[摘 要] 目的：探究连翘苷（PHN）调节高迁移率族蛋白B1（HMGB1）/晚期糖基化终产物受体（RAGE）信号通路对胶质瘤U251细胞增殖、侵袭及上皮间质转化（EMT）的影响。方法：将人胶质瘤U251细胞分为PHN-0组（0 µmol/L PHN处理）、PHN低、中和高剂量组（PHN-50、PHN-100、PHN-200组，分别用50、100和200 µmol/L PHN处理）、PHN + pcDNA-NC组（转染pcDNA-NC质粒后200 µmol/L PHN处理）和PHN + HMGB1组（转染过表达HMGB1质粒后200 µmol/L PHN处理）。CCK-8法和克隆形成实验检测各组细胞的增殖能力，流式细胞术检测各组细胞的凋亡水平，Transwell实验检测各组细胞的迁移和侵袭能力，ELISA检测各组细胞分泌IL-8水平，免疫荧光法检测各组细胞中神经钙黏素（N-cadherin）和上皮钙黏素（E-cadherin）阳性率，WB法检测各组细胞中Toll样受体4（TLR4）、核因子-κB（NF-κB）、HMGB1、RAGE、N-cadherin、E-cadherin、细胞周期蛋白D1（cyclin D1）、细胞周期蛋白依赖性激酶2（CDK2）、B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（BAX）蛋白的表达水平。结果：与PHN-0组相比，PHN-50、PHN-100、PHN-200组U251细胞增殖活力、克隆形成数、迁移和侵袭数、IL-8分泌水平、N-cadherin阳性率及其蛋白表达、TLR4、NF-κB、HMGB1、RAGE、cyclin D1、CDK2蛋白表达均显著降低（均P < 0.05），细胞凋亡率、E-cadherin阳性率及其蛋白表达、BAX/Bcl-2比值均显著升高（均P < 0.05）；同时过表达HMGB1则可逆转PHN对U251细胞增殖、迁移、侵袭及EMT的抑制作用和对凋亡的促进作用（均P < 0.05）。结论：PHN通过HMGB1/RAGE信号通路抑制胶质瘤U251细胞增殖、侵袭及EMT进程。

Objective To report two cases of dyskeratosis congenita(DC)and provide a comprehensive literature review to improve the understanding of the disease.Methods Clinical characteristics of two DC cases were retrospectively collected and analyzed in Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.Gene mutations were assessed by high-throughput sequencing analysis and telomere length was assessed by Terminal Restriction Fragment(TRF)analysis.A literature search was carried out using the National Knowledge Infrastructure(CNKI),Wanfang database,PubMed,and Web of Science,updated to June 2024,with"Dyskeratosis congenita"and"telomere biology disorders"as the keywords.Results Case 1 was a boy admitted with"nail dystrophy of fingers and toes for more than 8 years and pancytopenia for 1 week".Physical examination revealed fingernails and toenails dysplasia,reticular skin pigmentation over the neck,and restricted mouth opening.Genetic testing identified a mutation in the DKC1 gene and shorter telomeres.Case 2 was a girl admitted with"confirmed aplastic anemia over 3 years".Physical examination showed no specific abnormalities.A blood routine test showed pancytopenia,with missense mutations found in the RTEL1 and TERT genes.Case 1 received blood transfusion support,while Case 2 was treated with subcutaneous injections of PEGylated recombinant human granulocytes,cyclosporine,and eltrombopag olamine,but the outcomes were not satisfactory.Both cases developed bone marrow failure,prompting hematopoietic stem cell transplantation.However,both cases were lost to follow-up after discharge.Conclusions Dyskeratosis congenita is a rare disease with various clinical manifestations.It may present with skin manifestations or hematological abnormalities.A precise diagnosis is made through a genetic testing.Currently,efficacious medical treatment for DC is lacking,and hematopoietic stem cell transplantation is necessary for patients with bone marrow failure.

