Repair mechanism of radiation-induced salivary gland injury by hypoxia-pretreated human urine-derived stem cell exosomes.

OBJECTIVE: To explore the protective effect of human urine-derived stem cell exosomes (hUSC-Exos) on radiation-induced salivary gland (SG) injuries in Sprague Dawley rats. METHODS: Fresh adult urine was collected, and primary hUSCs were isolated and identified. The hUSCs were hypoxia-pretreated with 1% oxygen for 24 h and then transferred to a normoxic culture environment for 24 h. The hUSC-Exos were collected and identified for exosomes. A radiation-induced injury model was established in the rats, and exosomes were introduced by local injection in the SG and tail vein. The submandibular gland was excised for morphological observation 1 week later. Immunohistochemical detection of the glandular tissue was conducted by α-smooth muscle actin (a-SMA), stem cell growth factor receptor (c-Kit) staining, and periodic acid-Schiff staining. Qualitative polymerase chain reaction and western blot analysis were adopted to detect the gene and protein expression of Wnt3a, GSK3ß, and Axin. RESULTS: In both the normoxic and hypoxic hUSC-Exo groups, microvesicular structures with bilayer membranes of approximately 80 nm in diameter were detected, and the expressions of CD9 and CD63 were detected by nanoflow cytometry. Compared with the control group, in the radiation-induced injury model group, the expression of a-SMA was significantly higher, the expression of c-Kit was significantly lower, and the expressions of Wnt3a, GSK3ß, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). Compared with the model group, in the normoxic and hypoxic hUSC-Exo groups, the expression of a-SMA was significantly decreased, the expression of c-Kit was significantly increased, and the expressions of Wnt3a, GSK3ß, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). CONCLUSION: Hypoxia-pretreated hUSC-Exos could repair radiation-induced SG injuries by activating the Wnt3a/GSK3ß pathway to suppress the expressions of a-SMA and c-Kit.

Lactoferrin as a regenerative agent: The old-new panacea?

Lactoferrin (Lf) possesses various biological properties and therapeutic potentials being a perspective anti-inflammatory, antibacterial, antiviral, antioxidant, antitumor, and immunomodulatory agent. A significant body of literature has also demonstrated that Lf modulates regenerative processes in different anatomical structures, such as bone, cartilage, skin, mucosa, cornea, tendon, vasculature, and adipose tissue. Hence, this review collected and analyzed the data on the regenerative effects of Lf, as well as paid specific attention to their molecular basis. Furthermore, tissue and condition-specific activities of different Lf types as well as problems of their delivery to the targeted organs were discussed. The authors strongly hope that this review will stimulate researchers to focus on the highlighted topics thus accelerating the progress of Lf's wider clinical application.

Diagnosis of lymphoepithelial carcinoma in parotid gland with three dimensional computed tomography angiography reconstruction: A case report.

Lymphoepithelial carcinoma (LEC) is an uncommon malignant neoplasm. Due to the complicated anatomical structure of the human head, standard imaging modalities including ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) scan remain limited in detection of salivary tumors. We used three-dimensional computed tomography angiography (3D-CT angiography) for the assessment and pre-operative surgical planning of facial fractures of a case with LEC. The study results demonstrated that 3D-CT angiography provided an insightful approach to preoperative evaluation in the treatment of salivary tumors.

Short-Circuit Fault Detection and Classification Using Empirical Wavelet Transform and Local Energy for Electric Transmission Line.

In order to improve the classification accuracy of recognizing short-circuit faults in electric transmission lines, a novel detection and diagnosis method based on empirical wavelet transform (EWT) and local energy (LE) is proposed. First, EWT is used to deal with the original short-circuit fault signals from photoelectric voltage transformers, before the amplitude modulated-frequency modulated (AM-FM) mode with a compactly supported Fourier spectrum is extracted. Subsequently, the fault occurrence time is detected according to the modulus maxima of intrinsic mode function (IMF2) from three-phase voltage signals processed by EWT. After this process, the feature vectors are constructed by calculating the LE of the fundamental frequency based on the three-phase voltage signals of one period after the fault occurred. Finally, the classifier based on support vector machine (SVM) which was constructed with the LE feature vectors is used to classify 10 types of short-circuit fault signals. Compared with complementary ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and improved CEEMDAN methods, the new method using EWT has a better ability to present the frequency in time. The difference in the characteristics of the energy distribution in the time domain between different types of short-circuit faults can be presented by the feature vectors of LE. Together, simulation and real signals experiment demonstrate the validity and effectiveness of the new approach.

