Objective:To examine the effect of cumulative hemoglobin A 1c (HbA 1c) levels and insulin dosage on insulin resistance (IR)-related metabolic disturbances in newly diagnosed patients with type 1 diabetes (T1D). Methods:This retrospective cohort study included T1D patients admitted to the Second Xiangya Hospital of Central South University from November 2015 to March 2023. Clinical data collected comprised age, sex, disease duration, insulin dosage, body mass index, waist circumference, blood pressure, HbA 1c levels, islet autoantibodies, and fasting blood lipid profiles. IR-related metabolic disturbances assessed were overweight, obesity, central obesity, hypertension, and dyslipidemia. Cox regression and cluster analyses were applied to assess the influence of cumulative HbA 1c and insulin dosage on these metabolic disturbances. Results:A total of 235 patients were included, with 97 males (41.3%) and 138 females (58.7%). The median age was 19.8 (13.3, 31.1) years, and the median follow-up duration was 30.8 (20.8, 45.6) months. During follow-up, 41.6% (72/173) of patients developed IR-related metabolic disturbances. Multivariate Cox regression analysis revealed that a cumulative HbA 1c ≥60 mmol/mol was an independent risk factor for any IR-related metabolic disturbance [ HR (95% CI): 1.739 (1.067-2.835) ] and for triglyceride abnormalities [ HR (95% CI): 3.277 (1.176-9.127)]. Additionally, a cumulative insulin dosage ≥0.5 U·kg -1·d -1 was identified as an independent risk factor for overweight, obesity, or central obesity [ HR (95% CI): 2.374 (1.059-5.323)]. Cluster analysis further identified that patients with higher levels of cumulative HbA 1c and insulin dosage, particularly those with adolescent-onset diabetes, had the highest likelihood of developing hypertension ( HR=2.460, 95% CI 1.008-6.005), overweight/obesity/central obesity ( HR=2.707, 95% CI 1.062-6.900), triglyceride abnormalities ( HR=5.495, 95% CI 1.842-16.391), high-density lipoprotein cholesterol abnormalities ( HR=11.054, 95% CI 4.107-29.751), and any IR-related metabolic disturbance ( HR=5.833, 95% CI 2.602-13.077). Conclusions:Elevated cumulative HbA 1c and insulin dosage levels in T1D patients are associated with an increased risk of developing IR-related metabolic disturbances. These findings underscore the urgent need for novel therapeutic strategies tailored to this population.

Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.
Bufanolides/pharmacology* ; Nanoparticles/chemistry* ; Humans ; Drug Carriers/chemistry* ; Ursodeoxycholic Acid/chemistry* ; Antineoplastic Agents/pharmacology* ; Polysaccharides/chemistry* ; Scrophularia/chemistry* ; Liver Neoplasms/physiopathology* ; Hep G2 Cells

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. METHODS: Four patients diagnosed with PMS at Guangzhou Women and Children's Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Hospital (Ethics No. 2025-007). RESULTS: All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 Kb to 112.64 Kb, primarily involving the SHANK3 gene. CONCLUSION PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.
Child ; Humans ; Chromosome Deletion ; Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 22/genetics* ; Exome Sequencing ; Nerve Tissue Proteins/genetics* ; Phenotype

