Objective To investigated the effects of occupational exposure to N,N-dimethylformamide (DMF) on sterol regulatory element-binding protein (SREBP) and iron metabolism among workers. Methods A total of 20 workers occupationally exposed to DMF were selected as the exposure group, and 15 healthy workers without DMF exposure from the same factory were selected as the control group using the purposive sampling method. DMF exposure levels were assessed in individual samples of the workers. The urinary N-methylformamide (NMF) levels were measured by gas chromatography. The mRNA expression of SREBP-1a, SREBP-1c, and SREBP-2 in peripheral blood was measured by real-time quantitative polymerase chain reaction. Enzyme-linked immunosorbent assay was used to detect serum transferrin, soluble transferrin receptor (sTfR), and ferritin levels. Results The DMF exposure levels among the workers in the control group were below the detection limit, and urinary NMF was undetectable. The median DMF exposure level was 13.30 mg/m³, and the mean urinary NMF level was (9.72±1.78) mg/g Cr among the workers in the exposure group. Compared with the control group, the relative mRNA expression of SREBP-1a, SREBP-1c, and SREBP-2 in peripheral blood of workers in the exposure group increased (all P<0.05), while the levels of transferrin and sTfR decreased (both P<0.01). However, there was no statistically significant difference in serum ferritin levels between the two groups (P>0.05). In the exposure group, urinary NMF level of workers was negatively correlated with the relative mRNA expression level of SREBP-1c in blood [correlation coefficient (r)=-0.50, P=0.03], and positively correlated with the levels of serum transferrin, sTfR, and ferritin (r = 0.63, 0.58, and 0.52, respectively; all P<0.05). Conclusion Occupational exposure to DMF can upregulate the expression of the SREBP family and disrupt iron metabolism, with a potential association between these effects.

The plants of the genus Caragana Fabr. are desert plants of the Leguminosae family, which are widely used in traditional ethnomedicine, with the effects of nourishing Yin and nourishing blood, dispelling wind and removing dampness, clearing heat and detoxifying toxins. The anti-inflammatory effect of Caragana Fabr. has attracted much attention, the research on the related mechanism has made some progress, but it lacks systematic collation. By summarising the anti-inflammatory effects of the active ingredients of Caragana Fabr., the authors found that they have good anti-inflammatory activities on different inflammatory cell models in vitro, and have good improvement effects on rheumatoid arthritis, colitis, complex nephritis, and acute lung injury and other disease models. The anti-inflammatory effects of the active components of this genus mainly include the reduction of the levels of a variety of pro-inflammatory factors, and the signalling pathways involved mainly include TLR4/NF-κB, TLR4/MAPK, TLR4/NF-κB/IRF3, JAK/STAT-1, ERK/STAT-1 and so on. Therefore, the paper mainly reviews the research progress on the anti-inflammatory effects and mechanisms of the Caragana Fabr. plants and their active components according to disease types, with a view to providing reference for the in-depth study of their anti-inflammatory activities and the development of new products with related functions.

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective To investigate the longitudinal relationship between sleep duration(SD)and positive youth development(PYD)among primary and secondary school students in Chengdu city using a cross-lagged model,and to provide scientific evidence for enhancing sleep management practices for students.Methods A total of 4061 students of grades 3 through 9 from the Chengdu Child Positive Development Cohort were included in this three-wave longitudinal study.There was a one-year interval between one survey and the following round of survey,and the time points for the baseline,12-month follow-up,and 24-month follow-up surveys were designated T0,T1,and T2.The PYD of the participants was assessed using the Chinese version of the Positive Youth Development Scale.The demographic data and the average daily SD over the past month were collected.Spearman correlation analysis was performed to examine the associations between SD and PYD,and a cross-lagged model was used to investigate the longitudinal relationship between them.Results The average daily SD for the 3 rounds of surveys conducted at T0,T1,and T2 was 9.00(8.04,10.00)hours,10.44(9.67,11.11)hours,and 10.39(9.83,11.00)hours,respectively,while the PYD scores were 5.30(4.73,5.71),5.27(4.73,5.73),and 5.39(4.89,5.77),respectively.Statistical significance was found in the differences of SD and PYD scores across the 3 rounds(P＜0.05).Spearman correlation analysis revealed synchronous correlations between SD and PYD at all three time points(r=0.10 at T0,r=0.18 at T1,and r=0.21 at T2,P＜0.05)and significant lagged correlations(e.g.,r=0.10 for T1-PYD and T2-SD,and likewise,significant correlation was found for the 3 other cross-lagged paths).The cross-lagged model demonstrated that PYD at T0 and T1 positively predicted SD at T1 and T2,respectively(β0-1=0.116[95％CI,0.083-0.150],β1-2=0.097(95％CI,0.067-0.127),P＜0.05),and that SD at T0 and T1 also positively predicted PYD at T1 and T2(β0-1=0.028[95％CI,0-0.056],β1-2=0.042[95％CI,0.010-0.074],P＜0.05).According to these findings,a bidirectional predictive relationship between SD and PYD across different time points was observed in primary and secondary school students.Furthermore,PYD demonstrated better performance for predicting SD than SD did for PYD.Subgroup analysis by sex confirmed the robustness of the predictive power of PYD for SD.Conclusion This study reveals a positive bidirectional predictive relationship between SD and PYD among primary and secondary school students,suggesting that higher levels of PYD may contribute to adequate sleep.These findings provide critical scientific evidence for schools and families to strengthen sleep management and promote the holistic development and well-being of adolescents.

Objective To explore the value of shear wave elastography(SWE)combined with cervical length(CL)measurement in predicting spontaneous preterm birth(SPB)at 20 to 27 weeks of gestation.Methods A total of 161 pregnant women with antenatal care and examination in the hospi-tal from January 2020 to June 2022 were selected as research objects.All pregnant women underwent CL measurement and SWE detection by ultrasound during 20 to 27 weeks of gestation to obtain CL and SWE parameters.The occurrence of SPB was followed up,and the correlations of CL and SWE param-eters with the occurrence of SPB were analyzed.Results Among the 161 pregnant women,34 pa-tients experienced SPB.There were significant differences in the external os strain(EOS),elastic contrast index(ECI),internal os strain(IOS),and hardness ratio(HR)of SWE parameters between pregnant women with and without preterm birth(P＜0.05).Similarly,there was a significant differ-ence in CL between the two groups(P＜0.05).Spearman correlation analysis showed that ECI,IOS and EOS were positively correlated with the occurrence of preterm birth(P＜0.05),while HR and CL were negatively correlated with the occurrence of preterm birth(P＜0.05).The receiver operating characteristic(ROC)curve showed that the area under the curve(AUC)for CL in predicting preterm birth was 0.800,with a cut-off value of 2.710 cm.Among the SWE parameters,the AUCs for ECI,HR,IOS and EOS in predicting preterm birth were 0.651,0.642,0.705 and 0.653 respectively,with cut-off values of 5.140,53.650％,0.320 and 0.330 respectively.The ROC curve showed that the AUC for predicting preterm birth by SWE parameters combined with CL was 0.813,which was significantly higher than the AUC for prediction by the combination of the four SWE parameters(P＜0.05).The sensitivity and specificity at the maximum Youden index were 0.794 and 0.732 respectively.Conclusion CL,as well as ECI,HR,IOS and EOS among SWE parameters,have certain value in predicting SPB in pregnant women at 20 to 27 weeks of gestation,especially when the five indicators are combined for prediction.The critical values for prediction are 2.710 cm,5.140,53.650％,0.320 and 0.330 respectively.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female