Metabolic reprogramming， as one of the core hallmarks of malignant tumors， plays a key role in the occurrence， development and treatment of breast cancer （BC）. Abnormal changes in glucose metabolism， amino acid metabolism， lipid metabolism， as well as the tricarboxylic acid （TCA） cycle and oxidative phosphorylation （OXPHOS） pathways significantly influence the pathogenesis and progression of BC. Studies have shown that various active components of traditional Chinese medicine （TCM） （such as berberine， matrine， quercetin， curcumin， etc.） and their compound formulations （e.g. Xihuang pill， Danzhi xiaoyao powder， Yanghe decoction， etc.） can inhibit the proliferation and migration of BC cells and induce apoptosis by regulating key metabolic pathways such as glycolysis， lipid synthesis， and amino acid metabolism. TCM demonstrates multi-target and holistic regulatory advantages in intervening in BC metabolic reprogramming， showing significant potential in modulating key molecules like hypoxia inducible factor-1α， hexokinase-2， pyruvate kinase M2， lactate dehydrogenase A， glucose transporter-1， fatty acid synthase， and signaling pathways such as AKT/mTOR. However， current researches still focus predominantly on glucose metabolism， with insufficient mechanistic studies on lipid metabolism， amino acid metabolism， the TCA cycle， and OXPHOS. The precise targets， molecular mechanisms， and clinical translation value of these interventions require further validation and clarification through more high-quality experimental studies and clinical trials.

BACKGROUND:The combination of good biomechanical properties,controlled drug release and multi-functionality of core-shell structured nanofibers is receiving more and more attention,which also makes them promising for a wide range of applications in the field of oral tissue regeneration. OBJECTIVE:To summarize the preparation,drug loading and release mechanisms of core-shell structured nanofibers and their application in the regenerative repair of oral tissues. METHODS:A computer search of the literature collected in CNKI and PubMed from January 2000 to November 2022 was applied,and the search terms in English and Chinese were"electrospinning,core-shell structures,drug delivery systems,jaw bone regeneration,cartilage regeneration,periodontal tissue regeneration". RESULTS AND CONCLUSION:(1)There are various methods for the preparation of core-shell structured nanofibers,but the coaxial and emulsion methods of electrostatic spinning have unique advantages such as simple operation,diverse material selection and good biocompatibility.(2)Core-shell structured nanofibers can be used as bacteriostatic agents,carriers of different types of drugs,and scaffolds for cell adhesion,providing new therapeutic options for oral tissue regeneration.(3)Controlled degradation and drug release rate of core-shell structured nanofibers can better adapt to the healing process of oral tissue defect repair and achieve ideal tissue regeneration.

Objective:To investigate the effect of maintenance hemodialysis (MHD) combined with levocarnitine on vascular sclerosis and vascular endothelial function in patients with chronic renal failure.Methods:Patients with chronic renal failure receiving MHD treatment admitted to Shanxian Central Hospital of Shandong Province from June 2019 to May 2020 were selected as the research object and they were divided into the observation group (53 cases) and the control group (49 cases) by the random number table method. The patients in the control group were treated with maintenance hemodialysis and the patients in the observation group were treated with combined levocarnitine on the basis of the control group. The levels of serum creatinine (SCr), blood urea nitrogen (BUN) and other renal function indicators were determined before and 6 months after the treatment. The levels of nuclear factor kappa B (NF-κB), tumor necrosis factor (TNF-α) and other microinflammatory indexes, and advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and other oxidative response indexes were determined. The levels of endothelin-1 (ET-1), von Willebrand factor (vWF) and vascular reactive hyperemia index (RHI) were measured. Common carotid atherosclerosis β and pulse wave conduction velocity (PWV) were measured by color Doppler ultrasonography.Results:The levels of SCr, BUN in the two groups after treatment had no significant differences ( P>0.05). The levels of TNF-α and NF-κB in the observation group after treatment were lower than those in the control group: (20.22 ± 7.15) μg/L vs.(26.14 ± 5.96) μg/L, (6.10 ± 0.80) mg/L vs. (6.55 ± 1.10) mg/L, there were statistical differences ( P<0.05). The levels of AOPP, MDA in the observation group after treatment were lower than those in the control group and the level of GSH-PX was higher than that in the control group: (78.52 ± 17.41)μmol/L vs.(97.96 ± 18.29) μmol/L, (4.44 ± 1.02) μmol/L vs. (6.07 ± 1.26) μmol/L, (110.14 ± 22.17) mg/L vs.(90.63 ± 19.28) mg/L, there were statistical differences ( P<0.05). The levels of PWV, ET-1 and vWF in the observation group after treatment were lower than those in the control group and the RHI was higher than that in the control group: (7.29 ± 0.59) m/s vs. (7.89 ± 0.63) m/s, (44.15 ± 10.27) ng/L vs. (52.41 ± 12.74) ng/L, (30.26 ± 7.45) U/L vs. (35.71 ± 6.23) U/L, 1.54 ± 0.25 vs. 1.45 ± 0.20, there were statistical differences ( P<0.05). Conclusions:The combination of levocarnitine in the treatment of MHD can alleviate microinflammation, oxidative stress response and improve vascular endothelial function and arteriosclerosis.