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Aim To investigate the effect and mechanism of angiotensin Ⅱ(Ang Ⅱ)on ferroptosis in white adi-pocytes.Methods The 3T3-L1 preadipocytes were differentiated into white adipocytes by inducer stimulation.The experiment was divided into control group,Ang Ⅱ group,Ang Ⅱ+Fer-1(ferroptosis inhibitor)group and Ang Ⅱ+PFT-α(p53 inhibitor)group.Ang Ⅱ was used to treat cells.RT-qPCR and Western blot were used to detect the expression levels of ferroptosis factors and adipokines.JC-1 kit was used to detect mitochondrial membrane potential(MMP)level.Iron ion kit was used to detect intracellular iron content.Glutathione(GSH)kit was used to detect GSH content.Fer-1 and Ang Ⅱ were added to treat cells to detect the the changes of ferroptosis level.The expression of p53 and spermidine/spermine N1-acetyltransferase 1(SAT1)protein was detected.Subsequently,PFT-α and Ang Ⅱ were added to co-treat cells to detect the changes of p53 and SAT1 protein expression,and to observe the effect of inhibiting p53 expression on the expression levels of ferroptosis factors and adipokines.Results 3T3-L1 cells were successfully differentiated into white adipocytes by stimulator-induced differentiation.Ang Ⅱ induced ferroptosis in white adipocytes.RT-qPCR results showed that compared with control group,the mRNA expression of anti-ferroptosis factor glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11)and iron regulatory protein 1(IRP-1)was down-regulated in Ang Ⅱ group,and the mRNA expression of pro-ferroptosis factor acyl-CoA synthetase of long-chain family member 4(ACSL4)was up-regulated.Western blot results showed that compared with control group,the protein expression of SLC7A11 and GPX4 was down-regulated in Ang Ⅱ group,and the protein expression of ACSL4 was up-regulated.Ang Ⅱ treatment increased the content of intracellular iron ions and decreased the levels of GSH and MMP.Compared with Ang Ⅱ group,the mRNA expression of IRP-1 and SLC7A11 was up-regulated in Ang Ⅱ+Fer-1 group.Ang Ⅱ induced changes in the expression profile of adipokines in white adipocytes.Western blot results showed that compared with control group,the protein ex-pression of pro-inflammatory adipokine leptin(LEP),resistin(RETN),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)was up-regulated in Ang Ⅱ group,and the protein expression of anti-inflammatory adipokine adiponectin(AD-PN)and omentin 1(ITLN1)was down-regulated.In addition,Ang Ⅱ increased the protein expression of p53 and SAT1.Inhibition of p53 expression can improve the level of ferroptosis and adipokine expression in white adipocytes trea-ted with Ang Ⅱ.Western blot results showed that compared with Ang Ⅱ group,the protein expression of p53 and SAT1 was down-regulated in Ang Ⅱ+PFT-α group,the protein expression of SLC7A11 and GPX4 was up-regulated,and the protein expression of ACSL4 was down-regulated.The protein expression of ADPN was up-regulated in Ang Ⅱ+PFT-αgroup,and the protein expression of TNF-α,LEP and RETN was down-regulated.Conclusion Ang Ⅱ induces fer-roptosis in white adipocytes through activating the p53/SAT1 signaling pathway.

Objective:To explore the application effect of family participatory multisensory support programme based on the theory of enriched environment on preterm infants and their mothers in neonatal intensive care unit (NICU).Methods:A historical comparative study was conducted. One hundred and sixteen pairs of preterm infants and their mothers admitted to NICU, Affiliated Hospital of Youjiang Medical University for Nationalities from March to October 2023 were selected by convenience sampling method and divided into control group and experimental group according to the time of admission. The control group was given routine care, while the experimental group implemented a family participatory multisensory support programme based on the enriched environment theory on the basis of the control group. The amplitude-integrated electroencephalography (aEEG) scores and the Chinese version of Parent-Child Interaction Feeding Scale (PCI-FS-C) scores before and after intervention, the Gesell developmental quotients at 40 weeks and 3 months of gestational age, the Chinese version of Maternal Attachment Inventory (CMAI) scores of preterm mothers on the day of discharge and 1 and 3 months after discharge were compared between the two groups.Results:A total of 105 pairs of premature infants and their mothers were included, 52 premature infants of control group, 29 males and 23 females; 53 premature infants of experimental group, including 32 males and 21 females. Before intervention, there were no significant differences in aEEG scores and PCI-FS-C scores between the two groups (all P>0.05). After intervention, the scores of aEEG and PCI-FS-C in the experimental group were (10.91 ± 2.18) and (12.62 ± 1.32) points, respectively, which were higher than (9.67 ± 1.94) and (10.42 ± 1.45) points in the control group, and the differences were statistically significant ( t=3.06, 8.15, both P<0.05). The Gesell developmental quotient were (54.03 ± 9.73), (55.17 ± 11.19), (57.20 ± 11.04), (53.60 ± 9.74), (55.17 ± 10.11) at 40 weeks of gestational age, and (77.15 ± 11.55), (76.62 ± 9.90), (72.76 ± 11.90), (81.47 ± 10.01), (76.51 ± 12.25) at 3 months of gestational age, respectively, which were higher than the control group (49.70 ± 9.07), (49.06 ± 8.61), (52.41 ± 9.01), (49.28 ± 8.78), (50.07 ± 12.52), and (71.10 ± 11.87), (69.02 ± 12.53), (65.77 ± 12.24), (75.08 ± 11.08), (68.63 ± 10.89), the differences were statistically significant ( t values were 2.30-3.49, all P<0.05). The CMAI scores of preterm mothers in the experimental group were (82.81 ± 12.85), (87.70 ± 10.29), (95.91 ± 8.76) points on the day of discharge and 1 and 3 months after discharge, respectively, which were higher than (68.71 ± 14.15), (82.04 ± 11.87), (90.98 ± 11.13) points of the control group, the differences were statistically significant ( t=5.35, 2.61, 2.52, all P<0.05). Conclusions:The family participatory multisensory support programme based on the theory of enriched environment can accelerate the maturation of brain electrical activity in preterm infants and promote brain function and neurobehavioural development; meanwhile, it improves maternal sensitivity and promotes the establishment of mother-infant attachment relationship in preterm infants.

