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

At present, a common lack of basic scientific research training in the undergraduate education is one of the reasons restricting the innovation ability of undergraduates. Cultivating scientific research ability of undergraduates is one of the effective ways to improve the undergraduate professional education as well as the innovation ability. Therefore, after exploration and summary for years, we have formed a relatively mature new mode that cultivates the undergraduates' comprehensive abilities in scientific research, namely, the training system of scientific research ability of medical undergraduates guided by literature reading. It has improved the basic scientific quality and innovation ability of medical undergraduates in our university, and trained a group of outstanding undergraduates who have obtained various achievements, contributing to the construction of excellent postgraduate talents in our university. In addition, it is also an effective and feasible new teaching mode.

Objective To explore the impact of mindfulness on sleep and the mediating role of resilience.Methods A total of 540 medical staff in a three first-class hospital were assessed by five facet mindfulness questionnaire (FFMQ),Pittsburgh sleep quality index(PSQI) and Connor-Davidson resilience scale(CD-RISC).Results The average PSQI scores of medical staff was (6.67±3.20),of which the total score was equal or above 8 accounting for 37.04％.The positive rate of each factor of PSQI (factor score ≥2) was 51.67％ for daytime function,37.22％ for sleeping time,and 24.07％ for subjective sleep quality.The total score of PSQI was (6.67±3.20),the score of FFMQ was (119.55±9.90),and the score of CDRISC was (59.50± 12.77).PSQI was negatively correlated with FFMQ and CD-RISC (r=-0.29,-0.24;both P＜0.01),and there was a significant positive correlation between FFMQ and CD-RISC (r=0.48,P＜0.01).The factors of FFMQ associated with CD-RISC were followed by the description of mindfulness,the action of awareness,the non-reaction and the observation of mindfulness.The multi-linear regression analysis showed that resilience played a part mediating role between mindfulness and sleep quality,with a mediating effect of 20.9％.Conclusion Mindfulness has a positive impact on the quality of sleep of medical staff through resilience.

Objective To explore the role of Nogo-A receptor antagonist NEP1-40 in regulating regeneration of neural cells and related Wnt signaling pathway in neonatal rats with hypoxic ischemic encephalopathy (HIBD).Methods A total of 40 HIBD rats were divided into HIBD group and HIBD + NEP1-40 group,20 rats in each group.PCR Test,Western Blot Analysis,IHC test for cell proliferation and 8-isoprostane detection were used to evaluate regulation of NgR transcription factors in Wnt signaling pathway and proliferation of neural cells.Results The expressions of c-Jun and cMyc,at the protein level,were up-regulated after treatment with Nogo-A receptor antagonist NEP1-40 for 7 days,and the same change was observed at gene expression and Ki-67.There was no significant change of 8-isoprostane.Conclusion The c-Jun and c-Myc are the main transcription factors in Wnt signaling pathway by inhibition of NgR,and meanwhile the proliferation of nerve cells in subventricular zone increase.

Objective To explore the role of Nogo-A receptor antagonist NEP1-40 in regulating regeneration of neural cells and related Wnt signaling pathway in neonatal rats with hypoxic ischemic encephalopathy (HIBD).Methods A total of 40 HIBD rats were divided into HIBD group and HIBD + NEP1-40 group,20 rats in each group.PCR Test,Western Blot Analysis,IHC test for cell proliferation and 8-isoprostane detection were used to evaluate regulation of NgR transcription factors in Wnt signaling pathway and proliferation of neural cells.Results The expressions of c-Jun and cMyc,at the protein level,were up-regulated after treatment with Nogo-A receptor antagonist NEP1-40 for 7 days,and the same change was observed at gene expression and Ki-67.There was no significant change of 8-isoprostane.Conclusion The c-Jun and c-Myc are the main transcription factors in Wnt signaling pathway by inhibition of NgR,and meanwhile the proliferation of nerve cells in subventricular zone increase.

