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.

Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

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

[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 investigate the role of G protein signal regulator 2(RGS2)in regulating the formation of angiotensin Ⅱ(Ang Ⅱ)-induced aortic dissection.Methods C57BL/6 mice were divided into 3 groups:control group(n=10),Ang Ⅱ group(n=20),Ang Ⅱ+sh-RGS2 group(n=20).The Ang Ⅱ group and Ang Ⅱ+sh-RGS2 group established an aortic dissection model.The incidence of aortic dissection was evaluated in vivo,and the phenotypic transformation of VSMC was evaluated in vitro and in vivo.Results Knockdown of RGS2 largely coun-teracted Ang Ⅱ-induced inhibition of αSMA,ACTA2 and MYH11,and suppressed Ang Ⅱ-induced SPP1 and Vim-entin in VSMC.The incidence of aortic dissection in Ang Ⅱ group and Ang Ⅱ+sh-RGS2 group were 45％(9/20)and 10％(2/20),respectively.Fewer elastic lamina thickening,aortic rupture,and aortic wall collagen fiber con-tent were observed in Ang Ⅱ+sh-RGS2 group compared to Ang Ⅱ group.In addition,compared with the Ang Ⅱgroup,the maximum diameter of the aorta in the Ang Ⅱ+sh-RGS2 group was significantly reduced(P＜0.05).In addition,the ACTA2 and MYH11 proteins in the aorta of the Ang Ⅱ+sh-RGS2 group were significantly higher than those in the Ang Ⅱ group(P＜0.01),while the RGS2,SPP1,and Vimentin proteins significantly decreased(P＜0.01).Conclusion Knockdown of RGS2 inhibits the transformation of Ang Ⅱ-induced VSMC from a contractile phenotype to a synthetic phenotype,thereby reducing the incidence of aortic dissection formation.

Objective:To explore the values of single and combined detection of mammography,ultrasound Doppler and serum markers of tumor included serum prostate specific antigen(PSA),serum carbohydrate antigen 15-3(CA153),mucin 1(MUC1)and human growth differentiation factor 3(GDF3)in diagnosing early breast cancer.Methods:A total of 96 patients with breast cancer,who admitted to Tangshan People's Hospital from January 2018 to December 2021 and were confirmed by pathological examination,were selected as breast cancer group.At the same time,70 patients with benign breast diseases who received diagnosis and treatment in our hospital were selected as benign lesions group.In addition,50 normal people who were confirmed as health by physical examination in our hospital were selected as research subjects of healthy control group.The postoperative pathological examination was used as the gold standard to compare the diagnostic values of single mammography,ultrasonic Doppler examination,serum PSA,CA153,MUC1,GDF3 and the combined examination of them for breast cancer.Results:In the breast cancer group,78 cases of the 96 patients with breast cancer were diagnosed as malignant tumor by ultrasound on breast,with a positive detection rate of 81.3%,and 80 cases of them were diagnosed as malignant tumor by mammography X-ray examination,with a positive detection rate of 83.1%.The levels of serum PSA,CA153,MUC1 and GDF3 of breast cancer group were respectively higher than those of the benign lesion group and healthy control group,and the differences were statistically significant(t=8.783,10.361,11.258,18.965,9.564,12.658,12.688,20.163,P<0.05).Using breast cancer as the dependent variable,and using serum PSA,CA153,MUC1 and GDF3 as independent variable to perform Logistic regression analysis.The results of Logistic regression analysis indicated that serum PSA,CA153,MUC1 and GDF3 were important risk factors of breast cancer(OR value =1.165,1.168,1.472,1.248,P<0.05).The results of receiver operating characteristic(ROC)curve(95%CI),sensitivity and specificity of single application of each indicator of ultrasound on breast,mammography,serum PSA,CA153,MUC1 and GDF3 were respectively[0.723(0.595-0.851),82.56%and 67.32%],[0.761(0.636-0.886),85.79%and 65.36%],[0.833(0.726-0.941),81.48%and 85.73%],[0.837(0.738-0.926),61.25%and 70.17%],[0.768(0.648-0.889),71.49%and 80.87%],[0.613(0.469-0.758),52.94%and 50.57%].However,the AUC(95%CI),sensitivity and specificity of the combined application of 6 items were respectively 0.958(0.905-0.999),96.37%and 84.83%,which had higher diagnostic efficiency.Conclusion:The combined detection performance of mammography,ultrasound Doppler and serum PSA,CA153,MUC1 and GDF3 is higher than that of single each detection,which is helpful to conduct early identification and diagnosis for breast cancer.

Objective To provide references,this study investigated the clinical characteristics of patients with non-syndromic oligodontia.Methods The information of 178 patients with oligodontia was collected,including histories,oral examinations,and panoramic radiographs.Tooth agenesis characteristics were calculated and evaluated.All the data were statistically analyzed with SPSS 24.0 software.Results No significant difference in the number of missing teeth was found between sexes nor between the right and left sides,and congenitally missing teeth affected the maxillary arch(P<0.05).The highest prevalence of tooth agenesis was observed in the mandibular second premolars.In the maxillary arch,the most common pattern of tooth agenesis was agenesis of the bilateral first and second premolars.The agenesis of the bilateral second premolars was observed in the mandibular arch.The prevalence of a symmetric pattern between the right and left quadrants was significantly higher than that of matched patterns between the maxillary and mandibular an-tagonistic quadrants.Approximately 16.85%of patients with nonsyndromic oligodontia were affected by other tooth-re-lated anomalies.Conclusion The common patterns of tooth agenesis were successfully identified in patients with non-syndromic oligodontia.Dentists need to provide multidisciplinary treatments for patients with nonsyndromic oligodontia because of variations in occluding and full-mouth tooth agenesis patterns.

Objective:To investigate the carriage status of Neisseria meningitidis ( Nm) among the healthy population in Hebei Province for the prevention and control of meningitis. Methods:From 2015 to 2022, throat swabs were collected from health people, which were selected by cluster random sampling in 11 cities of Hebei.The positive rate of Nm was detected by bacterial culture. The serogroups of isolated strains were identified.The laboratory detection results of Nm strains, combined with epidemiological survey data, were synthetically analyzed. Results:A total of 20 245 people were investigated; 249 strains of Nm were isolated; the overall Nm carriage rate was 1.23%. The carriage rate was significantly higher in men than in women(χ 2=28.831, P<0.05). The positive rates of Nm in different age groups were significantly different(χ 2=428.018, P<0.05), with the highest rates in the 15-19 year-old group(4.90%, 149/3 042). The positive rates of Nm were significantly different in different regions(χ 2=177.512, P<0.05), with the highest positive rate of Nm in Xingtai, Shijiazhuang, Chengde and Baoding city in sequence. Among the isolated Nm strains, ungroupable serogroups, serogroup B, serogroup C, and serogroup W accounted for 71.49%(178/249), 13.65%(34/249), 6.83%(17/249) and 4.42%(11/249), respectively. Conclusions:The carriage rate of Nm among healthy population is generally low in Hebei Province. It is recommended to continue to strengthen monitoring, pay attention to the changes and distribution characteristics of Nm, and formulate scientific and targeted prevention and control measures of meningococcal disease.

Objective:To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD).Methods:Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ2 test according to different data. Results:Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations ( n=65), patients with homozygous p.Arg778Leu mutations ( n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time ( P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group ( P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids ( ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion:Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.