[Multiple primary tumors in children: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

[Adrenal cortical carcinoma in children: a clinicopathological analysis of 25 cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

[Preliminary application of the Asia-Pacific colorectal screening score combined with the quantitative fecal occult blood in colorectal neoplasia screening].

To evaluate the efficacy of the Asia-Pacific colorectal screening (APCS) score combined with the quantitative fecal immunochemical test in colorectal neoplasia screening. Subjects who appointment to receive colonoscopy were recruited from August 2017 to May 2019 in the digestive endoscopy center. Before the colonoscopy, all subjects were scored by the Asia Pacific colorectal cancer screening scoring system and measured by quantitative fecal immunochemical test (QFIT). The detection rates of colorectal neoplasia were compared to evaluate the efficacy of the combined assay in colorectal neoplasia screening between APCS score and QFIT. A total of 1 420 subjects were enrolled in this study, APCS score medium-risk (MR) and high-risk (HR) groups were 847 (59.7%) and 573 (40.4%) and 26 cases (1.8%) of colorectal cancer, 196 cases (13.8%) of advanced adenoma, and 395 cases (27.8%) of non-advanced adenoma were detected. With the combination of APCS score and QFIT, participants were classified into 4 groups high-risk with positive QFIT result group G1, high-risk with negative QFIT result group G2, medium-risk with positive QFIT group G3, medium-risk negative QFIT group G4. The prevalence of colorectal neoplasia was 64.3%, 16.4%, 55.0%, and 9.8%, respectively. The prevalence of advanced neoplasia in high-risk with QFIT results was significantly higher than that in other 3 groups. HR and positive QFIT were the indicators for further colonoscopy, and MR with FIT negative group could postpone colonoscopy and conduct annual QFIT follow-up. The combination of APCS score and QFIT for colorectal neoplasia screening can reduce unnecessary colonoscopy, improve colonoscopy compliance and screening efficiency, and has important clinical significance and promotion value in colorectal tumor screening.

[Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma].

OBJECTIVE: To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics. METHODS: Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve. RESULTS: The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis. CONCLUSION: High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.

Koebner phenomenon of discoid lupus erythematosus on old tattoos.

The Koebner phenomenon is the development of lesions in traumatized skin, often with spontaneously occurring lesions elsewhere. We report a case of a woman in her 20 s presenting with discoid lesions superimposed on tattoos that she obtained many years ago. Although a few case reports have been published describing development of lesions on red tattoos attributed to photosensitivity, or koebnerization occurring less than a month following tattoo placement, our patient demonstrates a unique delayed development of discoid lesions years after obtaining her tattoos in non-sun exposed skin. Patients with conditions associated with the Koebner phenomenon must be counseled regarding forms of preventable trauma such as tattoos, and should be made aware that the Koebner phenomenon may not only manifest immediately, but can also present many years later.

Analysis on safety assessment of Tephrosia vogelii Hook to Apis cerana cerana.

Tephrosia vogelii Hook was excellent insecticidal plant, it was introduced into China and planted over a large area in Guangdong province. The main active components of T. vogelii was rotenone and it widely found in leaves and pods of T. vogelii. This paper study of the safety assessment of T. vogelii flowers to worker bees. In this paper, the content of rotenone in T. vogelii petal, nectar, pollen, pistil, and stamen samples were investigated by HPLC, and tested the toxicity of T. vogelii flowers for Apis cerana cerana during 24 h. The dissipation and dynamic of rotenone in A. c. cerana different biological compartments were investigated under indoor conditions during 24 h. The results showed, The LT50 of T. vogelii flowers to worker bees were collected from the eastern, western, southern, northern and top were 13.95, 24.17, 12.55, 26.48, and 18.84 h, the haemolymph of worker bees have the highest content of rotenone, the least accumulation of rotenone in workers bee's thorax, and the rate of dissipation was slowly during the whole study. In conclusion, the results showed the T. vogelii create security risks to worker bees under some ecosystems.

[Diagnostic value of 18F-FDG PET/CT and tumor markers (CEA, CA19-9, CA24-2) in recurrence and metastasis of postoperative colorectal moderately differentiated adenocarcinoma].

