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.

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.

OBJECTIVE: To investigate the distribution characteristics of polymorphonuclear neutrophil (PMN) in the lungs during the early stage of severe burns and the mechanism of neutrophil elastase (NE) promoting lung injury. METHODS: 6-8-week-old male C57BL/6J mice were selected for the experiments. A 30% total body surface area (TBSA) III degree burn mouse model was established (severe burn group); the Sham-injury group was treated with 37 centigrade water. In the sodium sivelestat intervention group (SV intervention group), NE competitive inhibitor, sivelestat, 100 mg/kg, was injected via tail vein immediately after injury, while other groups received an equal volume of saline. Ten mice were harvested from each group to observe survival for 72 hours. Respiratory function tests were tested at 0 (immediate), 3, 6, 12, and 24 hours after molding. hematoxylin-eosin (HE) and immunohistochemical staining were used to observe lung tissue structure, inflammatory changes and PMN infiltration. The PMN absolute count in mice lung tissue was detected buy flow cytometry. At 6, 12, and 24 hours after molding, PMN counts and the concentration of NE [enzyme linked immunosorbent assay (ELISA)] in peripheral blood plasma, lung tissue, and bronchoalveolar lavage fluid (BALF) were detected. RESULTS: (1) HE staining results showed that compared with the Sham-injury group, the lungs of mice in the severe burn group showed inflammatory changes and PMN infiltration, with more significant changes at 6 hours. Immunohistochemistry results also confirmed that the expression of NE protein released from PMN significantly increased after 6 hours of severe burn injury [(3.79±0.62)% vs. (0.18±0.05)%, t = 11.56, P < 0.01]. (2) Compared with the Sham-injury group, the number of PMN and the concentration of NE in the peripheral blood and lung tissues in the severe burn group were significantly increased (F values were 13.709, 55.350 and 29.890, 13.286, respectively, all P < 0.01), peaking at 6 hours [plasma PMN count (×10⁹/L): 2.92±1.01 vs. 0.92±0.29, lung tissue PMN absolute count (cells): 48 788.03±11 833.91 vs. 1 516.72±415.35, plasma NE (ng/L): 24 522.71±3 842.92 vs. 7 009.34±4 067.86, lung tissue NE (ng/L): 262 189.04±9 695.13 vs. 65 026.03± 16 016.31, all P < 0.01]. The number of PMN in the lung of severely burned mice was highly correlated with NE concentration (r = 0.892, P < 0.001). There was no significantly difference in the PMN absolute count in the BALF of mice between the Sham-injury group and severe burn group (F = 1.403, P > 0.05). The Sham-injury group and severe burn group contained a small amount of NE in the BALF, and the concentration of NE in the BALF of the severely burned 6 hours and 12 hours groups were significantly higher than those of the Sham-injury group (ng/L: 328.58±158.10, 415.30±240.89 vs. 61.95±15.80, both P < 0.05). (3) Kaplan-Meier survival curve showed that the 72-hour survival rate of mice in the SV intervention group was significantly higher than that in the severe burn group (100% vs. 10%, Log-Rank test: χ² = 19.12, P < 0.001). (4) Compared with the Sham-injury group, all lung function indices of the severe burn group decreased significantly. All lung function indices of SV intervention group improved gradually over time, which were significantly better than those of the severe burn group. (5) Compared with the Sham-injury group, the PMN absolute count in lung tissue and the concentration of NE in plasma and lung tissue were significantly higher in the SV intervention group (F values were 46.709, 3.535, 32.701, respectively, all P < 0.05), with a peak at 6 hours. Compared with the severe burn group, the SV intervention group had a higher PMN absolute count in lung tissue (cells: 8 870.80±7 013.89 vs. 25 974.92±22 240.8, P < 0.05), and higher plasma and lung tissue NE concentrations (ng/L: 14 955.94±3 944.41 vs. 21 972.75±4 573.05, 81 956.87±38 658.35 vs. 168 182.30±83 513.91, both P < 0.01) were significantly decreased. CONCLUSIONS In the early stage of severe burns, there is a significant infiltration of PMN into the lungs. The NE promotes lung injury in the early stage of severe burn, and improve lung injury by inhibiting the action of NE.
Animals ; Burns/metabolism* ; Leukocyte Elastase/metabolism* ; Male ; Mice, Inbred C57BL ; Mice ; Neutrophils/metabolism* ; Lung/metabolism* ; Disease Models, Animal ; Neutrophil Infiltration ; Lung Injury/metabolism* ; Glycine/analogs & derivatives* ; Sulfonamides