Objective:To investigate the application value of nectin-4 targeting radiotracer 68Ga-N188 in the diagnosis of pancreatic cancer. Methods:The prospective study was conducted. The clinicopathologic data of 16 patients diagnosed as pancreatic cancer on enhanced computed tomography (CT) who were admitted to the Peking University First Hospital from August to December 2022 were collected. There were 9 males and 7 females, aged (62±8)years. All patients underwent 18F-flurodeoxyglucose ( 18F-FDG) and 68Ga-N188 positron emission tomography (PET)/CT examination. Observation indicators: (1) distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients; (2) expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer; (3) comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages. Results:(1) Distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients. Results of PET/CT examination showed that in 1 hour after injection, the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) of 68Ga-N188 in fat, muscle, skin, and brain tissues of 16 patients were 0.40±0.16 and 0.25±0.09, 0.68±0.20 and 0.44±0.12, 0.39±0.14 and 0.28±0.11, 0.09±0.04 and 0.05±0.02, respectively. In the tissues of the esophagus, liver, spleen, and pancreas, the above indicators were 1.53±0.48 and 1.16±0.31, 1.49±0.45 and 0.91±0.30, 1.40±0.30 and 1.02±0.24, 1.24±0.31 and 0.96±0.25, respectively. In tumor primary lesion, the above indicators were 3.28±1.02 and 2.14±0.62, respectively, showing significant differences in SUVmax and SUVmean compared with pancreatic tissue ( t=8.03, 6.75, P<0.05). The tumor background ratio in tumor primary lesion based on SUVmax was 1.82±0.58. (2) Expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer. Results of immunohistochemical staining in 16 patients showed that there were 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression. Results of PET/CT examination showed that the SUVmax of 68Ga-N188 in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 3.77±1.10 and 2.64±0.68, showing a significant difference between them ( t=2.64, P<0.05). The SUVmax of 18F-FDG in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 6.73±3.24 and 6.43±3.45, showing no significant difference between them ( t=0.17, P>0.05). (3) Comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Of the 16 patients, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 14 and 11, respectively, for the 14 pancreatic cancer patients diagnosed by postoperative histopathology. Among them, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 3 and 1 for the 3 pancreatic cancer patients receiving evaluation for chemotherapy. The SUVmax of 18F-FDG in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 2.80±0.69 and 6.97±2.11, showing a significant difference between them ( t=3.29, P<0.05). The SUVmax of 68Ga-N188 in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 3.38±1.12 and 2.93±0.50, showing no significant difference between them ( t=0.66, P>0.05). Cases with positive results of lymph node metastases in 68Ga-N188 and 18F-FDG PET/CT were 6 and 4, respectively, for the 6 pancreatic cancer patients diagnosed with lymph node metastases by postoperative histopathology, and the SUVmax of 68Ga-N188 and 18F-FDG in lymph node metastases were 2.25±1.12 and 4.02±1.27. Conclusion:68Ga-N188 PET/CT can be used for imaging diagnosis of tumor primary lesion and lymph node metastases of pancreatic cancer.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

The clinical data of a case of Niemann-Pick disease type C diagnosed at Beijing Children′s Hospital, Capital Medical University on December 22, 2017 were retrospectively analyzed.The patient, male, 1 year and 28 days old, was admitted to the hospital primarily due to intermittent fever, cough and dyspnea for 8 months, and hepatosplenomegaly for 20 days.The patient initially presented with cough, expectoration, and wheezing, followed by hypotonia and delayed motor development.At the age of 1 year, the child developed hepatosplenomegaly and diffuse interstitial changes in both lungs.At the age of 3 years, the child had obvious vertical supranuclear gaze palsy and gelastic cataplexy, followed by dysarthria and dysphagia.The foam cells were found by bone marrow cytology, while sphingomyelinase and glucocerebrosidase were normal, so Niemann-Pick disease type A/B and Gaucher disease were excluded.Finally, genetic testing revealed two pathogenic mutations in the NPC1 gene, so Niemann-Pick disease type C was confirmed.Miglustat treatment began when the child was 3 years old, and vertical supranuclear gaze palsy and gelastic cataplexy improved for a while, but then the neurological symptoms worsened again, with dysphagia and dyspnea gradually increasing, and finally he died at the age of 4 years and 11 months.

3 cases with dental implant entered into the maxillary sinus by accident during posterior maxillary dental implant surgery were reported in this work.The implants were localized by CBCT scanning and removed by endoscope assisted extraction through the refined Cald-well-Luc approach under local anesthesia.The results showed that all 3 implants were successfully removed,highlighting the efficacy of en-doscopic-assisted techniques in minimizing trauma,ensuring accurate positioning and providing a clear surgical field of vision.