The combination therapy of high-intensity focused ultrasound with radiotherapy in locally advanced pancreatic carcinoma.

BACKGROUND: The aim of the present study is to evaluate the effectiveness of the combined application of high-intensity focused ultrasound (HIFU) and radiotherapy in the treatment of locally advanced pancreatic carcinoma (LAPC). METHODS: A total number of sixteen patients with LAPC started treatment beginning with HIFU and radiotherapy 1 week after the HIFU treatment. Evaluation of the effectiveness of treatment was performed using main clinical symptoms, serum levels of CA-19-9, Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and the Kaplan-Meier method for estimating median overall survival (OS). The occurrence of adverse reactions was recorded. RESULTS: The main clinical symptoms including abdominal pain and lower back pain were alleviated, and the mean visual analog scale (VAS) pain score declined from 5.1 points to just 3.3 points immediately after the HIFU treatment. The median pain relief time was 5.6 months after radiotherapy, serum CA-19-9 levels began to decrease significantly 1 week after the HIFU treatment, from 102.1 to 60.8 U/ml, and the median continuous decline time was 4.3 months after radiotherapy. Partial response (PR) was observed in seven of sixteen patients, with stable disease (SD) in four patients, and progressive disease (PD) in the remaining five patients at 6 months after radiotherapy. Serum levels of amylopsin and lipase were not elevated to abnormal levels. The median OS was 14 months. No serious adverse reactions occurred. CONCLUSIONS: Treatment with both HIFU and radiotherapy can quickly improve symptoms and the quality of life and prolong survival lengths. This combination might be a promising therapeutic treatment for patients with LAPC.

Emerging role of mesenchymal stem cell-derived exosome microRNA in radiation injury.

PURPOSE: Radiation injury (RI) is a common occurrence in malignant tumors patients receiving radiation therapy. While killing tumor cells, normal tissue surrounding the target area is inevitably irradiated at a certain dose, which can cause varying results of radiation injury. Currently, there are limited clinical treatments available for radiation injuries. In recent years, the negative effects of stem cell therapy have been reported more clearly and non-cellular therapies such as exosomes have become a focus of attention for researchers. As a type of vesicle-like substances secreted by mesenchymal stem cells (MSC), MSC derived exosomes (MSC-exo) carry DNA, mRNA, microRNA (miRNAs), specific proteins, lipids, and other active substances involved in intercellular information exchange. miRNAs released by MSC-exo are capable of alleviating and repairing damaged tissues through anti-apoptosis, modulating immune response, regulating inflammatory response and promoting angiogenesis, which indicates that MSC-exo miRNAs have great potential for application in the prevention and treatment of radiation injury. Therefore, it is necessary to explore the underlying therapeutic mechanisms of MSC-exo miRNAs in this process, which may shed new lights on the treatment of radiation injury. CONCLUSIONS: Increasing evidence confirms that MSC-exo has shown encouraging applications in tissue repair due to the anti-apoptotic, immunoreactive, and pro-angiogenesis effects of the miRNAs it carries as intercellular communication carriers. However, miRNA-based therapeutics are still in their infancy and many practical issues remain to be addressed for clinical applications.

Efficacy of ifosfamide combined with liposome doxorubicin on osteosarcoma and its effects on serum IL-10, TNF-α, and IFN-γ in patients with osteosarcoma.

