Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36⁺ myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36⁺ myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.
Humans ; Adenoma, Pleomorphic/genetics* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Transcriptome ; Myoepithelioma

Proliferative verrucous leukoplakia (PVL) is one of the oral potentially malignant disorders (OPMD) with the highest malignant potential. PVL tends to be easily misdiagnosed owing to the resemblance in clinical manifestations between PVL and other diseases such as oral leukoplakia or oral lichen planus. PVL is considered as a special type of oral leukoplakia by some scholars, which is characterized by its tendency of recurrence and metastasis, along with its high risk of malignant transformation. So far, the accurate clinic diagnosis and management of PVL are still intractable due to the lack of definite histopathological definition, unified diagnostic criteria and effective treatment modalities. This review aims to provide the clinical practitioners with a series of advices on the clinical diagnosis and management of PVL by systematically reviewing the diagnostic logistics, therapeutic strategies, malignant transformation detection based on tremendous relevant data and evidence-based medicine.

Objective:Based on the principle that the aggregation-induced emission (AIE) fluorescent probe 6PD-DPAN could bind and aggregate with bacteria, and the fluorescence intensity could reflect the quantity of bacteria, a new method for rapid, convenient, and accurate bacterial drug sensitivity testing was established, which provided a basis for rapid and accurate clinical drug use.Methods:This was a methodological evaluation study. A total of 107 clinical isolates were collected from Houjie Hospital of Dongguan City from January to December 2022, among which 46 isolates were used for the establishment of the new method, and 61 isolates were used for methodological validation. The minimum inhibitory concentration (MIC) determined by broth microdilution method was used as the gold standard, and three antibacterial drugs, gentamicin, levofloxacin, and cefotaxime, were used as experimental drugs. The AIE plate was incubated for 4 hours, and the fluorescence intensity was measured every half an hour to draw a fluorescence change curve. The MIC results were compared with the CLSI breakpoints to determine the bacteria as sensitive, intermediate, or resistant. To simplify the detection process, the ratio of fluorescence intensity at 4 hours(R) was calculated, and the ROC curve was used to analyze the efficacy of R in determining bacterial growth and establish its cutoff value. The new method was used to determine the MIC of 61 clinical isolates, with broth microdilution method as the gold standard. The basic consistency, categorical consistency, very major errors, and major errors of the new method were analyzed, and the consistency between the two methods was determined by the Kappa test.Results:ROC curve analysis of the R after 4 hours of culture: The cut-off value was 3.0, with both sensitivity and specificity for determining bacterial growth being 100%. The median (interquartile) R for bacterial growth inhibition was 11.1 (8.6, 14.4); the median R-value for bacterial growth was 1.1 (1.0, 1.2). Compared to the gold standard, the newly established method showed 100% (61/61) essential agreement in detecting MICs of 61 clinical isolates, with a categorical agreement of 96.7% (59/61). There were no very major or major errors, and the Kappa value was 0.94, indicating good consistency between the newly established method and the microbroth dilution method.Conclusions:This study successfully established a new method for bacterial drug sensitivity testing based on AIE technology, which could obtain satisfactory results within 5 hours, providing a basis for early precision drug treatment in clinical practice.

Objective To analyze the factors affecting the prognosis of patients with pulmonary sarcomatoid carcinoma (PSC) and construct a nomogram prediction model for the prognosis of PSC patients. Methods Based on the SEER database, 1671 patients diagnosed as PSC from 1988 to 2015 were collected and divided into modeling group and validation group according to the ratio of 7:3. Univariate and multivariate Cox regression analysis were performed in the modeling group to explore independent risk factors affecting the prognosis and construct a nomogram survival prediction model. The consistency index and calibration curve were used for verification in the modeling group and the test module respectively. Results Age, gender, histological type, TNM stage, tumor diameter > 50mm, surgery, radiotherapy and chemotherapy were independent factors that affected the prognosis of PSC patients. The nomogram prediction model was constructed and verified based on independent factors. The C indexes of the modeling group and the test model were 0.790 (95%CI: 0.776-0.804) and 0.781 (95%CI: 0.759-0.803), respectively. The calibration curves of the modeling group and the test model indicated that the predicted survival rate was basically the same as the actual survival rate. Conclusion The nomogram prediction model constructed based on the results of multivariate analysis can predict the prognosis of PSC patients, and has high accuracy and consistency.

Objective:The purpose of this study is to establish the trajectory of targeted grafting for facial fat compartment based on anatomical research, and then bring it to clinical practice.Methods:The boundary of fat compartment and the relationship of adjacent vessel and nerve were clarified through autopsy. The recommended injection points and trajectory for targeted fat grafting were established on the anatomical findings. Retrospective clinical data of facial rejuvenation of 46 patients through targeted fat grafting were collected from June 2017 to June 2019 in Shanghai Ninth People’s Hospital. The result of 3D scanning were analyzed to evaluate the survival rate of fat grafts.Results:There were subcutaneous superficial fat compartments in the frontal region, and there were both deep and superficial fat compartments in the temporal and middle face. According to the anatomical characteristics, a targeted fat grafting technique was established with the frontal hairline and the oral commissure corner mucosa as the entry points. In the clinical study, 46 patients were evaluated by 3D scanning 6 months after the last fat grafting. The amount of fat grafts in the temporal region was (17.84±8.47) ml and (11.2±2.44) ml was left after operation, and the survival rate was 63%. The amount of fat grafts in mid-face was (26.81±10.36) ml and (16.09±4.48) ml was left after operation, and the survival rate was 60%. Overall satisfaction rate of patients was 93% (43/46).Conclusions:Compartment-based targeted fat grafting is an accurate injection method, which meets the requirement of physiological augmentation. The trajectory of targeted fat grafting will further improve the efficacy and safety of injection.