Objective:To investigate the level of serum lipoprotein a [Lp (a)] in patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:A retrospective cohort study was performed. The clinical data of 87 patients with DLBCL who were treated at Changshu No.2 People's Hospital from January 2017 to June 2022 (the newly treated DLBCL group) were retrospectively analyzed, and 78 healthy physical examination subjects were selected as the control group. The level of Lp(a) in the two groups and the level of Lp(a) in DLBCL patients achieving different therapeutic effects after treatment were compared. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum Lp(a) in predicting the therapeutic effect of DLBCL patients, and the area under the curve (AUC) was calculated to determine the optimal critical value. Based on the optimal critical value, patients with DLBCL were divided into low Lp(a) group and high Lp(a) group, and the clinicopathological characteristics of DLBCL patients with different Lp(a) levels were compared. Cox proportional hazards model was used to analyze the factors affecting the prognosis of DLBCL patients. Kaplan-Meier method was used to compare the relapse-free survival (RFS) and overall survival (OS) of DLBCL patients with different Lp(a) levels.Results:The level of Lp (a) in the newly treated DLBCL group was higher than that in the control group[ (0.24±0.09) g/L vs. (0.09±0.06) g/L], and the difference was statistically significant ( t = 3.61, P = 0.019). Among 87 patients, 54 achieved complete remission (CR), 23 achieved partial remission (PR), and 10 achieved progression of the disease (PD). The Lp (a) levels of patients achieving CR, PR, and PD were (0.09±0.09) g/L, (0.12±0.08) g/L, and (0.25±0.15) g/L, respectively. The Lp (a) levels in patients achieving CR and PR were lower than those in the newly treated DLBCL patients [(0.24±0.09) g/L], and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in the Lp (a) levels between patients achieving PD and the newly treated DLBCL patients ( P > 0.05). The ROC curve results showed that the optimal critical value of serum Lp (a) in predicting the efficacy of DLBCL patients was 0.25 g/L, AUC was 0.776 (95% CI: 0.676-0.876, P < 0.05), and its sensitivity and specificity was 66.67%, 82.76%, respectively. According to the optimal critical value of Lp (a) (0.25 g/L), patients were divided into the low Lp (a) group (≤ 0.25 g/L) (57 cases) and the high Lp (a) group (>0.25 g/L) (30 cases). The proportion of patients with lactate dehydrogenase level >227 U/L, Ann Arbor stage Ⅲ-Ⅳ, and extranodal organ involvement >1 in the high Lp (a) group was higher than that in the low Lp (a) group, and the differences were statistically significant (all P < 0.05). Cox multivariate analysis results showed that Ann Arbor stage Ⅲ-Ⅳ, international prognostic index (IPI) score 3-5, and Lp (a)>0.25 g/L were independent risk factors for OS in DLBCL patients (all P < 0.05); Ann Arbor stage Ⅲ-Ⅳ and IPI score 3-5 were independent risk factors for RFS in DLBCL patients (all P < 0.05). The median OS in the low Lp (a) group was not reached; the median OS of the high Lp (a) group was 21 months, and there was a statistically significant difference in OS between the two groups ( P = 0.001). The median RFS time was not reached in the low Lp (a) group and the high Lp (a) group; and there was no statistically significant difference in RFS between the two groups ( P = 0.102) . Conclusions:Lp(a) level of DLBCL patients is increased, and Lp(a) could be a factor influencing the prognosis of DLBCL.

Objective:To explore the feasibility of automatic assessment of abdominal and pelvic CT radiation dose index (CTDI vol) based on deep learning models. Methods:A retrospective analysis was conducted on clinical abdominal and pelvic CT data collected continuously from February 2021 to February 2022. A total of 1 084 sets of patient images were obtained using equipment of Siemens SOMATOM Definition Flash CT, Philips iCT, and GE lightspeed VCT. The volume CT dose index (CTDI vol) prediction model consisted of two functional modules: organ segmentation and dose prediction. Based on the result of actual scanning area segmentation in the abdominal and pelvic area, CTDI vol was evaluated automatically by dose regression prediction module. The images of 1 084 patients included in the study were randomly divided into a training set of 784, a validation set of 196 and a test set of 104. Dice coefficient was used to evaluate the abdominal and pelvic segmentation performance of the hybrid model, and accurate number proportion and root-mean-square logarithm error (RMSLE) were used as the evaluation index of the CTDI vol estimation model performance. Results:In the test set, the Dice coefficient of the deep learning model in the task of CT abdominal image segmentation was as high as 0.998, and the RMSLE of the CTDI vol regression model in estimation of radiation dose was 9.41%, with an accuracy rate of 92%. Scatter plot analysis showed that some CTDI vol estimates had significant errors, indicating that the model might need to be further optimized in these situations. Conclusions:The deep learning models can accurately and automatically segment CT abdominal images and estimate radiation dose, which can be used for clinical radiation dose monitoring and management.

Objective To investigate the impact of silymarin(SM)on the malignant growth of glioma cells and the regulatory mechanism on the miR-124-3p/WEE1 axis.Methods Glioma U87 cells were grouped into control,SM low,medium,and high concentration groups,and SM high concentration + miR-124-3p inhibitor group(SM high + miR-124-3p inhibitor group).CCK-8 was used to measure the proli-feration rate of cells;Transwell? assay was applied to assay the migration and invasion of cells;cell cycle progression was detected by flow cytometry;Western blotting was applied to measure the expression of cyclin D1 and apoptosis-related proteins;the levels of miR-124-3p and WEE1 mRNA were determined by qRT-PCR;and a luciferase activity test was applied to verify the targeting relationship between miR-124-3p and WEE1;in addition,the establishment,administration,and analysis of a NOD/SCID mouse model of intracranial trans-planted tumor were conducted.Results Compared with the control group,the cell proliferation,the numbers of migrating and invading cells,the expression of cyclin D1,and the level of WEE1 mRNA in the various SM treatment groups decreased,the number of cells in G0/G1 phase,the expression of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3 and miR-124-3p increased(P＜0.05);furthermore,transfection of miR-124-3p inhibitor reversed the inhibitory effect of SM on the malignant behavior of glioma cells.In vivo experiments with mice showed that the weights and volumes of tumors in the SM treatment group were lower than those in the model group(P＜0.05),and there was no discernible change in the weight of the mice(P＞0.05).Conclusion SM can inhibit the malignant growth of glioma cells by upregulating miR-124-3p and downregulating WEE1.