OBJECTIVE: To evaluate the effects of ifosfamide combined with liposome doxorubicin on osteosarcoma (OS) and its effects on serum IL-10, TNF-α, and IFN-γ in patients with OS. METHODS: A total of 86 patients with OS who received chemotherapy in Honghui Hospital, Xi'an Jiaotong University from Jan. 2017 to Dec. 2019 were enrolled. Patients treated by conventional doxorubicin + ifosfamide were assigned to the regular group (n=40). Others treated by liposome doxorubicin + ifosfamide were assigned to the research group (n=46). The clinical efficacy, 2-year survival rate, and adverse reactions of the two groups were evaluated and compared. ELISA was adopted for quantification of tumor specific growth factor (TSGF), vascular endothelial growth factor (VEGF), erb-b2 receptor tyrosine kinase 3 (ERBB3), tumor necrosis factor-α (TNF-α), interferon-gamma-γ (IFN-γ), and interleukin-10 (IL-10). The EORTC Quality of Life Questionnaire (QLQ-C30) was adopted to evaluate a patient's life quality. RESULTS: The research group showed a higher total effective rate and a higher 2-year survival rate than the regular group, but lower incidences of liver and kidney function injury, thrombocytopenia, and cardiotoxicity than the regular group. After therapy, lower levels of serum TSGF, VEGF, ERBB3, and TNF-α were found in the research group than those in the regular group. Higher levels of IFN-γ and IL-10 were found in the former than those in the latter. The research group got higher scores of QLQ-C30 than the regular group. CONCLUSION: Liposome doxorubicin + ifosfamide can improve the clinical efficacy on patients with OS and improve their recovery and life quality.

The immune checkpoint inhibitors treatment of head and neck squamous cell carcinoma: an expert consensus.

Immune checkpoint inhibitors (ICIs) present significant efficacy in the treatment of malignant tumors, and they have been approved as the first-line of treatment for various cancers. Pembrolizumab monotherapy or combined with chemotherapy has been recommended by domestic and foreign guidelines for the first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma. Although ICIs represent a milestone in the treatment of head and neck squamous cell carcinoma, potential problems still need to be addressed, such as the selection of the efficacy predictors for ICIs, the evaluation of the tumor response to ICIs, and the treatment of immune hyperprogression and immune-related adverse events. Therefore, to form a relatively unified understanding of ICIs treatment for head and neck squamous cell carcinoma, we integrated the clinical experience of multi-disciplinary experts of head and neck cancers on the basis of current clinical hot issues and finally developed this consensus.

Prognostic Significance of Inflammatory Biomarkers in Patients with Breast Cancer Skeletal Metastases.

PURPOSE: Skeletal metastases are a common problem in breast cancer patients. Identifying new prognostic factors can improve survival estimations and guide healthcare professionals in therapeutic decision-making. Our study aimed to determine the prognostic value of inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and C-reactive protein/albumin ratio (CAR) in patients with breast cancer skeletal metastases. PATIENTS AND METHODS: Clinical data from 212 patients with breast cancer skeletal metastases were retrospectively analyzed. The optimal cut-off values of each inflammatory biomarker were extracted from the receiver operating characteristic (ROC) curves. Patients were divided into high-value and low-value groups according to the cut-off values of NLR, LMR, and CAR. We investigated the relationship between inflammatory biomarkers and clinicopathological characteristics. The Kaplan-Meier method was used to measure progression-free survival (PFS) and overall survival (OS). The survival difference was compared by the univariate analysis. Cox multivariate regression analysis was performed to identify independent prognostic factors. RESULTS: The median age of the patients was 55 years, and the median follow-up was 45 months. LMR<3.43 (P<0.0001), NLR≥2.48 (P<0.0001), and CAR≥0.34 (P=0.035) were found to be associated with worse PFS in the univariate analysis. Meanwhile, LMR<3.43 (P<0.0001), NLR≥2.48 (P<0.0001), and CAR≥0.34 (P=0.025) were linked to the poor OS. The multivariate analysis revealed that NLR≥2.48 (HR 2.044, P=0.007) and LMR<3.43 (HR 0.532, P=0.012) were independent prognostic factors for OS; LMR<3.43 (HR 0.501; P=0.006) and NLR≥2.48 (HR 1.971, P=0.011) were similarly prognosticating worse PFS. Radiotherapy to the affected bone and ER (+) was favorable for the prognosis of breast cancer skeletal metastases. The number of involved sites of bone metastases>3 was adverse for PFS. CONCLUSION: LMR<3.43 and NLR≥2.48 were independently associated with worse prognosis of patients of breast cancer skeletal metastases.

