ObjectiveTo investigate the disease burden of non-alcoholic fatty liver disease （NAFLD） among young people in East Asian countries （including China， North Korea， Japan， Mongolia， and South Korea） in 1990—2023， and to provide a basis for formulating and adjusting the prevention and treatment strategies for NAFLD. MethodsRelated disease burden data of NAFLD among the young people in these five East Asian countries were collected from the Global Burden of Disease 2023 （GBD 2023） database， including incidence rate， prevalence rate， and disability-adjusted life years （DALY）， and the young people were divided into groups based on country， sex， and age. Estimated annual percentage change （EAPC） was used to comprehensively evaluate the changing trend of the disease burden of NAFLD among young people from 1990 to 2023， and the Autoregressive Integrated Moving Average model was used to predict the disease burden of NAFLD among the young people in China. ResultsIn 2023， the standardized incidence rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 926.57/100 000， 805.83/100 000， 412.66/100 000， 747.66/100 000， and 534.08/100 000， respectively； the standardized prevalence rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 16 817.94/100 000， 14 500.98/100 000， 8 534.40/100 000， 13 705.28/100 000， and 11 587.93/100 000， respectively； the standardized DALY rates of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea were 6.34/100 000， 10.18/100 000， 5.23/100 000， 47.93/100 000， and 6.76/100 000， respectively. From 1990 to 2023， there was a tendency of increase in the standardized incidence rate of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea， with an EAPC of 0.87%， 0.52%， 0.26%， 0.48%， and 0.87%， respectively； there was also a tendency of increase in the standardized prevalence rate of NAFLD among the young people in China， North Korea， Japan， Mongolia， and South Korea， with an EAPC of 0.99%， 0.49%， 0.24%， 0.59%， and 0.93%， respectively； conversely， there was a tendency of reduction in the standardized DALY rate of NAFLD among the young people in China， Japan， Mongolia， and South Korea， with an EAPC of -2.21%， -2.01%， -0.37%， and -4.62%， respectively， while the standardized DALY rate of NAFLD among the young people in North Korea remained relatively stable， with an EAPC of -0.01%. The subgroup analysis based on sex showed that there was a significant difference in the disease burden of NAFLD between the young people with different sexes in the five East Asian countries， and the subgroup analysis based on age showed that the incidence rate of NAFLD in young people decreased with the increase in age， while the prevalence rate and DALY rate of NAFLD increased with age. In addition， the standardized incidence rate and standardized prevalence rate of NAFLD among Chinese young people would further increase in the future， while there would be a reduction in standardized DALY rate in the future. ConclusionThere is a significant difference in the disease burden of NAFLD in young people across different countries， sexes， and age groups. In the future， targeted prevention and treatment measures should be developed based on the distribution characteristics of the disease burden of NAFLD， in order to effectively reduce the disease burden of NAFLD among young people.

Anxiety and fear,as common symptoms of psychiatric disorders,remain inadequately understood in terms of their pathogenesis.Changes in immune inflammation are considered to play a significant role in both the pathological and physiological processes associated with these mental illnesses.In recent years,it has been demonstrated that stress can regulate immune inflammation through multiple pathways,including the regulation of the autonomic nervous system,the hypothalamic-pituitary-adrenal axis,indoleamine 2,3-dioxygenase and its metabolite kynurenine,and the gut-brain axis.These pathways are implicated in the onset and treatment of anxiety and fear-related mental illnesses.This article focuses on the relationships between anxiety and fear-related mental illnesses and immune inflammatory responses.

