[Retrospective study of 70 cases with the head and neck non-parameningeal rhabdomyosarcoma].

Objective: To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS). Methods: A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children's Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test. Results: A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis (χ2=5.022, P=0.025), distant metastasis (χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group (χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion: Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

Construction of prediction model for fetal growth restriction during first trimester in an Asian population.

OBJECTIVE: To construct a prediction model for fetal growth restriction (FGR) during the first trimester of pregnancy and evaluate its screening performance. METHODS: This was a prospective cohort study of singleton pregnancies that underwent routine ultrasound screening at 11 to 13 + 6 weeks at the Affiliated Suzhou Hospital of Nanjing Medical University between January 2019 and April 2022. Basic clinical information, ultrasound indicators and serum biomarkers of pregnant women were collected. Fetal weight assessment was based on the fetal growth curve for the Southern Chinese population. FGR was diagnosed according to Delphi consensus criteria. Least absolute shrinkage and selection operator (lasso) regression was used to select variables for inclusion in the model. Discrimination, calibration and clinical effectiveness of the model were evaluated in training and validation cohorts. RESULTS: A total of 1188 pregnant women were included, of whom 108 had FGR. Lasso regression identified seven predictive features, including history of maternal hypertension, maternal smoking or passive smoking, gravidity, uterine artery pulsatility index, ductus venosus pulsatility index and multiples of the median values of placental growth factor and soluble fms-like tyrosine kinase-1. The nomogram prediction model constructed from these seven variables accurately predicted FGR, and the area under the receiver-operating-characteristics curve in the validation cohort was 0.82 (95% CI, 0.74-0.90). The calibration curve and Hosmer-Lemeshow test demonstrated good calibration, and the clinical decision curve and clinical impact curve supported its practical value in a clinical setting. CONCLUSION: The multi-index prediction model for FGR has good predictive value during the first trimester. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Bayesian Approaches in Exploring Gene-environment and Gene-gene Interactions: A Comprehensive Review.

Rapid advancements in high-throughput biological techniques have facilitated the generation of high-dimensional omics datasets, which have provided a solid foundation for precision medicine and prognosis prediction. Nonetheless, the problem of missing heritability persists. To solve this problem, it is essential to explain the genetic structure of disease incidence risk and prognosis by incorporating interactions. The development of the Bayesian theory has provided new approaches for developing models for interaction identification and estimation. Several Bayesian models have been developed to improve the accuracy of model and identify the main effect, gene-environment (G×E) and gene-gene (G×G) interactions. Studies based on single-nucleotide polymorphisms (SNPs) are significant for the exploration of rare and common variants. Models based on the effect heredity principle and group-based models are relatively flexible and do not require strict constraints when dealing with the hierarchical structure between the main effect and interactions (M-I). These models have a good interpretability of biological mechanisms. Machine learning-based Bayesian approaches are highly competitive in improving prediction accuracy. These models provide insights into the mechanisms underlying the occurrence and progression of complex diseases, identify more reliable biomarkers, and develop higher predictive accuracy. In this paper, we provide a comprehensive review of these Bayesian approaches.

[Procine recombinant NK-lysin inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 and inhibiting oxidative phosphorylation and glycolysis: a proteomic analysis].

OBJECTIVE: To investigate the potential mechanisms that mediate the inhibitory effect of porcine recombinant NKlysin (prNK-lysin) against liver cancer cell metastasis. METHODS: HPLC-tandem mass spectrometry was used to identify the differentially expressed proteins in prNK-lysin-treated hepatocellular carcinoma SMMOL/LC-7721 cells in comparison with the control and PBS-treated cells. GO functional annotation and KEGG pathway analysis of the differentially expressed proteins were performed using GO and KEGG databases. RT-qPCR was used to determine the mRNA expression levels of polypeptide-N-acetylgalactosaminotransferase 13 (GALNT13), transmembrane protein 51 (TMEM51) and FKBP prolyl isomerase 3 (FKBP3) in the cells, and the protein expression of FKBP3 was verified using Western blotting. RESULTS: Proteomic analysis identified 1989 differentially expressed proteins in prNK-lysin-treated cells compared with the control cells, and 2753 compared with PBS-treated cells. Fifteen proteins were differentially expressed between PBS-treated and the control cells, and 1909 were differentially expressed in prNK- lysin group compared with both PBS and control groups. These differentially expressed proteins were involved mainly in the viral process, translational initiation and RNA binding and were enriched mainly in ribosome, protein process in endoplasmic reticulum, and RNA transport pathways. RT-qPCR showed that compared with the control group, prNK-lysin treatment significantly increased the mRNA expressions of GALNT13 (P < 0.05) and TMEM51 (P < 0.01) and lowered FKBP3 mRNA expression (P < 0.05). Western blotting also showed a significantly decreased expression of FKBP3 protein in prNK-lysin-treated cells (P < 0.001). CONCLUSION: Treatment with prNK-lysin causes significant changes in protein expression profile of SMMOL/LC-7721 cells and inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 protein and affecting the cellular oxidative phosphorylation and glycolysis pathways.

