Hepatolenticular degeneration （HLD） is an autosomal recessive genetic disorder characterized by copper metabolism impairment， and it is one of the few treatable neurogenetic diseases. A retrospective analysis was performed for the clinical data of four patients with HLD who attended Beijing Ditan Hospital， Capital Medical University， from November 2023 to October 2024， and the genetic testing results of three patients were analyzed， along with a literature review. Among the four patients， there was one female patient and three male patients. All patients had the initial symptoms of dysarthria and limb tremors， and physical examination showed positive K-F rings， normal liver enzyme levels， a reduction in serum ceruloplasmin， and an increase in 24-hour urinary copper excretion. Three patients underwent ATP7B genetic testing， among whom two had compound heterozygous mutations， and one had a heterozygous mutation. In addition， two patients underwent cranial magnetic resonance imaging， and the results showed symmetrical long T1 and long T2 signals. All four patients received copper-chelating therapy and achieved a good outcome. This article reports the diagnosis and treatment of four patients with HLD and identifies a case of HLD resulting from a rare heterozygous mutation site， thereby expanding the variation spectrum of the ATP7B gene.

Objective To compare and analyze the epidemiological characteristics of the adverse events following immunization (AEFI) with measles containing vaccine (MCV) in Zibo City from 2018-2022, and to provide reference data for evaluating the safety of the immunization strategy adjustment. Methods AEFI surveillance data related to MCV in Zibo City from 2018 to 2022 were collected from the China Disease Prevention and Control Information System Immunization Planning System and Shandong Provincial Vaccination Information System. The AEFI reports and epidemic characteristics after adjusting the immunization strategy about MCV were compared. Results Before adjusting immunization strategy of MCV in Zibo City (January 1, 2018 to May 31, 2020), 114 cases of AEFI were reported in the first dose of measles and rubella combined attenuated live vaccine (MR), with a reported incidence rate of 131.50/100 000. After adjusting the immunization strategy (June 1, 2020- December 31, 2022), 156 cases of AEFI were reported in the first dose of MMR, with a reported incidence of 162.97/100,000. There was no statistically significant difference in the reported incidence of AEFI (χ²=3.049, P=0.081). AEFI cases were mainly characterized by general reactions, and the reported incidence rate of MR (88.82/100,000) was lower than that of MMR (137.90/100,000) (χ²=9.576, P=0.002). Their most common clinical manifestation was fever, with 71 cases reported (81.90/100 000) and 114 cases reported (119.10/100 000), respectively. The reported incidence of abnormal reactions in MR (42.68/100 000) was higher than that in MMR (22.98/100,000) (χ²=5.458, P=0.019). Among them, allergic rash was the most common, with 16 and 11 cases reported, respectively, and the reported incidence rates were 18.46/100 000 and 11.49/100 000, respectively. The proportion of reported cases in the age group ≥ 1 year old was higher in MMR than in MR (χ²=41.089, P<0.001). The proportion of reported cases in the first quarter was higher in MR than in MMR (29.82%, 17.95%), while the proportion in the third quarter was higher in MMR than in MR (34.64%, 17.54%) (χ²=14.197, P=0.003). Conclusion After adjusting the MCV immunization strategy in Zibo City, the report on AEFI is within the expected range, and no adverse changes have been found in the epidemic characteristics of MCV related AEFI.