Objective:The purpose of this study is to establish the trajectory of targeted grafting for facial fat compartment based on anatomical research, and then bring it to clinical practice.Methods:The boundary of fat compartment and the relationship of adjacent vessel and nerve were clarified through autopsy. The recommended injection points and trajectory for targeted fat grafting were established on the anatomical findings. Retrospective clinical data of facial rejuvenation of 46 patients through targeted fat grafting were collected from June 2017 to June 2019 in Shanghai Ninth People’s Hospital. The result of 3D scanning were analyzed to evaluate the survival rate of fat grafts.Results:There were subcutaneous superficial fat compartments in the frontal region, and there were both deep and superficial fat compartments in the temporal and middle face. According to the anatomical characteristics, a targeted fat grafting technique was established with the frontal hairline and the oral commissure corner mucosa as the entry points. In the clinical study, 46 patients were evaluated by 3D scanning 6 months after the last fat grafting. The amount of fat grafts in the temporal region was (17.84±8.47) ml and (11.2±2.44) ml was left after operation, and the survival rate was 63%. The amount of fat grafts in mid-face was (26.81±10.36) ml and (16.09±4.48) ml was left after operation, and the survival rate was 60%. Overall satisfaction rate of patients was 93% (43/46).Conclusions:Compartment-based targeted fat grafting is an accurate injection method, which meets the requirement of physiological augmentation. The trajectory of targeted fat grafting will further improve the efficacy and safety of injection.

[Summary] This paper was to investigate whether serum angiopoietin-like protein 2 (Angptl 2) is associated with macrovascular complications in type 2 diabetes mellitus.The results showed that there were statistically significant differences in serum Angptl 2 levels among control group and groups of type 2 diabetic patients with or without carotid atherosclerosis [0.98 (0.82-1.22),3.70 (2.69-4.85),1.17 (0.76-2.47) ng/ml].Logistic regression showed that Angptl 2 was an independent risk factor of macrovascular complications in the patients with type 2 diabetes.

BACKGROUND:Both calcium phosphate cement II and recombinant human bone morphogenetic protein have certain osteoinductive effects, which have the possibility of repairing tendon-bone interface injury. OBJECTIVE: To investigate the osteoinductive effect of calcium phosphate cement II and its biomechanics analysis of repairing tendon-bone interface injury. METHODS:Five out of 35 adult healthy New Zealand white rabbits were randomly selected and their bilateral shoulder joint tendon-bone interface specimens were taken as normal control group after being sacrificed. The remaining 30 rabbits were used to make animal models of tendon-bone interface injury and then randomly divided into experimental and model groups. Rabbits in the model group had no treatment, and those in the experimental group were treated with calcium phosphate cement II. RESULTS AND CONCLUSION: After repair with calcium phosphate cement II, the injured tendon-bone interface of rabbits was obviously restored, and the repair effect became better with time. The expression level of bone morphogenetic protein 2 was also increased accordingly. The maximum tensile strength and the maximum stiffness of the injured tendon-bone interface were obviously increased. These results demonstrate that calcium phosphate cement II combined with recombinant human bone morphogenetic protein has good osteoinductive and repair effect in repair of tendon-bone interface injury.

Objective To identify the metabolic levels in prefrontal lobe in patients with post-concussion syndrome by proton magnetic resonance spectroscopy (1H-MRS), and to explore the relationship between metabolic levels and executive function. Methods The study was conducted in 40 patients with post-concussion syndrome and 20 normal controls. 1H-MRS on prefrontal lobe was performed in patients and controls, the NAA, Cho and Cr were measured and the ratios of NAA/Cr, Cho/Cr and NAA/(Cho + Cr) were determined. They were also evaluated executive functions by verbal fluency test (animal), Wisconsin Card Sorting Test (WSCT) and Tower of Hanoi (TOH). Results Compared with normal controls, the patients with post-concussion syndrome were significantly lower NAA/Cr and NAA/(Cho+Cr) ratios in left prefrontal lobe (P < 0.05). The NAA/Cr ratio in left prefrontal was significantly positive correlated with total scores of verbal fluency (r = 0.66, P < 0.05), categories of WSCT (r = 0.54,P < 0.05) and total score of TOH(r = 0.58, P < 0.05). The NAA/Cr ratio was significantly negative correlated with total errors (r = -0.53, P < 0.05) and persistent errors (r = -0.47, P < 0.05) of WSCT and mean executive time of TOH(r = -0.67, P < 0.05). Conclusions The metabolic levels of NAA in left prefrontal lobe in patients with post-concussion syndrome is significantly decreased , it is one cause of impaired executive functions.