Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

Objective To evaluate the clinical efficacy of Guanxinning Tablets(composed of Salviae Miltiorrhizae Radix et Rhizoma and Chuangxiong Rhizoma)in patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI)presenting with qi stagnation and blood stasis syndrome.Methods Eighty AMI patients who underwent PCI and were diagnosed with qi stagnation and blood stasis syndrome were enrolled from Guangdong Second Traditional Chinese Medicine Hospital between January 2024 and December 2024.Patients were randomly divided into a control group(n=40)and an observation group(n=40)using a random number table.The control group received standard post-PCI treatment(Aspirin 0.1 g qd+Clopidogrel 75 mg qd),while the observation group received additional Guanxinning Tablets for 8 weeks.Serum myocardial injury markers[troponin I(TnI),N-terminal pro-B-type natriuretic peptide(NT-proBNP)],novel inflammatory indices[systemic immune-inflammation index(SII),systemic inflammation response index(SIRI)],and Seattle Angina Questionnaire(SAQ)scores were assessed before and after treatment.Clinical efficacy and safety were evaluated.Results(1)Efficacy:After 8 weeks,the total effective rate was 97.50％(39/40)in the observation group versus 92.50％(37/40)in the control group,showing a non-significant trend favoring the observation group(P＞0.05,by chi-square test).(2)Myocardial injury markers:Both groups exhibited significant improvements in TnI and NT-proBNP levels(P＜0.05),with greater improvements in the observation group(P＜0.05).(3)Inflammatory indices:SII and SIRI levels were significantly improved in both groups(P＜0.05),with superior reductions in the observation group(P＜0.01).(4)Quality of life:SAQ scores in the dimensions of physical limitation,angina stability,angina frequency,treatment satisfaction,and disease perception were improved in both groups(P＜0.05),and the observation group showed significantly better outcomes(P＜0.05 or P＜0.01).(5)Safety:No severe cardiovascular adverse events or allergic reactions occurred in either group.Mild adverse events(e.g.,dizziness,gastrointestinal discomfort)occurred in 5.00％(2/40)of both groups(P＞0.05).Conclusion Guanxinning Tablets combined with conventional post-PCI therapy significantly improve clinical symptoms,cardiac function,inflammatory response,and quality of life in AMI patients with qi stagnation and blood stasis syndrome,with excellent safety and tolerability.

Iodine is an essential micronutrient for human growth and development. It is crucial for neural development in fetuses and newborns in the early postnatal period, including neural migration, glial differentiation, and myelin formation in the central nervous system. Mothers must consume sufficient iodine during pregnancy to maintain fetal growth and development. However, the results of current researches on the potential effects of maternal iodine intake imbalance during pregnancy on offspring iodine nutrition, neurological and physical development are not completely consistant. This article reviews the research in recent years on the effects of maternal iodine intake imbalance during pregnancy on the iodine nutrition and development of offspring, aiming to provide scientific basis for improving offspring development from the perspective of maternal iodine nutrition.

OBJECTIVE: Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults. METHODS: A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality. RESULTS: Significant associations of PM ₁, PM _2.5, PM ₁₀, SO ₂, CO, and O ₃ exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio ( OR) for each 1 µg/m ³ increment was 1.49 [95% confidence interval ( CI): 1.46, 1.53] for PM ₁, 1.30 (1.27, 1.32) for PM _2.5, 1.05 (1.04, 1.06) for PM ₁₀, 5.84 (5.39, 6.32) for SO ₂, 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O ₃, respectively. Long-term PM ₁, PM _2.5, PM ₁₀, SO ₂, and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality. CONCLUSION Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults.
Humans ; Aged ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Air Pollutants/analysis* ; Aged, 80 and over ; Particulate Matter/adverse effects* ; Cardiovascular Diseases/mortality* ; Mortality ; Neoplasms/mortality* ; East Asian People