Objective To screen the targets related to the metabolic enzymes involved in the cholesterol synthesis pathway that inhibits the polarization of macrophages towards M1 phenotype,and verify the intervention effects and underlying mechanisms in colorectal cancer cells.Methods Mouse colorectal cancer MC38 cells were divided into control group(si-NC)and experimental groups(the expression of enzymes in cholesterol synthesis pathway was interfered with siRNA for corresponding targets).RT-qPCR was used to detect the mRNA levels of corresponding targets in MC38 cells after transfection.After peritoneal macrophages were extracted from male C57BL/6 mice(6 weeks old,weighing 13～18 g),the macrophages were then treated with the conditioned media of MC38 cells transfected with different siRNAs for 48 h.RT-qPCR was employed to detect the mRNA levels of IL-1β,IL-6 and TNF-α in the macrophages so as to evaluate the effect of the culture media on the M1 polarization.MC38 cells were divided into control groups(OE-NC and sh-NC),farnesyl-diphosphate farnesyltransferase 1(FDFT1)overexpression group(OE-FDFT1)and FDFT1 knockdown group(sh-FDFT1).RT-qPCR was applied to detect the mRNA expression of FDFT1,and Western blotting was conducted to measure the protein level of FDFT1.C57BL/6 mice were subjected randomly to construct a subcutaneous tumor-bearing model and a model of intraperitoneal metastatic tumor(n=5)respectively.The growth of tumor mass was then measured.Flow cytometry was used to observe the proliferation and apoptosis of MC38 cells,and Trans well assay to detect migration ability of MC38 cells.Five C57BL/6 macrophage-depleted mice(established with injection of clodronate liposome suspension through tail vein)received intraperitoneal implantation to construct a metastasis model,and then the obtained tumor masses were then weighted.Results Compared with MC38 cells after si-NC transfection,the mRNA levels of corresponding targets in MC38 cells in the experimental groups were significantly reduced(P＜0.05).Significant increases were found in the mRNA levels of IL-1β,IL-6 and TNF-α of the macrophages with FDFT1 interference than the control cells(P＜0.05).There were no statistical differences in the proliferation,apoptosis and migration of MC38 cells in the control group(OE-NC and sh-NC)and the cells of the FDFT1 overexpression group and FDFT1 knockdown group(P＞0.05).In both the subcutaneous tumor-bearing model and the model of intraperitoneal metastatic tumor,the mass weight was significantly heavier in the OE-FDFT1 group than the OE-NC group(P＜0.01),and was notably smaller in the sh-FDFT1 group than the sh-NC group(P＜0.01).For the macrophage-depleted mouse tumor model,no remarkable change was observed in the tumor weight between the OE-FDFT1 group and the OE-NC group as well as the sh-FDFT1 group and the sh-NC group.Conclusion FDFT1,the metabolic enzyme in the cholesterol synthesis pathway of colorectal cancer tumor cells,is a potential target for tumor immunotherapy targeting macrophages,which promotes tumor progression by regulating macrophages.

Objective:To analyze the distribution of tumor necrosis factor-alpha（TNF-α）308 gene loci polymorphism in children with febrile seizures（FS）and to explore the correlation between TNF-α 308 gene polymorphisms and FS in children.Methods:A total of 320 children diagnosed with FS in the Department of Emergency，Shanghai Children's Hospital from September 1st，2020 to June 30th，2021 were enrolled as the study subjects，which were divided into simple febrile seizures（SFS）group（232 cases）and complex febrile seizures（CFS）group（88 cases）based on their clinical characteristics，and the clinical characteristics and laboratory indexes of the two groups were compared. Children with no history of convulsions were selected as the control group（160 cases）. The high-resolution melting and gene sequencing technology were used to analyze the polymorphism of TNF-α 308 gene in each group and the distribution of different gene types and allele frequencies among the groups was compared. A multivariate Logistic regression model was constructed to analyze the relationship between TNF-α 308 gene polymorphism and FS.Results:The age，mean corpuscular volume，mean corpuscular hemoglobin and platelet distribution width of the CFS group were significantly higher than those in the SFS group，and the difference was statistically significant（all P<0.05）.There was no significant difference in gender distribution，family history of FS，history of FS，body temperature at time of convulsions，WBC，Hb，CRP and PLT between the two groups（all P>0.05）.The genotype frequency distribution of TNF-α 308 polymorphism in the three groups was in line with the Hardy-Weinberg equilibrium（ P>0.05）.The AA genotype of TNF-α 308 locus was not detected in the study.Compared with the control group［17 cases（10.6%）］，the distribution proportion of GA genotype in the CFS group［22cases（25.0%）］and the SFS group［52cases（22.4%）］was increased，and the difference was statistically significant（ χ2＝11.126， P＝0.004）；Compared with the control group［17 frequencies（5.3%）］，the frequency distribution proportion of allele A in the CFS group［22 frequencies（12.5%）］and SFS group［52 frequencies（11.2%）］was also increased，and the difference was statistically significant（ χ2＝9.960， P＝0.007）. Adding control factors such as gender，age，family history of FS，body temperature at time of convulsions and blood routine markers，the multivariate Logistic regression model was constructed to show that there was no statistically significant association between TNF-α 308 genotype and CFS in children（ OR＝1.805，95% CI：0.926~3.519， P＝0.083）. Conclusion:In this study，there was no significant correlation between TNF-α 308 gene loci polymorphism and CFS in children.