OBJECTIVE: To evaluate the diagnostic value of 18F-FDG PET/CT and tumor markers (CEA,CA19-9,CA24-2) in detection for recurrence and metastasis of postoperative colorectal moderately differentiated adenocarcinoma. METHODS: Fifty-five patients were enrolled in this study. All of the patients were tested with serum CEA within 2 weeks when they underwent 18F-FDG PET/CT scan, and some patients were tested with serum CA19-9 and CA24-2 simultaneously. According to the pathology and clinical results of their follow-up, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT and tumor markers were calculated based on different divided groups, respectively. RESULTS: According to the pathology and the results of their clinical follow-up, the sensitivity of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 95.74%, 68.09%, 28.57%, 40.00% and 74.47%, respectively. The specificity of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 75.00%, 50.00%, 66.67%, 71.43% and 50.00%, respectively. The positive predictive valueof 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 95.74%, 88.89%, 85.71%, 88.89% and 89.74%, respectively. The negative predictive value of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 75.00%, 26.67%, 11.42%, 17.24%, 25.00%, respectively. The accuracy of 18F-FDG PET/CT, CEA, CA19-9, CA24-2 and the combination of those three tumor markers were 92.73%, 65.47%, 32.65%, 44.68% and 70.91%, respectively. There were 2 cases of false positive and 2 cases of false negative in 18F-FDG PET/CT. CONCLUSION: 18F-FDG PET/CT has high value in detecting recurrence and metastasis of postoperative colorectal carcinoma. Tumor markers have the positive value to imply the recurrence and metastasis of postoperative colorectal carcinoma and are useful to indicate when to perform the 18F-FDG PET/CT. The combination of tumor markers could improve the diagnostic efficiency to some extent.

[A mini-incision on the anterior hip for pediatric femur neck fractures of type Delbet â ¡].

Objective: To investigate the early clinical outcomes of hip anterior short incision and open reduction and internal fixation for the treatment of children with Delbet Ⅱ femoral neck fracture. Methods: A retrospective analysis of 12 children with DelbetⅡ femoral neck fractures was performed with the anterior short incision approach at Department of Pediatric Orthopaedic, Children's Hospital, Nanjing Medical University from January 2014 to August 2016. There were 7 males and 5 females including 8 cases at left side and 4 cases at right side,aged (11.5±0.8) years (range: 8-14 years).Patients underwent surgery in (12.0±0.9) hours (range: 6-20 hours) after the injury. Displaced fractures were treated by open reduction if closed reduction failed.The surgical incision was performed with the anterior inferior iliac spine centered on, extending along the groin crease, and the length was 3 to 4 cm. The interval between the sartorius and the tensor fascia latae was applied, and the direct and indirect head of rectus femoris were resected to visualize the hip joint capsule. T-shaped incision was made in the capsule. After the reduction was obtained, two or three compression canulated screws were used to fix the fracture site. The healing time, complications and corresponding record outcome by X-ray and clinical examination were recorded. At the latest follow-up,the results were analyzed using the Ratliff criteria and clinical outcomes were assessed by pain, restrictive hip movement, normal activity or the avoidance of games, and the femoral neck in the radiograph. Results: Twelve patients had been followed-up for (30.0±4.1)months(range: 24-36 months). X-ray showed the fractures' healing time was (8.0±0.4) weeks(range: 7-9 weeks). Ten of the 12 fractures healed after one operation and were associated with no evidence of osteonecrosis of the femoral head. One case occurred premature physeal closure. There were no cases with fracture relocation, coaxvara, delayed union and nonunion or any significant postoperative complications. There was no infection, flexible internal fixation or ruptures. According to Ratliff grade, 9 cases of 12 patients were fine and 3 cases was acceptable. Conclusions: Satisfactory short-term effects can be achieved by a mini-incision on the anterior hip for Delbet Ⅱ pediatric femur neck fractures. The anterior incision has the advantage of less trauma, smaller incision scar, better fracture reduction and fixation, and less wound complications.

[In vivo imaging of breast tumors by a 99mTc radiolabeled probe targeting microRNA-155 in mice models].

OBJECTIVE: MicroRNA-155 (miR-155) is significantly highly expressed in breast cancer, lung cancer, liver cancer and other malignant tumors. This study was to design and construct a radiolabeled probe targeting miR-155 for in vivo imaging in breast cancer. METHODS: Anti-miR-155 oligonucleotide (AMO-155) was chemically synthesized with 2' OMe modification. Its 5' end was linked with acetyl amine group. After chelated with a bifunctional chelator NHS-MAG3, AMO-155 was radiolabeled with 99mTc using stannous chloride. The serum stability was evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing mice after the administration of 99mTc radiolabeled AMO-155 and scramble control probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB-231 tumor bearing mice with different expression level of miR-155 were imaged, respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the expression level of miR-155 in the bearing tumors. RESULTS: 99mTc-AMO-155 was prepared with high radiolabeled efficiency (97%), radiochemical purity (greater than 98%), and radioactive specific activity (3.75 GBq/µg). 99mTc-AMO-155 was stable in fresh human serum for 12 hours. After the administration via tail vein, 99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with high expression level of miR-155, whereas 99mTc-control showed little accumulation. After blocked with unlabeled AMO-155, the tumor could not be visualized clearly after the administration of 99mTc-AMO-155. Furthermore, 99mTc-AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor was shown with significantly higher radioactive accumulation than MDA-MB-231, based on its higher expression level of miR-155, which was verified by qRT-PCR. CONCLUSION: 99mTc-labeled AMO-155 with chemical modification showed good serum stability and in vivo tumor targeting ability. This study provides a potential probe for in vivo imaging of breast cancer.

MicroRNA-135b inhibits odontoblast-like differentiation of human dental pulp cells by regulating Smad5 and Smad4.

AIM: To investigate the function of miRNAs in odontoblast-like differentiation of human dental pulp cells (hDPCs). METHODOLOGY: Integrated comparative miRNA microarray profiling was used to determine the differential miRNAs expression in odontoblast-like differentiation of hDPCs. The abundance of microRNA-135b (miR-135b) was measured by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Bioinformatic analyses combined with luciferase assays were utilized to identify the targets interacting with miR-135b. Overexpression of miR-135b was performed to investigate the role and mechanism in odontoblast-like differentiation of hDPCs. Statistical analysis was performed by one-way analysis of variance (anova) or Student's t-test. RESULTS: Thirty-six differentially expressed microRNAs in odontoblast-like differentiation of hDPCs were identified. MiR-135b expression was significantly downregulated during hDPCs differentiation (P < 0.05). In addition, miR-135b was able to bind to the 3'-UTR of the Smad5 and Smad4 and repressed these two genes expression (P < 0.05). Furthermore, overexpression of miR-135b suppressed odontoblast-like differentiation of hDPCs and attenuated the expression of Smad5 and Smad4 (P < 0.05). CONCLUSIONS: These observations indicated a potential role of miR-135b in mediating odontoblast-like differentiation of hDPCs and inhibition of miR-135b might be a promising therapeutic way to facilitate dentine tissue engineering.

Direct growth of Ge quantum dots on a graphene/SiO2/Si structure using ion beam sputtering deposition.

The growth of Ge quantum dots (QDs) using the ion beam sputtering deposition technique has been successfully conducted directly on single-layer graphene supported by SiO2/Si substrate. The results show that the morphology and size of Ge QDs on graphene can be modulated by tuning the Ge coverage. Charge transfer behavior, i.e. doping effect in graphene has been demonstrated at the interface of Ge/graphene. Compared with that of traditional Ge dots grown on Si substrate, the positions of both corresponding photoluminescence (PL) peaks of Ge QDs/graphene hybrid structure undergo a large red-shift, which can probably be attributed to the lack of atomic intermixing and the existence of surface states in this hybrid material. According to first-principles calculations, the Ge growth on the graphene should follow the so-called Volmer-Weber mode instead of the Stranski-Krastanow one which is observed generally in the traditional Ge QDs/Si system. The calculations also suggest that the interaction between Ge and graphene layer can be enhanced with the decrease of the Ge coverage. Our results may supply a prototype for fabricating novel optoelectronic devices based on a QDs/graphene hybrid nanostructure.

