OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective:To investigate the expression of N6-methyladenosine(m6A)reader heterogeneous nuclear ribonucleoprotein A2/B1(hnRNPA2B1)in human gastric cancer(GC)tissue and its effect on the proliferation and invasion of MKN-28 cells.Methods:The Cancer Genome Atlas and Gene Expression Omnibus were used to analyze the expression of hnRNPA2B1 and long noncoding RNA(ln-cRNA)mir-100-let-7a-2-mir-125b-1 cluster host gene(MIR100HG)in GC tissue and their association with the clinical prognosis of patients with GC.Quantitative PCR and Western blotting were used to measure the effect of hnRNPA2B1 on the expression level of MIR100HG and its downstream Wnt/β-catenin signaling pathway;Methylated RNA immunoprecipitation(MeRIP)was used to mea-sure the m6A level of MIR100HG;CCK-8 assay and Transwell assay were used to observe cell proliferation and invasion.Results:Com-pared with paracancerous tissue,human GC tissue showed significant increases in the expression levels of hnRNPA2B1(t=6.101,P<0.001)and MIR100HG(t=2.191,P=0.036 7),and the high expression levels of hnRNPA2B1 and MIR100HG were associated with poor survival in patients with GC.Knockdown of hnRNPA2B1 reduced the mRNA expression level(t=5.156,P=0.007)and m6A level of MIR100HG(t=4.789,P=0.010),inhibited the proliferation and invasion of MKN-28 cells(t=4.915,P=0.008 and t=5.167,P=0.007),and blocked the activity of the Wnt/β-catenin signaling pathway(P<0.05).Overexpression of MIR100HG promoted cell pro-liferation and invasion(t=3.578,P=0.023 and t=8.411,P=0.001),activated the Wnt/β-catenin signaling pathway(P<0.01),and re-versed the antitumor effect induced by hnRNPA2B1 knockdown(t=3.667,P=0.021).Conclusion:This study shows that hnRNPA2B1-mediated m6A modification of MIR100HG promotes the proliferation and invasion of GC MKN-28 cells by activating the Wnt/β-catenin signaling pathway.

Objective To explore the mechanism of electroacupuncture in improving lipid metabolism in polycystic ovary syndrome(PCOS)based on metabolomics combined with transcriptomics.Methods Eight-een SD rats were divided into the control group,the PCOS group and the electroacupuncture group,with 6 rats in each group.The PCOS group and the electroacupuncture group used intragastric letrozole to establish the PCOS model.After the model was established,the electroacupuncture group was intervened with electroacu-puncture,while the control group was only given sodium carboxymethyl cellulose by gavage.Observed the changes in body weight and estrous cycle of the three groups,detected the sex hormones,blood lipids,liver function,ovarian morphology,plasma metabolism and liver function indicators of the three groups.Metabolo-mics was used to analyze the differences in metabolites in plasma,the differences in gene expression in the liv-er were detected by RT-qPCR.Results Weight gain and estrous cycle disorder occurred in the PCOS group,and the ovarian morphology showed a thinning of the granulosa cell layer,with a significant reduction in the number of corpus luteum and mature follicles.Meanwhile,sex hormones were abnormal(total testosterone and androgen levels were increased,estradiol and progesterone levels were decreased),dyslipidemia occurred(TC,TG,LDL-C were increased,HDL-C level was decreased),and liver function was abnormal(AST,total protein,ALB,TBIL were increased).The electroacupuncture group significantly reduced weight.It improved the estrous cycle,and the granulosa cell layer of the ovary thickened,with a significant increasing in the num-ber of corpus luteum and mature follicles.Meanwhile,sex hormone levels were improved(androgen and total testosterone levels were decreased,estradiol level was increased),lipid balance(TC,TG,LDL-C levels were reduced,HDL-C level was increased)and liver function(AST,total protein,ALB,and TBIL levels were de-creased)was restored.Transcriptomics suggested that electroacupuncture down-regulated the expression of cytochrome P450(CYPs)family genes related to steroid hormones and lipid metabolism,and the results were confirmed by RT-qPCR.Combined omics analysis revealed that electroacupuncture might mainly exert its effect on improving lipid metabolism disorders in PCOS rats through the linoleic acid metabolic pathway.Con-clusion Electroacupuncture can regulate lipid metabolism in rats with PCOS.

Objective To analyze the efficacy of different nucleoside(acid)analogs(NAs)used as monotherapy and in combination with pegylated interferon α-2b(Peg-IFN-α-2b)in the treatment of chronic hepatitis B(CHB).Methods A retrospective analysis was conducted on 229 CHB patients who visited the Hepatology Department of the Third People's Hospital of Kunming from September 2022 to August 2023.Patients were divided into six groups based on their antiviral regimen:entecavir(ETV)group(A,n=47),ETV combined with Peg-IFN-α-2b group(B,n=19),Tenofovir Alafenamide(TMF)group(C,n=64),TMF combined with Peg-IFN-α-2b group(D,n=35),Tenofovir Disoproxil Fumarate(TDF)group(E,n=29),and TDF combined with Peg-IFN-α-2b group(F,n=35).The blood routine,liver function,kidney function,HBV serological markers,and HBV-DNA levels were compared before and after 24 weeks of treatment.Results After 24 weeks of treatment,there were no statistically significant differences in efficacy rates and HBV-DNA positivity rates between the monotherapy with NAs and the combination with Peg-IFN-α-2b(P>0.05).Comparing before and after treatment,the ETV group had the highest effective rate,while TDF combined with Peg-IFN-α-2b group had the lowest effective rate.TDF group had the highest efficiency,while ETV combined with Peg-IFN-α-2b group had the lowest efficiency.Except for ETV+Peg-IFN-α-2b and TDF+Peg-IFN-α-2b groups,the HBV-DNA positivity rates in the other four groups were significantly lower after treatment compared to before(P<0.05).There was a significant difference in HBsAg levels among the different treatment regimens of monotherapy with NAs and combination with Peg-IFN-α-2b(P=0.0483).Additionally,except for the ETV and TDF groups,the serum HBsAg levels in the other four groups were significantly lower after treatment compared to before(P<0.05).There were no significant difference in LSM and GFR before and after treatment(P>0.05).In the monotherapy groups,ALT and GGT levels were significantly lower after treatment compared to before(P<0.05),while in the combination Peg-IFN-α-2b group,WBC,NEUT,and PLT levels were significantly lower after treatment compared to before(P<0.05).Conclusion Combination therapy with Peg-IFN-α-2b can reduce HBsAg levels and may be more effective in controlling the virus;however,it may cause adverse reactions such as bone marrow suppression,increasing risks.Physicians and patients need to weigh the benefits against the risks and develop personalized treatment plans based on individual circumstances.