Objective To investigate the relationship between serum kininogen-1(KNG1)and tissue inhib-itor of metalloproteinases-3(TIMP3)levels and coronary artery lesions(CAL)in children with Kawasaki dis-ease(KD)at the acute phase.Methods A total of 132 children with KD at the acute phase admitted to the hospital from October 2020 to February 2024 were selected as the KD group,and were divided into CAL group(66 cases)and non CAL group(66 cases)according to whether they were combined with CAL.In addition,66 healthy children during the same period were selected as the control group.Serum KNG1 and TIMP3 levels were measured using enzyme-linked immunosorbent assay.A multivariate unconditional Logistic regression model with CAL as the dependent variable was established to identify independent factors influencing CAL in children with KD at the acute phase.Receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of serum N-terminal pro-brain natriuretic peptide(NT-proBNP),KNG1,and TIMP3 levels for CAL in children with KD at the acute phase.Results Compared to the control group,serum KNG1 level was elevated in the KD group(P<0.05),and TIMP3 level was reduced(P<0.05).In the CAL group,serum KNG1 level was higher(P<0.05),and TIMP3 level was lower compared to the non CAL group(P<0.05).Independent risk factors for CAL in children with KD at the acute phase included immunoglobulin resistance(OR=5.618,95%CI:1.203-26.248),increased NT-proBNP level(OR=1.003,95%CI:1.000-1.005),and increased KNG1 level(OR=1.648,95%CI:1.251-2.173),while increased TIMP3 level was identified as an independent protective factor(OR=0.966,95%CI:0.949-0.983,P<0.05).The combination of serum NT-proBNP,KNG1,and TIMP3 levels yielded an area under the curve of 0.930 for predicting CAL in children with KD at the acute phase,which was larger than 0.785,0.801,0.792 of NT-proBNP,KNG1,and TIMP3 a-lone(P<0.05).Conclusion increased level of serum KNG1 and decreased level of TIMP3 are independently associated with the occurrence of CAL in children with KD at the acute phase.The combined prediction of ser-um NT-proBNP,KNG1,and TIMP3 levels has high value in predicting CAL in children with KD at the acute phase.

Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

Objective To investigate the clinical characteristics and influencing factors of pressure injury in patients with severe neurological diseases and to construct and evaluate a predictive model for it.Methods A retrospective research method was adopted to collect 250 patients with severe neuropathy admitted to the First Affiliated Hospital of Wenzhou Medical University from April 2020 to April 2024,and their clinical characteristics were collected.The patients were then divided into a pressure injury group(n=58)and a non-pressure injury group(n=192)based on whether they development pressure injury after treatment.Baseline data on patient coma or lethargy status,primary diagnosis requiring neurocritical care admission,and Acute Physiology and Chronic Health Evaluation(APACHE)Ⅱscores were collected.The area under the curve(AUC)of the receiver operating characteristic(ROC)curves for acute cerebrovascular disease,coma or lethargy status,and APACHE Ⅱ scores of the subjects was compared.Results Among the 250 patients with severe neurological diseases,58 had pressure injuries.Of these,35(60.34%)had mucosal pressure injuries,while 23(39.66%)had device-related pressure injuries.According to the National Pressure Injury Advisory Panel Pressure Injury Staging System,46 cases(79.31%)had stage 1 pressure injuries,8 cases(13.97%)had stage 2 pressure injuries,4 cases(6.90%)had stage 3 pressure injuries,and no patients had stage 4 pressure injuries.Logistic multivariate regression analysis showed that primary diagnosis requiring neurocritical care admission(odds ratio[OR]=3.102;95%CI,1.013-9.499),coma or lethargy status(OR=3.769;95%CI,1.237-11.478),and APACHE Ⅱ score(OR=0.201;95%CI,0.124-0.328)were influencing factors for pressure injury in patients with severe neurological diseases.The ROC results showed that the AUC of the prediction model combining the 3 influencing factors was 0.974(95%CI,0.957-0.992),and that the sensitivity and specificity were 91.40%and 93.70%,respectively.The prediction accuracy of the combination prediction model was 0.96,which was significantly higher than those of the prediction models based on the 3 separate influencing factors(P<0.05).The Hosmer-Lemeshow test showed that the model had a good fit(χ2=4.779,P=0.062),indicating that the model had a relatively high accuracy.Conclusion Acute cerebrovascular disease,coma or lethargy,and APACHE Ⅱ score have different predictive values for pressure injury in patients with severe neurological diseases.While acute cerebrovascular disease and coma or lethargy have the same predictive value separately,the combination prediction incorporating the 3 influencing factors demonstrated superior accuracy and holds considerable potential for clinical application.

