OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

Objective:To investigate the effect of nourishing yin and tonifying yang method on inflammatory response and bone metabolism in patients with T2DM complicated with osteoporosis (OP).Methods:A randomized controlled trial. From January 2022 to December 2023,80 patients with T2DM and OP in our hospital were selected as the observation objects, and they were divided into two groups by random number table method, with 40 cases in each group.On the basis of conventional treatment, the control group chewed vitamin D calcium chewable tablets, and the observation group added nourishing yin and tonifying yang Chinese medicine.Both groups were treated for 6 months. TCM syndrome scores were performed before and after treatment ;the levels of fasting blood glucose (FPG), 2 hPG and HbA1c were detected by intelligent blood glucose monitor;the levels of serum neutrophils and lymphocytes were detected by automatic blood analyzer, and the neutrophil/lymphocyte ratio (NLR) was calculated;the levels of serum IL-1β and TNF-α were detected by automatic chemiluminescence analyzer, the levels of type I procollagen amino terminal propeptide (PINP), type I collagen carboxy terminal peptide β special sequence (β-CTX) and 25-hydroxy vitamin D3 [25-(OH)D3] were detected by ELISA;Bone mineral density (BMD) was detected by bone mineral density detector. The adverse reactions during treatment were observed and recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 92.5 %(37/40) in the observation group and 75.0 % (30/40) in the control group,the difference between the two groups was statistically significant ( χ2=4.50, P=0.034).After treatment, the scores of soreness and weakness of waist and knees, soreness and pain of waist and back, clear and long urine, pale tongue and white coating in the observation group were lower than those in the control group ( t=3.11, 3.75, 3.51, 3.74, P<0.01);the levels of serum FPG, 2 hPG and HbA1c in the observation group were lower than those in the control group ( t=3.11,3.20,3.39, P<0.01).The levels of serum NLR (2.63 ± 0.68 vs. 3.24 ± 0.79, t=3.70), IL-1β [(81.65 ± 8.30) ng/L vs. (89.03 ± 8.98) ng/L, t=3.82] and TNF-α [(35.14 ± 5.11) μg/L vs. (39.96 ± 5.38) μg/L, t=4.11] in the observation group were lower than those in the control group ( P<0.01). After treatment, the levels of PINP [(29.83 ± 3.92) ng/L vs. (34.02 ± 4.03) ng/L, t=4.71] and β-CTX [(21.30 ± 3.95 ) ng/L vs. (25.32 ± 4.18) ng/L, t=4.42] in the observation group were lower than those in the control group ( P<0.01), the levels of 25-(OH)D3 [(42.86 ± 5.12) μg/L vs. (38.08 ± 4.55) μg/L, t=4.41] and BMD [(0.90 ± 0.18) g/cm 3vs. (0.78 ± 0.16) g/cm 3, t=3.15] were higher than those in the control group ( P<0.01).During the treatment, the incidence of adverse reactions was 12.5% (5/40) in the observation group and 10.0 % (4/40) in the control group,there was no significant difference between the two groups ( χ2=0.13, P=0.723). Conclusion:The method of nourishing yin and tonifying yang can effectively improve the TCM syndromes of T2DM patients with OP, reduce the levels of blood glucose and inflammatory factors, improve bone metabolism, improve clinical efficacy and have good treatment safety.

