This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Objective:To evaluate the utility of pulse oximetry-derived parameters—specifically, the pulse oximetry plethysmographic waveform area under the curve (POP AUC) and the peripheral perfusion index (PPI)—in assessing disease severity and predicting prognosis in patients with sepsis. Methods:In this prospective descriptive study, 68 patients with sepsis were categorized based on illness severity into septic shock and non-shock groups, and by 28-day outcome into survival and non-survival groups. POP AUC, PPI, and lactate (Lac) levels were recorded at 0, 24, 48, 72, and 96 hours after admission. APACHEⅡ and SOFA scores were calculated within the first 24 hours. The prognostic value of these parameters was evaluated. Results:Significant differences were observed between the septic shock and non-shock groups in POP AUC, PPI, Lac (all P < 0.05 except at 96 h), APACHEⅡ, and SOFA scores (all P < 0.05). These differences were most pronounced at admission: POP AUC0 (2475.1 ± 899.0) vs. (4260.3 ± 1028.5), PPI 0 (0.78 ± 0.74) vs. (3.13 ± 2.18), Lac 0 (4.95 ± 4.32) vs. (2.07 ± 1.55), APACHE Ⅱ (16.78 ± 5.59) vs. 11.82 ± 4.89), and SOFA (8.89 ± 3.25) vs. (5.06 ± 2.60). Optimal prognostic cut-off values were 2741.43 for POP AUC, 0.97 for PPI, 2.05 for Lac, 12.5 for APACHEⅡ, and 5.5 for SOFA. ROC curve analysis showed that at 24 hours, POP AUC and PPI had significantly larger AUC values than Lac ( P < 0.05), while no significant differences were found among other parameters. Significant differences between non-survivors and survivors were also found in POP AUC, PPI (at 0, 24, and 48 h), APACHE II, and SOFA (all P < 0.05). No significant differences were observed in PPI (72 h and 96 h) or Lac between the two outcome groups. Conclusions:POP AUC and PPI, as derived from pulse oximetry, are non-inferior to Lac, SOFA, and APACHEⅡ scores in evaluating disease severity and predicting 28-day mortality in sepsis patients. These parameters show promise as practical and non-invasive tools for clinical assessment in sepsis.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

In this study, we investigated the anti-inflammatory effect and mechanism of tilianin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The cell viability was detected by cell counting kit-8 (CCK-8) assay. The content of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immuno sorbent assay (ELISA) kits. The content of nitric oxide (NO) was assayed by Griess reagent method. The level of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. The protein levels of Toll like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88), nuclear factors κB p65 (NF-κB p65), phosphorylated nuclear factor κB p65 (p-NF-κB p65), nuclear factor κB inhibitory protein α (IκBα) and phosphorylation nuclear factor κB inhibitory protein α (p-IκBα) were detected by Western blot. The mRNA and protein levels of NLRP3, pro-IL-1β, pro-IL-18 and pro-caspase-1 were detected by qRT-PCR and Western blot. Immunofluorescence staining was used to detect the nuclear translocation of NF-κB p65. The effect of tilianin on the TLR4/Myd88/NF-κB signaling pathway was further validated by using the TLR4 signaling inhibitor restatorvid (TAK242). The results showed that tilianin significantly reduced the levels of TNF-α, IL-6 and NO in the supernatant of RAW264.7 cells and decreased the content of intracellular ROS. Tilianin reduced the levels of TLR4, Myd88, p-NF-κB p65 and p-IκBα protein and nuclear translocation of NF-κB p65. Tilianin could reduce the protein levels of NLRP3, pro-IL-1β, pro-IL-18 and pro-caspase-1. Tilianin significantly inhibited the mRNA levels of NLRP3 and pro-IL-1β. The above research results indicated that tilianin could significantly alleviate the LPS-induced inflammatory response in RAW264.7 cells and its mechanism might be related to downregulate the TLR4/Myd88/NF-κB signaling pathway to inhibit NLRP3 inflammasome.

