Ulcerative colitis(UC) is a recurrent, chronic, nonspecific inflammatory bowel disease. The longer the course of the disease, the higher the risk of cancerization. In recent years, the incidence and mortality rates of colon cancer in China have been increasing year by year, seriously threatening the life and health of patients. Therefore, studying the mechanism of "inflammation cancer transformation" in UC and conducting early intervention is crucial. The "Kenang" theory is an important component of traditional Chinese medicine(TCM) theory of phlegm and blood stasis. It is based on the coexistence of phlegm and blood stasis in the body and deeply explores the pathogenic syndromes and characteristics of phlegm and blood stasis. Kenang is a pathological product formed when long-term Qi stagnation leads to the internal formation of phlegm and blood stasis, which is hidden deep within the body. It is characterized by being hidden, progressive, and difficult to treat. The etiology and pathogenesis of "inflammation cancer transformation" in UC are consistent with the connotation of the "Kenang" theory. The internal condition for the development of UC "inflammation cancer transformation" is the deficiency of healthy Qi, with Qi stagnation being the key pathological mechanism. Phlegm and blood stasis are the main pathogenic factors. Phlegm and blood stasis accumulate in the body over time and can produce cancer toxins. Due to the depletion of healthy Qi and a weakened constitution, the body is unable to limit the proliferation and invasion of cancer toxins, eventually leading to cancer transformation in UC. In clinical treatment, the focus should be on removing phlegm and blood stasis, with syndrome differentiation and treatment based on three basic principles: supporting healthy Qi to strengthen the body's foundation, resolving phlegm and blood stasis to break up the Kenang, and regulating Qi and blood to smooth the flow of energy and resolve stagnation. This approach helps to dismantle the Kenang, delay, block, or even reverse the cancerization process of UC, reduce the risk of "inflammation cancer transformation", improve the patient's quality of life, and provide new perspectives and strategies for early intervention in the development of colon cancer.
Humans ; Colitis, Ulcerative/immunology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Cell Transformation, Neoplastic

Five flavonoid glycosides were isolated from the methanol and ethyl acetate fractions of the ethanol extract of Diphylleia sinensi by using various chromatographic methods, including silica gel, MCI gel, Sephadex LH-20, ODS and semi-preparative HPLC. The structures of the isolated compounds were identified as diphyflavonoid A (1), diphyflavonoid B (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4), kaempferol-3-O-(6″-O-acetyl)-β-D-glucopyranoside (5) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, and MS). Compounds 1 and 2 were two new flavonoid glycosides, and compounds 3 and 5 were isolated from the genus Diphylleia for the first time.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

OBJECTIVE: To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-β1 (TGF-β1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs). METHODS: The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-β1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016. RESULTS: LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-β1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-II (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of -8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1. CONCLUSION RSV inhibited LPS-induced GMCs proliferation and TGF-β1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.
Animals ; Rats ; Lipopolysaccharides/pharmacology* ; Mesangial Cells ; Resveratrol/pharmacology* ; Transcription Factor AP-1 ; Transforming Growth Factor beta1 ; Intercellular Signaling Peptides and Proteins ; Cell Proliferation ; DNA ; Cells, Cultured

Ischemic stroke is one of the leading causes of death and disability worldwide. In Han dynasty， HUA Tuo proposed the original preventive medicine idea that "with good blood circulation， the disease cannot be born"， which opened a broad space for the cross-research of blood-related mechanical factors and pharmacology. In the pathogenesis of ischemic stroke， mechanical factors comprehensively affect the function and crosstalk of platelets and endothelial cells. In recent years， as the well-known effects on thrombosis and stroke， more attention has been paid to hemodynamic factors as the participants involved in pathological mechanisms and potential therapeutic targets of ischemic stroke. The mechanical force ion channel Piezo1 widely exists on the surface of many types of cells. Besides being regulated by chemical and endogenous substances， Piezo1 responds to different mechanical conditions， regulates the opening and closing of channels， and activates different downstream signaling pathways. Piezo1 is now regarded as an important connection between mechanical and biochemical signals. A variety of Chinese medicine can affect the activity of Piezo1 protein， which may prevent and treat thrombotic diseases such as ischemic stroke through Piezo1 protein. In this paper， the effects of Piezo1 protein on the physiological and pathological functions of endothelial cells and platelet under different mechanical conditions and the role of Piezo1 in the process of thrombosis were reviewed， as well as the effects of Chinese medicine， chemical medicine， and endogenous substances targeting Piezo1 channel. These could provide new ideas for further exploring the mechanisms of Chinese medicines in activating blood circulation， developing new drugs， and deepening biomechanical-pharmacology research.