[Identification of the priority conservation areas of national park: A case study of Lishui City, Zhejiang Province, China]. / å›½å®¶å ¬å›­ä¼˜å ˆä¿æŠ¤åŒºåŸŸè¯†åˆ«­­ä»¥æµ™æ±Ÿä¸½æ°´ä¸ºä¾‹.

It is the goal of protected area management to make full use of limited resources to better protect biodiversity. Currently, the main tasks of developing national park system in China are to combine conservation features, optimize the spatial network of protected areas, and identify the prio-rity conservation areas of national parks effectively. In this study, we assessed the spatial distribution of key ecosystem services (carbon sequestration, oxygen release, hydrological regulation, water resources, and soil retention) using ecological model, and simulated the distribution of suitable habitats for 37 endangered species by MaxEnt in Lishui City, Zhejiang Province. The irreplaceability index of each planning unit in Lishui was calculated on the 0.4 km×0.4 km grid using the systema-tic conservation planning model (MARXAN), setting key ecosystem services and endangered species as the conservation objects. Combined with the local management needs, the priority protection areas of national parks were identified comprehensively. The results showed that during 2005 to 2015, the annual carbon storage, oxygen release, hydrological regulation, water resource, and soil retention in the study area was 0.05 kg C·m-2·a-1, 0.13 kg O2·m-2·a-1, 83.25×108 m3·a-1, 803 mm·a-1, and 95.53 t·hm-2·a-1, respectively. The irreplaceability index of different land use types was significantly different. The irreplaceability index of forest, river and reservoir, garden, cultivated land, residential land was 50-100, 60-100, 30-50, 15-35, 0-25, respectively. The priority conservation areas accounted for 11.8% of the study area. This study put forward a systematic conservation planning idea combining biodiversity and ecosystem services, which could provide a useful framework and technical support for optimizing the network layout of protected areas and priority conservation areas of national parks, and help to enhance the overall effectiveness of the establishment of the protected areas system with national parks as its main type in China.

Platelet-rich plasma shows beneficial effects for patients with knee osteoarthritis by suppressing inflammatory factors.

Knee osteoarthritis is a degenerative disease that may develop due ageing, obesity, strain, congenital abnormal joints, joint deformity or trauma. It is caused by many factors, such as degradation of articular cartilage injury, joint edge and subchondral bone hyperplasia of reactivity. Platelet-rich plasma (PRP) is an autologous blood sample that contains highly concentrated platelets and multiple cell growth factors. PRP promotes synovial cell proliferation and differentiation and may recover cartilage morphology. In the present study, the clinical efficacy of PRP was investigated in patients with knee osteoarthritis aged between 18 and 30 years in a phase-III clinical study. Following an 8-week baseline, patients with knee osteoarthritis were randomized into once-weekly, double-blind treatment with PRP (2-14 ml) or placebo groups. The results indicated that patients with osteoarthritis treated with PRP had modulated plasma concentrations of inflammatory factors and pro-angiogenic factors compared with the placebo group. Treatment responses were assessed by median percent reduction in inflammatory and pro-angiogenic factors and these improved with PRP treatment compared with the placebo. Clinical data indicated that PRP alleviated knee osteoarthritis and reduced humoral and cellular immune responses that led to beneficial effects on histological parameters. Inflammation was significantly alleviated in patients receiving PRP compared with the placebo group. The most common treatment-emergent adverse events in the presence of PRP were hypertension and proteinuria. In conclusion, treatment with PRP for patients with knee osteoarthritis presented beneficial effects in alleviating joint inflammation, cartilage destruction and bone damage, and repairing joint tissue. These results suggested that PRP may be a potential therapeutic agent for knee osteoarthritis.