Objective To evaluate the effect of intraperitoneal water soluble lipopolymer (WSLP)/ N-methyl-D-aspartate receptor subunit 2B (NR2B) siRNA compound on the neuropathic pain (NP) in rats.Methods Eighty-four healthy male Sprague-Dawley rats,aged 6 weeks,weighing 180-220 g,were randomly divided into 7 groups (n =12 each) using a random number table:control group (group C),sham operation group (group S),NP group,WSLP/NR2B siRNA group (siWSLP group),WSLP/negative control siRNA group (ncWSLP group),PEI/NR2B siRNA group (PEI group) and WSLP group (WSLP group).NP was produced by ligation of the left L5 spinal nerve.In group S,the left L5 spinal nerve was only exposed,but not ligated.In group C,the rats underwent no treatment.Groups siWSLP,ncWSLP,PEI and WSLP received single intraperitoneal injection of WSLP/NR2B siRNA,WSLP/negative control siRNA,PEI/NR2B siRNA and WSLP compound 2 ml,respectively,at 10 days after NP.At 1 day before operation,7 days after operation,and 3,7,14 and 21 days after intraperitoneal injection,6 rats in each group were chosen randomly to measure mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL).At 3 days after intraperitoneal injection,the left 6 rats in each group were sacrificed and the spinal cord was removed for detection of NP2B mRNA expression (using PCR) and NR2B expression (by Western blot).Results Compared with group C,MWT was significantly decreased,and TWL was shortened on 7 days after operation and 3,7 and 21 days after intraperitoneal injection,and the expression of NR2B mRNA and protein was down-regulated on 3 days after administration in the other groups.Compared with group NP,MWT was significantly increased,and TWL was prolonged on day 3 and 7 after intraperitoneal injection,and the expression of NR2B mRNA and protein was down-regulated on day 3 after administration in siWSLP group.Conclusion Intraperitoneal WSLP/NR2B siRNA compound can effectively relieve the NP in rats.

Eight-year medical education is to train medical personnel with high research abi lity and innovative ability, while the experimental teaching, as an important part of physiology teaching, plays an important role in training students in observation, problem-solving skills and practical ability. This article mainly discusses our exploration and practice of teaching in physiology experiment for eight-year program medical students from teaching contents and organization of class teaching, in order to fully increase the studying enthusiasms and meet the scientific mind of these students.

In order to supply some reference about the construction of network course of physiology, we summed up the establishing experience from the course design, construction and application.

Objective To investigate the feasibility of NR2B small interference RNA(NR2B siRNA)carried by water-soluble lipopolymer(WSLP)for treatment of neuropathic pain in rats.Methods One hundred healthy male SD rats weighing 180-200 g were randomly divided into 5 groups(n=20 each):normal control group (group C),sham operation group(group S),neuropathic pain group(group NP),group WSLP-NR2B siRNA (group W)and group WSLP-negative NR2B siRNA(group WN).Neuropathic pain was induced by partial ligation of sciatic nenre.WSLP-NR2B siRNA complex was formed by binding WSLP and NR2B siRNA.Normal saline.WSLP-NR2B siRNA complex and WSLP-negative NR2B siRNA 20μl were injected intrathecally after operation in NP,W and WN groups respectively.Mechanical withdrawal threshold(MWT)and thermal withdrawal duration (TWD)were measured before(baseline)and at 3,7,14 and 21 days after operation.Ten animals in each group were sacrificed on the 3rd day after operation and the lumbar segment(L4-6)of the dorsal root ganglia was removed for determination of the expression of NR2B mRNA and protein using RT-PCR and Western blot analysis.Results Sciatic nerve ligation significantly decreased MWT and prolonged TWD and increased NR2B mRNA and protein expression in group NP as compared with group C.WSLP-NR2B siRNA complex significantly reduced sciatic nerve ligation-induced hyperalgesia and decreased NR2B mRNA and protein expression in group W as compared with group NP.Conclusion WSLP not only mediates NR2B siRNA successfully and inhibits the expression of NR2B,but also reduces neuropathic pain in rats.