Objective:To explore the key targets and mechanism of Bielong Ruangan decoction in the treatment of liver cancer based on network pharmacology and molecular docking.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, PubChem database and PharmMapper database were used to search and screen the chemical components and related targets of Bielong Ruangan decoction and the targets of liver cancer diseases. The network diagram of " Bielong Ruangan decoction-traditional Chinese medicine-active ingredient-predicted target-disease" was constructed; Protein-protein interaction (PPI) network were analyzed through String database; gene ontology (GO) enrichment analysis was performed through WebGestalt database; Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out through KEGG Orthology Based Annotation System (KOBAS) database; Molecular docking of the active components and core target proteins of Bielong Ruangan decoction was carried out by using PyMOL, Auto DockVina and other software.Results:Bielong Ruangan decoction had 67 active components, 154 liver cancer targets and 244 pathways. According to the analysis of network pharmacology, Bielong Ruangan decoction may play an anti-cancer role through key targets such as epidermal growth factor receptor (EGFR), mitogen activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), MAPK8, serine threonine protein kinase 1 (AKT1), MAPK14, cysteine protease 3 (CASP3), cyclin-dependent kinase 2 (CDK2), bone morphogenetic protein 2 (BMP2), aldose reductase (AKR1B1) and other key targets. KEGG enrichment analysis showed that the treatment of liver cancer by Bielong Ruangan decoction involved the regulation of vascular endothelial growth factor (VEGF) signaling pathway, tumor necrosis factor (TNF) signaling pathway, thyroid hormone signaling pathway, T cell receptor signaling pathway and other pathways. The results of molecular docking showed that the binding energy of all compounds to protein was less than -5.6 kcal/mol, indicating that each compound and each protein could bind well.Conclusions:Bielong Ruangan decoction participates in the treatment of liver cancer through " multi-component, multi-target and multi-channel" ways, and plays an anti-cancer role mainly by regulating the proliferation and invasion of tumor cells and tumor inflammatory microenvironment.

Objective:To evaluate the intelligence, movement and physical development of 2-month-old infants, and to explore the influencing factors of early infant development.Methods:A total of 203 infants aged 42 days who underwent physical examination in the Department of Neonatology of the Fourth Affiliated Hospital of Harbin Medical University from May to December 2021 were selected as subjects. At the age of 2 months, 184 infants were followed up for their intelligence, movement and physical development. The intelligence and movement development of infants were evaluated with the intelligence development scale. Their body length, weight, and head circumference were measured, and physical development was assessed by Z-score method. Logistic regression was used to analyze the influencing factors of intelligence, movement and physical development of 2-month-old infants.Results:The median mental developmental index (MDI) of 184 2-month-old infants was 101; the median psychomotor developmental index (PDI) was 89; the body length was (59.3 ± 2.0) cm, the body weight was (5.8 ± 0.6) kg, and the head circumference was (38.9 ± 1.1) cm. Multiple logistic regression analysis showed that the influencing factors of MDI were maternal delivery age and infant gestational age [odds ratio ( OR) = 0.849, 0.463, P < 0.05]; the influencing factors of PDI were maternal prenatal education and average sleep time per night during pregnancy ( OR = 0.512, 0.666, P < 0.05); the influencing factor of body mass index (BMI) was maternal iodine supplements during pregnancy ( OR = 2.858, P = 0.018); the influencing factor of length-for-age Z-score (LAZ) was maternal prenatal education during pregnancy ( OR = 0.265, P = 0.026); the influencing factors of weight-for-age Z-score (WAZ) included maternal average sleep time per night, the frequency of sleeping time exceeding 12 am and the average weekly exercise duration during pregnancy ( OR = 0.277, 1.106, 0.990, P < 0.05). Conclusion:Maternal delivery age, prenatal education, sleep duration, intake of iodine supplements, exercise duration during pregnancy, and infant gestational age are factors affecting the intelligence, movement and physical development of 2-month-old infants, which should be paid attention to and measures should be taken to improve the population quality.

Liver fibrosis is the common result of various chronic liver injuries and can progress to liver cirrhosis and even liver cancer, and at present, there is still no effective means to reverse liver fibrosis. The transformation of activated hepatic stellate cells (HSC) in perisinusoidal space into myofibroblasts and the secretion of collagen are a central event in the process of liver fibrosis. NLRP3 inflammasome can be activated by various injury stimuli and mediate inflammatory response and pyroptosis. Recent studies have found that the activation of NLRP3 inflammasome is closely associated with HSC activation. This article introduces the activation of NLRP3 inflammasome in different pathways in HSC under various pathological factors and role of NLRP3 inflammasome in the formation of extracellular inflammatory microenvironment, thereby mediating HSC activation and playing an important role in promoting liver fibrosis.