[Targeting microRNA-125b inhibited the metastasis of Alisertib resistance cells through mediating p53 pathway].

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and ß-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.

[A case-control study of occupational noise exposure induced high-frequency hearing loss and the risk of hypertension].

Objective: To investigate the relationship between high frequency hearing loss caused by occupational noise and the risk of hypertension. Methods: In March 2020, a case-control study was conducted. All noise exposed workers who participated in occupational health examination in Wuxi City in 2019 were selected as the study subjects (95432 cases in total) . The hypertension group was defined as the case group, and the normotensive group was defined as the control group. According to the hearing threshold, they were divided into the non high frequency hearing loss group (<40 dB) and the high frequency hearing loss group (≥ 40 dB) . Univariate statistical method and binary logistic regression were used to evaluate the relationship between high-frequency hearing loss and hypertension risk. Stratified analysis was used to compare the risk of hypertension among workers with high-frequency hearing loss of different ages and length of service. Results: There were significant differences in gender, age, length of service, enterprise scale, economic type and high-frequency hearing loss between control group and hypertension group (P<0.05) . Binary logistic regression analysis showed that after adjusting for gender, age, length of service, enterprise scale and economic type, the risk of hypertension in the high-frequency hearing loss group was still increased (OR=1.062, 95%CI: 1.007~1.121, P=0.027) . The risk of hypertension in high-frequency hearing loss patients was higher than that in non high-frequency hearing loss patients in 20-39 years old and 40-59 years old age groups (OR=1.536, 95%CI: 1.353~1.743; OR=1.179, 95%CI: 1.111~1.250; P<0.05) . The risk of hypertension in high-frequency hearing loss patients in <5years, 5-9years, 10-14 years, 15-19 years and ≥20 years working age groups were higher than that in non high-frequency hearing loss groups (OR=1.926, 95%CI=1.007-1.121; OR=1.635, 95%CI=1.478-1.810; OR=1.312, 95%CI=1.167-1.474; OR=1.445, 95%CI=1.238-1.686; OR=1.235, 95%CI=1.043-1.463; P<0.05) . Conclusion: There is a certain relationship between high-frequency hearing loss caused by occupational noise and the risk of hypertension, and the risk of hypertension is different among high-frequency hearing loss patients of different ages and working years.

[Honokiol reduces doxorubicin-induced cardiotoxicity in vitro by inhibiting pyroptosis via activating AMPK/Nrf2 signaling].

OBJECTIVE: To investigate the effect of honokiol (HKL) for reducing doxorubicin (DOX)-induced cardiotoxicity in H9c2 cells and the underlying mechanisms. METHODS: H9c2 cells were divided into control group, DOX group, HKL + DOX group, and HKL+compound C+DOX group. After 24 h of corresponding treatment, the cells were examined for morphological changes and cell viability using CCK-8 assay. The mRNA expressions of the inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) were detected by RT-PCR, and the protein levels of cleaved caspase-3, cytochrome c, NOD-like receptor pyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), p-AMPK and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) were detected with Western blotting; the expressions of NLRP3 and p-AMPK also detected with immunofluorescence staining. RESULTS: DOX treatment caused swelling and significantly lowered the viability of H9c2 cells (P < 0.05), resulting also in increased mRNA expressions of TNF-α, IL-6 and IL-1ß (P < 0.05) and protein expressions of cleaved caspase-3, cytochrome c, NLRP3, caspase-1 and ASC (P < 0.05) but reduced protein levels of p-AMPK and Nrf2 (P < 0.05); fluorescence staining showed significantly increased NLRP3 expression and decreased expression of p-AMPK in DOX-treated cells (P < 0.05). All these changes in COX-treated cells were significantly alleviated by HKL treatment (P < 0.05). The application of compound C obviously mitigated the protective effects of HKL against DOX-induced cardiotoxicity in H9c2 cells. CONCLUSIONS: HKL can alleviate DOX-induced cardiotoxicity by inhibiting pyroptosis in H9c2 cells, and this effect is mediated by activation of AMPK to regulate Nrf2 signaling.

[Effect of dNLR and LIPI scores on the prognosis of elderly patients with non-surgical treatment of non-small cell lung cancer].

Objective: To investigate the effects of derived neutrophil to lymphocyte ratio (dNLR) and lung immune prognostic index (LIPI) score on the overall survival (OS) of non-surgical elderly non-small cell lung cancer (NSCLC) patients. Methods: Clinical and pathological data of NSCLC patients in Hebei General Hospital from January 2014 to June 2018 were collected retrospectively. The dNLR value was calculated based on the results of blood routine before treatment, and the optimal cut-off value of dNLR was obtained by ROC curve. The patients were divided into low dNLR level group and high dNLR level group based on the optimal dNLR cut-off value. The groups were classified as good, intermediate and poor based on the LIPI score consisting of lactate dehydrogenase (LDH) and dNLR tested before treatment. The Kaplan-Meier method and Log rank test were used for survival analysis, and the Cox risk proportional regression model was used for analysis of prognostic influences. Results: The area under the ROC curve for dNLR predicting prognosis in non-surgical elderly NSCLC patients was 0.591 (95% CI: 0.491, 0.692; P=0.093). The optimal cut-off value for dNLR predicting prognosis in elderly NSCLC patients was 2.515, with a sensitivity of 45.5% and a specificity of 81.8%. The gender, BMI, pathological type and degree of tumor differentiation were associated with dNLR levels (P<0.05). The median survival times were 16 and 10 months for patients in the low dNLR level group (dNLR<2.51) and high dNLR level group (dNLR≥2.51), respectively (P<0.001), and 15, 10 and 6 months for patients with good, intermediate and poor LIPI scores, respectively (P<0.001). The age, gender, smoking, pathological type, tumor differentiation, clinical stage, BMI, dNLR level, LDH level and LIPI scores were all associated with patient prognosis (P<0.05), and age≥76 years, tumor differentiation and clinical stage Ⅲ and Ⅳ were independent factors influencing patient prognosis (P<0.05). Conclusion: No matter what treatment measures are taken, dNLR level and LIPI score are related to patients' prognosis, and non-surgical elderly NSCLC patients with high dNLR level and poor LIPI score before treatment have worse prognoses.

Management of paediatric laryngotracheal trauma.

OBJECTIVE: To summarise and describe the clinical presentations, diagnostic approaches and airway management techniques in children with laryngotracheal trauma. METHODS: The clinical data related to laryngotracheal trauma diagnosed and treated at the Beijing Children's Hospital, between January 2013 and July 2018, were retrospectively reviewed. Disease diagnosis, treatment, management and outcomes were analysed. RESULTS: A total of 13 cases were enrolled, including 7 cases of penetrating laryngotracheal trauma. The six cases of blunt laryngotracheal trauma were caused by collisions with hard objects. In all cases, voice, airway and swallowing outcomes were graded as 'good', except for one patient who had residual paralysis of the vocal folds. CONCLUSION: Flexible fibre-optic laryngoscopy and computed tomography can play an important role in diagnosing laryngotracheal trauma. The airway should be secured and, if necessary, opened by tracheal intubation or tracheostomy.

[Effects of ursolic acid on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure].

Objective: To investigate the effects of ursolic acid (UA) on oxidative stress and inflammatory factors in a rat model of AR after PM2.5 exposure. Methods: Sixty healthy female SD rats were randomly divided into five groups: normal control group (NC group), PM2.5 unexposed AR group (AR group), PM2.5 exposed AR group (ARE group), UA intervention AR group (AR+UA group), and UA intervention PM2.5 exposed AR group (ARE+UA group), with 12 rats in each group. AR model was performed by a basal sensitization with intraperitoneal injection of ovalbumin (OVA) and followed by nasal instillation. PM2.5 exposure was carried out by inhalation exposure system at a concentration of 200 µg/m3 for 3 h/d for 30 days. UA intervention group was given UA intragastric administration at 20 mg/(kg·d). AR symptoms including sneezing, nasal scratching and nasal secretion of rats in each group were observed. The activities of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in nasal mucosa were tested. The pathological changes of nasal mucosa were observed by HE staining. The levels of OVA-sIgE, IL-6 and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Protein microarray was used to measure the expression of multiple inflammation cell factors in nasal mucosa. Statistical analysis was performed with SPSS 20.0. Results: After UA intervention, the frequency of nasal sneezing, scratching and nasal secretion in ARE+UA group were lower than those of ARE group (P<0.05). Pathological examination of nasal mucosa showed that ARE+UA group had less inflammatory granulocyte infiltration and less pathological damage to the epithelial layer than ARE group. The activities of SOD in nasal mucosa of ARE+UA group were higher than those of ARE group ((50.10±3.09) U/mg vs (20.13±1.30) U/mg, F value was 597.54, P<0.01). The contents of MDA in nasal mucosa of ARE+UA group were lower than those of ARE group ((57.78±12.36) nmol/g vs (124.12±9.40) nmol/g, F value was 115.51, P<0.01). The expression levels of OVA-sIgE, IL-6 and IL-17 proteins were lower in the ARE+UA group than those in ARE group ((11.61±0.27) ng/ml vs (20.30±0.67) ng/ml, (47.59±15.49) pg/ml vs (98.83±10.98) pg/ml, (623.30±8.75) pg/ml vs (913.32±9.06) pg/ml, F value was 283.42, 80.45, 683.73, respectively, all P<0.01). After UA intervention, protein microarray analysis showed that the expression of IL-4, IL-6, IL-13, chemokine CXCL7, IL-1α, IL-1ß, MMP-8 and MCP-1 in ARE+UA group was decreased compared with ARE group while IFN-γ and IL-10 increased (all P<0.01). Conclusion: UA can reduce the aggravated AR symptoms and pathological damage of nasal mucosa, inhibit oxidative stress and release of inflammatory factors after PM2.5 exposure, and thus plays a protective role in the pathological damage of AR induced by PM2.5 exposure.

[Clinical characteristics and prognostic analyses of cervical neuroblastoma].

Objective: To determine the characteristics of cervical neuroblastoma and the effect of resection extent on survival and outcomes. Methods: We performed a retrospective review of 32 children with cervical neuroblastoma treated at Beijing Children's Hospital between April 2013 and August 2020. Data were collected from the medical record. The individualized therapy was designed based on staging and risk group. Based on the extent of resection, patients were divided into incomplete and complete resection groups. Event free and overall survival rates were compared between two groups using the Kaplan-Meier method. Results: The ages of patients ranged from 1 month to 81 months, with a median age of 11 months, including 7 males and 15 females. Twenty-nine patients (90.6%) presented with cervical painless mass. The average diameter of the primary tumors was (5.12±1.43) cm. Tumors were located in the parapharyngeal space in 25 cases (78.1%) and in the root of the neck in 7 cases (21.9%). None had MYCN amplification. According to International Neuroblastoma Staging System (INSS), 15 patients (46.9%) were identified as stage 1, 11 patients (34.3%) as stage 2B, 3 patients (9.4%) as stage 3 and 3 patients (9.4%) as stage 4. There were 12 patients (37.5%) at low risk, 17 patients (53.1%) at intermediate risk and 3 patients at high risk according to Children's Oncology Group (COG) risk classification system. All patients underwent tumor resection. Postoperatively Horner's syndrome occurred in 13 patients (40.6%), pneumonia in 9 patients (28.1%), pharyngeal dysfunction in 8 patients (25.0%) and transient hoarseness in 4 patients (12.5%). At a median follow-up of 36.5 months, the overall survival rate was 96.4%, with no significant difference between incomplete and complete resection groups (100.0% vs. 96.3%, χ2=0.19, P=0.667); the event free survival rate was 78.1%, with a significant difference between the two groups (40.0% vs. 85.2%, χ²=6.71, P=0.010). Conclusions: Primary cervical neuroblastoma has a young onset age, mostly in low and medium risk groups, and represents favorable lesions with good outcomes after multidisciplinary therapy. Less aggressive surgery with preservation of important structures is recommended. Complete resection should not be attempted if it would compromise vital structures.

[Anatomical characteristics of profunda artery perforator flap in the posteromedial femoral region and its application in the reconstruction of oral and maxillofacial defects].

Objective: To investigate the anatomical basis for the preparation of the profunda artery perforator flap (PAPF) in the posteromedial femoral region and its application in the reconstruction of oral and maxillofacial defects. Methods: Six lower limbs of Chinese adult cadavers were micro-surgically dissected. CT angiography (CTA) data of bilateral lower limbs of 6 patients was also collected retrospectively. The number, external diameter, pedicle length, and distribution of perforators in the posteromedial femoral region were recorded from the specimens and CTA data. Meanwhile, 10 patients with oral squamous cell carcinoma in the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University from August 2018 to June 2021 were treated with the PAPF. At each follow-up, contour and function of recipient and donor site, as well as swallowing and speech function were evaluated. Results: A total of 19 profunda artery perforator were identified in 6 lower limb specimens. The outer diameter at the beginning of the source artery was (2.34±0.25) mm and the total length of the pedicle was (11.12±1.06) cm. CTA data analysis of 12 legs identified 15 perforators of profunda artery in the posteromedial region. Eleven perforators were septocutaneous, including 2 perforators with a common trunk, while the remaining 4 perforators were musculocutaneous. As for different patterns of perforators (septocutaneous perforators, musculocutaneous perforators and perforators with a common trunk), the longitudinal distance to the pubic tubercle was (19.95±2.43), (21.84±2.54) and (19.48±0.55) cm respectively. The horizontal distance to the posterior edge of gracilis was (3.54±1.10), (3.72±0.30) and (3.85±1.48) cm, respectively. The initial diameters of perforators was (2.4±0.4), (2.6±0.6) and 1.9 mm respectively. Ten cases of the profunda artery perforator flaps survived successfully after operation. The flap sizes ranged from 8 cm×6 cm to 12 cm×7 cm. The patients were evaluated at 1, 3 and 6 months, and with 6 months interval ever since. During the follow-up, the shape of the recipient site was ideal, and the swallowing and language functions were not significantly affected. There was only linear scar in the donor area, and the function of the thigh was basically normal. Conclusions: PAPF possessed a good anatomic stability, suitable vascular pedicle length and diameter, minor influence to the donor area, sufficient amount tissue with good quality. It is an ideal choice for head and neck reconstruction.

Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin.

Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA. The released DOX then accumulates in the mitochondria causing cell starvation, reduced migration and apoptosis. The HA+DOX delivery system was also tested in-vivo on osteosarcoma bearing mice. Locally delivered DOX via the HA particles had a stronger tumor eradication effect compared to the controls as seen by PET-CT and immunohistochemical staining of proliferation and apoptosis markers. These results indicate that in addition to systemic chemotherapy, an adjuvant nHA could be used as a carrier for intracellular delivery of DOX for prevention of tumor recurrence after surgical resection in an osteosarcoma. Furthermore, we demonstrate that nHA particles are pivotal in this approach but a combination of nHA with mHA could increase the safety associated with particulate nanomaterials while maintaining similar therapeutic potential.

[Efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma].

Objective: To evaluate the efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma (HNRMS). Methods: Information from 45 children diagnosed as non-orbital HNRMS and subjected to surgery combined with neoadjuvant chemoradiotherapy in Beijing Children's Hospital affiliated to Capital Medical University from August 2017 to July 2021 was analyzed. The patients included 25 males and 20 females, aged from 1 to 17 years old. The primary tumor site, pathological subtype, clinical stage, risk group, therapeutic regimen, resection range and outcome of all cases were also collected. The survival curves were made using the Kaplan-Meier method and the potential prognostic factors were investigated by Cox regression analysis. Results: Fifteen (33.3%) of 45 children achieved negative surgical margin under complete tumor resection. The postoperative pathological results showed that there were 20 cases of embryonic subtype, 19 cases of alveolar subtype and 6 cases of spindle sclerosis subtype. The postoperative follow-up time ranged from 4 to 71 months, with a median of 26 months. During the follow-up period, 13 children died, among whom brain metastasis was the most common cause of death, accounting for 7/13. The 3-year overall survival rate was 67.6%. Multivariate analysis showed that non-embryonic subtype (HR=6.26, 95%CI: 1.52-25.87, P=0.011) and failure to reach R0 resection (HR=9.37, 95%CI: 1.18-74.34, P=0.034) were independent risk factors affecting overall survival rate. Conclusion: Surgery combined with neoadjuvant chemoradiotherapy can offer a good efficacy for children with non-orbital HNRMS. Non-embryonic subtype and resection without negative operative microscopic margins are independent risk factors for poor prognosis, and brain metastasis is the main cause of death in these children.

The Application of Bayesian Methods in Cancer Prognosis and Prediction.

With the development of high-throughput biological techniques, high-dimensional omics data have emerged. These molecular data provide a solid foundation for precision medicine and prognostic prediction of cancer. Bayesian methods contribute to constructing prognostic models with complex relationships in omics and improving performance by introducing different prior distribution, which is suitable for modelling the high-dimensional data involved. Using different omics, several Bayesian hierarchical approaches have been proposed for variable selection and model construction. In particular, the Bayesian methods of multi-omics integration have also been consistently proposed in recent years. Compared with single-omics, multi-omics integration modelling will contribute to improving predictive performance, gaining insights into the underlying mechanisms of tumour occurrence and development, and the discovery of more reliable biomarkers. In this work, we present a review of current proposed Bayesian approaches in prognostic prediction modelling in cancer.

[Application of acellular dermal matrix loaded collagen binding domain-vascular endothelial growth factor patch in urethral wound repair in beagles].

Objective: To investigate the application value of acellular dermal matrix (ADM) loaded collagen binding domain-vascular endothelial growth factor (CBD-VEGF) patch in the repair of urethral wound in beagles. Methods: Twenty-one healthy adult beagles were selected to establish urethral wound model and randomly divided into 3 groups, which were treated with different repair methods. CBD-VEGF patch was prepared and instantaneous implantation was performed as the models were successfully built. The blank control group was treated without any repair materials;the ADM group was treated with collagen patch for repair and the ADM loaded with CBD-VEGF group was treated with collagen patch loaded with VEGF for repair. The safety and effectiveness of the three groups of materials implanted into the urethral wound model at 6 months after surgery were compared. Urodynamic examination, urethral angiography and pathological examination were used to evaluate the recovery of urethral tissue in the three groups. Result: Compared with blank control group and ADM patch group, there was no complications or other adverse conditions in the ADM-loaded CBD-VEGF patch group. Urethrography was performed to measure the diameter of the urethra in the experimental segment, the mean urethral diameter of blank control group [(3.07±0.43) mm] was significantly smaller than that of ADM patch group [(3.73±0.11) mm] and ADM loaded CBD-VEGF patch group [(3.64±0.32) mm], with statistical difference (P<0.05). Pathological examination with HE and Masson staining showed more proliferative blood vessels in the ADM loaded CBD-VEGF patch group. HE staining indicated that there were more proliferative vessels in the group of CBD-VEGF patch loaded with ADM. Masson staining showed that the positive area percentage of collagen tissue in the three groups was 34.27%±7.40%, 29.08%±3.79% and 28.02%±2.39%, respectively, with no statistical difference between the three groups(all P>0.05). There was no excessive deposition of collagen tissue in the two groups using collagen patch. The percentage of positive staining per unit area in the three groups were 1.4%±0.1%,1.8%±0.1%3.1%±0.2%, respectively, and the difference was statistically significant among three groups and between every two groups (all P<0.01), indicating the vascular density of CBD-VEGF group loaded with ADM was the highest. Conclusion: ADM loaded CBD-VEGF patch is a good biological support material for covering the wound after urethral surgery, and it provides an alternative direction for promoting the healing of the urethral wound.