Risk factors for incidence and case-fatality rates of healthcare-associated infections: a 20-year follow-up of a hospital-based cohort.

Information is lacking on the integrated evaluation of mortality rates in healthcare-associated infections (HAIs). Our aim was to differentiate the risk factors responsible for the incidence from those for the case-fatality rates in association with HAIs. We therefore examined the time trends of both incidence and case-fatality rates over a 20-year period at a tertiary-care teaching medical centre in Taiwan and the mortality rate was expressed as the product of the incidence rate and the case-fatality rate. During the study period the overall mortality rate fell from 0·46 to 0·32 deaths/1000 patient-days and the incidence rate fell from 3·41 to 2·31/1000 patient-days, but the case-fatality rate increased marginally from 13·5% to 14·0%. The independent risk factors associated with incidence of HAIs were age, gender, infection site, admission type, and department of hospitalization. Significant prognostic factors for HAI case-fatality were age, infection site, intensive care, and clinical department. We conclude that the decreasing trend for the HAI mortality rate was accompanied by a significant decline in the incidence rate and this was offset by a slightly increasing trend in the case-fatality rate. This deconstruction approach could provide further insights into the underlying complex causes of mortality for HAIs.

Molecular cloning and analysis of a receptor-like promoter of Gbvdr3 gene in sea island cotton.

Verticillium wilt caused by soil borne fungus Verticillium dahliae could significantly reduce cotton yield. The Ve1 homologous gene Gbvdr3 is resistant to Verticillium wilt. In order to understand of the function of the promoter Gbvdr3 in Gossypium barbadense, the promoter region of the receptor-like gene Gbvdr3 was obtained by genome walking, and the cis-element in the promoter was identified using the PLACE software in this study. The sequence analysis showed that the promoter contained elements related to stress resistance and light regulation. The cloned promoter was fused to the GUS reporter gene and transformed into Arabidopsis. GUS expression was specifically detected in roots, flowers, and seeds, suggesting that the expression of Gbvdr3 is tissue-specific. Separation and characterization analysis of the promoter of Gbvdr3 provides a platform for further research and application of this gene. Thorough understanding of the function of the Gbvdr3 promoter is important for better understanding of Gbvdr3 function. These results indicated that the promoter of Gbvdr3 was a tissue-specific promoter.

Electronic properties of single Ge/Si quantum dot grown by ion beam sputtering deposition.

The dependence of the electronic properties of a single Ge/Si quantum dot (QD) grown by the ion-beam sputtering deposition technique on growth temperature and QD diameter is investigated by conductive atomic force microscopy (CAFM). The Si-Ge intermixing effect is demonstrated to be important for the current distribution of single QDs. The current staircase induced by the Coulomb blockade effect is observed at higher growth temperatures (>700 °C) due to the formation of an additional barrier between dislocated QDs and Si substrate for the resonant tunneling of holes. According to the proposed single-hole-tunneling model, the fact that the intermixing effect is observed to increase as the incoherent QD size decreases may explain the increase in the starting voltage of the current staircase and the decrease in the current step width.

Acoustic radiation force impulse elastography for non-invasive assessment of disease stage in patients with primary biliary cirrhosis: A preliminary study.

AIM: To investigate the diagnostic performance of the acoustic radiation force impulse (ARFI) elastography for the assessment of primary biliary cirrhosis (PBC) stage. MATERIALS AND METHODS: Sixty-one patients with PBC in which liver biopsy and ARFI elastography measurements were performed in the same session were included in the study. The diagnostic performance of ARFI elastography for predicting the PBC stage was determined from the area under receiver operating characteristics (AUROC) curve analysis. RESULTS: ARFI elastography correlated significantly with histological stage (r = 0.74, p < 0.001) in patients with PBC. The AUROC of ARFI elastography for predicting histological stage equal to or higher than II, III, and equal to IV were 0.83, 0.93, and 0.91, respectively. The optimal cut-off values of ARFI elastography were 1.51 m/s, 1.79 m/s, and 2.01 m/s for PBC stage equal to or higher than II, III, and equal to IV, respectively. CONCLUSION: ARFI elastography is an acceptable and powerful technique for quantitative assessment of PBC stage.