[Research progress in cell therapy and tissue engineering approach to regenerate salivary gland].

Objective: To review the research progress in cell therapy and tissue engineering approach to regenerate salivary gland so as to provide a theoretical basis for the treatment of salivary hypofunction. Methods: The recent literature on cell therapy and tissue engineering for the regeneration of salivary glands was reviewed and summarized. Results: It is feasible to repair the salivary function by using various stem cells to repair damaged tissue, or by establishing salivary gland tissue ex vivo for salivary gland function restoration and reconstruction. However, the mechanism of three dimensional culturing salivary organoids during organogenesis and function expressing and the potential influence of tissue specific extracellular matrix during this process should be further studied. Conclusion: Basic research of cell therapy and salivary tissue engineering should be deeply developed, and a standardized culturing system should be established in vitro. In addition, it is of great significance to study the in vivo effects of salivary gland-specific cells, non salivary gland epithelial cells and transplanted gene-transfected stem cells.

[Effects of aspirin on dendritic cells in the inflammatory microenvironment of rabbit buccal VX-2 squamous cell carcinoma].

OBJECTIVE: To explore the effects of aspirin and inflammation on the maturation and function of dendritic cells (DC) on the supernatant of VX-2 squamous cell carcinoma. METHODS: The rabbit buccal VX-2 squamous cell carcinoma models with inflammation were established by tumor particle implantation, mechanical trauma, and high sugar diet. The rabbits were divided into three groups. For the experimental group (rabbit buccal VX-2 squamous cell carcinoma with local inflammation), aspirin were given by gavage for three consecutive days. For the control group (rabbit buccal VX-2 squamous cell carcinoma with local inflammation), normal saline was given by gavage for three consecutive days. For the blank group (tumor without inflammation), normal saline was given by gavage for three consecutive days. Each tumor specimens were collected in three days and made into tissue homogenate. The supernatant was collected after centrifugation. Normal rabbit peripheral blood mononuclear cells were separated and co-cultured with different states of supernatant. The expression of DC surface markers CD83, CD86, and human leukocyte antigen-DR (HLA-DR) were detected by flow cytometry. The state of function of DC was tested by mixed lymphocyte reaction. RESULTS: The positive rate of CD83, CD86, and HLA-DR of the experimental and control groups were both lower than that of the blank group (P<0.05). In addition, the ability to stimulate T cell proliferation of the experimental and control groups were weaker than that of the blank group (P<0.05). No significant difference was observed between the experi- and HLADR of DC. The short-term administration of aspirin is not conducive to the phenoty and function of DC in a rabbit mental and control groups (P>0.05). CONCLUSION: Inflammation may inhibit the function and expression of CD83, CD86, buccal VX-2 squamous cell carcinoma inflammatory environment

Therapeutic efficacy of paclitaxel and carboplatin via arterial or venous perfusion in rabbits with VX-2 tongue cancer.

OBJECTIVE: This study aimed to investigate the therapeutic efficacy of paclitaxel in combination with carboplatin in different ways in rabbits with VX-2 tongue cancer. METHODS: Rabbit VX-2 tongue cancer model was established and animals were then divided into 6 groups, in which animals received perfusion with paclitaxel liposome and carboplatin via the lingual artery, with free paclitaxel and carboplatin via the lingual artery, with 5% glucose via the lingual artery, with paclitaxel liposome and carboplatin via ear vein, with free paclitaxel and carboplatin via the ear vein and with 5% glucose via the ear vein independently. When the maximum diameter of cervical lymph nodes was larger than 5 mm, chemotherapy was initiated. Seven days later, flow cytometry and immunohistochemistry were performed to detect the apoptosis of VX-2 cells and P53 expression in the primary cancer and metastatic lymph nodes. RESULTS: Targeted arterial perfusion with paclitaxel liposome in combination with carboplatin was more effective to induce the apoptosis of cancer cells in the primary cancer and metastatic lymph nodes and inhibit their proliferation. CONCLUSION: Targeted arterial perfusion with paclitaxel liposome in combination with carboplatin is effective to reduce tumor size, attenuate the surgery induced injury and improve the post-operative quality of life of oral cancer patients.

