Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

OBJECTIVE: To observe the effect of electroacupuncture combined with enhanced recovery after surgery (ERAS) protocol on promoting intestinal function in patients after gastric cancer surgery. METHODS: Forty-four patients who underwent radical gastrectomy for gastric cancer were randomly divided into an experimental group (22 cases, 3 cases were excluded) and a control group (22 cases, 4 cases were excluded). Both groups received treatment under ERAS protocol, the experimental group was given electroacupuncture at bilateral Neiguan (PC6), Hegu (LI4), Zusanli (ST36) and Quchi (LI11), disperse-dense wave was selected, with frequency of 2 Hz/100 Hz. The control group received placebo electroacupuncture intervention, with the same acupoints as the experimental group, electrode pads were placed on the acupoints without electrical stimulation. Each session lasted 30 min, starting from 1 h after surgery, once every 24 h, until the patient resumed anal flatus. The intestinal sound rate of both groups was observed 24 h before surgery and 24, 48 h after surgery. The bowel sound recovery time (BSRT), time to first anal flatus, time to first defecation, and tolerance to oral enteral nutrition suspension were compared between the two groups. The levels of serum C-reactive protein (CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured 24 h before surgery and 24 h after surgery in both groups. RESULTS: The intestinal sound rate 24 h after surgery was decreased compared with that 24 h before surgery in the two groups (P<0.05), the intestinal sound rate 24, 48 h after surgery in the experimental group was higher than that in the control group (P<0.05). The BSRT in the experimental group was earlier than that in the control group (P<0.05) .The levels of serum CRP, IL-6, IL-10 24 h after surgery in the experimental group were higher than those 24 h before surgery (P<0.05), while the levels of serum CRP, IL-4, IL-6, IL-10, IFN-γ in the control group were higher than those 24 h before surgery (P<0.05); the levels of serum CRP、IL-4、IFN-γ 24 h after surgery in the experimental group were lower than those in the control group (P<0.05) .The tolerance rate of oral enteral nutrition suspension in the experimental group was 84.2% (16/19), which was higher than 50.0% (9/18) in the control group (P<0.05). CONCLUSION Electroacupuncture combined with ERAS protocol can improve the intestinal motility, shorten the BSRT, enhance the tolerance of oral intake, and reduce inflammatory response in patients after gastric cancer surgery.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Points ; C-Reactive Protein/metabolism* ; Electroacupuncture ; Gastrectomy ; Interleukin-10 ; Interleukin-6 ; Intestines/physiopathology* ; Stomach Neoplasms/therapy*

This paper focuses on extreme environments and systematically analyzes sleep disorders caused by multiple pathogenesis,including circadian rhythm disorder,yin-yang imbalance and qi-blood disorder under weightlessness,emotional depression due to environmental changes,abnormal diet and excretion,and six excesses pathogenic factors,in accordance with the theory of correspondence between nature and human.It proposes harmonizing yin and yang as the core therapeutic principle and guiding framework,with specific methods including calming rebellious qi-blood,regulating qi movement,harmonizing heart and kidney,and dredging and regulating blood vessels,thus forming the"one guiding principle and four specific methods"treatment strategy.Additionally,by integrating the modified application of classic formulas,a diagnostic and therapeutic approach targeting multi-dimensional pathogenesis is established.This study aims to promote the in-depth integration of Traditional Chinese Medicine(TCM)in extreme environmental medicine through TCM theories and innovative application of prescriptions,provide TCM-characterized solutions for health management of workers in extreme environments,and facilitate the transformation of extreme environmental medicine toward the modern medical model of"prevention-treatment integration".

The incomplete degradation of tumour cells by macrophages(Mφ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mφ is mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mφ to degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mφ to degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mφ phagosomes,causing Mφ to produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mφ by liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subse-quently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mφ cannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mφ to degrade tumour cells by suppressing NOX2.

Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

Objective::Patients with untreated severe aortic regurgitation (AR) have a high risk of mortality. Transfemoral transcatheter aortic valve replacement (TF-TAVR) is a treatment option for AR; however, the safety and efficacy of this technique have not been sufficiently established. This study aimed to evaluate the clinical and anatomical variables correlating with device success of TF-TAVR using a self-expanding valve system for pure AR.Methods::Patients with pure native severe AR who underwent TF-TAVR using a self-expanding valve system were registered at 5 Chinese centers. The primary endpoint was device success at 1 month after TAVR. The secondary endpoint was the composite of major adverse cardiovascular events (MACE) at 6 months, including all-cause death, ischemic stroke, emergency conversion to cardiac surgery, and permanent pacemaker implantation. Echocardiography was used to analyze the left ventricular function before the TAVR procedure and during follow-up. Multivariable logistic regression and Cox regression analyses were performed to find relevant independent risk factors.Results::Between September 2019 and February 2022, 79 patients with AR were enrolled in the study. At 1 month, device success was achieved in 60 (75.9%) patients. By 6 months, 29 (36.7%) patients had MACE. Echocardiography revealed improved left ventricular function after TAVR. Multivariate regression analysis demonstrated that the Society of Thoracic Surgeons risk score (odds ratio 0.760, 95% confidence interval (CI): 0.584-0.989; P = 0.041) and annulus perimeter (odds ratio 0.888, 95% CI: 0.796-0.992; P = 0.035) were 2 predictors of device success. Moreover, annulus perimeter (<80.2 mm), but not Society of Thoracic Surgeons risk score, was associated with a significant reduction in MACE at 6 months (hazard ratio 2.223, 95% CI: 1.060-4.659; P = 0.028). Conclusions::TF-TAVR using a self-expanding valve system appears to be a safe and feasible treatment for patients with pure native severe AR, particularly those with a less enlarged annulus.

Objective:To analyze the clinical symptoms and epidemiological characteristics of patients with tsutsugamushi disease (TD) in Utica County, Shiyan City, providing reference for scientific prevention and control of TD.Methods:The information of 57 TD patients admitted to the Department of Infectious Diseases of the People's Hospital of Utica County in Shiyan City from January to December 2022 was collected, including age, gender, occupation, clinical manifestations (tarsus or chigger, high fever, rash and accompanying syndromes), laboratory and imaging test results, and field work and travel history. Blood samples and body crusts were collected, and enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) were used to detect antibodies against Orientia tsugamushi (Ot-Ab-IgM) and Orientia tsutsugamushi (Ot). The scores of each patient were calculated using the TD Diagnostic Scale. A score of ≥8.5 was considered a clinical diagnosis of TD. According to the number of system functional damages (0, 1, 2, ≥3), 57 patients were divided into 4 groups, A, B, C, and D, TD was analyzed for system functional damages of each system.Results:Among the 57 TD patients, 26 (45.61%) were male and 31 (54.39%) were female, and the proportion of patients aged 40 - 79 years was 92.98% (53/57); farmers accounted for 89.47% (51/57). May was the peak of TD incidence, with 19 cases, which accounted for 33.33% (19/57) of the total number of patients affected that year. Fifty-four patients had a history of fieldwork or field trips before the onset of the disease. The incidence of high fever in 57 TD patients was 100.00%(57/57), the detection rate of body scorch or chiggers was 80.70% (46/57), and the incidence rate of rash was 98.25% (56/57); the incidence rate of tsutsugamushi disease triad (accompanied by scabs, high fever, and rash) was 80.70% (46/57); the incidence of eosinophil decline was 100.00%(57/57), and 77.19% (44/57) of TD patients experienced multiple-system functional damage (MSFD). The TD score diagnostic scale for 57 patients ranged from 8.5 to 10.5 points. After being hospitalized for 1 - 5 days, all TD patients experienced a decrease in body temperature to the normal range, and the damage to various systems functional gradually recovered.Conclusions:TD has become one of the most common natural infectious diseases in Utopia County, Shiyan City, Hubei Province. The patients are mainly middle-aged and elderly people, and the triple syndrome is a typical clinical manifestation. Asymptomatic injuries to the blood system, liver and kidneys are the most common.