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.
Animals ; Disease Models, Animal ; Dopamine ; Melatonin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Retina ; Sensory Deprivation

Humans ; Immune Checkpoint Inhibitors ; Myocarditis ; Myositis/chemically induced* ; Antineoplastic Agents, Immunological

OBJECTIVE: To explore the risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants. METHODS: A retrospective analysis was performed for 455 very preterm infants who were admitted to the neonatal intensive care unit from January 2017 to December 2019. They were divided into an intubation group ( RESULTS: The intubation rate was 17.4% (79/455). Compared with the intubation group, the non-intubation group had significantly higher gestational age, birth weight, and rates of caesarean birth, delayed cord clamping (DCC), resuscitation quality improvement, regular use of antenatal glucocorticoids in mothers and premature rupture of membranes > 18 hours ( CONCLUSIONS Very preterm infants with younger gestational age, birth weight < 750 g, maternal diabetes mellitus, placenta previa or placenta previa status may have a higher risk for endotracheal intubation after birth. The regular use of antenatal glucocorticoids and DCC can reduce the risk of intubation during resuscitation in very preterm infants.
Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Intubation, Intratracheal ; Pregnancy ; Retrospective Studies ; Risk Factors

Objective:To investigate the effects and potential mechanisms of resveratrol on obesity in elderly mice.Methods:In this study, 3 groups were randomly formed for 32-week-old mice and for 48-week-old mice.The normal diet group received regular chow and 0.3 ml saline by gavage once a day, the high-fat diet group received a high-fat diet(containing 21% fat and 1.25% cholesterol)and 0.3 ml saline once a day, and the high-fat diet plus resveratrol group received a high-fat diet and resveratrol(22.4 mg/kg, dispersed in 0.3 ml saline)by gavage once a day.After 12 weeks, body weight and adipose tissues were measured.Plasma leptin concentrations were determined by an enzyme-linked immunosorbent assay(ELISA), and values for hypertrophic obesity-related indexes of mice were obtained by quantitative real-time PCR.Results:The body weight and the proportion of subcutaneous fat tissues were lower in the high-fat diet plus resveratrol group than in the high-fat diet group[(34.43±3.23)g vs.(53.16±2.16)g, (3.21±1.58)% vs.(4.86±0.64)%, P<0.01], and were similar to those in the normal diet group.Resveratrol had a more obvious inhibitory effect on leptin in elderly mice than in middle-aged mice.In elderly mice, the plasma leptin concentration was lower in the high-fat diet plus resveratrol group than in the high-fat diet group[(0.015±0.009)g/L vs.(0.100±0.027)g/L]and the normal diet group( F=19.85, P=0.001), and it was similar to that in the middle-aged mice on a normal diet.Resveratrol significantly increased the expression of peroxisome proliferator-activated receptor gamma(PPARγ)and glucose transporter 4(GLUT4)and reduced the expression of tumor necrosis factor-α(TNF-α)( F=10.79, 9.31 and 7.02, P=0.003, 0.006 and 0.010). Conclusions:Resveratrol can significantly improve hypertrophic obesity in elderly mice, and the inhibition of leptin secretion and up-regulation of PPARγ may be the key mechanisms.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome