Objective:To explore the value of the imaging nomogram model based on preoperative CT features of patients with small intestinal stromal tumor (SIST) in predicting pathological risk classification.Methods:This was a cohort study. The patients who were diagnosed as primary SIST by postoperative pathology in Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to October 2023 were retrospectively included. According to the modified 2008 National Institutes of Health classification criteria, the patients were divided into a pathological intermediate/high-risk group (86 cases) and a very low/low-risk group (56 cases). The features of preoperative enhanced CT images of SIST were analyzed, including tumor boundary, necrosis, intra-tumoral hemorrhage, intra-tumoral calcification, growth pattern, enhancement pattern, enhancement degree, enlarged vessels feeding or draining the mass (EVFDM), and tumor location. Patients were followed up to determine the recurrence-free survival (RFS). Univariate and multivariate logistic regression were used to screen the independent predictors of SIST with pathological medium/high-risk group. The independent predictors were combined to construct an imaging prediction model, and a nomogram was drawn. The receiver operating characteristic curve was used to evaluate the predictive efficacy of the model. The Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the differences in RFS.Results:Univariate logistic regression results showed that tumor shape, necrosis, intra-tumoral hemorrhage, EVFDM, and tumor location were potentially related to medium/high-risk SIST. Multivariate logistic regression results showed that tumor shape ( OR=3.92, 95% CI 1.58-9.71, P=0.003), necrosis ( OR=4.60, 95% CI 1.91-11.09, P<0.001), and EVFDM ( OR=6.25,95% CI 1.74-22.47, P=0.005) were independent predictors of pathological intermediate/high-risk SIST. The area under the curve of the imaging predictive model combining the three predictors to predict the intermediate/high-risk SIST was 0.835 (95% CI 0.769-0.901), the sensitivity was 0.810, the specificity was 0.839, and the accuracy was 0.789. Taking the cut-off value (0.810) as the boundary value, the patients were divided into the high-risk group (74 cases) and the low-risk group (68 cases) according to the prediction results. The median RFS of the predicted high-risk group was poorer than that of the predicted low-risk group, and the difference was statistically significant ( χ2=5.20, P=0.023). Conclusions:The imaging nomogram model based on preoperative CT image features shape, necrosis, and EVFDM can effectively predict the pathological intermediate/high-risk SIST before surgery and has important predictive value for postoperative recurrence.

OBJECTIVE: To explore the genetic basis for a child with multiple malformations. METHODS: A child who had presented at Shanxi Provincial Children's Hospital in February 2021 was selected as the study subject. Clinical data of the patient was collected, and whole exome sequencing (WES) was carried out to screen pathogenic variants associated with the phenotype. Candidate variant was validated by Sanger sequencing of her family members. RESULTS: The child had normal skin, but right ear defect, hemivertebral deformity, ventricular septal defect, arterial duct and patent foramen ovale, and separation of collecting system of the left kidney. Cranial MRI showed irregular enlargement of bilateral ventricles and widening of the distance between the cerebral cortex and temporal meninges. Genetic testing revealed that she has harbored a heterozygous variant of NM_178014.4: c.217A>G (p.Met73Val) in the TUBB gene, which was unreported previously and predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The child was diagnosed with Complex cortical dysplasia with other brain malformations 6 (CDCBM6). CONCLUSION CDCBM is a rare and serious disease with great genetic heterogeneity, and CDCBM6 caused by mutations of the TUBB gene is even rarer. Above finding has enriched the variant and phenotypic spectrum of the TUBB gene, and provided important reference for summarizing the genotype-phenotype correlation of the CDCBM6.
Humans ; Child ; Female ; Abnormalities, Multiple ; Blood Group Antigens ; Family ; Malformations of Cortical Development/genetics* ; Brain ; Mutation

Objective:To explore the relationship and underlying mechanism between exosomes derived from doxorubicin-resistant osteosarcoma cells and MDR1 and miRNAs. Methods:MG63 and U2OS cell lines were selected to construct doxorubicin-resistant strains, and the 50% inhibitory concentration (half maximal inhibitory concentration, IC 50) of drug-resistant and sensitive strains was detected by MTT, and fluorescence staining was performed at intervals of 15 min between 15 and 120 min to detect the change of fluorescence intensity. RT-PCR and Western Blot were used to detect the expression levels of MDR1 P-gp to verify the drug resistance of osteosarcoma cells. Exosomes were identified by particle size analysis and Western Bolt detection. The endocytosis of PKH26-labeled exosomes from doxorubicin-resistant cells was observed, and the proliferation level and migration of exosomes from doxorubicin-resistant cells co-cultured with osteosarcoma cells were detected by MTT assay and cell scratch assay. The differential expression levels of miRNAs in osteosarcoma-sensitive and drug-resistant cells were verified by sequencing and bioinformatics analysis and RT-PCR assay. Tumor growth, serum exosome identification and mRNA expression level of miR-21-5p in tumor-bearing nude mice between normal osteosarcoma cell group and drug-resistant group, drug-resistant+normal exosome group, drug-resistant+drug-resistant+drug-resistant exosome group were observed. MDR1 expression level in tumor tissue was detected by RT-PCR, Western Blot and immunohistochemistry. Results:The IC 50 of two adriamycin resistant strains were 2.21 vs. 11.81 μg/ml and 0.93 vs. 11.81 μg/ml, respectively, and the fluorescence intensity decreased faster than that of normal strains. The relative mRNA expression levels of MDR1 in two cell lines were normal 1.12±0.16, 1.02±0.11 and drug-resistant 2.15±0.10, 2.127±0.12, respectively. The relative protein expression of P-gp was normal 0.92±0.11, 0.73±0.10 and drug-resistant 0.46±0.03, 0.30±0.04, the differences were statistically significant ( P<0.05). Drug-resistant exosomes can enter osteosarcoma cells through endocytosis and concentrate in the cytoplasm when co-cultured with normal strains. Osteosarcoma cells were co-cultured with drug-resistant exosomes at 2, 4, 6, and 8 μg/ml adriamycin, respectively. Compared with normal group, the proliferation level in drug-resistant group was significantly increased. Compared with the normal cell group 35.95±3.92, 6.72±3.55 and the normal exosome group 51.22±5.55, 19.31±1.93, the drug-resistant cell group 54.20±9.32, 19.24±2.88 and drug-resistant exosome group 76.40±5.41, 30.26±4.87, all had significantly higher cell mobility, the difference was statistically significant ( P<0.05). Exosome sequencing and biogenic analysis of 10 highly upregated miRNAs to validate mRNA expression differences between normal and drug-resistant strains by RT-PCR, showing a significant increase in miR-21-5p expression level of drug-resistant strains (5.89±0.26 vs. 0.99±0.06; 1.05±0.07 vs. 8.80±0.93, P<0.05), the difference was statistically significant ( P<0.05). In MG63 and U2OS, the normal cell group and drug-resistant cell group, and the normal exosome group and drug-resistant exosome group were compared, the tumor volume and the terminal tumor weight of nude mice were increased to varying degrees. MRNA relative expression levels of miR-21-5p in serum exosomes of nude mice after drug intervention were 0.86±0.07 and 0.86±0.05 in normal cell group, respectively. The values were 1.13±0.12, 1.14±0.12 in drug-resistant cell group, 0.71±0.05, 0.75±0.03 in normal exosome group, and 0.90±0.07, 0.93±0.04 in drug-resistant exosome group. Compared with normal and drug-resistant strains, the expression levels of normal and drug-resistant exosome groups were increased, with statistical significance ( P<0.05). Conclusion:The exosomes of drug-resistant cells in osteosarcoma could enhance the proliferation level and migration ability of cells through intercellular transfer of MDR1 and miRNAs. The expression of MDR1 and miR-21-5p in drug-resistant cells and tumor-forming nude mouse serum and tumor tissues were up-regulated which suggested that it might be involved in regulating the drug resistance process of osteosarcoma.

Objective: To investigate the relationship between 18F-FDG PET/CT semi-quantitative parameters and the International Association for the Study of Lung Cancer, American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histopathologic classification, including histological subtypes, proliferation activity, and somatic mutations. Materials and Methods: This retrospective study included 419 patients (150 males, 269 females; median age, 59.0 years;age range, 23.0–84.0 years) who had undergone surgical removal of stage IA–IIIA lung adenocarcinoma and had preoperative PET/CT data of lung tumors. The maximum standardized uptake values (SUVmax), background-subtracted volume (BSV), and background-subtracted lesion activity (BSL) derived from PET/CT were measured. The IASLC/ATS/ERS subtypes, Ki67 score, and epidermal growth factor/anaplastic lymphoma kinase (EGFR/ALK) mutation status were evaluated. The PET/CT semiquantitative parameters were compared between the tumor subtypes using the Mann–Whitney U test or the Kruskal–Wallis test. The optimum cutoff values of the PET/CT semi-quantitative parameters for distinguishing the IASLC/ATS/ERS subtypes were calculated using receiver operating characteristic curve analysis. The correlation between the PET/CT semi-quantitative parameters and pathological parameters was analyzed using Spearman’s correlation. Statistical significance was set at p < 0.05. Results: SUVmax, BSV, and BSL values were significantly higher in invasive adenocarcinoma (IA) than in minimally IA (MIA), and the values were higher in MIA than in adenocarcinoma in situ (AIS) (all p < 0.05). Remarkably, an SUVmax of 0.90 and a BSL of 3.62 were shown to be the optimal cutoff values for differentiating MIA from AIS, manifesting as pure ground-glass nodules with 100% sensitivity and specificity. Metabolic-volumetric parameters (BSV and BSL) were better potential independent factors than metabolic parameters (SUVmax) in differentiating growth patterns. SUVmax and BSL, rather than BSV, were strongly or moderately correlated with Ki67 in most subtypes, except for the micropapillary and solid predominant groups. PET/CT parameters were not correlated with EGFR/ALK mutation status. Conclusion As noninvasive surrogates, preoperative PET/CT semi-quantitative parameters could imply IASLC/ATS/ERS subtypes and Ki67 index and thus may contribute to improved management of precise surgery and postoperative adjuvant therapy.

