BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Objective A neuroblastoma(NB)liver transplantation model was established and compared with the adrenal orthotopic transplantation model to explore its characteristics.Methods 5× 105 SK-N-SH cells were implanted along the long axis of the left lobe of mouse livers with a micro-injection needle.The growth,metastasis,expression of related genes,and histopathological changes of tumors were detected after the modeling.Results The tumor formation rate in mice inoculated with tumor cells reached 100％after 21 days,and tumor growth,metastasis,related gene expression changes,and pathological characteristics were apparent.Conclusions In this study,a neuroblastoma liver transplantation model was successfully constructed via a relatively simple surgical method to provide a more suitable choice for future scientific NB experiments.

Urinary tract infections (UTIs) are infectious diseases caused by uropathogenic bacteria, characterized clinically by high infection and recurrence rates, with uropathogenic Escherichia coli (UPEC) being the main causative agent. This bacterium possesses various virulence factors that enable it to adhere, colonize, invade, and cause disease in the bladder. This article reviews the pathogenic mechanisms of UPEC, focusing on its virulence factors, interactions with the host, and persistence in the body, aiming to expand our understanding of the processes involved in the occurrence and recurrence of UTIs.

Objective:To study the clinical efficacy of roxadustat capsule combined with recombinant human erythropoietin (rhEPO) in the treatment of chronic kidney failure (CKD).Methods:A total of 105 patients with CKD complicated with renal anemia who received treatment in Yiwu Fuyuan Hospital from October 2019 to October 2022 were prospectively selected and divided into observation group (53 cases) and control group (52 cases) according to random number table method. Both groups received maintenance hemodialysis treatment, while the control group received rhEPO intravenous injection treatment. On the basis of the control group, the observation group received roxadustat oral treatment. After 8 weeks of continuous treatment, the clinical efficacy of both groups was determined, and the anemia indicators, micro inflammatory factors and iron metabolism indicators were compared.Results:The total effective rate in the observation group was higher than that in the control group: 96.23%(51/53) vs. 80.77% (42/52), there was statistical difference ( χ2 = 4.46, P<0.05). After treatment, the levels of hemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) in the observation group were higher than those in the control group: (102.54 ± 9.37) g/L vs. (91.82 ± 10.20) g/L, (3.62 ± 0.59) × 10 12/L vs. (2.77 ± 0.63) × 10 12/L, 0.369 ± 0.068 vs. 0.288 ± 0.056, there were statistical differences ( P<0.05). After treatment, the levels of tumor necrosis factor-α, C-reactive protein and interleukin-6 in the observation group were lower those in the control group: (2.14 ± 0.56) μg/L vs. (3.26 ± 0.72) μg/L, (8.17 ± 2.44) mg/L vs. (10.73 ± 3.05) mg/L, (101.27 ± 14.95) μg/L vs. (123.74 ± 18.38) μg/L, there were statistical differences ( P<0.05). After treatment, The levels of ferritin, transferrin, transferrin saturation in the observation group were higher than those in the control group and hemodulin was lower than that in the control group: (288.47 ± 26.65) μg/L vs.(259.66 ± 24.80) μg/L, (2.81 ± 0.31) g/L vs. (2.43 ± 0.35) g/L, 0.351 ± 0.051 vs. 0.299 ± 0.053, (95.17 ± 17.56) μg/L vs. (106.49 ± 19.28) μg/L, there were statistical differences ( P<0.05). Conclusions:Roxadustat combined with rhEPO has a significant therapeutic effect on CKD complicated with renal anemia, which can effectively improve the patient′s micro inflammatory state and iron metabolism, alleviate anemia symptoms.

Objective To investigate the resistance level of Aedes albopictus to commonly used insecticides in Jinshan District, Shanghai, to provide a reference for standardizing the use of insecticides. Methods The larval dipping test was used to detect the resistance of Ae. Albopictus larvae to five kinds of insecticides, the SPSS 18.0 software was utilized to calculate the toxic regression equation and the median lethal concentration (LC50) of insecticides on the larvae. The resistance level was determined by evaluating the 24-hour mortality of adult Ae. Albopictus exposed to diagnostic doses of commonly used insecticides with the adult mosquito contact tube method. Results In 2018 and 2019, Ae. Albopictus larvae in the Jinshan District of Shanghai displayed moderate and high resistance to beta-cypermethrin, with resistance ratios of 25.03 and 65.96 folds respectively; high resistance to deltamethrin, with resistance ratios of 57.25 and 211.75 folds respectively; high resistance to permethrin, with resistance ratios of 46.17 and 243.36 folds. In 2018, 2019, 2021, and 2023, they showed moderate to high resistance to temephos with resistance ratios of 19.55, 23.94, 53.48, and 22.12 folds respectively. In 2021 and 2023, moderate resistance to fenitrothion was observed, with resistance ratios of 30.04 and 12.54 folds respectively. Adult Ae. Albopictus adults exhibited resistance to 0.03% deltamethrin, 0.07% lambda-cyhalothrin, 0.4% permethrin, and 0.08% beta-cypermethrin, with mortality rates ranging from 17.20% to 49.67% in 2021 and 2023. Potential resistance was observed to 0.7% lambda-cyhalothrin and 0.2% fenitrothion, with mortalities of 97.48% and 83.74% respectively. Sensitivity was noted to 0.05% propoxur with a mortality rate of 100.00%. Conclusions Ae. Albopictus in the Jinshan District, Shanghai, has developed varying resistance levels to different types of insecticides, including pyrethroids and organophosphates. It is recommended to strengthen the dynamic monitoring of the resistance of Ae. Albopictus and implement comprehensive prevention and control measures with a focus on environmental management, scientifically and rationally selecting hygienic insecticides to delay and mitigate the emergence of resistance.