Objective To synthesize high-quality synthetic CT (sCT) images from cone beam CT (CBCT) by learning lung CT domain image features with a deep learning algorithm. Methods A sCT generation algorithm which employs perceptual loss-based cyclic generative adversarial network model (CycleGAN) and iterative registration was presented. CycleGAN model was trained to generate high-quality sCT images by combining perceptual loss and cycle consistency loss;and Elastix was used to register the generated sCT image and the planned CT (pCT) image,and iterate CycleGAN generator model. Results Experiments were conducted on the obtained pCT and CBCT data of 70 patients with lung tumors. From a quantitative perspective,the SSIM between sCT generated by the proposed algorithm and pCT was improved by 11.9％ as compared with that between CBCT and pCT,increasing from 0.825 to 0.923;additionally,RMSE dropped from 110.97 HU to 78.62 HU,PSNR increased from 32.21 dB to 34.74 dB,and mutual information increased from 1.187 to 1.418. The visual evaluation revealed that the proposed algorithm greatly eliminated the scattering artifacts of CBCT slices,highlighted the bone structure,and repaired the soft tissue structure. The comparisons with U-CycleGAN,R-CycleGAN and CUT models confirmed the effectiveness of the proposed algorithm. Conclusion Using the proposed algorithm for sCT images generation can effectively reduce the dose error and structural error between CBCT and pCT,making it possible to apply the proposed algorithm to accurate dose calculations and assist doctors in clinical diagnosis.

Objective:To construct a competency-oriented assessment index system based on entrustable professional activities (EPAs) for 5-year undergraduate clinical medical students in oncology internship.Methods:From June to December 2023, the scoping review approach and Bicomb 2.0 were used to construct and manage an item pool. The draft of EPAs and competencies was designed based on truncated word frequency. SPSS 25.0 was used for cluster analysis and UCINET 6.0 was used for visualization. Combining the characteristics and consensus of oncology, a multi-center expert group used the KJ method to draft the framework of EPAs and competencies. Subsequently, the expert group defined milestones and mapped the milestones to the framework to establish the assessment system.Results:Based on 26 included studies, a draft was created containing 19 EPA indicators and 72 competency characteristic indicators. After cluster analysis, 13 experts from 6 medical institutions established a framework including 13 EPAs and 10 competencies as well as 50 milestones, leading to the construction of the "EPAs-competencies-milestones" assessment system.Conclusions:The "EPAs-competencies-milestones" assessment system aligns with the trend of reform, demonstrating universality, specificity, and scientificity. It provides a reference for the development and assessment of oncology internship courses in medical universities.

Objective:To establish a method to detect IDH2 gene mutations in the cell-free DNA (cfDNA) sample of angioimmunoblastic T-cell lymphoma (AITL) based on the digital droplet PCR (ddPCR) method. The performance of this method was evaluated.Methods:Specific primers and probes were designed for IDH2 p. R172K, IDH2 p. R172M, and IDH2 p. R172W mutations, and primer combinations were optimized to establish the optimal ddPCR reaction system. In addition, the accuracy, precision, specificity, and detection limit of the method were evaluated using clinical cfDNA samples obtained from 40 patients with AITL at the First Affiliated Hospital of Nanjing Medical University.Results:The IDH2 R172K/M/W F2/R2 primer combination was selected to establish the ddPCR detection method for IDH2 R172K/M/W mutations. Specific standard samples showed no false-positive results. The accuracy test revealed that the relative deviation of the standard sample measurements was within ±10%. The detection limit test indicated that the method could detect 1 ng/μl with a 0.2% mutation rate for IDH2 R172K/M/W mutations. The precision measurements (inter-experimenter, inter-run, and inter-laboratory) all had a coefficient of variation of <5%. ddPCR was applied to 40 clinical samples with IDH2 R172K/M/W mutations, and the results were fully consistent with gene sequencing.Conclusion:ddPCR can detect IDH2 gene mutations in cfDNA from AITL with high sensitivity, specificity, and absolute quantification. This method offers a simple, rapid, and reliable approach for diagnosing and monitoring.