Objective:To construct an index system for evaluating the development of research-oriented disciplines in medical institutions, and to provide a basis for guiding the superior disciplines towards international high-level disciplines.Methods:Through literature research and expert discussions, the basic framework of the research-oriented disciplines development evaluation system was established. The final version of the index system was determined using the Delphi method and expert interviews, and the weights of each index were established using the hierarchical analysis method.Results:After consultation, the framework of 5 first-class indexes, 16 second-class indexes, and 51 third-class indexes was finally constructed for the evaluation system of research-oriented discipline development, and the weights of indexes at different classes were calculated. The high-frequency terms " research mechanism construction" , " research team construction" and " representative research results" extracted from the expert interviews echoed the results of the weighting calculation.Conclusions:The evaluation system for research-oriented disciplines constructed in this study is relatively reasonable, scientific, reliable, and operable. The construction of the index system adapts to the characteristics of the development of research-oriented disciplines, with guiding significance for enhancing the development of research-oriented disciplines.

OBJECTIVE: To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity. METHODS: Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents. RESULTS: WES revealed that the patient has carried a previously unreported de novo heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.4906C>T variant of KMT2A gene was predicted to be pathogenic (PVS1+ PS2+ PM2+PP3). CONCLUSION The heterozygous nonsense c.4906C>T (p.Arg1636Ter) variant of the KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the KMT2A gene.
Abnormalities, Multiple/genetics* ; Child ; Histone-Lysine N-Methyltransferase/genetics* ; Humans ; Intellectual Disability/genetics* ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Syndrome

Purpose: Gastric cancer (GC) has a very poor prognosis when diagnosed at a late stage. Acyl-CoA thioesterase 7 (ACOT7) is a major isoform of the acyl coenzyme family that catalyzes the hydrolysis of fatty acyl-CoAs into unesterified free fatty acid and coenzyme A. The purpose of this study was to investigate the expression levels of ACOT7 in GC and mechanisms related therewith. Materials and Methods: Screening of systematic biology studies revealed ACOT7 as a key gene in GC, as well as involvement of the long non-coding RNA NMRAL2P in ACOT7 expression. In this study, GC tissues and adjacent tissue samples were obtained from 10 GC patients at the Department of Gastrointestinal Surgery. GES1 and SGC-7901 cells were collected and treated to silence ACOT7 and overexpress NMRAL2P. The expressions of ACOT7 and NMRAL2P were detected by real-time quantitative PCR and Western blot. Additionally, cell proliferation, apoptosis, migration, and invasion were examined. Results: ACOT7 was upregulated in gastric tumor tissues and GC cell lines. ACOT7 gene silencing induced a less malignant phenotype and was closely correlated to reduced cell proliferation and migration, altered cell cycle, and increased apoptosis. Furthermore, NMRAL2P was downregulated in tumor tissues and GC cell lines. NMRAL2P overexpression induced a more malignant phenotype and significantly inhibited the expression of ACOT7. Importantly, NMRAL2P indirectly methylated ACOT7 by binding to DNMT3b, thereby suppressing ACOT7 expression. Conclusion NMRAL2P activation suppresses ACOT7 expression in GC. Thus, ACOT7 could be a promising target for the treatment of GC.