[CLINICAL APPLICATION OF NASOLABIAL ISLAND PEDICLED FLAP FOR REPAIRING MOUTH FLOOR DEFECTS].

OBJECTIVE: To investigate the effectiveness of nasolabial island pedicled flap in repairing mouth floor defects. METHODS: Between July 2010 and July 2013, 13 cases of mouth floor defects were repaired with nasolabial island pedicled flap. There were 7 males and 6 females, aged 36-73 years (mean, 58 years). Defects were caused by lesion resection, including 4 cases of leukoplakias, 2 cases of erythema, 1 case of mucoepidermoid carcinoma, 2 cases of the month floor cancer, and 4 cases of tongue cancer. The locations of defects were the mouth floor in 5 cases, the mouth floor and tongue body in 6 cases, and the mouth floor and gingival in 2 cases; the mucosa and submucosa were involved in 6 cases, and the sublingual gland, tongue muscle or alveolar process in 7 cases. The size of defect was 1-4 cm. The size of the flaps ranged from 4.5 cm x 2.0 cm to 6.5 cm x 3.5 cm. RESULTS: The operation was successfully performed in all patients; the flaps survived; and the primary healing of incisions at donor site and recipient site were obtained. Thirteen patients were followed up 5-24 months (mean, 11 months). No tumor recurrence was observed; the patients had normal functions of eating, swallowing, and speech. The facial appearance was satisfactory. No obvious deformity was observed at donor sites. CONCLUSION: The nasolabial island pedicled flap is fit for repairing small or middle sized defects of the mouth floor, and it has the advantages of flexible flap transplantation, less injury at donor site, easy operation, and high flap survival rate.

Functional regeneration of irradiated salivary glands with human amniotic epithelial cells transplantation.

This study aimed to investigate the functional restoration of radiation-damaged salivary gland with human amniotic epithelial cells (hAECs) transplantation by intra-glandular injection. hAECs were isolated from the amnion tissues. After primary culture, the phenotype of hAECs of the second passage was identified by flow cytometry (FCM) and immunocytochemical staining. Then, hAECs were intra-glandularly injected into the irradiated glands of mice. At different time points after transplantation, the glands were collected for hematoxylin-eosin (HE) staining and immunofluorescence staining, and the saliva flow rate was also determined. Results showed these cells were positive for CD29, CD73 and CK19 and negative for CD44, CD34, CD45 and CD71. The transplanted hAECs in the recipient glands could differentiate into acinar-like cells and resulted in morphological and functional restoration of salivary gland.

Transdifferentiation of human amniotic epithelial cells into acinar cells using a double-chamber system.

This study investigated the transdifferentiation of stem cells from human amnion tissue into functional acinar cells (ACs) using a co-culture system. Human amniotic epithelial cells (hAECs) were isolated from amnion tissue by mechanical mincing and enzymatic digestion. After primary culture, the phenotype of the cells was identified by flow cytometry (FCM) and immunocytochemical staining. hAECs were co-cultured with submandibular gland acinar cells of SD rats using a double-chamber system. The expression of α-amylase was determined by immunocytochemical method and fluorescent real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) after induction for 1 and 2 weeks, respectively. Digestion with trypsin is an effective method for isolating hAECs from amnion tissue. These cells were positive for CD29 and CK19 and weakly positive for CD44 and α-amylase. Within 2 weeks, α-amylase in hAECs increased with induction time. The expression of α-amylase in hAECs was increased 3.38-fold after co-culturing for 1 week. This ratio increased to 6.6-fold, and these cells were positive for mucins, after co-culturing for 2 weeks. hAECs possess the potential to differentiate into ACs in vitro. They might be a stem cell resource for clinical applications of cell replacement therapy in salivary gland dysfunction diseases.