Objective:To investigate the effects of circular RNA circ_0086376 on the expression of acne-related inflammatory factors by targeting microRNA (miR) -5195-3p.Methods:Circ_0086376-overexpressing or -interferred stable HaCaT cell lines were constructed and co-cultured with Propionibacterium acnes ( P.acne). Quantitative real-time PCR was used to detect the effect of co-culture on circ_0086376 expression, while enzyme-linked immunosorbent assay (ELISA) was performed to measure the expression of inflammatory factors in the cell culture supernatant. The overexpression or interference of circ_0086376 plasmid and lentivirus mimicking or inhibiting miR-5195-3p fragment were transfected into HaCaT cells, and ELISA was used to detect the expression of inflammatory factors in the culture supernatant of HaCaT cells after overexpression or interference of circ_0086376 cultured alone or with P.acne. The luciferase reporter assay was conducted to verify the targeting relationship between circ_0086376 and miR-5195-3p. Additionally, ELISA was used to detect the effects of overexpression/interference of circ_0086376 and mimic/inhibition of miR-5195-3p on the expression of inflammatory factors in the culture supernatant of HaCaT cells co-cultured with P.acne. Results:After co-culture with P.acne, the levels of inflammatory factors in the culture supernatant were significantly higher than those in the HaCaT cells cultured alone, including Interleukins (IL) -1β ([355.80 ± 23.20] vs. [260.50 ± 16.58] pg/ml, t = 5.79, P < 0.01), IL-6 ([38.04 ± 2.69] vs. [14.33 ± 0.75] pg/ml, t = 14.65, P < 0.01), IL-12 ([10.87 ± 0.78] vs. [6.52 ± 0.77] pg/ml, t = 6.89, P < 0.01), IL-18 ([222.60 ± 21.07] vs. [146.10 ± 9.14] pg/ml, t = 5.77, P < 0.01), and Tumor necrosis factor (TNF) -α ([50.39 ± 1.29] vs. [20.46 ± 0.83] pg/ml, t = 33.83, P < 0.01). The expression levels of IL-1β, IL-6, IL-12, IL-18 and TNF-α in the culture supernatant of HaCaT cells in the circ-empty vector + P.acne group were higher than those in the circ-empty vector overexpression group. The levels of inflammatory factors mentioned above in circ-overexpression + P.acne group were lower than those in circ-overexpression empty vector + P.acne group ( P < 0.01). The expression levels of inflammatory factors mentioned above in the culture supernatant of HaCaT cells in the interference circ-empty vector + P.acne group were higher than those in the interference circ-empty vector group. Compared with the interference circ-empty vector + P.acne group, the expression of circ in the interference circ + P.acne group was higher ( P < 0.01). Luciferase reporter assay confirmed that circ_0086376 could bind to miR-5195-3p. The expression levels of IL-1β, IL-6, IL-12, IL-18 and TNF-α in the circ-overexpression group were lower than those in the empty vector group ( P < 0.05), and the levels of these inflammatory factors in the circ-overexpression + miR mimic group were higher than those in the circ overexpression group ( P < 0.05). The expression levels of inflammatory factors in the interference circ group were higher than those in the empty vector group, levels of inflammatory factors in the circ + miR-inhibiting group were lower than those in the circ interference group ( P < 0.05) . Conclusion:Circ_0086376 can inhibit the expression of acne-related inflammatory factors by targeting and downregulating miR-5195-3p.

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

AIM: To investigate the impacts of periocular injection of triamcinolone acetonide on healing effect and inflammatory factor in patients with acute iridocyclitis.METHODS:Totally 90 patients(90 eyes)with acute iridocyclitis, admitted to our hospital between September 2018 and September 2023, were grouped via random number table, including a triamcinolone acetonide group and a control group, each comprising 45 patients(45 eyes). The control group underwent conventional treatment, whereas the triamcinolone acetonide group adopted triamcinolone acetonide through periocular injection. The healing effect, levels of inflammatory cytokines, anterior chamber inflammatory cell scores, keratic precipitates(KP)scores, best-corrected visual acuity(BCVA), untoward reactions, and relapse rates of the two groups of patients were compared.RESULTS:The triamcinolone acetonide group had significantly higher overall efficacy rate than the control group(P<0.05). The levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interferon-γ(IFN-γ)decreased in both groups at 30 d after treatment, and the levels in the triamcinolone acetonide group were lower(all P<0.05). After treatment for 30 d, the scores of anterior chamber inflammatory cells and KP in both groups decreased, and the scores in the triamcinolone acetonide group were lower than those in the control group(all P<0.05); the BCVA of both groups improved, and the triamcinolone acetonide group had a better BCVA(all P<0.05). There was no statistically significant difference in untoward reactions between the two groups(P=1.000). The relapse rate of the triamcinolone acetonide group was lower than that of the control group(P=0.030).CONCLUSION: Periocular injection of triamcinolone acetonide has obvious healing effects on patients with acute iridocyclitis, and it can alleviate the inflammatory state of patients and reduce the relapse rate of inflammation.