Although indigenous malaria has been eliminated in Wuhan since 2013,imported malaria remains a potential threat as an infectious source of local malaria transmission.The epidemiological and clinical characteristics of imported malaria are particularly important in areas where local malaria has been eliminated.This study was aimed at analyzing the epidemiological and clinical characteristics of imported malaria in Wuhan from 2012 to 2019,to provide a basis for further improving the preven-tion and control of imported malaria.Patients in Wuhan diagnosed with imported malaria from January 1,2012,to December 31,2019,were included in this study.A case-control study was con-ducted to analyze the features of patients with severe malaria.Uni-variate and multivariate logistic regression was used to identify risk factors for prolonged hospital length of stay(LOS).Among 229 imported malaria cases,212(92.6％)were in Chinese citizens,and most cases were in men(96.5％).The gender ratio is 28:1,and the age of cases is mainly concertrated between 18 and 50 years old(89.1％).More than 80％of patients were mi-grant workers,and most cases were infections from African countries(92.6％).Plasmodium falciparum(80.8％)was the dominant species.Fifty-three severe malaria cases were identified during the study period.Compared with uncomplicated cases,severe cases tended to occur in patients with no history of malaria(P=0.008),patients infected with Plasmodium falciparum(P=0.009),and patients who were initially misdiagnosed(P＜0.001).The median LOS was 6 days,and the species of infec-tion(Plasmodium falciparum),the use of antimalarial drugs(group B),antipyretic time(longer than 3 days),and the turn-around time of blood smear microscopy(longer than 3 days)were significantly associated with longer LOS(all P＜0.05).Al-though malaria has been eradicated in Wuhan for many years,imported cases continue to pose a threat.Efforts should be made to strengthen malaria knowledge education for outbound personnel.Additionally,medical institutions must enhance diagnosis and treatment capabilities for malaria,and adhere to standardized treatment processes,and the development of drug resistance and occurrence of severe malaria must be prevented.

Tamoxifen(TAM)has been widely used for the treatment of ER+breast cancer.However,the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer.The tumor suppressor gene N-myc downstream-regulated gene 2(NDRG2)plays a significant role in the de-velopment of ER+breast cancer.However,it is unclear whether NDRG2 participates in mediating TAM resistance in ER+breast cancer.Here,we investigate the expression of NDRG2 mRNA and protein in TAM-sensitive and TAM-resistant ER+breast cancer cells.The results of immunoblotting experiments re-vealed a negative correlation between NDRG2 expression and TAM resistance ability in ER+breast cancer cells(P＜0.001).CCK-8 cell viability assays and soft agar colony formation assays showed that NDRG2 overexpression in TAM resistant cells significantly reduced the TAM IC50 value and the soft agar colony formation rate(P＜0.001).For the mechanism,the ERAD reporter protein assays showed that NDRG2 overexpression upregulated the expression of the ERAD reporter protein CD3ε-YFP and increased the lev-els of spliced XBP1s mRNA,leading to severe endoplasmic reticulum stress in TAM resistant cells(P＜0.001).Immunoblot analysis confirmed that overexpression of NDRG2 significantly increased the level of phosphorylation of the endoplasmic reticulum stress sensor IRE 1α and the expression levels of its down-stream protein factors,including ERdj4,P58IPK,EDEM and PDIA5(P＜0.001).The in vivo xenograft tumor experiments in mice further verified that NDRG2 overexpression significantly inhibited the growth of resistant tumors,which enhanced the therapeutic effect of TAM(P＜0.001).These findings indicate that increasing NDRG2 expression and triggering severe endoplasmic reticulum stress upon TAM treatment can reverse the resistance of ER+breast cancer cells to TAM and inhibits the growth of ER+breast canc-er tumors.Our results provide valuable new insights and potential targets for improving the clinical man-agement of TAM-resistance and prognosis in ER+breast cancer.

Objective:To evaluate the effect of workshop-based incontinence associated dermatitis (IAD) training course for geriatric nurse specialists, and to provide references and evidence for the application of workshop teaching model in specialized nursing training.Methods:The convenience sampling method was used to select 40 participants in the 9th Chongqing Geriatric Nurse Specialist Training Program in May 2021 as the intervention group, and IAD training was conducted using the workshop method. The 42 participants in the 8th Chongqing Geriatric Nurse Specialist Training Program in May 2020 were selected as the control group, who received IAD training through traditional teaching methods. After the training, the achievement of teaching objectives and teaching satisfaction were compared between the two groups using questionnaire survey, and IAD nursing knowledge and attitudes were compared using scales. SPSS 27.0 was used for the t-test and chi-square test. Results:The questionnaire survey showed that the intervention group achieved higher teaching objectives in all dimensions compared to the control group ( P<0.05). Compared with the control group, the intervention group had higher scores in teaching satisfaction regarding teaching format, interest in learning, practical skills, theoretical understanding, integration of theory and practice, and problem-solving abilities ( P<0.05). Compared with the control group, the intervention group demonstrated significantly higher scores in IAD nursing knowledge [(11.32±1.56) vs. (9.02±2.26), P<0.05] and attitudes [(37.63±3.54) vs. (32.81±2.97), P<0.05]. Conclusions:The workshop training has been highly recognized by the trainees, contributing to improved implementation effectiveness of teaching, enhancing the scores of IAD nursing knowledge and attitudes. This approach offers a new perspective for training with a practical focus in the specialized nursing field.

Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.