Objective To investigate the expression of Toll-like receptor 2(TLR2)and Toll-like receptor 4(TLR4)in peripheral blood mononuclear cells(PBMC)in children with recurrent respiratory tract infection(RRTI)and its relationship with T helper cell 1(Th1)/T helper cell 2(Th2)immune response.Methods A total of 65 children diagnosed with RRTI who admitted to the hospital from December 2020 to December 2022 were enrolled in the study as the RRTI group,and 45 healthy children who underwent physical examination in the hospital during the same period were enrolled as the control group.The relative expression levels of TLR2 and TLR4 mRNA in PBMCs were detected by real-time fluorescence quantitative PCR(qPCR).The expres-sion rates of TLR2 and TLR4 protein in PBMCs were detected by flow cytometry.The levels of Th1 cytokine interferon-γ(IFN-γ),Th2 cytokine interleukin-4(IL-4)and their ratio(IFN-γ/IL-4)in plasma were detected by enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the corre-lation between TLR2,TLR4 protein expression rates and plasma IFN-γ,IL-4 levels.Results The RRTI group had significantly higher plasma level of Th2 cytokine IL-4 than the control group,significantly lower plasma level of Th1 cytokine IFN-y than the control group,and significantly lower ratio of IFN-γ/IL-4 than the con-trol group,the differences were all statistically significant(P＜0.05).The relative expression levels of TLR2 and TLR4 mRNA and protein expression rates in PBMC of children in the RRTI group were higher than those in the control group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that the protein expression rates of TLR2 and TLR4 in PBMC of children with RRTI were both nega-tively correlated with both plasma IFN-γ levels and IFN-γ/IL-4(P＜0.05)and positively correlated with plasma IL-4 levels(P＜0.05).Conclusion The expression of TLR2 and TLR4 in PBMC and plasma Th1/Th2 cytokines in children with RRTI may be involved in the occurrence and development of the disease.Ex-cessive activation of TLR2 and TLR4 may weaken Th1 function and enhance Th2 function.

Objective: To analyse the correlation between unhealthy lifestyles and anxiety symptoms among high school students in Inner Mongolia Region, so as to provide a scientific basis for the prevention of anxiety symptoms among high school students. Methods: From September to November 2023, 35 362 high school students were selected by stratified cluster random sampling method from 12 cities (103 counties) in Inner Mongolia Region, and the survey was conducted by using the questionnaire on student health status and influencing factors. The χ2 test and multivariate Logistic regression analyses were used to determine the influencing factors of anxiety symptoms. Results: The total number of students with anxiety symptoms was 2 747, and the detection rate of anxiety symptoms was 7.77%. The results of multivariate Logistic regression analyses showed that female students, father having higher education background, never eating breakfast, being overweight and obese, sleeping <8 h/d, being scolded by parents in the past 30 days, and depressive symptoms were positively correlated with the anxiety symptoms of the high school students (OR=1.31, 1.23, 1.53, 1.14, 1.22, 1.51,28.92); nonsmoking, having no alcohol consumption, no Internet addiction and no use of sedatives without doctors permission were all negatively correlated with anxiety symptoms of high school students (OR=0.84, 0.73, 0.57,0.40) (P<0.05). Conclusions Anxiety symptoms of high school students are closely related to unhealthy lifestyle. Measures should be taken to improve unhealthy lifestyle, so as to reduce the occurrence of anxiety symptoms in high school students.

Purpose/Significance To investigate the effectiveness of experiential teaching in perinatal healthcare management contin-uing education.Method/Process The perinatal healthcare team of Peking Union Medical College Hospital holds a four-day experiential learning program for 30 maternity-related medical staffs from China.Through the self-administered experiential teaching questionnaire(ETQ)and satisfaction questionnaire,the researchers analyze the participants'post-teaching skill acquisition,clinical application abil-ity and educational needs,as well as their satisfaction with course content,course duration,teaching design,classroom atmosphere,and teaching format,which are quantified with Likert scale.Result/Conclusion The experiential teaching mode shows good teaching effects in perinatal healthcare management continuing education,and has higher application value.In the future,the researchers should combine it with theoretical teaching and carry out more comprehensive and structured periodic learning classes throughout the country,so as to im-prove both the theoretical foundation and practical ability of healthcare workers for better healthcare services for pregnant women.