Purpose To explore the diagnostic efficacy of texture analysis in grading multiple ligament injuries of the knee Joint.Materials and Methods MRI images of 203 patients with knee injuries in the Second Affiliated Hospital of Shantou University School of Medicine from June 2018 to September 2020 were retrospectively collected,and then graded the injuries of multiple ligaments.Extraction of texture features and discriminant analysis were accomplished by MaZda software.Spearman correlation analysis and LASSO penalized Logistic regression analysis were used to further explore the differential diagnostic efficacy of each texture parameter for grading knee ligament injuries.Results(1)MaZda software was found to have the highest diagnostic efficacy for patellar ligament injury grading by using different texture feature screening methods in combination with discriminant analysis.Non-linear discriminant analysis had the lowest misclassification rate of 4.43%.(2)The texture parameters that were ultimately included in the analysis of the subjects'work characteristic curves appeared more frequently in the gray level co-occurrence matrix and the run length matrix.(3)The area under the curve of the texture parameters finally included in the analysis were 0.870-0.975,0.772-0.912,0.836-0.929 and 0.766-0.920,respectively in patellar ligament,anterior cruciate ligament,posterior cruciate ligament and lateral collateral ligament for the diagnosis of knee ligament injury grading.The diagnostic efficacy for patellar ligament injury grading was the highest,which was consistent with the lowest misclassification rate for patellar ligament in the discriminant analysis of texture features.And the texture parameters ultimately included in patellar ligament were all highly correlated with its injury grading.Conclusion The texture analysis technique has high diagnostic efficacy for grading knee ligament injuries,and can provide a more accurate diagnostic imaging basis for the clinic.

BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Objective To explore the correlation between helicobacter pylori(Hp)infection and inflam-matory factors,as well as its association with the progression of liver fibrosis in patients with metabolically associ-ated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM).Methods A total of 300 patients diag-nosed with MAFLD and T2DM who were admitted to the Hepatology Department of Hebei Hospital of Traditional Chinese Medicine between April 2023 and March 2024 were recruited.Based on Hp infection status,these patients were classified into an Hp-positive group and an Hp-negative group.Subsequently,the clinical data,inflammatory factors,and liver fibrosis indices of the two groups were comprehensively compared.Furthermore,the patients in the Hp-positive group were randomly assigned to an intervention group and a control group.The intervention group received standard Hp eradication therapy,whereas the control group was administered placebo therapy.Pearson correlation analysis was employed to investigate the associations among Hp infection,inflammatory factors,and liver fibrosis indices.Binary logistic regression analysis was utilized to identify the independent risk factors influencing the progression of liver fibrosis.Results In both the Hp-positive and Hp-negative groups,parameters including age,fasting blood glucose(FPG),glycosylated hemoglobin(HbA1c),total bilirubin(TBIL),direct bilirubin(DBIL),indirect bilirubin(IBIL),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),along with C-reactive protein(CRP)and liver stiffness measurement(LSM),were meticulously measured.Statistical analysis revealed that the differences in these parameters between the two groups were significant(P<0.05).Specifically,within the experimental setup,the levels of TNF-α,IL-6,CRP,and LSM in the intervention group were notably lower than those in the control group(P<0.05).Pearson correlation analysis was employed to explore the relation-ships among variables,and the results indicated a positive correlation between the Hp detection value(DPM)and the levels of TNF-α,IL-6,CRP,and LSM(P<0.05).Furthermore,binary logistic regression analysis was con-ducted to identify independent risk factors.The findings demonstrated that positive Hp infection,elevated TNF-α,elevated IL-6,and elevated CRP were independent risk factors for the progression of liver fibrosis(P<0.05).To evaluate the diagnostic performance,the receiver operating characteristic(ROC)curve analysis was carried out.The areas under the curve(AUC)for HP infection,TNF-α,IL-6,and CRP were 0.800,0.786,0.769,and 0.783,respectively.These values were significantly lower than the AUC of 0.896 obtained from the combined detection(P<0.05).Conclusions In MAFLD patients with T2DM,DPM is closely associated with inflammatory factors(such as TNF-α,IL-6,and CRP)and the advancement of liver fibrosis.The combined detection of these factors holds significant value in predicting the progression of liver fibrosis.It can offer a reliable foundation for the clinical assessment of the risk of liver fibrosis progression.