BACKGROUND:Although aromatase inhibitors significantly improve the clinical benefit of patients with hormone receptor-positive breast cancer,its associated adverse event-osteoporosis seriously affects the quality of life of patients.Huangqi Bushen Huoxue Decoction can effectively prevent the occurrence of aromatase inhibitor-induced osteoporosis,but its mechanism of action is unclear.OBJECTIVE:To investigate the effects of Huangqi Bushen Huoxue Decoction on osteoclast activity in a mouse model of osteoporosis induced by aromatase inhibitors and relevant mechanisms.METHODS:Sixty 8-week-old female C57BL/6J mice were randomly divided into sham operation group,model group,high-,medium-and low-dose Huangqi Bushen Huoxue Decoction,and positive control group,with 10 mice in each group.Bilateral ovaries were removed to establish postmenopausal animal models in all the groups except for the sham operation group.After 1 week of recovery,letrozole was injected subcutaneously to establish postmenopausal osteoporosis models via subcutaneous injection of letrozole(an aromatase inhibitor).The high-,medium-and low-dose Huangqi Bushen Huoxue Decoction groups were intragastrically given 19.24,9.62 and 4.81 g/kg/d Huangqi Bushen Huoxue Decoction(once a day),respectively.The positive control group was given alendronate 5mg/kg once a week.After 3 months of administration,Micro-CT was used to detect tibial bone mineral density and bone microstructure.Hematoxylin-eosin staining and tartrate-resistant acid phosphatase staining of the femur were performed.Immunohistochemistry was used to detect the protein expression of receptor activator of nuclear factor-κB ligand and osteoprotectin in the femur.ELISA was used to detect the serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the model group showed a significant decrease in bone mineral density,sparse and fractured trabecular morphology,and a significant increase in serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,indicating that the model of aromatase inhibitor-induced osteoporosis was successfully constructed.(2)Compared with the model group,the high-,medium-,and low-dose Huangqi Bushen Huoxue Decoction groups showed significant improvement in bone mineral density and bone microstructure,thickening and densification of trabecular morphology,significantly decreased serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,a decrease in the number of osteoclasts and the expression of receptor activator of nuclear factor-κB ligand proteins,and an increase in the expression of osteoprotegerin.To conclude,Huangqi Bushen Huoxue Decoction may regulate the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin signaling pathway,inhibit osteoclast activity,improve trabecular morphology and bone microstructure,and increase bone mineral density,thus preventing the occurrence and development of aromatase inhibitor-induced osteoporosis.

OBJECTIVE To explore the colonization rates of carbapenem-resistant gram-negative bacteria(CRGNB)in intestinal tracts of intensive care unit(ICU)patients and analyze the influencing factors.METHODS The ICU patients were recruited from a three-A general hospital of Shanghai from Jan.2024 to Dec.2024,an ac-tive screening was carried out for intestinal tract CRGNB,and the detection rates of 5 types of carbapenems resist-ance genes(CRGs)in the CRGNB strains were observed.The baseline data and hospitalization data before the ac-tive screening were collected from the patients,logistic regression analysis was performed for the influencing fac-tors for the colonization of CRGNB.The effects of targeted infection control measures on length of ICU stay,hos-pitalization cost and prognosis were observed and compared before and after the active screening was carried out.RESULTS A total of 748 patients were included in the active screening,and the colonization rate of CRGNB in intestinal tracts was 11.50％(86/748).Among the CRGs,the detection rate of blaNDM was the highest(6.82％),followed by blaIMP(4.55％)and blaKPC(2.54％).The result of logistic regression analysis showed that,with an increase of 1 each day of hospital stay before the admission to ICUs,the risk was increased by 1.055 times(OR=1.055,95％CI:1.030 to 1.081,P＜0.001),the risk was 0.442 times the use of as aminoglycosides as the use of β-lactams(OR=0.442,95％CI:0.244 to 0.801,P=0.007).The targeted infection control measures that were taken after the active screening shortened the length of hospital stay(Z=-3.514,P＜0.001),reduce the hospitalization cost(Z=3.030,P=0.002)and improve the prognosis of the patients(x2=7.470,P=0.006).CONCLUSIONS The colonization rates of CRGNB in intestinal tracts are high among the ICU patients.It is necessary to reduce the length of hospital stay prior to ICU and strengthen the surveillance of drug-resistant strains and management of antibiotics.

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.