Objective To establish the evaluation index system of seaman health literacy.Methods Two rounds of questionnaire consultation was conducted by Delphi method among 17 experts,and the indexes were modified according to expert opinions,so as to establish seaman health literacy.Results The response rates of the 2 rounds of questionnaires were 94.4%and 100%,the expert authority coefficients were 0.821 and 0.844,and the Kendall's coefficient of concordance were 0.398 and 0.411,respectively.After the 2 rounds of consultation,the importance score of indexes at all levels was 4.00-4.94,and the coefficient of variation was 0.05-0.21.Finally,the evaluation system of seaman health literacy was constructed,including 4 first-level indicators,20 second-level indicators and 27 items.Conclusion The evaluation system of seaman health literacy constructed in this study is reliable,scientific and practical.It can provide a basis for the decision-making to regulate seaman health literacy.

Objective To investigate the current status and influencing factors of health literacy in seamen.Methods The random cluster sampling method was adopted to select 302 naval officers and soldiers,and a questionnaire survey was conducted to investigate their health literacy.Results The proportion of respondents with health literacy was 55.1%.The level of health literacy ranked from high to low as follows:basic health concept(72.1%),basic health behaviors(54.0%),basic health knowledge(41.3%),and basic health skills(33.4%).Multivariate logistic regression analysis showed that education background,the length of time to board,smoking and sleep late were influencing factors for health literacy in seamen(P<0.05).Conclusion The overall health literacy level is unbalanced in seamen,especially in health knowledge and health skills,which need to be strengthened.It is essential to carry out targeted health education,correct unhealthy lifestyles and constantly improve the level of health literacy of seamen.

Objective:To evaluate the distribution characteristics of choroidal vascularity index (CVI) in macula among normal children using swept-source optical coherence tomography (SS-OCT), and to investigate the influencing factors.Methods:A cross-sectional study was conducted.Sixty-three children aged 6 to 12 years were enrolled in The First Affiliated Hospital of Zhengzhou University from May 2021 to November 2021.Spherical equivalent refraction, axial length (AL) and other ocular biological parameters were measured.Macula-centered CVI and choroidal thickness (ChT) were measured by SS-OCT angiography.According to the ETDRS partition, the obtained image was divided into macular central fovea (0-1 mm diameter), inner ring (1-3 mm diameter) and outer ring (3-6 mm diameter) zones.Data from the right eye were selected for statistical analysis.CVI in the three rings and four zones (superior, temporal, inferior and nasal zones) of the inner and outer rings were compared.Univariate and multiple linear regression analyses were used to analyze the correlation between CVI and sex, AL, anterior chamber depth (ACD), ChT and pupil diameter.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2021-KY-0399-003). Written informed consent was obtained from each guardian.Results:The average CVI in the macular central fovea, inner ring and outer ring were 0.35±0.12, 0.32±0.10 and 0.27±0.08, respectively, with a significant difference ( F=10.96, P<0.001), and significant differences in CVI were found in pairwise comparisons of the three ring zones (all at P<0.05). Significant differences in CVI were found among superior, temporal, inferior and nasal zones in inner and outer rings ( Fring=11.60, P=0.001; Fzone=12.02, P<0.05). The CVI was smaller in superior and nasal zones in inner ring than in temporal zone, greater in superior, temporal and inferior zones in outer ring than in nasal zone, smaller in superior zone of outer ring than that of the inner ring, and the differences were statistically significant (all at P<0.001). The single factor linear regression analysis showed that ChT in the fovea, inner ring and outer ring were the influencing factors of CVI in the three ring zones (all at β=0.001, P<0.001). Pupil diameter ( β=0.034, P=0.038; β=0.040, P=0.003; β=0.024, P=0.011) and ACD ( β=0.097, P=0.034; β=0.097, P=0.013; β=0.061, P=0.032) were the influencing factors of CVI in fovea, inner ring and outer ring.After multiple linear regression analysis, the regression equations were established as follows: CVI in the macular fovea=0.001×ChT in the macular fovea + 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring-0.301 ( R2=0.514, F=6.875, P<0.001); CVI in the inner ring=0.001×ChT in the macular fovea+ 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring+ 0.088×AL-0.307 ( R2=0.603, F=9.870, P<0.001); CVI in the outer ring=0.001×ChT in the macular fovea+ 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring-0.135 ( R2=0.601, F=9.781, P<0.001). Conclusions:In children aged 6-12 years old, the CVI is higher in the macular central fovea than in inner and outer rings, and the CVI in nasal zone is the smallest in both inner and outer rings.The thicker the ChT, the higher the CVI in all zones in the macular area; the deeper the anterior chamber, the higher the CVI in the inner ring.