Objective To observe the effects of Yinqin Qingfei Granules on oxidative injury in lung tissue of mice with mycoplasma pneumoniae infection;To explore the mechanism of the Keap1/Nrf2/HO-1 signaling pathway in it.Methods Totally 100 BALB/c mice were randomly divided into blank group,model group,Yinqin Qingfei group,Azithromycin group and combination group,with 20 mice in each group.Except for the blank group,the other groups of mice were used to establish mycoplasma pneumoniae pneumonia model through bacterial solution nasal drip,and the blank group was given the same amount of normal saline nasal drip for 3 days.After modeling,the drug groups were given corresponding drugs by gavage,the blank group and the model group were given the same amount of distilled water by gavage,and the materials were taken at 3 and 7 days after administration,respectively.HE staining was used to observe the morphology of lung tissue,ELISA was used to detect the contents of interleukin(IL)-1β and tumor necrosis factor(TNF)-α in serum,biochemical method was used to detect the contents of nitric oxide(NO),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in lung tissue,Western blot was used to detect the expressions of Kelch like ECH associated protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)protein in lung tissue.Results Compared with the blank group,the lungs of mice in the model group showed severe inflammatory changes on day 3 and 7,with alveolar fusion or disappearance,and lung consolidation,which were more severe on day 7;the contents of IL-1β and TNF-α in serum significantly increased(P<0.05),the contents of SOD and GSH in lung tissues significantly decreased(P<0.05),and the contents of MDA and NO significantly increased(P<0.05),the protein expression of Keap1 in lung tissues increased(P<0.05),and Nrf2 and HO-1 protein expressions decreased(P<0.05).Compared with the model group,the histopathological changes in lung tissue showed different degrees of improvement on day 3 and 7 of drug treatment in Yinqin Qingfei group,Azithromycin group and combination group groups,the serum contents of IL-1β and TNF-α were significantly decreased(P<0.05),the contents of SOD and GSH in lung tissue were significantly increased on day 7 of drug treatment(P<0.05),the contents of MDA and NO significantly decreased(P<0.05),the protein expression of Keap1 in lung tissue decreased on day 3 and 7 of drug treatment(P<0.05),and the protein expressions of Nrf2 and HO-1 increased(P<0.05).Conclusion Yinqin Qingfei Granules can regulate the level of inflammatory factors,reduce lung inflammation and oxidative damage of mice with mycoplasma pneumoniae infection.The mechanism may be related to down-regulating the expression of Keap1,up-regulating the expressions of Nrf2 and HO-1,reducing the contents of NO and MDA,improving the activities of SOD and GSH,and playing an antioxidant role.