Objective To investigate the feasibility of sodium glycididazole(CMNa)on the radio-sensitization of esophageal cancer(EC)by 18F-fluoromisonidazole(FMISO)PET/CT.Methods A total of 60 patients with EC from December 2016 to December 2017 were enrolled prospectively and were divided into control group(n = 30;21 males,9 females;age:(56.6±10.0)years)and experimental group(n=30;20 males,10 females;age:(59.3±9.0)years)using completely randomized grouping design.Patients in the control group received radiotherapy alone,and those in the experimental group were treated with conventional radiotherapy and CMNa.All patients underwent 18F-FMISO PET/CT imaging 1 week before and after radiotherapy.The imaging results were visually and semi-quantitatively analyzed.The maximum standardized uptake value(SUVmax),tumor/muscle ratio(T/M),and hypoxia volume(HV)were calculated.Paired t test,two-sample t test and/x2 test were used to analyze the data.Results T/M and HV in the control group before and after radiotherapy were 3.92±0.57 vs 1.66±0.35,(1.84±0.31)vs(1.04±0.15)mm3,respectively;T/M and HV in the experimental group before and after radiotherapy were 4.01±0.68 vs 1.27±0.11,(2.01±0.22)vs(0.90±0.09)mm3,respectively.The primary tumor T/M,HV after radiotherapy in 2 groups were significantly lower than those before radiotherapy(t values:12.15-24.43,all P<0.05)and the amplitudes of T/M and HV in the experimental group were significantly higher than those in the control group(?T/M:2.77±0.60vs 2.25±0.49,?HV:(1.12±0.18)vs(0.81±0.26)mm3;t values:3.00 and 1.80,both P<0.05).Meanwhile,the local control rate of EC after 3 months in the experimental group was higher than that in the control group(80.0%(24/30)vs 53.3%(16/30);x2=4.80,P<0.05).Conclusion CMNa has the radiosensitizing effect on EC and the 18F-FMISO PET/CT can evaluate the radiosensitization effect.

Objective To investigate the outcomes of patients with diabetic retinopathy (DR) in Shanghai communities and the influencing factors.Methods From October 2015 to April 2016,533 type 2 diabetic patients with DR were selected by target sampling and cluster random sampling method from six community health service centers in Shanghai.Patients were followed up for 1 year.The demographic information,physical examination,laboratory tests and eye fundus exam results were documented and the DR was graded.The factors associated with the regression of DR were analyzed.Results Total 478 patients,including 280 females (58.6％) and 198 males (41.4％),were followed up for 1 year.The mean age of patients was (64±7) years and the mean disease duration was (8.85±4.20) years.The original DR lesion was remitted in 35 patients with an improvement rate of 7.3％;while the original DR lesion was aggravated in 29 patients with a progression rate of 6.1％.Ordinal logistic regression analysis revealed that age (OR=0.197,95％CI:0.056-0.699),body mass index (BMI) (OR=0.383,95％CI:0.171-0.856),glycosylated hemoglobin (HbAlc) (OR=0.287,95％CI:0.102-0.803),triglycerides (TG) (OR=0.541,95％CI:0.295-0.991),urinary albumin to creatinine ratio (ACR)(OR=0.218,95％CI:0.066-0.720) were associated with DR in type 2 diabetic patients.Conclusion The regression of DR is closely related to age,BMI,glucose,serum lipids and renal function,so it is suggested that lowering BMI,controlling glucose and serum lipids and maintaining normal kidney function are necessary for preventing the progression and promoting the improvement of DR in diabetic patients.

Objective To study the radiosensitization of irisquinone on the Warburg effect of MDA-MB231 cells.Methods MDA-MB231 cells in the exponential growth phase were divided into 6 groups:control group,irisquinone group,radiation group,irisquinone plus radiation group(Irisquinone + RA),negative control group,and experimental group (siRNA).Colony formation assay was used to measure cell survival fraction of MDA-MB231 cells.Single-hit multi-target model was used to fit the survival curve and calculate the sensitive enhancement ratio (SER).Flow cytometry was used to measure cell apoptosis.The relative expression levels of HK Ⅱ mRNA and protein in each group were detected by qRT-PCR and Western blot respectively.Results The values of D0,Dq and SF2 in the irisquinone plus radiation group were obviously lower than those in the radiation group.The SER of irisquinone was 1.52.Compared with the other groups,the cell apoptosis rate was increased (t =13.29,12.09,5.90,3.83,P ＜ 0.05),while the relative expression levels of HK Ⅱ mRNA (t =9.14,10.48,3.40,P＜0.05) and protein (t=13.39,16.08,5.81,P ＜ 0.05) were decreased in the irisquinone plus radiation group significantly.Conclusions Radiosensitization function of irisquinone inhibits the Warburg effect of MDA-MB231 cells by down-regulating the expression of HK Ⅱ.