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 14^th 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 28^th and 98^th 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.

AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

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.

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.

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.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Specific gut microbiota can identify high-risk populations for colorectal cancer and may slow disease progression by regulating apoptosis， producing intestinal metabolites， and enhancing chemotherapy efficacy （reducing side effects and improving chemotherapy resistance）. Saponins represented by ginsenoside K are found widely in traditional medicines such as Panax ginseng and Panax notoginseng. After metabolized by gut microbiota， they play a role in preventing and treating colorectal cancer by modulating chronic inflammation， adjusting the composition of gut microbiota， generating microbial metabolites， and participating in immune regulation.

Background Macrophages are essential components of the natural immune system. They play a significant role in resisting foreign bodies in the respiratory tract and maintaining the homeostasis of the internal environment of lung tissue. Objective To investigate the mechanism of macrophage pyroptosis induced by silica dust with different particle sizes. Methods The modified murine macrophage cell line, RAW-ASC cells, was cultured and divided into a blank control group, a lipopolysaccharide (LPS) group (1 μg·mL⁻¹ LPS), a nano-SiO₂ group (1 μg·mL⁻¹ LPS+100 μg·mL⁻¹ nano-SiO₂), a micro-SiO₂ group (1 μg·mL⁻¹ LPS+750 μg·mL⁻¹ micro-SiO₂), and a positive control group [1 μg·mL⁻¹ LPS+3 mmol·L⁻¹ adenosine triphosphate (ATP)]. Apart from the blank control group, cells in other groups were pretreated with LPS for 6 h, and then exposed to SiO₂ or ATP for 4 h. According to the molecular target NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and reactive oxygen species (ROS), we applied MCC950 (NLRP3 inhibitor) and N-acetyl cysteine (NAC, ROS scavenger) to macrophages. CCK-8 assay was used to detect cell viability; 5-ethynyl-2'-deoxyuridine (EdU) staining was used to detect cell proliferation; lactate dehydrogenase (LDH) assay kit was used to detect LDH in supernatant; calcein AM/PI fluorescent double-staining was applied to evaluate cell rupture; 2',7'-dichlorofluorescin diacetate (DCFH-DA) fluorescent probe was used to measure the content of ROS; Western blotting was used to measure the expressions of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-1, gasdermin D (GSDMD), and interleukin-1β (IL-1β). Results Compared with the blank group, 100 μg·mL^-1nano-SiO₂ and 750 μg·mL^-1micro-SiO₂ dust exposure reduced the cell viability to 40% and 68% (P<0.05), and the cell proliferation rate to 30% and 33% (P<0.01), respectively; they also induced cell lysis and ROS release, upregulated NLRP3, ASC, Caspase-1, GSDMD, and IL-1β at protein level (P<0.05), and induced macrophage pyroptosis. After intervening with MCC950 (10 μmol·L^-1) and NAC (10 mmol·L^-1), the expressions of NLRP3, ASC, Caspase-1, and IL-1β decreased (P<0.05), and, specifically, NAC effectively reduced ROS levels (P<0.05). Conclusion Both nano- and micro-SiO₂ dust have cytotoxicity, can upregulate ROS level, activate NLRP3 inflammasome, and promote the release of cytokines, leading to pyroptosis. These results are helpful to reveal the molecular mechanism of macrophage pyroptosis induced by SiO₂ dust.

