rubrum, and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the volatile components were analyzed by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). According to the principle of variable importance in the projection(VIP) value>1.5, volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose, the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum, of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected, including α-pinene, β-myrcene, linalool, sabinene, ocimene isomer mixture, A-ocimene, and δ-elemene. After being processed with Halloysitum Rubrum, the brightness value(L*), yellow-blue value(b*) and total chromatic value(E*ab) of CRP were decreased(P<0.01), and red-green value(a*) was increased(P<0.01), the response values of S4, S5, S10 and S13 sensors were significantly increased(P<0.05), and the response values of S3 and S8 sensors were significantly decreased(P<0.05). Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L* and E*ab, but positively correlated with a*. Sabinene was positively correlated with L* and E*ab. Linalool was positively correlated with L* and E*ab, and negatively correlated with a*. The ocimene isomer mixture was positively correlated with the L*. ConclusionAfter being processed with Halloysitum Rubrum, the appearance color, odor and volatile components of CRP change significantly, and α-pinene, β-myrcene, sabinene, linalool and A-ocimene are the characteristic volatile components before and after processing, which can provide references for the quality evaluation and clinical application of CRP and its processed products.
9.Regulation of Tumor Immune Homeostasis by Programmed Cell Death and Intervention Effect of Traditional Chinese Medicine Under Theory of Regulating Qi and Resolving Toxins
Bingwei YANG ; Xue CHEN ; Chenglei WANG ; Haoyu ZHAI ; Weidong LI ; Baojin HUA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):212-220
Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death (PCD) is a kind of regulable cell death including various forms such as apoptosis, autophagy, pyroptosis, necrosis, and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years, modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation, PCD can control tumor development in time by playing a specific immune clearance role, while in the later tumorigenic stage, PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment, resulting in carcinogenic effects. Therefore, PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui, the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins'', the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis, while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis, which led to the escape and development of tumor cells. Therefore, under the guidance of ''regulating Qi and removing toxins'', the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation, the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage, the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells, with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.
10.Survival outcomes of segmentectomy versus lobectomy for T1c non-small cell lung cancer: A systematic review and meta-analysis
Xinyu XUE ; Kai ZHAO ; Ningsu CHEN ; Youping LI ; Jiajie YU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(03):393-400
Objective To evaluate the survival outcomes of segmentectomy versus lobectomy for T1c non-small cell lung cancer (NSCLC). Methods We searched PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI (China National Knowledge Infrastructure), and Wanfang Data, with the search time limit set from the inception of the databases to February 2024. Three researchers independently screened the literature, extracted relevant information, and evaluated the risk of bias of the included literature according to the Newcastle-Ottawa Scale (NOS). Meta-analysis was conducted using STATA 15.1. Results A total of 8 retrospective cohort studies were included, involving 7 433 patients. The NOS scores of the included studies were all ≥7 points. Patients who underwent lobectomy had significantly higher five-year overall survival (OS) rates compared to those who underwent segmentectomy (adjusted HR=1.11, 95%CI 0.99-1.24, P=0.042). Compared with lobectomy, segmentectomy showed no significant difference in adjusted three-year OS rate (adjusted HR=0.88, 95%CI 0.62-1.24) and adjusted five-year lung cancer-specific survival (adjusted HR=1.10, 95%CI 0.80-1.51, P=0.556) of patients with T1c NSCLC. Moreover, there were no differences in the five-year adjusted relapse-free survival (adjusted HR=1.23, 95%CI 0.82-1.85, P=0.319), and adverse events (OR=0.57, 95%CI 0.37-0.90, P=0.015) in the segmentectomy group were significantly less than those in the lobectomy group. Subgroup analysis based on whether patients received neoadjuvant therapy showed that among studies that excluded patients who received neoadjuvant therapy, no significant difference in 5-year adjusted OS rate was observed between the segmentectomy group and lobectomy group (adjusted HR=1.02, 95%CI 0.81-1.28, P=0.870). Conclusion Segmentectomy and lobectomy show no significant difference in long-term survival in stage T1c NSCLC patients, with segmentectomy associated with fewer postoperative complications. Further high-quality research is needed to confirm the comparative efficacy and safety of lobectomy and segmentectomy for T1c NSCLC patients.

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