Objective:To investigate the adverse childhood experience (ACE) effects on the risk of chronic diseases among middle-aged and elderly.Methods:A retrospective cohort study was conducted using the China Health and Retirement Longitudinal Study data. We used life history study data in 2014 as baseline data and data of chronic diseases of middle-aged and elderly in 2015 as outcomes. A zero-inflated negative-binominal model was used to estimate the incidence rate ratio ( IRR) for the association between ACE and chronic diseases. Results:Compared with the less than 4 points of ACE exposure in childhood, individuals with ACE exposure 4-, 6- and ≥9 were associated an increased risk of chronic disease, adjusted IRR (95% CI), 1.10(1.04-1.16), 1.18 (1.13-1.25), 1.34 (1.27-1.42), respectively, with a significant dose-response relationship that chronic diseases risks increase parallel with the increase of ACE exposure. Conclusions:ACE might serve as one of the critical risk factors of chronic diseases in middle-aged elderly. It's of public health significance for early screening and intervention of ACE, reducing the incidence of chronic diseases, and improving middle-aged and older adults' quality of life and health.

[Abstract] Objective:ToinvestigatetheroleofmiR-125a-5pininducingthegefitinib(Gef)-resistance of non-small cell lung carcinoma (NSCLC) cells and its possible mechanism. Methods: Human NSCLC drug-resistant cell line A549/GR and NSCLC cell line A549 were chosen for this study. miR-125a-5p mimic, miR-125a-5p inhibitor, pcDNA3.1-APAF1 and empty vector pcDNA3.1 were transfected into A549/GR cells. The expression level of miR-125a-5p in cell lines was detected by qPCR. MTT, Transwell and Flow cytometry were used to detect the effects of Gef on proliferation, migration and apoptosis of cell lines, respectively. The targeting relationship between miR-125a-5p and APAF1 (apoptotic peptidase activating factor 1) was verified by Dual-luciferase reporter gene system. In addition, the expression of APAF1 protein in A549/GR cells was detected by Western blotting. The expression levels of caspase-3 and caspase-9 were assessed by colorimetry. Results: Expression level of miR-125a-5p was upregulated significantly in Gefresistant A549/GR cells (P<0.01). AndtheinfluencesofGefonA549/GRcellswereenhancedby knockdown of miR-125a-5p, including inhibiting cell proliferation and migration (all P<0.05) and inducing apoptosis (P<0.01). Dual luciferase reporter gene assay confirmed that miR-125a-5p targeted APAF1 and negatively regulated its expression. Furthermore, by targetedly downregulating APAF1, miR-125a-5p alleviated the inhibition of proliferation and migration (all P<0.05) and promotion of apoptosis (P<0.05) of A549/GR cells caused by Gef, and attenuated Gef-induced upregulation of apoptosis-related proteins caspase-3 and caspase-9 (all P<0.05). Conclusion: miR-125a-5p promotes Gef-resistance of A549/GR cells, and the underlying mechanisms are promotion of proliferation, migration and inhibition of apoptosis of non-small cell lung cancer cells by targetingAPAF1.

Objective: To explore the spatial distribution of low birth weight (LBW) and the potential environmental risk factors and provide the evidence for the prevention and intervention of LBW. Methods: Data were from a surveillance system for newly born population and adverse pregnancy outcome between 2007 and 2012 in Pingding county, Shanxi province. The data from 313 villages were analyzed. Spatial hierarchical Bayesian model was used to adjust the risk of LBW at village level, Moran’s I and Getis-Ord Gi* were used to analyze the difference in distribution of LBW risk area. Spatial negative binomial model was used to evaluate the association between the risk of LBW and chemical fertilizer application. Results: A total of 18 749 new births were recorded between 2007 and 2012, including 911 LBW cases, the total incidence of LBW was 4.86%. The result of the spatial hierarchical Bayesian model showed that high-risk area of LBW was in the southeast of Pingding and low-risk area was in the middle west of Pingding. The result of Moran’s I showed that there was a clustering pattern of LBW risk, and Getis-Ord Gi* found a high risk (hot spot) area in the south area. Moreover, the findings of association analysis showed that the risk of LBW increased with the increased chemical fertilizer application at village level. Conclusions There were area specific differences in the risk of LBW, and dose-response relationship between chemical fertilizer application and the risk of LBW. Our findings suggest that maternal exposure to chemical fertilizer during pregnancy might be a potential risk factor for LBW in rural area.