Objective:To investigate the effect of heme oxygenase-1 (HO-1) modified rat bone marrow mesenchymal stem cells (BMSCs) on fibrotic rats.Methods:110 male SD rats aged 6-8 weeks were selected randomly divided into model group, BMSCs group and HO-1/BMSCs group with 11 rats in each group after intraperitoneal injection of CCl 4, PBS, BMSCs and HO-1/BMSCs were injected respectively. Another 11 rats were selected as control group. After 4 weeks of intervention, tracer experiment was used to detect the location of BMSCs. Rats in each group were executed, and liver function were detected by biochemical analyzer, liver fibrosis indexes were detected by ELISA, liver histopathology were detected by HE and Sirius red staining. Immunohistochemistry, Western blot and RT-PCR were used to detect the protein and mRNA expression of E-cadherin and Vimentin. Results:The rat fibrosis model was successfully established. Tracer experiment showed that BMSCs were implanted in rat liver after transplantation. Compared with the model group, the liver function and liver fibrosis indexes of BMSCs group and HO-1/BMSCs group were improved, and Ishak score and stage were significantly decreased, and HO-1/BMSCs group was superior to BMSCs group. The expression of E-cadherin in HO-1/BMSCs group (0.92±0.21), (0.84±0.03) were higher than those in BMSCs group [(0.54±0.16), (0.53±0.04)] and model group [(0.49±0.06), (0.11±0.06)] both at protein and mRNA level, while protein and mRNA level of Vimentin (1.21±0.23), (3.82±0.80) were lower than that in BMSCs group [(1.32±0.17), (6.39±0.75)] and model group [(1.41±0.18), (16.94±1.30)]. The difference was statistically significant ( P<0.05). Conclusion:HO-1/BMSCs can improve liver function and liver fibrosis in fibrotic rats more effectively than BMSCs alone. The mechanism was possibly through inhibiting liver epithelial mesenchymal transition.

Objective:To investigate the effect and mechanism of bone marrow mesenchymal stem cells (BMMSCs) on liver transplantation with 50% reduced-size in rat models.Methods:For 40 normal male Brown Norway(BN) and Lewis rats weighing 210-250 g were included respectively to generate the acute rejection models following 50% reduced-size liver transplantation in rats. The recipients were divided into BMMSCs group ( n=20) and normal saline group ( n=20). Healthy male BN rats were used to prepare BMMSCs. Transplanted liver tissues were collected at 0h, 1d, 3d, 7d post the transplantation for further analysis. Pathological changes and the extent of rejection were evaluated under the light microscope. The levels of microtubule-associated protein 1 light 3 (LC3) and autophagy regulator Beclin-1 proteins were detected by immunohistochemical analysis and Western blotting. Results:Rejection activity indices of the normal saline group at 0d, 3d, 7d after the surgery were (2.33±0.58), (4.00±0.00), (6.33±0.58). The BMMSCs group were (2.10±0.58), (3.73±0.58), (5.67±1.15), which was decreased comparing with normal saline group, difference was statistically significant ( P<0.05). On the 1d, 3d, 7d after the transplantation, compared with normal saline group, expression of autophagy-related proteins LC3 and Beclin-1 in BMMSCs group was increased ( P<0.05). Conclusions:It showed that autophagy has an effect on the protection of BMMSCs liver graft of rats.

Objective:To investigate the effects of heme oxygenase-1 (HO-1)-modified rat bone marrow mesenchymal stem cells (BMMSCs) on T lymphocyte subsets in cirrhotic rats.Methods:A rat model of liver cirrhosis was established by intraperitoneal injection of carbon tetrachloride (CCL 4) in 110 rats. These rats were randomly divided into three groups, model group, BMMSCs group and HO-1/BMMSCs group, and injected with PBS, BMMSCs and HO-1/BMMSCs through dorsal penile vein, respectively. Another 10 rats were selected as control group. All rats were executed four weeks after intervention. Pathological changes in liver tissues were observed with HE and Sirius red staining. Serum albumin (ALB) and alanine aminotransferase (ALT) were detected by biochemical analyzer. Serum hyaluronidase (HA) and collagen type Ⅳ (Ⅳ-C) were detected by ELISA. T lymphocyte subsets in peripheral blood and spleen were detected by flow cytometry. Results:The rat model of cirrhosis was successfully established. Compared with the model group and BMMSCs group, the HO-1/BMMSCs group had significantly lower Ishak score and disease stage ( P<0.05), increased serum ALB level and CD4 + T/CD8 + T cell ratio ( P<0.05), and decreased serum ALT, HA and Ⅳ-C levels and Th17/Treg ratio ( P<0.05). Conclusions:HO-1/BMMSCs could improve liver function and liver fibrosis in cirrhotic rats more effectively than BMMSCs alone. The mechanism was possibly through regulating the immunomodulatory function of T lymphocyte subsets in cirrhotic rats.