OBJECTIVE To explore the colonization rates of carbapenem-resistant gram-negative bacteria(CRGNB)in intestinal tracts of intensive care unit(ICU)patients and analyze the influencing factors.METHODS The ICU patients were recruited from a three-A general hospital of Shanghai from Jan.2024 to Dec.2024,an ac-tive screening was carried out for intestinal tract CRGNB,and the detection rates of 5 types of carbapenems resist-ance genes(CRGs)in the CRGNB strains were observed.The baseline data and hospitalization data before the ac-tive screening were collected from the patients,logistic regression analysis was performed for the influencing fac-tors for the colonization of CRGNB.The effects of targeted infection control measures on length of ICU stay,hos-pitalization cost and prognosis were observed and compared before and after the active screening was carried out.RESULTS A total of 748 patients were included in the active screening,and the colonization rate of CRGNB in intestinal tracts was 11.50％(86/748).Among the CRGs,the detection rate of blaNDM was the highest(6.82％),followed by blaIMP(4.55％)and blaKPC(2.54％).The result of logistic regression analysis showed that,with an increase of 1 each day of hospital stay before the admission to ICUs,the risk was increased by 1.055 times(OR=1.055,95％CI:1.030 to 1.081,P＜0.001),the risk was 0.442 times the use of as aminoglycosides as the use of β-lactams(OR=0.442,95％CI:0.244 to 0.801,P=0.007).The targeted infection control measures that were taken after the active screening shortened the length of hospital stay(Z=-3.514,P＜0.001),reduce the hospitalization cost(Z=3.030,P=0.002)and improve the prognosis of the patients(x2=7.470,P=0.006).CONCLUSIONS The colonization rates of CRGNB in intestinal tracts are high among the ICU patients.It is necessary to reduce the length of hospital stay prior to ICU and strengthen the surveillance of drug-resistant strains and management of antibiotics.

BACKGROUND:Although aromatase inhibitors significantly improve the clinical benefit of patients with hormone receptor-positive breast cancer,its associated adverse event-osteoporosis seriously affects the quality of life of patients.Huangqi Bushen Huoxue Decoction can effectively prevent the occurrence of aromatase inhibitor-induced osteoporosis,but its mechanism of action is unclear.OBJECTIVE:To investigate the effects of Huangqi Bushen Huoxue Decoction on osteoclast activity in a mouse model of osteoporosis induced by aromatase inhibitors and relevant mechanisms.METHODS:Sixty 8-week-old female C57BL/6J mice were randomly divided into sham operation group,model group,high-,medium-and low-dose Huangqi Bushen Huoxue Decoction,and positive control group,with 10 mice in each group.Bilateral ovaries were removed to establish postmenopausal animal models in all the groups except for the sham operation group.After 1 week of recovery,letrozole was injected subcutaneously to establish postmenopausal osteoporosis models via subcutaneous injection of letrozole(an aromatase inhibitor).The high-,medium-and low-dose Huangqi Bushen Huoxue Decoction groups were intragastrically given 19.24,9.62 and 4.81 g/kg/d Huangqi Bushen Huoxue Decoction(once a day),respectively.The positive control group was given alendronate 5mg/kg once a week.After 3 months of administration,Micro-CT was used to detect tibial bone mineral density and bone microstructure.Hematoxylin-eosin staining and tartrate-resistant acid phosphatase staining of the femur were performed.Immunohistochemistry was used to detect the protein expression of receptor activator of nuclear factor-κB ligand and osteoprotectin in the femur.ELISA was used to detect the serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b.RESULTS AND CONCLUSION:(1)Compared with the sham operation group,the model group showed a significant decrease in bone mineral density,sparse and fractured trabecular morphology,and a significant increase in serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,indicating that the model of aromatase inhibitor-induced osteoporosis was successfully constructed.(2)Compared with the model group,the high-,medium-,and low-dose Huangqi Bushen Huoxue Decoction groups showed significant improvement in bone mineral density and bone microstructure,thickening and densification of trabecular morphology,significantly decreased serum levels of carboxyterminal cross-linked telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b,a decrease in the number of osteoclasts and the expression of receptor activator of nuclear factor-κB ligand proteins,and an increase in the expression of osteoprotegerin.To conclude,Huangqi Bushen Huoxue Decoction may regulate the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin signaling pathway,inhibit osteoclast activity,improve trabecular morphology and bone microstructure,and increase bone mineral density,thus preventing the occurrence and development of aromatase inhibitor-induced osteoporosis.

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.