With the effective implementation of universal salt iodization measures to prevent iodine deficiency disorders, severe iodine deficiency in pregnant women has been rare. However, due to the difficulty in changing the state of iodine deficiency in natural environment and insufficient iodine intake in diet to meet the iodine nutritional needs during pregnancy, mild or moderate iodine deficiency in pregnancy still occurs frequently, and may have adverse effects on the development of nervous system of their offspring. At the same time, the effect of excessive iodine intake of pregnant women on the development of nervous system of their offspring can not be ignored. In addition, if the ability of thyroid regulation in pregnant women is out of balance that leads to thyroid dysfunction and even hormone secretion disorder, which can not meet the needs of fetal growth and development, it may also affect the nervous system function of their offspring. This paper summarizes the human population studies in recent years: the effects of maternal mild to moderate iodine deficiency, iodine excess, abnormal thyroid function and thyroid hormone treatment on neuro development of offspring, and the mechanism of corresponding animal iodine related exposure experiments, in order to provide scientific basis for "precise prevention and treatment" of iodine deficiency disorders in the future.

BACKGROUND/OBJECTIVES: The aim of this study was to examine the validity and reproducibility of a food frequency questionnaire (FFQ) developed in Korea for breast cancer survivors. SUBJECTS/METHODS: Ninety-nine breast cancer survivors who completed an FFQ twice and three 3-day dietary records (DRs) between 2016–2017 were included. Energy and 14 nutrient intakes were calculated from FFQs and DRs. To determine the validity of the FFQ, energyadjusted de-attenuated Pearson correlations between two FFQ assessments and the average of the three 3-day DRs were calculated, and to determine reproducibility, energy-adjusted Pearson correlations and degrees of agreement were calculated between the first and second FFQ assessments. RESULTS: Correlation coefficients of validity ranged from 0.29 (protein) to 0.47 (fat) (median value = 0.36) for the FFQ assessment and from 0.20 (riboflavin) to 0.53 (calcium) (median value = 0.37) for the second. Correlation coefficients of reproducibility ranged from 0.22 (sodium) to 0.62 (carbohydrate) (median value = 0.36). Regarding FFQ reproducibilities, percentage classifications of exact agreements for energy-adjusted nutrients ranged from 27.3% (sodium) and 45.5% (fat). A median 76.8% of participants were classified into the same or adjacent quartiles, while a median of 5.6% of participants were classified in extreme quartiles. Bland–Atman plots for the majority of data points of three macronutrients, calcium and vitamins A and C fell within limits of agreement. CONCLUSIONS These results indicated that the newly developed FFQ for Korean breast cancer survivors has acceptable validity and reproducibility as compared with three 3-day DRs collected over a one-year period.

Objective:To investigate the expression of mBmi-1 in papillary thyroid cancer (PTC) and to analyze its relationship with clinical features of PTC and its mechanism.Methons:A total of 60 tissue samples were collected from Jun. 2018 to Dec. 2018 in Department of Oncology Surgery of Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the expression level of B cell-specific MLV integration site-1 (mBmi-1) in PTC tissues and its relationship with pathological features was analyzed. Bmi-l microRNAs (miRNAs) were predicted by bioinformatics sites targetscan and microRNA.org and confirmed by luciferase reporter gene experiments. CCK-8 (Cell Counting Kit-8) kit and Transwell chamber were used to measure changes in PTC proliferative capacity and invasive ability.Results:In this study, we found that mBmi-1 expression was positively correlated with PTC lesion size and invasion ability. Bioinformatics prediction results suggested that Bmi-1 was a target gene of microRNA-203 (MicroRNA-203, miR-203) , and the 3’-UTR target sequence of miR-203 against Bmi-1 was GUAAAGU. After transfection of the miR-203 mimetic, the expression of Bmi-1 mRNA in the PTC cell line TPC-1 was significantly down-regulated. The dual luciferase reporter gene assay demonstrated that miR-203 can act on the 3’UTR region of the Bmi-1 gene to predict the target. In addition, the transfection of miR-203 mimetic effectively inhibited the proliferation and invasion of PTC cells, and the ability of proliferation and invasion of PTC cell TPC-1 was restored after overexpression of Bmi-1 in PTC cell TPC-1 transfected with miR-203 mimic.Conclusions:Bmi-1 is positively correlated with the proliferation and invasion ability of PTC. miR-203 can inhibit the proliferation and invasion of PTC cells by directly targeting Bmi-1 gene.