OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45⁺ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3⁺ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Heterografts ; Bone Marrow ; Disease Models, Animal ; T-Lymphocytes ; Mice, SCID

OBJECTIVE: To investigate the therapeutic effect of Epothilone D on traumatic optic neuropathy (TON) in rats. METHODS: Forty-two SD rats were randomized to receive intraperitoneal injection of 1.0 mg/kg Epothilone D or DMSO (control) every 3 days until day 28, and rat models of TON were established on the second day after the first administration. On days 3, 7, and 28, examination of flash visual evoked potentials (FVEP), immunofluorescence staining and Western blotting were performed to examine the visual pathway features, number of retinal ganglion cells (RGCs), GAP43 expression level in damaged axons, and changes of Tau and pTau-396/404 in the retina and optic nerve. RESULTS: In Epothilone D treatment group, RGC loss rate was significantly decreased by 19.12% (P=0.032) on day 3 and by 22.67% (P=0.042) on day 28 as compared with the rats in the control group, but FVEP examination failed to show physiological improvement in the visual pathway on day 28 in terms of the relative latency of N2 wave (P=0.236) and relative amplitude attenuation of P2-N2 wave (P=0.441). The total Tau content in the retina of the treatment group was significantly increased compared with that in the control group on day 3 (P < 0.001), showing a consistent change with ptau-396/404 level. In the optic nerve axons, the total Tau level in the treatment group was significantly lower than that in the control group on day 7 (P=0.002), but the changes of the total Tau and pTau-396/404 level did not show an obvious correlation. Epothilone D induced persistent expression of GAP43 in the damaged axons, detectable even on day 28 of the experiment. CONCLUSION Epothilone D treatment can protect against TON in rats by promoting the survival of injured RGCs, enhancing Tau content in the surviving RGCs, reducing Tau accumulation in injured axons, and stimulating sustained regeneration of axons.
Animals ; Disease Models, Animal ; Epothilones ; Evoked Potentials, Visual ; Nerve Regeneration/physiology* ; Optic Nerve Injuries/metabolism* ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/physiology*

OBJECTIVE: To investigate the clinicopathological characteristics of micro and mini parotid gland tumors and to provide reference for their clinical diagnosis and treatment. METHODS: Patients with parotid gland tumors treated in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from December 2012 to April 2020 were selected. Relevant clinical data of the patients with tumor diameter ≤20 mm detected by preoperative CT were collected to analyze the clinicopathological characteristics and prognosis of micro and mini parotid gland tumors. And the collected data were divided into two groups with diameter 11-20 mm and diameter ≤10 mm according to tumor diameter measured by preoperative CT. The clinicopathological differences between the two groups were statistically analyzed. RESULTS: A total of 2 067 patients with primary epithelial parotid gland tumors were collected, and 685 patients with tumor diameter ≤20 mm were examined by CT, accounting for 33.1%. The ratio of male to female patients with micro and mini parotid gland tumors was 1 ∶1.93, the average age was (45.3±13.8) years (12-83 years), and the median course of disease was 12 months (1 week to 30 years). Among them, 635 cases (92.7%) were benign tumors, 50 cases (7.3%) were malignant tumors, and the ratio of benign to malignant was 12.7 ∶1. The most common benign tumor was pleomorphic adenoma, and the most common malignant tumor was mucoepidermoid carcinoma. The micro and mini parotid gland tumors were divided into 11-20 mm group (n=611) and ≤10 mm group (n=74), the clinical characteristics comparison of the two groups of gender ratio, average age, course of di-sease had no statistical difference (P>0.05). In the 11-20 mm diameter group, the percentage of benign and malignant tumor was 92.8% (567/611) and 7.2% (44/611) respectively, and the ratio of benign to malignant tumors was 12.9 ∶1. In the ≤10 mm diameter group, the percentage of benign and malignant tumor was 91.9% (68/74) and 8.1% (6/74) respectively, and the ratio of benign to malignant tumors was 11.3 ∶1. There was no significant difference between the two groups (P>0.05). Fifty patients with malignant tumor were followed up for the median follow-up period of 39.5 months (1-91 months). Local recurrence occurred in 2 patients with one death. The overall 2-year survival rate was 93.7% and the 5-year survival rate was 89.3%. CONCLUSION The majority of micro and mini parotid gland tumors was benign lesion. There was a good prognosis for micro and mini parotid gland carcinoma. Early surgical treatment was recommended for micro and mini parotid gland tumors.
Adenoma, Pleomorphic/surgery* ; Adult ; Carcinoma, Mucoepidermoid/pathology* ; Female ; Humans ; Male ; Middle Aged ; Parotid Gland ; Parotid Neoplasms/surgery* ; Retrospective Studies