Objective To investigate the curative effect and mechanism of α lipoic acid combined with epalrestat and methylcobalamin in patients with type 2 diabetes mellitus (T2DM) complicated with pe-ripheral neuropathy ( DPN) . Methods A total of 160 cases of patients with DPN were randomly divided into the control group ( treated with methylcobalamin and epalrestat) and the observation group ( treated with methylcobalamin, epalrestat and α lipoic acid) , and all patients were treated for 4 weeks. The therapeutic effect, nerve conduction velocity, oxidative stress index and related proteins expression in serum were ob-served in two groups. Results The effective rate of treatment in the observation group was higher than that in the control group (87. 50％ vs 75. 0％) (χ2 = 4. 103,P<0. 05). After treatment, the sensory nerve conduction velocity ( SNCV) and motor nerve conduction velocity ( MNCV) of median nerve and common peroneal nerve were significantly better in the observation group than the control group ( P<0. 05 ) . After treatment, the level of superoxide dismutase ( SOD) was significantly higher in the observation group than the control group, while the level of malondialdehyde ( MDA ) was significantly lower the control group (P<0. 05). After treatment, the level of Bcl-2 protein was significantly higher in observation group than the control group, while the levels of Bax and Caspase-3 proteins were significantly lower than the control group (P<0. 05). Conclusions The application ofαlipoic acid combined to epalrestat and methylcobal-amin in the treatment of DPN can significantly improve the sensory and motor nerve conduction.

OBJECTIVEOur objective is to build a model that explains the association between the exposure to trace elements in the soil and the risk of neural tube defects.

METHODSWe built a function with different parameters to describe the effects of trace elements on neural tube defects. The association between neural tube defects and trace element levels was transformed into an optimization problem using the maximum likelihood method.

RESULTSTin, lead, nickel, iron, copper, and aluminum had typical layered effects (dosage effects) on the prevalence of neural tube defects. Arsenic, selenium, zinc, strontium, and vanadium had no effect, and molybdenum had one threshold value that affected the prevalence of birth defects.

CONCLUSIONAs an exploratory research work, our model can be used to determine the direction of the effect of the trace element content of cultivated soil on the risk of neural tube defects, which shows the clues by the dosage effect of their toxicological characteristics. Based on our findings, future biogeochemical research should focus on the direct effects of trace elements on human health.

China ; epidemiology ; Dose-Response Relationship, Drug ; Environmental Exposure ; Female ; Humans ; Metals ; chemistry ; toxicity ; Models, Biological ; Neural Tube Defects ; chemically induced ; epidemiology ; Pregnancy ; Prevalence ; Soil Pollutants ; chemistry ; toxicity ; Trace Elements ; chemistry ; toxicity

The study was aimed to investigate the extensive amplification and the cytotoxicity of dendritic cells (DC) derived from chronic myeloid leukemia cells. DC were cultured in two steps: firstly, extensive amplification in primary culture of CD34(+) or mononuclear cells isolated from CML patients' bone marrow and peripheral blood with rhFlt3-L and rhTPO for 7 days; secondly, inducing culture of DC with rhGM-CSF, rhTNF and rhIL-4 for 14 days. A system inducing DC directly were established for comparison. DC were identified by immunophenotype with flow cytometry, chromosome analysis by displaying G banding and electric microscopy analysis. The function of stimulating T cells proliferation and cytotoxicity of CML cells were confirmed through MTT assay. The results showed that after first extensive amplification in primary culture with rhFlt3-L and rhTPO for 7 days, CD34(+) cells had a total cell number with (77 +/- 5) fold expansion, and DC were (39 +/- 8)% of total cell respectively after induction culture of DC with rhGM-CSF, rhTNF and rhIL-4 for 14 days. Both the amplification of cell number and yield of DC were higher than the system without extensively culture (P < 0.01). Such DC could stimulate T cells to proliferate and kill leukemia cells finally. In conclusion, two-step culture method can obviously improve the cell number of DC required, that is better than inducing them directly. DC derived from CML cells induce the generation of anti-leukemia immunization.
Adolescent ; Adult ; Aged ; Antigens, CD34 ; immunology ; Cell Proliferation ; Cells, Cultured ; Child ; Cytotoxicity, Immunologic ; Dendritic Cells ; immunology ; pathology ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; immunology ; pathology ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic ; immunology