Objective To investigate the effects of synovial fluid from patients with rheumatoid arthritis(RA)on the polarization of normal neutrophils and the MEK/ERK signaling pathway,thereby providing experimental evidence to elucidate the pathological mechanisms of RA and offering novel insights into its treatment.Methods Synovial fluid samples were collected from 20 RA patients and 20 osteoarthritis(OA)patients.ELISA was used to measure the levels of interferon-gamma(IFN-γ),tumor necrosis factor-alpha(TNF-α),transforming growth factor-beta(TGF-β)and interleukin-8(IL-8)in the synovial fluid.Neutrophils were isolated from the peripheral blood of healthy donors,and their purity was confirmed by flow cytometry.Neutrophils were then treated with synovial fluid and divided into four groups:Control(untreated),RA(treated with 10％RA synovial fluid),OA(treated with 10％OA synovial fluid),and anti-IFN-β(treated with 20 μg anti-IFN-β antibody as an N2-type control).Western blot was used to assess the changes in the expression of IFN-γ,TNF-α,TGF-β,MEK,p-MEK,ERK and p-ERK.Additionally,the MEK inhibitor PD0325901 was used to block the MEK/ERK pathway,and subsequent changes in IFN-γ and TGF-β expression in neutrophils were evaluated.Results The levels of IFN-γ,TNF-α,TGF-β and IL-8 in the synovial fluid of RA patients were significantly higher than those in OA patients.After intervention with RA synovial fluid,the relative expression of IFN-γ and TNF-α in neutrophils were significantly increased compared to those in the untreated control group and the OA group.While,TGF-β expression in the RA group was lower than that in both the control and anti-IFN-β groups.The relative expression of p-MEK and p-ERK in the RA group were significantly higher than those in the control,OA and Anti-IFN-β groups.Upon addition of the MEK inhibitor,the relative expression of p-MEK and p-ERK were reduced.Furthermore,in both the RA and OA groups,the relative expression levels of IFN-γ decreased,while the expression of TGF-β increased.Conclusion Synovial fluid from RA patients contains higher of IFN-γ,TNF-αand TGF-β,which activate neutrophils through phosphorylation of the MEK/ERK signaling pathway,promoting their polarization toward the pro-inflammatory N1 phenotype.

Aim To explore the underlying molecular mechanism of Alisol A 24-acetate(24A)in improving oxygen-glucose deprivation/reoxygenation(OGD/R)injury in brain microvascular endothelial cells(BMECs)and its correlation with miR-98-5p/transi-ent receptor potential melastatin-2(TRPM2).Meth-ods The ischemia-reperfusion injury in brain micro-vascular endothelial cells(BMECs)was established u-sing bEnd.3 cells subjected to 8 h of oxygen-glucose deprivation followed by 16 h of re-oxygenation.The cells were intervened by miR-98-5p mimics and/or 18.77 μmol·L-1 24A for 24 h and divided into the control group,OGD/R group,OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group and OGD/R+miR-98-5p mimics group.The mRNA levels of miR-98-5p and TRPM2 were detected by qPCR.IL-1 β and TNF-α levels were detected by ELISA.The expression levels of TRPM2,p-AKT,p-GSK3 β,AKT,GSK3 β,Bcl-2,Bax,ZO-1,Occludin,Claudin-5 were detected by Western blot.Apoptosis and reactive oxygen species(ROS)levels were detected by flow cytometry.The targeting relationship between miR-98-5p and TRPM2 was verified using dual luciferase assay.Results Compared with the control group,the apoptosis of OGD/R group was obvious,Bcl-2/Bax decreased,ZO-1,Occludin,Claudin-5 decreased,IL-1 β,TNF-α and ROS increased,miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β decreased but TRPM2 increased.But com-pared with the OGD/R group,except the control group,the other three groups showed the opposite trend in the above aspects;compared with the OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group showed decreased apoptosis,decreased degradation of ZO-1,Occludin and Claudin-5,and decreased inflam-mation and ROS.miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β increased and TRPM2 decreased.However,compared with the OGD/R+24A+miR-98-5p mimics group,the OGD/R+miR-98-5p mimics group reversed this trend.Dual luciferase confirmed that miR-98-5p targeted regulation of TRPM2.Conclusion 24A in-hibits the expression of TRPM2 in BMECs through miR-98-5p,regulates AKT/GSK3β signal pathway,re-duces OGD/R inflammation and oxidative stress-medi-ated apoptosis,prevents the degradation of ZO-1,Oc-cludin and Claudin-5,and improves BBB permeability.