OBJECTIVE: To establish a Parotid Imaging Reporting and Data System (PI-RADS) for CT diagnosis of the parotid gland neoplasms and to investigate the clinical applicable value and feasibility of PI-RADS. METHODS: Patients who had been diagnosed with primary parotid gland neoplasms and had received surgical treatments in Peking University School and Hospital of Stomatology during the period of January 2013 to December 2016 were included in this study. The diagnoses were confirmed by the postoperative pathological examinations in all the patients. The CT imaging data of all patients were retrospectively reviewed and analyzed by two readers in consensus. Imaging characteristics related to the parotid neoplasms were extracted and quantified. Based on comprehensive analysis of the imaging characteristics, the probabilities of the benign and malignant neoplasms were evaluated and classified into six grades, PI-RADS 1-6 (PI-RADS 1: normal parotid gland; PI-RADS 2: confidently benign lesions; PI-RADS 3: probably benign lesions without confirmed evidence of malignancy; PI-RADS 4: suspected malignancy without sufficient evidence of malignancy; PI-RADS 5: confidently malignant lesions; PI-RADS 6: lesions with confirmed pathological evidence of malignancy). RESULTS: A total of 897 patients with 1 003 parotid lesions were included. The lesions included 905 benign and 98 malignant lesions. The proportions of the malignancies in PI-RADS 2, PI-RADS 3, PI-RADS 4 and PI-RADS 5 according to the two readers in consensus were 0.4%, 5.7%, 35.5% and 96.7% respectively. The overall Cohen's Kappa test showed medium consistency between the two independent researchers (κ=0.614, P<0.001, 95%CI: 0.569-0.695). Pearson Chi-square test showed that the proportions of malignancies increased with the diagnostic PI-RADS grades (Cochran-Armitage trend test, Z=-15.579, P<0.001). The results of Pearson Chi-square tests showed significant differences between the grades [PI-RADS 2 and 3 (χ²=12.048, P=0.001); PI-RADS 3 and 4 (χ²=75.231, P<0.001); PI-RADS 4 and 5 (χ²=32.266, P<0.001)]. CONCLUSION PI-RADS can be used to evaluate the risk of malignancy and will be helpful to improve the imaging diagnosis and clinical treatment of parotid gland neoplasms.
Humans ; Magnetic Resonance Imaging ; Male ; Parotid Gland/diagnostic imaging* ; Parotid Neoplasms ; Prostatic Neoplasms ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVE: To explore the application of mixed reality technique for the surgery of oral and maxillofacial tumors. METHODS: In this study, patients with a diagnosis of an oral and maxillofacial tumor who were referred to Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from December 2018 to January 2020 were selected. The preoperative contrast-enhanced computed tomography data of the patients were imported into StarAtlas Holographic Medical Imaging System (Visual 3D Corp., Beijing, China). Three-dimensional (3D) model of tumor and key structures, such as skeleton and vessels were reconstructed to three-dimensionally present the spatial relationship between them, followed with the key structures delineation and preoperative virtual surgical planning. By using mixed reality technique, the real-time 3D model was displayed stereotactically in the surgical site. While keeping sterile during operation, the surgeon could use simple gestures to adjust the 3D model, and observed the location, range, and size of tumor and the key structures adjacent to the tumor. Mixed reality technique was used to assist the operation: 3D model registration was performed for guidance before tumor excision; intraoperative real-time verification was performed during tumor exposure and after excision of the tumor. The Likert scale was used to evaluate the application of mixed reality technique after the operation. RESULTS: Eight patients underwent mixed reality assisted tumor resection, and all of them successfully completed the operation. The average time of the 3D model registration was 12.0 minutes. In all the cases, the surgeon could intuitively and three-dimensionally observe the 3D model of the tumor and the surrounding anatomical structures, and could adjust the model during the operation. The results of the Likert scale showed that mixed reality technique got high scores in terms of perceptual accuracy, helping to locate the anatomical parts, the role of model guidance during surgery, and the potential for improving surgical safety (4.22, 4.19, 4.16, and 4.28 points respectively). Eight patients healed well without perioperative complications. CONCLUSION By providing real-time stereotactic visualization of anatomy of surgical site and guiding the operation process through 3D model, mixed reality technique could improve the accuracy and safety of the excision of oral and maxillofacial tumors.
Augmented Reality ; China ; Humans ; Imaging, Three-Dimensional ; Neoplasms ; Retrospective Studies ; Surgery, Computer-Assisted