Objective To establish and validate the diagnostic model of ferroptosis genes for acute myocardial infarction (AMI) based on bioinformatics. Methods Five AMI gene expression data were obtained from Gene Expression Omnibus (GEO), namely GSE66360, GSE48060, GSE60993, GSE83500, GSE34198. Among them, GSE66360 was used as the training set to perform differential analysis, and intersection of differential genes and ferroptosis genes was taken to obtain differentially expressed ferroptosis genes in AMI. GO and KEGG enrichment analyses were performed using Metascape website. Subsequently, random forest (RF) algorithm was used to screen out key genes with high classification performance according to the Keeny coefficient score, and artificial neural network (ANN) diagnostic model of AMI ferroptosis feature gene was constructed by model group GSE83500. The area under the receiver operating characteristic curve (AUC) of 10-fold cross-validation was used to evaluate the performance and generalization ability of the model, and 3 external independent datasets were used to verify the diagnostic performance of this model. The single sample gene set enrichment analysis was used to explore the difference in immune cell infiltration between infarcted myocardium and normal myocardium after AMI. In addition, correlation analysis between immune cells and key genes was also conducted. Finally, potential drugs that would prevent and treat AMI by regulating ferroptosis were screened out from the Coremin Medical platform. Results A total of 16 differentially expressed ferroptosis genes were obtained in the training set, GO enrichment analysis showed that they mainly participated in biological functions such as cellular response to biological stimuli and chemical stress, and regulation of interleukin 17. KEGG enrichment analysis showed that these genes were significantly enriched in NOD-like receptor signaling pathway, programmed cell necrosis, Leishmaniasis and other pathways. Four genes with good classification performance were screened out using RF algorithm, namely EPAS1, SLC7A5, FTH1, and ZFP36. The results of 10-fold cross-validation showed that the minimum AUC value was 0.746, the maximum value was 0.906, and the average value was 0.805. The AUC of the ANN model was 0.859, and the AUC values of the three independent validation sets were 0.763 (GSE48060), 0.673 (GSE60993), 0.698 (GSE34198). Immune cell infiltration found that macrophages, mast cells and monocytes were significantly active after AMI. Correlation analysis found that there were positive correlations between 4 key genes and activated dendritic cells, eosinophils and γδT cells. A total of 20 potential western medicines were predicted which could prevent and treat AMI by regulating ferroptosis, and the predicted potential Chinese medicine was mainly heat-clearing and detoxifying and blood-activating and removing blood stasis drugs. Conclusion The identified AMI ferroptosis genes by bioinformatics method have certain diagnostic significance, which provides a reference for disease diagnosis and treatment.

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

[摘 要] 目的：研究芳香烃受体（AHR）在乳腺癌中的表达及其对乳腺癌细胞增殖、凋亡和药物敏感性的调控机制。方法：通过GEPIA数据库数据分析乳腺癌组织及癌旁组织中AHR的表达水平，探讨其与患者生存期的关联。利用基因敲低和过表达技术构建AHR表达变化的乳腺癌细胞，采用CCK-8实验、细胞计数和流式细胞分析等方法评估AHR对细胞增殖、凋亡和药物敏感性的影响，通过免疫印迹法验证相关分子机制。此外，利用AHR激动剂6-甲酰基吲哚并[3,2-B]咔唑（FICZ）研究外源性激活AHR对乳腺癌细胞多柔比星（DOX）敏感性的影响。结果：GEPIA数据库数据分析结果显示，乳腺癌组织中AHR呈明显低表达（P < 0.05）；对155例乳腺癌患者的生存期进行统计分析也显示AHR低表达与不良预后呈正相关（P < 0.05）。敲低AHR促进细胞增殖（P < 0.05），过表达则能抑制其增殖（P < 0.05）并促进其凋亡（P < 0.05）。外源激活AHR能增强乳腺癌细胞对DOX的敏感性（P < 0.05）。AHR可与MYC基因启动子结合，抑制MYC表达（P < 0.05），从而影响乳腺癌的进展。结论：AHR在乳腺癌中通过调控MYC表达影响细胞增殖和凋亡，外源激活AHR可能成为提高乳腺癌细胞对DOX敏感性的治疗策略。

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Jiangsu Provincial People's Hospital takes the reform of DRG payment method as an opportunity,based on the theory of incentive behavior,uses literature research,expert consultation,and key performance indicator methods to develop evaluation indicators,and applies PDCA management tools to establish a continuously improving medical insurance service quality evaluation system.It introduces the process of medical insurance service quality evaluation system construction and its application in medical insurance performance management,and analyzes the implementation effect:DRG operation is improving,disease group structure is optimized,medical quality and efficiency continue to improve,and medical service evaluation scores are improving.