OBJECTIVE In this study,the effects of live Lactobacillus murinus(L.m)and heat-killed L.muri-nus(H-k L.m)on DA neuronal damage in rats and the underlying mechanisms were investigated.METHODS Male SD rats were randomly divided into five groups:vehicle group,L.m/H-k L.m(1×109 cfu)group,6-OHDH group,6-OHDH + L.m/H-k L.m(1×107 cfu)group,and 6-OHDH + L.m/H-k L.m(1×109 cfu)group.Wild-type and NLRP3 knockout mice were divided into three groups:sham(vehicle),6-OHDH,and 6-OHDH + H-k L.m(1×109 cfu).The model was established after five weeks of pre-administration.Motor ability of experimental mice was assessed by rotarod,mine,and stepping experiments;the expression of dopaminergic neuron markers—tyro-sine hydroxylase(TH),microglial cell markers—ionized calnexin 1(IBA-1),and NOD-like receptor family protein 3(NLRP3)in the substantia nigra was detected by immunohistochemistry and immunofluorescence experi-ments.The expression changes of TH,IBA-1,NLRP3,apoptosis-associated microparticle protein(ASC),cas-pase 1,and inflammatory factors such as interleukin-1β(IL-1β),IL-18,and tumor necrosis factor-α(TNF-α)were detected by immunoblotting experiments.RESULTS H-k L.m ameliorated 6-OHDH-induced motor dysfunctions and loss of substantia nigra DA neurons,while no protec-tion was shown in live L.m treatment.At the same time,H-k L.m reduced the activation of NLRP3 inflammasome in microglia and the secretion of pro-inflammatory factors,thus inhibiting the development of neuroinflammation.Fur-thermore,H-k L.m failed to display its original neuropro-tective properties in NLRP3 inflammasome knockout mice.CONCLUSION H-k L.m conferred neuroprotec-tion against DA neuronal loss via the inhibition of microglial NLRP3 inflammasome activation,these findings provide a promising potential for future applications of L.m,and also beneficial strategy for PD treatment.

Objective:To analyze the Risk factors for rapid progression of inpatients with anti-melanoma differentiation associated gene5 (MDA5) antibody-positive dermamyositis (DM) complicated with interstitial lung disease (ILD), and construct a clinical predictive model.Methods:A total of 63 hospitalized patients with anti MDA5 positive DM combined with ILD (MDA5+ DM-ILD) from January 1, 2016 to May 30, 2022 at the Second Affiliated Hospital of the Air Force Military Medical University were included in the study. They were divided into a control group (DM-ILD) and an observation group (DM-RPPILD) based on whether they had rapidly progressing interstitial lung disease (RPILD). Retrospective collection and organization of clinical case data from patients were conducted, and binary logistic regression was used to summarize the risk factors of DM-RPILD. R software was used to construct a clinical prediction model for RPILD occurrence using training set data, and validation set data was used to verify the predictive ability of the model.Results:The proportion of patients with SpO 2<90% at the initial diagnosis of ILD, the titers of anti MDA5 antibodies, immunoglobulin M (IgM), serum ferritin (FER) levels, and positive rates of anti Ro52 antibodies in the observation group were higher than those in the control group, the lymphocyte (LYM) count level was lower than that of the control group (all P<0.05). Binary logistic regression analysis showed SpO 2<90% at the initial diagnosis of ILD, FER level, LYM count, and anti Ro52 antibody were the influencing factors for the occurrence of RPILD (all P<0.05). The area under the curve (AUC) of the training set prediction model for predicting resistance to MDA5+ DM-RPILD was 0.922(95% CI: 0.887-0.957), with a sensitivity of 95.7% and a specificity of 72.5%; In the validation set, the prediction model predicted an AUC of 0.939(95% CI: 0.904-0.974) for resistance to MDA5+ DM-RPILD, with a sensitivity of 90.0% and a specificity of 88.9%; The calibration curves of the training and validation sets indicated that the predictive model had good calibration ability. Conclusions:SpO 2<90% at the initial diagnosis of ILD, FER levels increase, LYM count levels decrease, and anti Ro52 antibody positivity are risk factors for RPILD. The constructed clinical model has good predictive ability and has certain guiding significance for clinical work.