OBJECTIVE: To study the effects of different melatonin treatment regimens on the proliferation of neural stem cells (NSCs) and long-term histopathology in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to identify better melatonin treatment regimens. METHODS: A total of 96 Sprague-Dawley rats aged 7 days were randomly divided into normal control, HIBD, single-dose immediate melatonin treatment (SDIT), and 7-day continuous melatonin treatment (7DCT) groups, with 24 rats in each group. The rat model of HIBD was prepared by isolation and electrocoagulation of the right common carotid artery as well as hypoxic treatment in a hypoxic chamber (oxygen concentration 8.00% ± 0.01%) for 2 hours. On day 7 after modeling, proliferating cell nuclear antigen/Nestin double-labeling immunofluorescence was used to measure the proliferation of endogenous NSCs in the subventricular zone (SVZ) and the hippocampal dentate gyrus (DG) region in 8 rats in each group, and Western blot was used to measure the protein expression of Nestin in brain. On day 28 after modeling, hematoxylin-eosin (HE) staining and Nissl staining were used to observe the changes in the histopathology and the number of pyramidal cells in the hippocampal CA1 region in 8 rats in each group. RESULTS: Immunofluorescent staining showed that compared with the HIBD group, the SDIT and 7DCT groups had a significant increase in the number of PCNA+Nestin+DAPI+ cells, and the 7DCT group had a significantly higher number than the SDIT group (P<0.01). Western blot showed that the SDIT and 7DCT groups had significantly higher protein expression of Nestin than the HIBD group, and the 7DCT group had significantly higher expression than the SDIT group (P<0.05). HE staining showed that the SDIT and 7DCT groups had alleviated cell injury, and Nissl staining showed that compared with the HIBD group, the SDIT and 7DCT groups had a significant increase in the number of pyramidal cells, and the 7DCT group had a significantly higher number than the SDIT group (P<0.01). CONCLUSIONS Both single-dose immediate melatonin treatment and 7-day continuous melatonin treatment can promote the proliferation of endogenous NSCs and alleviate long-term histological injury in the brain of neonatal rats with HIBD. A 7-day continuous melatonin treatment has a better effect than single-dose immediate melatonin treatment.
Animals ; Animals, Newborn ; Brain ; Cell Proliferation ; Hypoxia-Ischemia, Brain ; Melatonin ; Neural Stem Cells ; Neurons ; Rats ; Rats, Sprague-Dawley

AIM:To investigate the effect of 27nt-microRNA (27nt-miRNA) on the expression of smooth muscle 22α protein (SM22α) and the cell viability, migration and phenotypic changes of vascular smooth muscle cells (VSMCs).METHODS:The highly expression plasmids of 27nt-miRNA, and anti-27nt-miRNA and negative control plasmids were constructed, packaged with lentivirus and transfected into the rat primary VSMCs.Platelet-derived growth factor BB (PDGF-BB) was added to induce VSMCs phenotype conversion.The cell viability was measured by MTT assay.The migration ability was detected by scratch assay.The mRNA and protein expression of SM22αwas determined by RT-PCR, immunocytochemical staining and Western blot.RESULTS:Compared with normal group, the cell viability in PDGF-BB group was increased (P<0.05) , the migration ability was increased (P<0.05) and the expression of SM22αat mRNA and protein level was decreased (P<0.05).Compared with negative control lentiviral group, the cell viability in 27ntmiRNA over-expression group was decreased (P<0.05) , the migration ability was decreased (P<0.05) , and the mRNA and protein expression of SM22αwas increased (P<0.05).While in anti-27nt-miRNA group, the cell viability was increased (P<0.05) , the migration ability was increased (P<0.05) , and the mRNA and protein expression of SM22αwas decreased (P<0.05).CONCLUSION:27nt-miRNA significantly increases the expression of SM22α, while inhibits the viability and migration ability of VSMCs, and inhibits its phenotypic shift from contractile to synthetic.

Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated disease and one of immunoglobulin G4-related diseases (IgG4-RD). Our multidisciplinary research group investigated the clinicopathological characteristics and diagnosis of IgG4-RS during the past 10 years. Clinically, it showed multiple bilateral enlargement of major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands. The comorbid diseases of head and neck region including rhinosinusitis, allergic rhinitis, and lymphadenopathy were commonly seen, which could occur more early than enlargement of major salivary glands. Internal organ involvements, such as autoimmune pancreatitis, sclerosing cholangitis, and interstitial pneumonia could also be seen. Thirty-five (38.5%) patients had the symptom of xerostomia. Saliva flow at rest was lower than normal. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in almost all the cases and the majority of the patients had increased IgE levels. CT, ultrasonography, and sialography showed their imaging characteristics. Histologically it showed marked lymphoplasmacytic inflammation, large irregular lymphoid follicles with expanded germinal centers, prominent cellular interlobular fibrosis, eosinophil infiltration, and obliterative phlebitis. Their immunohistological examination showed marked IgG-positive and IgG4-positive plasma cell infiltration and high IgG4/IgG ratio. The disease could be divided into three stages according to severity of glandular fibrosis. The serum IgG4 level was higher and the saliva secretion lower as glandular fibrosis increased. IgG4-RS should be differentiated from other diseases with enlargement of major salivary gland and lacrimal gland, such as primary Sjögren syndrome, chronic obstructive submandibular sialadenitis, and eosinophilic hyperplastic lymphogranuloma.
Autoimmune Diseases ; Humans ; Immunoglobulin G ; Sialadenitis ; Sjogren's Syndrome ; Submandibular Gland