Objective:This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed.Results:Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) .Conclusions:Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

Objective:To investigate the influence of bacterial outer membrane vesicles (OMVs) tumor vaccine on tumor cell proliferation and CD8 + T cell infiltration of mouse with pancreatic cancer. Methods:The experimental study was conducted. The ovalbumin (OVA) lentivirus vector plasmid pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro was used to construct the mouse pancreatic cancer Pan02-OVA cells. The ClyA-Catchers-OMVs (CC-OMVs) originated from Escherichia coli and labeled antigenic peptide SpyTag-OVA were used to construct the OMVs tumor vaccine. Mouse CD8 + T cells were stimulated by OMVs tumor vaccine, and the effects of OMVs tumor vaccine on inhibiting pancreatic cancer cells proliferation and stimulating CD8 + T cell infiltration were analy-zed by in vitro cell killing assay, including the OMVs tumor vaccine stimulated T cell group and the control T cell group, subcutaneous pancreatic cancer model, including the OMVs tumor vaccine group and the control group, and immunohistochemical staining. Observation indicators: (1) identification of mouse pancreatic cancer Pan02-OVA cells; (2) morphological observation of CC-OMVs; (3) inhibi-tion of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells; (4) inhibi-tion of mouse pancreatic cancer by OMVs tumor vaccine; (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages. Results:(1) Identification of mouse pancreatic cancer Pan02-OVA cells. Results of laser scanning confocal microscopy showed that the mNeongreen fluorescence was expressed in Pan02-OVA cells infected with the OVA lentivirus vector plasmid of pLV-EF1a-hluc-P2A-mNeongreen-CMV-OVA-3Xflag-P2A-puro. Results of Flow cytometry showed that using the mouse pancreatic cancer Pan02 cells as references, the protein expression rate of Flag on the Pan02-OVA cells was 90.7%. (2) Morphological observation of CC-OMVs. Results of transmission electron microscopy analysis showed that the CC-OMVs were in spherical shape, with a diameter <50 nm. (3) Inhibition of mouse pancreatic cancer Pan02-OVA cells by OMVs tumor vaccine specific T cells. Results of cell proliferation toxicity test showed that the absorbance at 450 nm of mouse pancreatic cancer Pan02-OVA cells was 0.41±0.12 and 1.05±0.15 in the OMVs tumor vaccine-stimulated T cell group and the control T cell group, respectively, showing a significant difference between the two groups ( t=9.54, P<0.05). (4) Inhibition of mouse pancreatic cancer by OMVs tumor vaccine. The weight of subcutaneous tumor tissue in the back of mouse was (81±10)g and (153±17)g in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.26, P<0.05). (5) CD8 + T cell infiltration in pancreatic cancer tissue of mouse stimulated by OMVs tumor vaccine. Results of immuno-histochemical staining showed that the numbers of CD8 + T cells staining in the mouse back subcu-taneous tumor tissues was 28.7±3.5 and 9.3±1.5 in the OMVs tumor vaccine group and the control group, respectively, showing a significant difference between the two groups ( t=8.74, P<0.05). Conclusion:Bacterial OMVs tumor vaccine can inhibit proliferation of pancreatic cancer cells and increase the numbers of CD8 + T cells infiltrated in pancreatic cancer tissue of mouse.